Ciy745 PDF

Clinical Infectious Diseases
IDSA GUIDELINE
2018 Infectious Diseases Society of America Clinical

Practice Guideline for the Management of Outpatient
Parenteral Antimicrobial Therapya
Anne H. Norris,1 Nabin K. Shrestha,2 Genève M. Allison,3 Sara C. Keller,4 Kavita P. Bhavan,5 John J. Zurlo,6 Adam L. Hersh,7 Lisa A. Gorski,8
John A. Bosso,9 Mobeen H. Rathore,10 Antonio Arrieta,11 Russell M. Petrak,12 Akshay Shah,13 Richard B. Brown,14 Shandra L. Knight,15 and
Craig A. Umscheid16
1
Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia; 2Department of Infectious Diseases, Cleveland Clinic, Ohio; 3Division of Geographic Medicine
and Infectious Diseases, Tufts Medical Center, Boston, Massachusetts; 4Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; 5Division of Infectious Diseases,
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas; 6Division of Infectious Diseases, Thomas Jefferson University, Philadelphia, Pennsylvania; 7Division
of Pediatric Infectious Diseases, Department of Pediatrics, University of Utah, Salt Lake City; 8Wheaton Franciscan Home Health & Hospice, Part of Ascension at Home, Milwaukee, Wisconsin;
Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

9
Departments of Clinical Pharmacy and Outcome Sciences and Medicine, Colleges of Pharmacy and Medicine, Medical University of South Carolina, Charleston; 10University of Florida Center for
HIV/AIDS Research, Education and Service and Wolfson Children’s Hospital, Jacksonville; 11Department of Pediatric Infectious Diseases, Children’s Hospital of Orange County Division of Pediatrics,
University of California–Irvine School of Medicine; 12Metro Infectious Disease Consultants, Chicago, Illinois; 13Metro Infectious Disease Consultants, Northville, Michigan; 14Division of Infectious
Disease Medical Center, University of Massachusetts School of Medicine, Worcester; 15Library & Knowledge Services, National Jewish Health, Denver, Colorado; and 16Department of Medicine,
Perelman School of Medicine, University of Pennsylvania, and Center for Evidence-based Practice, University of Pennsylvania Health System, Philadelphia
A panel of experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2004 clinical practice guideline
on outpatient parenteral antimicrobial therapy (OPAT) [1]. This guideline is intended to provide insight for healthcare professionals
who prescribe and oversee the provision of OPAT. It considers various patient features, infusion catheter issues, monitoring ques-
tions, and antimicrobial stewardship concerns. It does not offer recommendations on the treatment of specific infections. The reader
is referred to disease- or organism-specific guidelines for such support.
Keywords. OPAT; parenteral antimicrobial therapy; treatment guideline; IV antimicrobial.
EXECUTIVE SUMMARY the recommendation and quality of evidence using Grading of

Outpatient parenteral antimicrobial therapy (OPAT) is defined Recommendations Assessment, Development and Evaluation
as the administration of parenteral antimicrobial therapy in at (GRADE) (Figure 1) [2–5]. This revision focuses on systemat-
least 2 doses on different days without intervening hospitali- ically reviewing the literature to answer specific OPAT practice
zation. Recommendations made in the updated guideline for questions using published evidence. Readers are referred to the
the prescription and management of OPAT are summarized 2016 IDSA OPAT eHandbook for a more in-depth discussion
below. The panel followed a process used in the development of background and hands-on advice on the practice of OPAT
of other Infectious Diseases Society of America (IDSA) guide- [6]. Best practice tables that address pharmacokinetic features,
lines, which included a systematic weighting of the strength of administration options, and potential adverse effects of selected
antimicrobials are included in this guideline. The guideline is
not intended to replace clinical judgment in the management
Received 22 August 2018; editorial decision 24 August 2018; published online November of individual patients. A detailed description of the methods,
13, 2018.
a
background, and evidence summaries that support each recom-
This guideline represents the proprietary and copyrighted property of the Infectious
Diseases Society of America (IDSA). Copyright 2018 Infectious Diseases Society of America. mendation can be found online in the full text of the guideline.
All rights reserved. No part of this guideline may be reproduced, distributed, or transmitted in
any form or by any means, including photocopying, recording, or other electronic or mechanical PATIENT CONSIDERATIONS
methods, without the prior written permission of IDSA. Permission is granted to physicians and
healthcare providers solely to copy and use the guideline in their professional practices and I. Should patients (or their caregivers) be allowed to self-administer
clinical decision-making. No license or permission is granted to any person or entity, and prior OPAT?
written authorization by IDSA is required, to sell, distribute, or modify the guideline or to make Recommendation
derivative works of or incorporate the guideline into any product including, but not limited to,
clinical decision-support software or any other software product. Any person or entity desiring
1. Patients (or their caregivers) should be allowed to self-admin-
to use the guideline in any way must contact IDSA for approval in accordance with IDSA’s terms ister OPAT (strong recommendation, low-quality evidence).
and conditions of third-party use, in particular, any use of the guideline in any software product.
Correspondence: A. H. Norris, Perelman School of Medicine, University of Pennsylvania–Penn II. Should patients (or their caregivers) be allowed to self-administer
Presbyterian Medical Center, 3910 Powelton Ave, Philadelphia, PA 19104 ([email protected]).
OPAT at home without visiting nurse support?
Clinical Infectious Diseases® 2019;68(1):e1–e35 Recommendation
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society
of America. All rights reserved. For permissions, e-mail: [email protected]. 2. Patients (or their caregivers) may be allowed to self-admin-
DOI: 10.1093/cid/ciy745 ister OPAT at home without visiting nurse support as long
2018 IDSA Clinical Practice Guideline for the Management of OPAT • CID 2019:68 (1 January) • e1
Figure 1. Approach and implications to rating the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development
and Evaluation (GRADE) methodology. Unrestricted use of the figure granted by the USA GRADE Network.
as there is a system in place for effective monitoring for vas- been duly considered and that the patient or caregiver is able
cular access complications and antimicrobial adverse events to communicate with the treatment team if necessary.
(weak recommendation, low-quality evidence).
V. Should infants aged <1 month be treated with OPAT at home?
III. Can persons who inject drugs (PWID) be treated with OPAT at home?
Recommendation
Recommendation
5. No recommendation can be made regarding whether infants
3. No recommendation can be made about whether PWID
aged <1 month may be treated with OPAT at home (no rec-
may be treated with OPAT at home (no recommendation,
ommendation, very low-quality evidence). Decisions should
low-quality evidence). Decisions should be made on a case-
be made on a case-by-case basis.
by-case basis.
ANTIMICROBIAL UTILIZATION
IV. Should elderly patients be allowed to be treated with OPAT at home? VI. Is it safe and appropriate to administer the first OPAT dose of a new
Recommendation antimicrobial at home?
4. Elderly patients should be allowed to be treated with OPAT at Recommendation
home (strong recommendation, low-quality evidence). This 6. In patients with no prior history of allergy to antimicrobials in the
recommendation assumes that potential challenges to OPAT same class, the first dose of a new parenteral antimicrobial may
in the elderly, such as cognition, mobility, and dexterity, have be administered at home under the supervision of healthcare
e2 • CID 2019:68 (1 January) • Norris et al

personnel who are qualified and equipped to respond to ana- prophylactic oral anticoagulation while on OPAT (no rec-
phylactic reactions (weak recommendation, very low-quality ommendation, no evidence).
evidence).
XIII. Should children receive OPAT through a PICC or a LTCC?
Recommendation
VASCULAR ACCESS DEVICES
13. For most children requiring OPAT, a PICC should be
VII. In patients needing short courses of OPAT, is it acceptable to use a placed rather than a LTCC (strong recommendation, very
midline catheter (MC) instead of a central venous catheter?
low-quality evidence).
Recommendation
7. In adult patients needing short courses of OPAT (less than MONITORING
14 days), a MC may be used rather than a central venous XIV. Should patients receiving OPAT have laboratory test monitoring
catheter (weak recommendation, very low-quality evidence). while on therapy? If so, which tests should be done and how often?
No recommendations can be made regarding the use of MCs Recommendation
in pediatric patients. 14. Serial laboratory testing should be monitored in patients
receiving OPAT (strong recommendation, high-quality evi-
VIII. Should vesicant antimicrobials (medications associated with tissue
dence). Data are insufficient to make evidence-based rec-

damage caused by extravasation) be administered via central catheters vs
noncentral catheters only? ommendations about specific tests and specific frequencies
Recommendation of monitoring for individual antimicrobials used in OPAT.
8. Mandatory use of a central catheter over a noncentral catheter
XV. For patients receiving vancomycin as part of OPAT, should vancomycin
for OPAT with vancomycin is not necessary (weak recom- serum levels be measured regularly throughout the course of treatment?
mendation, very low-quality evidence). No recommendation Recommendation
can be made for choice of vascular catheter for OPAT with 15. Vancomycin blood levels should be measured regularly
other vesicant antimicrobials such as nafcillin and acyclovir throughout the course of OPAT treatment (strong rec-
(no recommendation, very low-quality evidence). ommendation, very low-quality evidence). The optimal
frequency of measurement is undefined, but the general
IX. Should patients with chronic kidney disease (CKD) requiring OPAT
practice in the setting of stable renal function is once weekly.
have a tunneled central venous catheter (t-CVC) for vascular access rather
than a peripherally inserted central catheter (PICC)?
Recommendation XVI. How frequently should patients on OPAT have scheduled physician
office visits for monitoring of treatment?
9. For patients with advanced CKD requiring OPAT, a t-CVC is
Recommendation
recommended rather than a PICC (strong recommendation,
16. No generalized recommendation on frequency of outpa-
tient follow-up can be made for patients treated with OPAT
X. Should patients requiring frequent OPAT courses have a long-term (no recommendation, no evidence). The treating physician
central catheter (LTCC) inserted with the intention of leaving it in place should dictate the frequency of office visits, giving consid-
between courses? eration to patient characteristics, the nature of the infection,
Recommendation the patient’s tolerance of and response to therapy, and indi-
10. No recommendation can be made about whether patients who vidual patient social factors.
require frequent courses of OPAT should have a LTCC left in
place between courses (no recommendation, no evidence). ANTIMICROBIAL STEWARDSHIP
XVII. Should all patients have infectious diseases (ID) expert review prior
XI. Should the vascular access device be removed if a patient develops
to initiation of OPAT?
symptomatic catheter-associated venous thromboembolism (CA-VTE)
while on OPAT? Recommendation
Recommendation 17. All patients should have ID expert review prior to initia-
11. It is not necessary to remove a vascular access device tion of OPAT (strong recommendation, very low-quality
if CA-VTE develops during OPAT, as long as the cath- evidence).
eter remains well positioned and arm pain and swelling
decrease with anticoagulation (weak recommendation, very INTRODUCTION AND BACKGROUND
low-quality evidence). The first description of successful administration of OPAT was
XII. Should patients with prior CA-VTE be treated with prophylactic anti-
published in 1974, where the safety and efficacy of its use to
coagulation while on OPAT? treat chronic bronchopulmonary infections in children with
Recommendation cystic fibrosis was reported [7]. Since then, numerous stud-
12. No recommendation can be made regarding the need ies have detailed the benefits of using OPAT in various pop-
to treat patients with a history of prior CA-VTE with ulations and settings, including private practices, traditional
academic programs, and Veteran’s Affairs medical centers [8– in outpatient clinics are a covered benefit of Medicare part B,
13]. Potential benefits to the healthcare system include shorter the infusion center model tends to minimize a patient’s out-
or avoided hospital stays [14, 15], prevention of hospital-asso- of-pocket expense. This model is resource intensive, requiring
ciated conditions [16], and significant cost savings [8, 16–23]. reliable transportation, availability of a skilled nurse to infuse
Advantages of OPAT to patients include the ability to return antimicrobial agents, and all the accompanying office resources
to work or school faster, care for children or dependents, and, but offers additional oversight with daily in-person visits.
generally, resume activities of daily living with minimal inter- Another model of OPAT administration occurs in the SNF.
ruption in their lives [24, 25]. An in-depth discussion of the Patients with additional nursing needs or no home infusion
following OPAT considerations can be found in the 2016 IDSA insurance benefits are typically admitted to a SNF, where on-site
OPAT eHandbook [6]. nurses perform all infusion functions and other activities such
as physical therapy or wound care. Since a SNF is a healthcare
Models of Care Delivery
facility, patients are more likely to encounter resistant organ-
Three basic models of outpatient parenteral antimicrobial ther-
isms, including Clostridium difficile. Overall, this option is sig-
apy (OPAT) delivery exist, each with inherent advantages and
nificantly more expensive to the healthcare system compared
drawbacks: home based, infusion center based, and skilled

to any of the other OPAT models [17] but may minimize the
nursing facility (SNF) based. The various features of these mod-
patient’s out-of-pocket expense.
els are outlined in Table 1. A 2006 Emerging Infections Network
In addition, an unknown proportion of OPAT occurs in dia-
(EIN) survey of infectious diseases (ID) physicians in North
lysis units, where advantage can be taken of preexisting vascular
America noted that 89% of respondents reported their patients
access and impaired renal function allows less-frequent dosing.
receiving OPAT at home, with the remaining 11% distributed
When OPAT programs were first introduced, great emphasis
among hospitals, infusion clinics, offices, and long-term care
was placed on appropriate patient selection. Currently in the
facilities [26]. A follow-up EIN survey in 2014 confirmed the
United States, patients rarely remain hospitalized solely to com-
ongoing majority of OPAT occurring in the home [27].
plete a course of parenteral antimicrobial therapy. Except for
In the home-based models of OPAT, all medications are
some persons who inject drugs (PWID), most patients are eli-
administered in the home by the patient, patient’s family mem-
gible for some form of OPAT. The current focus is on identify-
ber, or a home health nurse. The most common application of
ing the appropriate setting for OPAT, that is, whether patients
OPAT at home incorporates oversight by home infusion nurs-
will receive their antimicrobials at home, in an infusion center,
ing, which provides initial home training and periodic home
or in a SNF. The exact delivery model chosen for an individual
visits, generally weekly but frequently more often. Home-
patient is typically determined based on a variety of elements,
based infusion without home nursing offers another model of
including payer factors (Medicare covers virtually no home
self-administered OPAT (S-OPAT). Here, a physician’s office
infusion care), available resources (competent home nursing is
provides training and supervision, either in private practice or
not always accessible; hospital-based infusion suites may not be
in a clinic setting. Typically, patients make weekly visits to the
open on weekends), as well as patient preference, competencies,
office to collect supplies and undergo assessment and catheter
and supports. Despite pressure to control inpatient costs, finan-
dressing changes. Critical to the success of home-based OPAT is
cial concerns related to the setting in which IV antimicrobials
the presence of a competent and adherent patient and/or care-
are delivered should not take precedence over patient well-be-
giver. Minimal features required for safe home infusion include
ing and safety. For some patients, treatment in hospital may be
adequate refrigeration and storage and the presence of at least 1
safer than OPAT.
adult who can reliably learn and perform sterile infusion tech-
nique and communicate with the treatment team. A modified General Considerations in the Choice and Administration of Antimicrobials
version of the home OPAT model is the Hospital at Home, in OPAT
commonly used in Australia and some European countries and Tables 2 and 3 outline selected features of a variety of antimi-
in some US Veteran’s Affairs programs. Here, antibiotics are crobials used for OPAT. Advances in infusion device technology
infused in the home, but a visiting nurse rather than the patient have made it possible to administer medications in the outpa-
or caregiver performs each administration. tient setting that would previously not have been practical.
The infusion center model delivers OPAT in physicians’ Given appropriate resources, almost any antimicrobial can now
offices or free-standing infusion centers. Healthcare workers be administered as part of OPAT. The choice of antimicrobial
administer medications. This model works well for patients now depends more on the OPAT model than on the pharma-
who are physically incapable or unwilling to infuse themselves cokinetic properties of the drug. For instance, for OPAT given
and for Medicare patients (who lack a home infusion insurance in infusion centers, it is impractical to use medications that
benefit). Since intravenous (IV) antimicrobials administered require more frequent administration than once daily. Drug

Table 1. Models of Care
Who Performs Patient Training

Model Infusion Location Administration Location Nursing Location Comments Advantages Disadvantages
Home Home Self/Caregiver Home Homea Home Infusion: Weekly Patient convenience; regular Requires patient/caregiver compe-
home nursing visits for skilled clinical assessments; tence and compliance; requires
supplies, line care, labsb opportunity for home in- reliable home infusion nursing;
spection; availability of a increased cost to patient in the
registered nurse on 24-hour absence of home infusion insur-
basis ance benefit; may entail substantial
co- pays
Home Self/Caregiver Office Office Teach and Train: Weekly of- Patient convenience; regular Requires patient/caregiver compe-
fice visits for supplies, line skilled clinical assessments tence and compliance
care, labs, nursing
Home HCW No training Home Hospital at Home: Twice- Cost savings for patient who Not reimbursed by traditional fee-
daily home nursing visits would otherwise be hospi- for-service payors; limited up-
and once-daily home phy- talized; potential for reduced take in United States, but may be
sician visits hospital-acquired conditions expanding
and increased patient
satisfaction
Infusion center Office based HCW None ID office In-Office Infusion: Daily visits High degree of clinical over- Patient must be able to travel daily;
with nursing staff sight; usually covered by requires extensive infrastruc-
Medicare; minimizes out- ture and weekend office staffing;
of-pocket costs to patient; limited to once-daily dosing of
potential for weekly office antimicrobials
visits with ID physician
Nonoffice basedc HCW None Hospital based Nonoffice Infusion: Daily vis- High degree of clinical over- Patient must be able to travel daily;
its with nursing staff sight; usually covered by requires extensive infrastruc-
Medicare; minimizes out-of- ture and weekend office staffing;
pocket costs to patient limited to once-daily dosing of
antimicrobials
SNF SNF HCW None SNF Nursing on site Usually covered by payers/ Variable levels of clinical oversight;
Medicare; other skilled patients may dislike staying in SNF;
nursing needs (eg, physical may exhaust patient’s SNF benefits;
therapy, wound care) can most expensive for overall health-
be met; may be less labor care system
intensive for supervising
physicians when treating
patients with multiple
comorbid conditions; mini-
mizes out-of-
pocket costs to patient
Abbreviations: HCW, home care worker; ID, infectious diseases; SNF, skilled nursing facility.
a
Some training may occur in hospital prior to discharge.
b
More frequent nursing visits may be possible.
c
May be hospital based, free standing, or emergency room.
Table 2. Features of Selected Antibacterials Used in Outpatient Parenteral Antibiotic Therapy
Monitoring
Frequencyd
(Weekly)
Liver profile:
Oral Bioavailability, Doses per BMP: including ALT, AST, ALK, Most Common Potentially Torsades de
c
Antiinfective %a dayb Infusion Time Delivery Device CBC-diff K, Cr, BUN Tbil Serious ADRs Pointes Riske Other Comments
Antibacterials
Amikacin NA 1–3 30–60 min depending on Grav, Elas 1 2 … Nephrotoxicity; ototoxicity See aminoglycoside monitoringf
dose
Ampicillin 50 4–6 3–5 min push or 10–15 min Grav, EID, IVP 1 1 1 Hypersensitivity including Stable once reconstituted for only
infusion anaphylaxis 3 days; see stability footnoteg
Ampicillin-sulbactam NA 3–4 10–15 min push or Grav, EID, Elas, IVP 1 1 1 Hypersensitivity including Stable once reconstituted for only
15–30 min infusion anaphylaxis 3 days; see stability footnoteg

Azithromycin 28–52 1 60 min Grav 1 … … Known Consider change to po
Aztreonam NA 2–4 3–5 min push or 20–60 min Grav, EID, Elas, IVP 1 1 1 Rare cross-allergenicity with other
infusion beta-lactams
Cefazolin NA 3–4 3–5 min push or 30–60 min Grav, Elas, IVP 1 1 … Hypersensitivity including Dialysis-only dosing possible
infusion anaphylaxis
Cefepime NA 2–3 5 min push or 30 min Grav, Elas, IVP 1 1 … Hypersensitivity including Dialysis-only dosing possible
Cefoxitin NA 3–4 3–5 min push or 20–30 min Grav, Elas, IVP 1 1 … Hypersensitivity including
Ceftaroline NA 2–3 5 min push or Grav, IVP 1 1 … Hypersensitivity including
5–60 min anaphylaxis
Ceftazidime NA 3 3–5 min push or 15–30 min Grav, Elas, IVP 1 1 … Hypersensitivity including NA Dialysis-only dosing possible
Ceftazidime-avibactam NA 3 120 min Grav, EID 1 1 … Hypersensitivity including …
anaphylaxis
Ceftolozane-tazobactam NA 3 60 min Grav, EID 1 1 … Hypersensitivity including …
anaphylaxis
Ceftriaxone NA 1–2 1–4 min push or 30 min Grav, Elas, IVP 1 1 1 Hypersensitivity including See monitoring footnoted
Ciprofloxacin 50–85 2–3 60 min Grav, Elas … … … Tendonitis/tendon rupture; Known Consider change to po; see
peripheral neuropathy monitoring footnoted
Clindamycin 90 3–4 10–60 min (not to exceed Grav, Elas 1 1 1 Consider change to po; see
30 mg/min) monitoring footnotef
Colistin NA 2–4 3–5 min IVP; 30 min for Grav, IVP 1 2 … Nephro- and neurotoxicity Inhaled colistin may be an option
infusion for respiratory tract infections
Daptomycin NA 1 2 min push or 30 min Grav, Elas, IVP 1 1 … Myopathy; rhabdomyolysis Baseline and weekly CK,
infusion discontinue if symptomatic and
CK >1000 U/L (~5× ULN) or
asymptomatic and CK >2000
U/L (~10× ULN);
dialysis-only dosing possible
Dalbavancin NA Once per 30 min Grav … … … Hypersensitivity including Red man syndrome more likely if
week anaphylaxis infusion <30 min; monitoring
requirements unknown for
treatment duration greater than
2 weeks

Table 2. Continued
Monitoring
Frequencyd
(Weekly)
Liver profile:
Antiinfective %a dayb Infusion Time Delivery Devicec CBC-diff K, Cr, BUN Tbil Serious ADRs Pointes Riske Other Comments
Ertapenem NA 1 30 min Grav, Elas 1 1 1 Hypersensitivity including NA See stability footnoteg
anaphylaxis
Gentamicin NA 1–3 30–120 min depending on Grav, EID, Elas 1 2 … Nephrotoxicity; ototoxicity See aminoglycoside monitoringf
dose
Imipenem NA 3–4 20–60 min depending on Grav 1 1 1 Hypersensitivity including See stability footnoteg
dose anaphylaxis; seizures
Levofloxacin 90 1 60–90 min depending on Grav … … … Tendonitis/tendon rupture; Known Consider change to po; see
dose cardiac arrhythmias; monitoring footnote;d dialysis-
peripheral neuropathy only dosing possible
Linezolid 100 2 30–120 min Grav, EID 1 … 1 Thrombocytopenia; Consider change to po; monitor
leukopenia; anemia; for neuropathy, optic neuritis in
peripheral neuropathy; optic prolonged use; see monitoring
neuritis footnote;d potential for drug
interactions
Meropenem NA 3–4 30 min Grav, Elas 1 1 1 Hypersensitivity including Dialysis-only dosing possible; see
anaphylaxis stability footnoteg
Metronidazole 100 2–4 30–60 min Grav, EID, Elas 1 … … Peripheral neuropathy Conditional Consider change to po
Nafcillin NA 4–6 30–60 min Grav, EID 1 1 1 Hypersensitivity including Central line commonly used
anaphylaxis because of concern for
phlebitis risk
Oritavancin NA Once 180 min Grav … … … Hypersensitivity including Red man syndrome more likely if
anaphylaxis; infusion infusion <60 min; monitoring
related requirements unknown for
treatment duration greater than
a single dose
Oxacillin NA 4–6 10–30 min Grav, Elas 1 1 1 Hypersensitivity Central line commonly used
including anaphylaxis; because of concern for
hepatotoxicity phlebitis risk
Penicillin G 25–73 4–6 15–30 min Grav, EID 1 1 1 Hypersensitivity including Oral penicillin V K is not a
anaphylaxis substitute for IV treatment
of most clinical conditions
requiring IV penicillin, eg,
syphilis
Piperacillin-tazobactam NA 3–4 30–240 min (extended Grav, EID 1 1 1 Hypersensitivity including
infusion) anaphylaxis
Polymyxin B NA 1 60–90 min Grav 1 2 … Nephro- and neurotoxicity Monitor for nephrotoxicity,
neurotoxicity
Rifampin 70–90 1–3 30 min Grav 1 1 1 Hepatitis; hypersensitivity NA Potential for drug–drug
interactions; consider change
to po
Tedizolid 91 1 60 min Grav 1 … 1 Thrombocytopenia; Consider change to po; monitor
leukopenia; anemia; for neuropathy, optic neuritis
peripheral neuropathy; in prolonged use; potential
optic neuritis for drug interactions; see
monitoring footnoted
Table 2. Continued
Monitoring
Frequencyd
(Weekly)
Liver profile:
c
Antiinfective %a dayb Infusion Time Delivery Device CBC-diff K, Cr, BUN Tbil Serious ADRs Pointes Riske Other Comments
Telavancin NA 1 60 min Grav 1 2 … Nephrotoxicity; Possible High rate of renal injury in
hypersensitivity including patients aged >65 years, with
anaphylaxis; infusion- preexisting renal impairment
related prolongation of or other nephrotoxins; red
QTc man syndrome more likely if
infusion <60 min
Tigecycline NA 2 30–60 min Grav 1 1 1 Nausea/ vomiting

Tobramycin NA 1–3 30–120 min depending on Grav, EID, Elas 1 2 … Nephrotoxicity; ototoxicity See aminoglycoside monitoringf
dose
Trimethoprim/ 85 2–4 60–90 min Grav 1 1 1 Hyperkalemia; rash; Special Consider change to po; potential
sulfamethoxazole nephrotoxicity; Stevens for drug–drug interactions; high
Johnson syndrome fluid requirement; spurious
increase in serum creatinine
Vancomycin NA 1–2 60–120 min depending on Grav, EID, Elas 1 1 … Nephrotoxicity; infusion- Dialysis-only dosing possible;
dose related reactions vancomycin trough levels or
area under the curve/minimum
inhibitory concentration weekly
and with dose changes;
red man syndrome more likely if
infusion <60 min
This table has been adapted from the OPAT eHandbook 2016 [6]. It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients
or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient’s individual circumstances.
Abbreviations: ADR, adverse drug reaction; ALK, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; BMP, basic metabolic profile; BUN, blood urea nitrogen; CBC, complete blood cell count; CK, creatine kinase; Cr, creatinine;
EID, electronic infusion device; Elas, elastomeric; Grav, gravity; IV, intravenous; IVP, intravenous push; K, potassium; LFT, liver function tests; NA, not applicable/no oral formulation; po, by mouth; QTc, corrected QT-interval; Tbil, total bilirubin; ULN, upper
limit of normal.
a
Bioavailability: changing to oral medications when possible is part of good antimicrobial stewardship. Clinicians should consider the full clinical situation, including the appropriateness of oral antimicrobials for the condition being treated. Potential for inter-
action with foods and other medications as well as concomitant illnesses and the potential for impaired gut absorption must also be considered.
b
Doses per day: assumes normal renal and hepatic function. More than 2–3 doses per day may be impractical for pediatric outpatient parenteral antimicrobial therapy (OPAT) that requires adult infusion assistance for every dose. Dosing more frequently
than once daily is typically not practical for patients who receive care in infusion centers.
c
Devices: very limited published information on the use of these devices in OPAT. Individual infusion pharmacies have variable policies and device availability. Not all drugs are compatible with all delivery options. EIDs can be programmed to automati-
cally deliver multiple doses per day but they require that the patient be connected to a small device virtually continuously and are not covered by all insurance carriers. Elas are very simple to use but also are not covered by all insurance carriers. Gravity
delivery (infusion without a pump, using a roller clamp) is less expensive but also less convenient due to longer infusion times and complexity for patients to learn. Depending upon care setting, use of a traditional infusion pump may be selected in lieu of
gravity for rate control. IVP is very convenient because of rapid infusion time.
d
These are recommendations based on frequency and seriousness of reported adverse events. The monitoring plan for an individual patient may be different based on the comorbid conditions and anticipated duration of OPAT. For instance, for shorter
courses of linezolid, ceftriaxone, or clindamycin, it may not be necessary to monitor LFTs and/or renal function. Alternatively, for longer courses of fluoroquinolones, weekly lab monitoring may be appropriate. For patients with normal baseline labs, less
intense monitoring may be appropriate.
e
Risk of Torsades de Pointes (TdP): known, known to prolong QTc interval and cause TdP even when taken as recommended; possible, can cause QTc prolongation but not known to cause TdP when taken as recommended; conditional, associated with
TdP but only under certain conditions (ie, excessive dose, with hypokalemia, with other interacting drugs) or by creating conditions that induce TdP (inhibiting metabolism of QTc prolonging drugs); special, high risk of TdP in patients with congenital long
QT syndromes due to other actions. Source for TdP risk [28].
f
Aminoglycoside monitoring: monitor concentrations minimum weekly. Goal aminoglycoside trough values differ according to the drug, infection, and dosing strategy.
g
For medications with limited stability, home delivery more frequently than once weekly will be required. Some drugs may be reconstituted in the home using a use-activated container, if available.

cost and insurance coverage frequently influence the model Administration Considerations
of care and, in some instances, the selection of antimicrobial A suitable antimicrobial for OPAT should have favorable physi-
agents for OPAT. For instance, Medicare patients without a cal and chemical characteristics. The agent should have adequate
secondary infusion benefit are typically required to choose stability, once reconstituted, in common IV solutions, in a variety
between self-pay and receipt of antimicrobials in a SNF or infu- of containers (plastic bags, syringes, elastomeric containers), and
sion center, if available. Despite the availability of a number of under various storage/use conditions. For example, ampicillin-sul-
dialysis-friendly agents [29], patients who receive their paren- bactam is only stable for 3 days once formulated, so more than
teral antimicrobials during dialysis sessions may be limited to once weekly delivery of medications will be required for home
a choice of vancomycin, cefazolin, or aminoglycosides only, infusion. Stability may vary with diluent, final concentration to be
depending on what their dialysis center is willing to pay for. administered, infusion container type, and storage conditions (eg,
refrigerated vs room temperature). The pH and osmolality of solu-
Therapeutic Considerations tions prepared for IV administration directly affect tolerability and
Correct treatment begins with the correct diagnosis. Before may influence the type of vascular access device (VAD) needed.
embarking on a course of treatment, it is essential to identify Drugs are prepared and supplied to the patient/caregiver in
the infection being treated. This includes gaining an under- a variety of delivery devices suitable for administering anti-

standing of the primary site of infection, the extent of infection microbials in the outpatient setting. Each method has advan-
around the primary site, and distant sites seeded secondarily. tages and disadvantages but should be selected based upon
Additionally, treatment is always more effective if adequate patient preferences and capabilities, drug characteristics (con-
source control is achieved, such as debridement of necrotic tis- centration/solubility, stability, infusion time), VAD, and cost/
sue, drainage of abscesses, and removal of infected prosthetic insurance coverage. Intravenous push is a rapid and conveni-
devices. Whenever possible, control at the primary site of infec- ent delivery method for many cephalosporins but may need a
tion should be addressed appropriately early in treatment. dexterity beyond some patients’ or caregivers’ comfort level or
The selected antimicrobial agent should have activity against physical ability. Electronic infusion devices can be programmed
the identified or presumptive causative pathogen(s), known dis- to improve ease of use by automatically delivering multiple
tribution to the site of infection, and proven therapeutic efficacy doses per day but they require the patient to be connected to
in the infection being treated. Patient factors that may impact a small device virtually continuously and are not covered by all
efficacy must be considered, including comorbidities, concomi- payers. Elastomeric devices are very simple to use but may not
tant therapies (drug and non-drug), patient age, and organ func- be reimbursed by all insurance carriers. Gravity delivery is the
tion. Programmable infusion pumps and elastomeric devices simplest to use and least expensive but is less convenient than
(disposable balloons that push medication through tubing) have other methods due to longer infusion times.
made it more convenient to use drugs that require multiple infu-
sions a day. In general, for OPAT, drugs that allow for infrequent The Role of the Physician and the OPAT Team
dosing and rapid/bolus infusions are preferred. However, if the Regardless of the OPAT model chosen, it is the responsibility of
resources exist to administer multiple doses of antimicrobials at the treating physician to manage and direct the patient’s care.
home daily, efficacy should not be sacrificed for convenience. The treating physician addresses the indication for OPAT, selec-
tion of antimicrobial agent, duration of therapy, and subsequent
Safety Considerations medical evaluations. In the modern healthcare system, however,
While the types of adverse events observed with various anti- the physician does not work alone. He or she is supported by
microbials would not be expected to differ in OPAT patients vascular access teams, social workers, nurses, and pharmacists,
vs inpatients, the incidence of such reactions may differ. The all working in collaboration to support the patient. Recognition
cumulative incidence of adverse events to a variety of anti- of the contributions of multiple healthcare professionals and
microbial classes increases with length of treatment [29–33]. roles has led to the proposal of an OPAT bundle, which iden-
For some patients, OPAT courses may extend for weeks or tifies several components that require attention when planning
months. Monitoring for adverse events while on treatment has an OPAT program [37].
been standard of care [1]; the particular tests required depend
on the potential adverse event profile of the antimicrobials Emerging Trends in OPAT
being administered. Additionally, some antiinfective agents The role of remote-access delivery of OPAT oversight is currently
require plasma concentration monitoring to ensure that they under investigation [38]. The use of telemedicine to support
are in the desired therapeutic/nontoxic range (eg, vancomycin, OPAT in geographically isolated locations is appealing but chal-
aminoglycosides, and voriconazole). Occurrence of adverse lenged in the United States by reimbursement models and inter-
events is a common reason for a change in antimicrobial agent state regulatory requirements. Also unknown, but promising,
or a complete discontinuation of OPAT [31, 33–36]. are the roles of the long-acting semisynthetic lipoglycopeptides
Table 3. Features of Selected Antivirals and Antifungals Used in Outpatient Parenteral Antibiotic Therapy
Monitoring Frequencyd (Weekly)
Oral Liver profile: Torsades

Bioavailability, Doses per Delivery BMP: including ALT, AST, ALK, Most Common Potentially de Pointes
Antiinfective %a Dayb Infusion Time Devicec CBC-diff K, Cr, BUN Tbil Serious ADRs Riske Other Comments
Antifungals
Amphotericin B NA 1 Liposomal: 2 hours EID (including 1 2 1 Rates >10%; hypotension, Conditional Sodium loading recommended;
Deoxycholate: 2–4 pole pump) rigors, nausea, vomit- chemistry 10 preferredf
hours Elas ing, diarrhea, anemia,
thrombocytopenia,
electrolyte abnormalities (K,
Mg, Ca), renal failure, hypo-

glycemia, LFT abnormalities
Anidulafungin NA 1 1.5 hours Grav 1 1 1
Caspofungin NA 1 1 hour Grav, EID, Elas 1 1 1
Fluconazole ≥90 1 1–2 hours (not to ex- Grav, Elas … … 1 Known Consider change to po; watch
ceed 200 mg/h) for drug-drug interactions
Isavuconazole 98 1–3 ≥1 hour Grav (with … … 1 Consider change to po; watch
pump) for drug–drug interactions
Micafungin NA 1 1 hour Grav 1 1 1
Posaconazole Highly depen- 1–2 90 min with in-line Grav 1 1 1 Conditional Consider change to po; watch
dent on gastric filter for drug–drug interactions
pH
Voriconazole 96 2 1–2 hours Grav 1 1 1 Hallucinations; auditory/ Conditional Consider change to po; watch
visual disturbances; skin for drug–drug interactions;
changes; fluorosis with pro- monitor plasma concentra-
longed use tions; avoid intravenous for-
mulations if CrCl <50 unless
benefits clearly outweigh
risks (accumulation of cyclo-
dextrin vehicle)
Antivirals
Acyclovir 10–30 3 1 hour Grav, Elas 1 1 … Crystalluria; acute renal injury Hydration critical in preventing
nephrotoxicity;
consider change to po valacy-
clovir, famciclovir, or acyclovir
Cidofovir NA 1 1 hour EID (including 1 2 1 Rash; anemia; neutropenia; Hydrate with NS before and
pole pump) iritis; uveitis; decreased intra- after dose; consider pro-
ocular pressure; nephrotox- benecid; urinalysis weekly;
icity; metabolic acidosis chemistry 10 preferredf
Foscarnet NA 1–3 1–2 hours (not to ex- EID, Elas 1 2 1 Nephro- and neurotoxicity; Hydrate with NS or D5W prior
ceed 1 mg/kg/ anemia; granulocytopenia; to first dose; chemistry 10
min) electrolyte disturbances preferredf

Table 3. Continued
Monitoring Frequencyd (Weekly)
Oral Liver profile: Torsades

Bioavailability, Doses per Delivery BMP: including ALT, AST, ALK, Most Common Potentially de Pointes
Antiinfective %a Dayb Infusion Time Devicec CBC-diff K, Cr, BUN Tbil Serious ADRs Riske Other Comments
Ganciclovir 5–10 1–2 1 hour Grav, Elas 2 1 … Dose-dependent Consider change to
myelosuppression po valganciclovir
This table has been adapted from the OPAT eHandbook 2016 [6]. It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular
patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient’s individual circumstances.
Abbreviations: ADR, adverse drug reaction; ALK, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; BMP, basic metabolic profile; BUN, blood urea nitrogen; Ca, calcium; CBC, complete blood cell count; CK, creatine kinase;
Cl, chloride; Cr, creatinine; D5W, 5% dextrose; EID, electronic infusion device; Elas, elastomeric; Grav, gravity; IV, intravenous; IVP, intravenous push; K, potassium; Mg, magnesium; NA, not applicable/no oral formulation; NS, normal saline; po, by mouth;
Tbil, total bilirubin; ULN, upper limit of normal.
a
Bioavailability: changing to oral medications when possible is part of good antimicrobial stewardship. Clinicians should consider the full clinical situation, including the appropriateness of oral antimicrobial for the condition being treated and potential for
interaction with foods and other medications as well as concomitant illnesses and the potential for impaired gut absorption that may decrease serum levels.
b
Doses per day: assumes normal renal and hepatic function. More than 2–3 doses per day may be impractical for pediatric OPAT that requires adult infusion assistance for every dose.
c
Devices: very limited published information on the use of these devices in OPAT. Individual infusion pharmacies have variable policies and device availability. Not all drugs are compatible with all delivery options. EIDs can be programmed to automati-
cally deliver multiple doses per day but they require that the patient be connected to a small device virtually continuously and may not be covered by all insurance carriers. Elas are very simple to use but also may not be covered by all insurance carriers.
Gravity delivery (infusion without a pump, using a roller clamp) is less expensive but also less convenient due to longer infusion times and complexity for patients to learn. Depending upon care setting, use of a traditional infusion pump may be selected
in lieu of gravity for rate control. IVP is very convenient because of rapid infusion time.
d
These are recommendations based on frequency and seriousness of reported adverse events. The monitoring plan for an individual patient may be different based on the comorbid conditions and anticipated duration of OPAT.
e
Risk of Torsades de Pointes (TdP): known, known to prolong QTc interval and cause TdP even when taken as recommended; possible, can cause QTc prolongation but not known to cause TdP when taken as recommended; conditional, associated with
TdP but only under certain conditions (eg, excessive dose, with hypokalemia, with other interacting drugs) or by creating conditions that induce TdP (inhibiting metabolism of QTc prolonging drugs); special, high risk of TdP in patients with congenital long
QT syndromes due to other actions. Source for TdP risk [28].
f
Chemistry 10 includes sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose, calcium, magnesium, and phosphate.
Process Overview
Panel Composition
METHODOLOGY
the level of evidence available.

Evidence Review and Formulation of Recommendations
apy or forgo IV antimicrobial treatment [42–45].
health sciences librarians performed literature searches.

The last version of the IDSA OPAT Guideline was published
met face-to-face 4 times and conducted numerous conference

responsibility to review the literature, assess the risk of bias of the
clinical trials or observational studies. Specific features of the
evidence and the formulation of recommendations from that
VAD. Delivery of antimicrobials by subcutaneous administra-
Additionally, one source of complications during OPAT is the
lives and infrequent dosing requirements. The role of these
Two to 3 panel members were assigned to each section with

trade-offs resulting from that recommendation, in addition to
recommendation reflected the net benefits and net harms or
experienced ID pharmacist, a member of the Infusion Nursing
evidence, as outlined in Figure 1. The strength assigned to a

evidence base (such as risk of bias or large effect size) war-
and began as “low” quality if it only included nonrandomized
[2–5, 46, 47]. The evidence informing a given question began
Development and Evaluation (GRADE) approach (Figure 1)
evidence using the Grading of Recommendations Assessment,
ously required to either remain in hospital for IV antibiotic ther-
calls to develop the guideline questions and literature search

mulate recommendations informed by this synthesis. The panel
individual studies identified, synthesize the evidence, and for-
Finally, newer models of care delivery for PWID, homeless
expensive agents, particularly in PWID, remains to be defined.
siderations, antimicrobials, VADs, monitoring, and stewardship.

Five overarching topics were identified for review: patient con-
dalbavancin and oritavancin, currently approved narrowly,
as “high” quality if it included randomized, controlled trials

IDSA guidelines that includes a systematic review of the relevant
The panel followed a process used in the development of other
Society, and a guideline methodology expert. Two professional
the Pediatric Infectious Diseases Society. Also included were an
tings, including 3 pediatric ID physicians who are members of
ranted decreasing or increasing the rating of the quality of the

11 ID physicians from both academic and private practice set-
in 2004 [1]. For the current update, 1 of the chairs assembled
patients, and other challenging populations have shown promise
in the potential to deliver OPAT for patients who were previ-
[39–41] but their use in the United States is still investigational.
antimicrobials have been used in other countries for some time
but offering potential promise because of their very long half-
tion has the potential to avoid the need for a VAD. Subcutaneous
strategy and to review and discuss all recommendations, their of the questions posed. Twenty-six articles were included in the
strengths, and their underlying evidence base. Inconsistencies final evidence tables; numerous others were referenced in dis-
and differences were discussed and resolved, and all final recom- cussion sections but did not meet criteria for inclusion in the
mendations represent a consensus opinion of the entire panel. systematic reviews.
All recommendations were labeled as either “strong” or
“weak” using the GRADE approach [5]. Although there is ongo- Risk of Bias Assessment of Individual Studies
ing need for research on virtually all of the subjects addressed The Newcastle-Ottawa scale (NOS) was used to assess risk
in this guideline, research needs were highlighted in areas the of bias for cohort and case control studies, and the Cochrane
panelists felt were of the highest priority; these are summa- Collaboration’s Risk of Bias Tool was used to assess risk of bias
rized in “Future Directions” at the end of this document. High- in clinical trials. Risk of bias was independently checked by 3
quality evidence was lacking for most of the recommendations. reviewers for each study. Discrepancies were addressed through
Strong recommendations were sometimes made in the setting consensus discussion.
of low-quality evidence when the panelists believed that most A summary assessment of “overall risk of bias” was created
individuals would endorse the recommended course of action by first grouping the criteria in the NOS into 3 domains and
the criteria in the Cochrane Collaboration tool into 4 domains

and that most well-informed clinicians would agree, despite the
low-quality evidence [2, 3]. based on the nature of their respective threats to validity. The
The panel obtained feedback from 3 external peer reviewers. elements examined in each domain are shown in Table 4.
The guideline was also reviewed and approved by the IDSA General rules were developed to guide the grading process.
Standards and Practice Guidelines Committee and the IDSA Each observational study was evaluated and assigned stars for
Board of Directors. criteria as laid out in the NOS [48]. An individual study was
then considered to be at “high” overall risk of bias if it lacked
Literature Search Methodology 1 or more stars in each of the 3 domains or if it lacked all stars
Health sciences librarians identified studies using medical sub- in 1 domain and 2 or more stars in other domains. A study was
ject headings and text words for OPAT (Supplementary Table considered to be at medium risk of bias if it lacked all stars in 1
A). Additional searches were run for the concepts of dialysis, domain or lacked stars in at least 2 domains.
VADs, monitoring, and stewardship (Supplementary Tables Each clinical trial was examined and rated as introducing
B–E). After excluding duplicates, 23 435 citations remained. “low,” “high,” or “unclear” risk of bias in each criterion in each
Results were limited to human studies published between domain. A clinical trial was then considered to be at “high”
January 1980 and October 2015. All publications in English or overall risk of bias if it was assigned a “high” risk rating for 1
containing English abstracts were included, except editorials, or more discrete criteria in at least 2 domains. A clinical trial
letters, and comments. Databases accessed on the Ovid plat- was determined to be at “medium” overall risk of bias if it was
form included MEDLINE In-Process & Other Non-Indexed assigned a “high” risk rating in only 1 domain or if it was deter-
Citations and MEDLINE (1946 to present), Embase (1980 to mined to be at “unclear” risk of bias in 1 or more discrete crite-
present), Cochrane Central Register of Controlled Trials (1991 ria in at least 2 domains.
to present), Health Technology Assessment Database (2001 to
present), and National Health Service Economic Evaluation Data Synthesis
Database (1995–2015). To supplement the electronic search, The evidence was synthesized using strength-of-evidence
members contacted experts and hand-searched journals, tables. Due to the heterogeneity and small number of included
conference proceedings, and reference lists. Initial literature studies in each individual evidence table, data from the studies
searches were done in October 2014, with updates performed were not combined quantitatively using metaanalyses.
28 October 2015 and 31 January 2017. For each question, clinically relevant outcomes were sought.
When available from individual studies, point estimates, con-
Literature Review Methodology fidence intervals, and P values were reviewed. If errors were
A total of 23 435 citations were divided equally among a panel found, corrected values were used. P values of <.05 were con-
of 6 reviewers who prescreened them and retained 3102 cita- sidered statistically significant.
tions. Using EndNote, citations were divided into topical
libraries for each writing group. One to 2 independent review- Strength of the Body of Evidence
ers (depending on the writing group) used predetermined The strength of evidence for each outcome was evaluated using
inclusion and exclusion criteria to complete a 2-step screening the GRADE criteria [5]. This method initially assigns a start-
method: the first screen consisted of a title and abstract review ing level of evidence strength based on the design of the studies
to ascertain relevance to OPAT, and the second screen entailed informing that evidence base. The method then evaluates the
review of the full text to determine if the study addressed any evidence base for 8 characteristics that may increase or decrease

Table 4. Domains Evaluated in Assessing Risk of Bias
Cohort Study Domains
Subjects and Exposures Comparability Outcome Evaluation

• Representative cohort • Controlled for the most important variable • Outcome assessment
• Selection of nonexposed control • Controlled for any other variable • Duration of follow-up
• Exposure ascertained • Adequate follow-up
• Not present at outset
Case Control Study Domains
Subjects and Exposures Comparability Exposure Evaluation
• Exposure • Controlled for the most important variable • Exposure ascertainment
• Case definition • Controlled for any other variable • Nonresponse rate
• Representative cases
• Control selection
• Control definition
Clinical Trials Domains
Participant Enrollment Blinding Outcome Data Other Bias
• Sequence generation • Blinding of participants and personnel • Incomplete outcome data

• Allocation concealment • Blinding of outcome assessors • Selective outcome reporting
the level of evidence to arrive at a final level of evidence strength. definition, is an outpatient activity. Downgrading for indirect-
Randomized, controlled trials start at a high level of evidence ness was done if 50% or more of the studies evaluating the given
strength, while observational studies (cohort and case-control outcome suffered from indirectness.
studies) start at a low level. Precision is the degree of certainty surrounding an effect esti-
General rules were developed to guide the assessment of mate with respect to a given outcome and is affected by sample
strength of evidence. The characteristics that have the poten- size and number of events; it is most commonly represented by
tial to decrease the strength of evidence are risk of bias, incon- the width of confidence intervals. We considered the evidence to
sistency, indirectness, imprecision, and publication bias. The be imprecise when the width of the confidence interval spanned
characteristics that have the potential to increase the level of more than 1 logarithm on a base 10 scale. We also downgraded
evidence strength are large magnitude of effect, dose–response, for imprecision when key components of the outcome data pro-
and a potential increase in effect size when considering vided by studies were not fully reported (eg, measures of vari-
unmeasured confounders. For each outcome considered, the ance were not included) or when it was not possible to derive
starting level of evidence strength was the highest level of evi- an estimate of effect based on the available data. Downgrading
dence strength of any study examining that outcome. Each of for imprecision was done if 50% or more of the studies evaluat-
the 8 characteristics of the body of evidence for that outcome ing the given outcome suffered from imprecision or if there was
was then evaluated using the criteria described in the following only 1 study evaluating a particular outcome.
paragraphs, and the level of evidence strength was downgraded Reporting bias includes publication bias, outcome report-
or upgraded accordingly. ing bias, and analysis reporting bias. Given the small number
Downgrading for risk of bias was done if 50% or more of the of studies, funnel plots were not examined. We downgraded
studies evaluated for a given outcome were at medium or high for reporting bias when we detected a likelihood of outcome
overall risk of bias as described above. In these situations, if 50% reporting bias (important clinical outcomes appeared to have
or more of the studies evaluated for a given outcome were at been collected but not reported) or analysis reporting bias
high overall risk of bias, the level of evidence was downgraded (important comparisons were not analyzed) in 50% or more of
by 2 points, otherwise by 1 point. the studies evaluating the given outcome.
Consistency of results for the same outcome among the avail- The level of evidence was upgraded for large magnitude
able studies in terms of the direction and magnitude of effect of effect. If 50% or more of the studies evaluated for a given
was examined. Downgrading for inconsistency was done when outcome had an effect size ≥2 or ≤0.5, 1 point was added to
there was heterogeneity in the effects of an intervention across the level of evidence. If 50% or more of the studies evaluated
studies for a given outcome that could not be explained through for a given outcome had an effect size ≥5 or ≤0.2, the level of
identifiable differences in study characteristics. evidence was upgraded by 2 points. Upgrading for a dose–
Evidence was considered indirect if the populations, inter- response relationship was done if 50% or more of the studies
ventions, comparisons, or outcomes used within studies did not evaluating a given outcome demonstrated a dose–response
directly correspond to the question of interest and this indirect- relationship. Upgrading for confounders was done if in 50% or
ness could realistically result in different findings. For example, more of the studies evaluating a particular outcome, the consid-
some included studies were performed on inpatients; the evi- eration of unmeasured confounders would have been expected
dence was considered indirect in this setting because OPAT, by to increase the magnitude of the effect reported. For example, if
2 or more out of 3 studies that reported on a particular outcome PATIENT CONSIDERATIONS
found a positive effect, and inclusion of residual confounders in I.Should patients (or their caregivers) be allowed to self-administer outpa-
2 or more of these studies would have been expected to increase tient parenteral antimicrobial therapy (OPAT)?
the magnitude of the effect found, the level of evidence was Recommendation
upgraded. 1. Patients (or their caregivers) should be allowed to self-admin-
The gathered evidence was used to draw a summary conclu- ister OPAT (strong recommendation, low-quality evidence).
sion for each outcome examined. If the final level of evidence
strength was very low, we considered it to be insufficient to Evidence Summary
draw a conclusion about the outcome of interest. Three observational studies allow for comparison of outcomes
among patients treated by self-administered OPAT (S-OPAT)
Formulation of Recommendations vs healthcare-administered OPAT (H-OPAT) [49–51]. S-OPAT
Interventions associated with benefit also often have proven refers to administration of IV antimicrobials by the patient, rel-
or theoretical harms. Recommendations were made consider- ative, or caregiver, whereas H-OPAT refers to administration of
ing the strength of the evidence available and the net benefits, IV antimicrobials by a healthcare worker. One study compared
outcomes between 473 S-OPAT and 1536 H-OPAT patients

net harms, or trade-offs resulting from those interventions
(Figure 1). The bulk of the OPAT literature base is composed of in the United Kingdom [49]. S-OPAT patients were selected
nonrandomized studies that, by their nature, compare groups patients who were deemed capable of self-administration.
that have inherent differences, thus limiting the quality of the Another study compared outcomes for patients in Singapore,
evidence. For instance, outcomes for patients treated at home categorized into 1 of 3 groups: self OPAT (379 patients), termed
might differ from those treated in SNFs, not necessarily due S-OPAT; H-OPAT (156 patients), where infusions were done by
to the care received at the respective sites but because patients a healthcare worker in the patient’s home; and hospital OPAT
selected for treatment at home may be younger and healthier (1694 patients), which was essentially infusion center–based
than those selected for treatment in SNFs. Evidence tables are treatment [50]. For this question, only the first 2 groups are rel-
presented for each question. A detailed analysis of the risk of evant. The study reported hazard ratios (HRs) based on hospi-
bias for individual studies included in the evidence tables is pro- tal OPAT as the reference group. At our request, the HRs were
vided in Supplementary Tables F–H. recalculated by the original investigators, changing the refer-
ence level to H-OPAT. The third study examined associations of
Conflicts of Interest various factors, including self-administration (vs OPAT clinic
The expert panel complied with the IDSA policy on con- staff administration), with line infection and with other line
flicts of interest, which requires disclosure of any financial event, in a multivariable analysis in a cohort of 2766 patients in
or other interest that may be construed as constituting an the United Kingdom treated with OPAT [51].
actual, potential, or apparent conflict. Panel members were Readmission rates for S-OPAT vs H-OPAT were compared in 2
provided IDSA’s conflicts of interest disclosure statement and of these 3 studies [49, 50]. S-OPAT was associated with a lower
were asked to identify ties to companies that develop prod- HR of readmission compared to H-OPAT (HR 0.36, 95% confi-
ucts that may be affected by promulgation of the guideline. dence interval [CI] 0.24–0.53, P < .001) in 1 study [49] and was
Information was requested regarding employment, consultan- not associated with an increase (10.5% vs 12.6%, risk ratio [RR]
cies, stock ownership, honoraria, research funding, expert tes- 0.83, 95% CI 0.59–1.14, P = .30) in the other [50]. A comparison
timony, and membership on company advisory committees. of complication rates for S-OPAT vs H-OPAT could be obtained
Decisions were made on a case-by-case basis as to whether an from 2 of these studies [49, 51]. Complication rates did not dif-
individual’s role should be limited due to conflict. Potential fer for S-OPAT vs H-OPAT in 1 study (24% vs 23%, RR 1.03,
conflicts of interests are listed in the Notes section at the end 95% CI 0.86–1.24, P = .80) [49]. No significant associations
of the guideline. were found between OPAT administration group (self vs OPAT
clinic staff administration) and vascular access complications
Future Revision Dates in the other study (odds ratio [OR] 0.84, 95% CI not reported
At annual intervals, the panel chairs, Standards and Practice [NR], P = .72 for line infection; OR 1.32, 95% CI NR, P = .22
Guidelines Committee (SPGC) liaison advisor, and SPGC chair for other line events) [51]. The evidence from these 3 studies is
will determine the need for guideline revisions by reviewing summarized in Table 5. In addition to these comparative stud-
current literature. If necessary, the entire panel will be recon- ies, there have been many descriptive studies in the adult and
vened. When appropriate, the panel will recommend revisions pediatric literature documenting the successful administration
to the IDSA SPGC, Board, and other collaborating organiza- of OPAT medications at home by patients or family members,
tions for review and approval. with few complications [8, 52–55].

Rationale for the Recommendation II. Should patients (or their caregivers) be allowed to self-administer
Readmissions, emergency department (ED) visits, and compli- OPAT at home without visiting nurse support?
Recommendation
cations were the critical outcomes. There was moderate-quality
evidence for absence of an increase in readmission risk with 2. Patients (or their caregivers) may be allowed to self-admin-
S-OPAT compared to H-OPAT and low-quality evidence for ister OPAT at home without visiting nurse support as long as
equivalence in complications. There were no data for ED vis- there is a system in place for effective monitoring for vascular
its. These findings amount to overall low-quality evidence for access complications and antimicrobial adverse events (weak
equivalence in S-OPAT vs H-OPAT. recommendation, low-quality evidence).
When OPAT was originally introduced into medical prac- Evidence Summary
tice, it involved training patients or their caregivers to admin- A direct comparison of S-OPAT at home with vs without visiting
ister parenteral antimicrobials at home. In the United States, nurse support has not been described. However, comparison of
once the patient has established infusion competency, the outcomes for S-OPAT at home without visiting nurse support
home care model generally includes a once-weekly visit by vs usual care (which may include some nursing support) has
a nurse who performs clinical assessment, changes the VAD been reported in 1 study. Usual care included S-OPAT at home

dressings, and draws blood for monitoring tests, with the with visiting nurse support as well as patients whose OPAT was
option to visit patients’ homes more frequently if needed. In administered at a SNF. This study was done among uninsured
time, other models of care have evolved, including the use patients in the United States, and the analysis used a multivar-
of various office or infusion center settings. However, the iable Cox proportional hazards regression model that adjusted
majority of OPAT in the United States continues to be deliv- for the propensity to be included in one or the other group
ered by patients or their caregivers in the home [27]. Most of [52]. The patients without visiting nurse support, so-called
these infusions, however they may be labeled, are essentially teach-and-train OPAT (TT-OPAT) patients were instructed to
S-OPAT treatments. self-administer IV antimicrobials by gravity and were followed
There is vast clinical experience with S-OPAT in the United at designated intervals in clinic for IV access care, laboratory
States. Many descriptive studies of S-OPAT in the United monitoring, and physician follow-up. Following training, com-
States for different infectious conditions in different settings petency was established before discharge through a standardized
have reported successful outcomes [8, 52–55]. Allowing peo- protocol, requiring patients to repeatedly demonstrate mastery
ple to self-administer their parenteral antimicrobials after of all the steps in self-administration by gravity. The comparison
appropriate training and with appropriate support mecha- group included patients who were treated with S-OPAT at home
nisms in place reduces unnecessary burden on the healthcare with the support of weekly nurse visits or who were treated in
system and enhances patient satisfaction. These considera- SNFs, so called nurse-administered OPAT (NA-OPAT).
tions warrant a strong recommendation that patients or their The 30-day readmission rate was significantly lower for the 944
caregivers be allowed to self-administer OPAT. TT-OPAT patients compared to the 244 OPAT patients who
Table 5. Evidence Table: Comparison of Outcomes in Self-Administration of Outpatient Parenteral Antimicrobial Therapy (OPAT) Medications Versus
Healthcare Personnel Administration of OPAT Medications
Factors That Alter

Quantity and Type Starting Level of the Strength of Final Evidence
Outcome Conclusion Summary of Findings of Evidence Evidence Evidence Strength
Readmission No increase Lower hazard of readmissiona for S-OPAT (HR 0.36,b 2 cohort studies Low Large effect (+1) Moderate
95% CI 0.24–0.53, P < .001) in 1 study [50] (n = 2059,
No difference in readmission rates (10.5% vs 12.6%, 2229) [49, 50]
RR 0.83, 95% CI 0.59–1.14, P = .30) in 1 study [49]
Complicationsc No increase Similar overall complication rate (24% vs 23%, RR 2 cohort studies Low … Low
1.03, 95% CI 0.86–1.24, P = .80) in 1 study [49] (n = 2059,
S-OPAT at home (vs administration by staff in OPAT 2766) [49, 51]
clinic) was not associated with line infection (OR
0.84, 95% CI NR P = .72) or other line events (OR
1.32, 95% CI NR, P = .22) in 1 study [51]
Abbreviations: CI, confidence interval; H-OPAT, administration of IV antimicrobials by a healthcare worker; HR, hazard ratio; NR, not reported; OR, odds ratio; RR, relative risk; S-OPAT, admin-
istration of IV antimicrobials by the patient, relative, or caregiver rather than by a healthcare worker.
a
The outcome reported in the study was “clinical deterioration,” which was a composite outcome of readmission or death. There were 2 deaths so, effectively, the outcome could be
considered readmission.
b
Estimates recalculated by original authors at our request after changing the reference level to more directly answer the question posed in this section.
c
Complications were drug associated, line associated, and other.
received NA-OPAT (16.7% vs 23.7%, HR 0.53, 95% CI 0.35– complications in a multivariable analysis in a cohort of 1461
0.81, P = .003) [52]. The evidence from this study is summa- patients, 16 of whom were PWID [55]. IDU was found to be a risk
rized in Table 6. factor for vascular access complications (incidence rate ratio [IRR]
3.32, 95% CI 1.16–7.46, P = .01). The findings are summarized in
Rationale for the Recommendation Table 7.
Readmissions, ED visits, and complications were considered Experience with OPAT for PWID has been described in sev-
critical outcomes. There was low-quality evidence for a lower eral case series. In 1 study, 29 PWID were sent home with an
hazard of readmission with TT-OPAT vs NA-OPAT, but no data indwelling vascular device but brought to an infusion center
to determine risk of complications or ED visits. for daily antibiotic infusions. Patients were prescreened, coun-
In traditional home-based infusion models in the United seled, and had standardized measures to detect peripherally
States, patients self-administer their OPAT medications and inserted central catheter (PICC) abuse, including use of a secu-
have a weekly visit by a visiting nurse. In other countries, OPAT rity seal over the PICC. No deaths or episodes of PICC abuse
at home may mean daily visits by an infusion nurse. In the were noted [43]. Another study reported an intensive treatment
TT model of home-based OPAT, there are no home visits by program for 83 patients with substance abuse, where patients
a nurse. Patients self-administer their OPAT medications and

were managed in a hospital outpatient unit by day and sent to
follow-up in a physician’s office or clinic for monitoring. an off-site supervised residential shelter at night. Treatment for
The study by Bhavan et al provides reassurance that patients 70% of patients included a parenteral antibiotic. No informa-
or their caregivers can be trained to safely administer OPAT tion on choice of vascular access or complications was reported.
medications at home without the need for visiting nurse sup- However, about 70% of patients completed the medical treat-
port and without an increased risk of readmission if there is a ment course and 64% transitioned to an outpatient substance
system to follow them regularly [52]. Demonstration of the lack abuse treatment program [44]. These descriptive studies cannot
of increase in risk of readmission and the potential advantages be taken as evidence of safety in OPAT in PWID but are exam-
of such self-administration allow for a weak recommendation ples of how OPAT has been successfully administered in highly
that OPAT may be done at home via self-administration with- structured settings to a very challenging population.
out the need for visiting nurse support. However, such a model
requires strict training and monitoring systems that may not be Rationale for the Recommendation
readily available, and all patients may not be able to master the Mortality, clinical cure, readmission, ED visits, and vascular
skills to do this. access complications were considered critical outcomes. There
were no data to evaluate mortality, clinical cure, readmission,
III. Can people who inject drugs (PWID) be treated with OPAT at home? and ED visits. There was low-quality evidence for increased risk
Recommendation of vascular access complications for PWID vs non-PWID, but
3. No recommendation can be made about whether PWID no data to determine if the risk was lower, the same, or greater
may be treated with OPAT at home (no recommendation, than when OPAT for PWID was carried out in a SNF.
low-quality evidence). Decisions should be made on a case- PWID are treated with OPAT around the world [42, 43, 55].
by-case basis. However, such treatment at home in PWID is controversial [56,
57]. The theoretical concerns are 3-fold. First, patients could mis-
Evidence Summary use their vascular access, leading to catheter complications. Second,
No studies have directly compared outcomes for OPAT at home largely due to psychosocial factors, patients may not adhere to the
between PWID (equivalent term for injection drug use [IDU]) treatment plan, which may result in lower cure rates. Accidental
vs people who do not inject drugs. One study examined associ- drug overdose is an additional concern, but it is not known if hav-
ations of various factors, including PWID, with vascular access ing a VAD for OPAT increases the risk for drug overdose. Typical
Table 6. Evidence Table: Comparison of Outcomes in Teach-and-Train Outpatient Parenteral Antimicrobial Therapy (OPAT) Versus Nurse-Administered
OPAT
Study Design and Starting Level of Factors That Alter the Final Evidence
Outcome Conclusion Summary of Findings Sample Size Evidence Strength of Evidence Strength
Readmission Lower hazard of Lower hazard of readmission 1 cohort study Low Large effect (+1) Low
readmission (HR 0.53, 95% CI 0.35–0.81, (n = 1168) [52] Imprecision (–1)
P = .003) [52]
Mortality Insufficient evidence No difference in 1–year 1 cohort study Low Imprecision (–1) Very low
mortality (HR 0.86, 95% CI (n = 1168) [52]
0.37–2.00, P = .73) [52]
Abbreviations: CI, confidence interval; HR, hazard ratio.

Table 7. Evidence Table: Outpatient Parenteral Antimicrobial Therapy at Home in Patients Who Inject Drugs: Comparison of Outcomes in Patients With
and Without Injection Drug Use
Quantity and Type of Starting Level of Factors That Alter the Final Evidence
Outcome Conclusion Summary of Findings Evidence Evidence Strength of Evidence Strength
Vascular access IDU is a risk factor IDU was a risk factor 1 cohort study Low Large effect (+1) Low
complications for vascular access (n = 1461, 16 with Imprecision (–1)
complications (IRR 3.32, 95% IDU) [55]
CI 1.16–7.46, P = .01) [55]
Abbreviations: CI, confidence interval; IDU, injection drug use; IRR, incidence rate ratio.
alternatives to OPAT at home include discharging patients to 58–64]. The relevant outcomes examined in these studies were
SNFs, sending patients home without a VAD but bringing them clinical improvement, hospital readmission, adverse events, and
to an outpatient facility for each antimicrobial administration, or healthcare utilization.
keeping them in hospital for the duration of their parenteral anti- Clinical improvement for elderly patients treated with OPAT
biotic treatment course. It should be noted that there are no data to was examined in 2 observational studies [10, 58]. The first

suggest that the risk of device misuse is any lower in SNFs, where compared outcomes among patients aged ≥60 years with those
patients have ample opportunity for illicit drug administration. aged <60 years in a population of military veterans treated with
Confirmation about whether PWID are at higher risk of vascular OPAT with a teach-and-train model [10]. The study was lim-
access complications during OPAT and, if so, refinement of the ited in that it did not control for confounders. The second study
estimate of this risk requires additional studies. examined risk factors for failure of OPAT in the treatment of
There are other practical considerations that make it difficult infective endocarditis in the United Kingdom, but it was not
to arrange for OPAT at home for PWID. In addition to a serious designed with a specific intent of examining age as a risk factor
infection, these patients also have an addiction and often associ- [58]. The proportion of patients cured, improved, or made stable
ated mental health disorders that may require treatment. A large was similar in older (>60 years) and younger patients in the first
proportion of these patients lack insurance. Many such patients of these studies (90% vs 94% of OPAT courses, RR 0.97, 95%
are homeless or have a home environment that is unsuitable for CI 0.90–1.05, P = .4]) [10]. Similarly, in the other study, older
the provision of OPAT. Two recent studies have reported suc- age was not associated with OPAT failure on univariable ana-
cessful OPAT administration in homeless patients (some of lysis (OR 1.01, 95% CI 0.98–1.05, P = .47) [58]. However, given
whom were identified as PWID) using externally funded respite that both studies suffer from significant risk of bias, the avail-
housing for the duration of the OPAT course [44, 45]. able data provide insufficient evidence to conclude that there
In summary, there is insufficient evidence to make a recommen- is no difference in clinical improvement with OPAT between
dation for or against treating PWID with OPAT at home. In some older and younger patients.
situations, there may be no safe alternatives to in-hospital treat- Hospital readmission for older patients treated with OPAT
ment. Decisions must be made on a case-by-case basis depending at home was examined in 7 observational studies [50, 59–64].
on the patient’s unique circumstances and the resources available. The first was a direct comparison between older (>70 years)
Studies examining innovative models of care for this challenging and younger patients, but it was not controlled for factors
group of patients that involve management of addiction in add- that differed across the groups [59]. The other 6 reports were
ition to treatment of infection are needed. The role of long-acting observational studies where factors associated with hospi-
glycopeptides in this population needs to be explored. tal readmission were examined in multivariable analyses [50,
60–64]. No difference in early readmission (8% vs 7% of OPAT
IV. Should elderly patients be allowed to be treated with OPAT at home?
courses, RR 1.07, 95% CI 0.33–3.49, P = .93) or readmission
Recommendation within 3 months (14% vs 16% of OPAT courses, RR 0.88, 95%
4. Elderly patients should be allowed to be treated with OPAT at CI 0.40–1.93, P = .75) was found between older and younger
home (strong recommendation, low-quality evidence). This patients in the direct comparison [59]. Age was not found to
recommendation assumes that potential challenges to OPAT be associated with unplanned 30-day readmission (OR 1.09 per
in the elderly, such as cognition, mobility, and dexterity, have decade, 95% CI 0.99–1.21, P = .10 [60]; HRs 1.27, 1.13, 1.20
been duly considered and that the patient or caregiver is able for higher age groups vs 18- to 63-year-old age group were not
to communicate with the treatment team if necessary. significant [61]; not significantly associated on univariable ana-
lysis, not examined in multivariable analysis [62]), readmis-
Evidence Summary sion while on OPAT (OR 0.99, 95% CI 0.97–1.00, P = .13 [63]),
Eleven observational studies allow for an evaluation of the or 6-week readmission (OR NR, 95% CI NR, P = .16) [64].
effect of age on outcomes associated with OPAT [10, 50, 51, 55, However, age >70 years was associated with a higher hazard of
clinical deterioration (readmission or death) in 1 study (HR 1.6, for equivalence in readmission and adverse events between older
95% CI 1.1–2.2, P = .008) [50]. Although 1 in 7 studies found and younger patients on OPAT and very low-quality evidence
increased risk of readmission in patients aged >70 years, the for comparison of clinical improvement or healthcare utilization.
preponderance of evidence suggests that OPAT in older patients Many elderly patients are consigned to receive OPAT in SNFs
is not associated with increased risk of readmission compared because of lack of insurance coverage for various components
to OPAT in younger people. of the home OPAT package (medications, supplies, nursing),
Adverse events in older patients while on OPAT and associ- but most patients prefer to be discharged to home. For some
ation of age and adverse events while on OPAT were examined patients, treatment in an infusion center may be an option. For
in 5 studies [10, 51, 55, 59, 62]. Two were direct comparisons others, this this may not be an option because of the lack of a
of adverse events in older patients vs younger patients [10, suitable infusion center in the patient’s geographic area or ina-
59]. Neither study controlled for other variables that differed bility to make daily trips to the infusion center. OPAT at home
between the older and younger patients. Rates of adverse is generally less labor intensive for the healthcare system than
events overall (16% vs 16% of OPAT courses, RR 0.94, 95% OPAT in a SNF.
CI 0.38–2.35, P = .89) [59], catheter-associated bloodstream Accounting for patient’s values and preferences, the overall

infection (0.76 vs 0.23 per 1000 OPAT days, IRR 3.26, 95% CI balance of costs, benefits, and harms, the equivalence in crit-
0.17–192.10, P = .65 [10], and catheter occlusion (3.03 vs 2.32 ical outcomes, and lack of evidence of harm, there is sufficient
per 1000 OPAT days, IRR 1.30, 95% CI 0.45–3.67, P = .74) [10] evidence to make a strong recommendation that older patients
did not differ between older patients and younger controls in may be treated with OPAT at home. This recommendation
these 2 observational studies. A higher rate of nephrotoxicity in assumes that potential challenges to OPAT in the elderly, such
the elderly group (3.03 vs 0.46 per 1000 IV antibiotic days, IRR as cognition, mobility, and dexterity, have been duly considered
6.51, 95% CI 1.30–44.89, P = .02) was found in 1 study [10]. and that the patient or caregiver is able to communicate with
Older age was not found to be a risk factor for vascular access the treatment team if necessary.
complications on multivariable analyses in 2 observational
V. Should infants aged <1 month be treated with OPAT at home?
studies (IRR = 0.99, 95% C.I. 0.98–1.00, P = .04 [55]; OR 1.0, Recommendation
95% CI 0.99–1.01, P NR [62]) or for line infection (P = .57 on 5. No recommendation can be made regarding whether infants
univariable analysis, age not included in multivariable analysis) aged <1 month may be treated with OPAT at home (no rec-
and other line events (OR 0.997, 95% CI NR, P = .57) in another ommendation, very low-quality evidence). Decisions should
large observational study [51]. The preponderance of evidence be made on a case-by-case basis.
from these studies suggests that OPAT in older patients is not
associated with increased risk of adverse events compared to Evidence Summary
OPAT in younger patients. Treatment failure, adverse events, and hospital readmission have
Healthcare resource utilization related to administering not been directly compared between neonates (aged <1 month)
OPAT to elderly patients at home was examined in 1 observa- and older infants and children treated with OPAT in any pub-
tional study comparing older (>60 years) and younger patients lished studies. Successful use of OPAT at home for neonates has
[10]. The study did not control for other variables that dif- been reported in 2 case series. No infectious relapses or treat-
fered between the older and younger patients. Older patients ment complications were noted in 1 study that included 51 neo-
had lower rates of ability to self-administer (20% vs 41%, RR nates treated with ceftriaxone at home (majority intramuscular)
0.48, 95% CI 0.31–0.74, P < .001), higher rates of urgent care [65]. Additionally, few complications were reported in a study
visits (31.4 vs 14.3 per 1000 OPAT days, IRR 2.20, 95% CI that described OPAT care for 95 neonates with an average age
NR, P < .001), higher rates of calls to physicians and pharma- at discharge of 5 days [66]. Four patients required an antimicro-
cies (14.3 vs 8.57 per 1000 OPAT days, IRR 1.67, 95% CI NR, bial change due to loss of vascular access, and 4 had a change
P = .04), and higher rates of requirement for social work inter- in antimicrobial (ceftriaxone to ampicillin and gentamicin) due
vention (7.1 vs 2.9 per 1000 OPAT days, IRR 2.45, 95% CI NR, to hyperbilirubinemia. Of note, all patients were treated with a
P = .01) than younger patients [10]. Given the substantial risk peripheral, rather than a central, catheter.
of bias in this single study, the available data provide insufficient
evidence to allow a conclusion that more resources are required Rationale for the Recommendation
to deliver OPAT in the elderly than in younger patients. The evi- The extremely limited number of reports of use of OPAT for
dence from the relevant studies is summarized in Table 8. neonates is reinforced by the fact that patient age is reported as
among the most important considerations that impact the deci-
Rationale for the Recommendation sion to use OPAT by pediatric ID specialists [67]. Several clinical
Clinical improvement, readmission, and adverse events were and logistical factors make OPAT more challenging for neonates
considered critical outcomes. There was low-quality evidence than for other children. OPAT use in neonates has generally been

Table 8. Evidence Table: Outpatient Parenteral Antimicrobial Therapy in the Elderly: Comparison of Outcomes in Older Versus Younger Patients
Outcome Conclusion Summary of Findings Evidence Evidence Strength of Evidence Strength
Clinical improvement Insufficient evidence No difference in rate of cured, improved, or stable (90% vs 94% of OPAT courses 2 cohort studies Low Risk of bias (–1) Low
[RR 0.97, 95% CI 0.90–1.05, P = .43]) in 1 study [10] (n = 231, 80) [10, 58] Confounding (+1)
Age was not associated with OPAT failure among patients treated with OPAT for
infective endocarditis (OR 1.01, 95% CI 0.98–1.05, P = .47) in 1 study [58]
Readmission No difference in No difference in rate of readmission during the clinical episode (8% vs 7% of 7 cohort studies Low … Low
readmission OPAT courses, RR 1.07, 95% CI 0.33–3.49, P = .93) or within 3 months (14% (n = 2229, 420,
vs 16% of OPAT courses, RR 0.88, 95% CI 0.40–1.93, P = .75)a in 1 study [59] 145, 782, 379, 400,
Higher age was not associated with 30-day readmission (OR 1.09 per decade, 96) [50, 59–64]
95% CI 0.99–1.21, P = .10 [60]; HRs 1.27, 1.13, 1.20 for higher age groups vs
18–63 years age group, none significant [61]; not significant on univariable
analysis, age not included in multivariable analysis [62]), or readmission while
on OPAT (OR 0.99, 95% CI 0.97–1.00, P = .13) [63], or 6-week readmission
(OR NR, 95% CI NR, P = .16) [64], in a total of 5 studies
Age >70 years was associated with a higher hazard of clinical deterioration
(readmission or death)b (HR 1.6, 95% C.I. 1.1–2.2, P = .008)5 in 1 study [50]
Adverse events No difference in No difference in overall rate of adverse events (16% vs 16% of OPAT courses 5 cohort studies Low … Low
adverse events (RR 0.94, 95% CI 0.38–2.35, P = .89)a in 1 study [59] (n = 231, 2638,
Similar rates of catheter-associated bloodstream infection (0.76 vs 0.23 per 1000 1461, 145,
OPAT days, IRR 3.26, 95% CI 0.17–192.10, P = .65)a in 1 study [10] 420) [10, 51, 55,
Similar rates of catheter occlusion (3.03 vs 2.32 per 1000 OPAT days, IRR 1.30, 59, 62]
95% CI 0.45–3.67, P = .74)a in 1 study [10]
Increasing age was not associated with more vascular access complications (IRR
0.99, 95% C.I. 0.98–1.00, P = .04 [55]; OR 1.0, 95% CI 0.99–1.01, P NR) [62] in
2 studies
Increasing age was not associated with line infection (P = .57 on univariable
analysis, not included in multivariable model) or other line events in a
multivariable model (OR 0.997, 95% CI NR, P = .57) in 1 study [51]
Higher rate of nephrotoxicity in the elderly (3.03 vs 0.46 per 1000 IV antibiotic
days, IRR 6.51, 95% CI 1.30–44.89, P = .02)a in 1 study [10]
Healthcare resource Insufficient evidence Lower rate of ability to self-administer (20% of courses vs 41% of courses (RR 1 cohort study Low Risk of bias (–1) Very low
utilization 0.48, 95% CI 0.31–0.74, P < .001)a [10] (n = 231) [10] Imprecision (–1)
Higher rate of urgent care visits (31.4 vs 14.3 per 1000 OPAT days, IRR 2.20,
95% CI NR, P < .001)a [10]
Higher rate of calls to physicians or pharmacists (14.3 vs 8.57 per 1000 OPAT
days, IRR 1.67, 95% CI NR, P = .04) [10]
Higher rate of requirement for social work intervention (7.1 vs 2.9 per 1000 OPAT
days, IRR 2.45, 95% CI NR, P = .01)a [10]
Abbreviations: CI, confidence interval; IRR, incidence rate ratio; NR, not reported; OPAT, outpatient parenteral antimicrobial therapy; RR, relative risk.
a
Calculated from data reported in the study.
b
The outcome reported in the study was “clinical deterioration,” which was a composite outcome of readmission or death. There were 2 deaths so, effectively, the outcome could be considered readmission.
discouraged for serious infections such as meningitis [68]. For Among 1000 courses of OPAT at home, allergic reactions were
such serious infections, the signs suggestive of treatment failure or noted in 28 courses, with the mean time to allergic reaction
clinical worsening may be relatively subtle. Therefore, clinicians being 19.6 days [69]. Of the 3 episodes of perioral angioedema
may feel that the entire course of treatment must be completed that were noted, onset of symptoms was delayed, ranging from
in an inpatient setting where both compliance and continuous 13 to 33 days after the start of therapy.
clinical monitoring are ensured. However, it should be acknowl-
edged that the consequences of prolonged hospitalization instead Rationale for the Recommendation
of OPAT for neonates may be especially substantial in terms of For many patients starting OPAT, therapy is continued from
economic and social costs to the family, as certain infections (eg, hospital discharge to an outpatient setting, and the patient has
bacterial or herpes simplex virus meningitis) require treatment already demonstrated adequate tolerance to the chosen anti-
duration of up to 3 weeks. Another important factor is that some microbial. However, in some instances, OPAT initiation may
home care companies will not provide services for neonates. involve starting a new or entirely different treatment as an out-
Additionally, some hospitals may not have the technical capabili- patient. The most serious concern about administering the first
ties to place a central line suitable for OPAT at home in neonates. dose of an antimicrobial at home is the ability to manage an

In summary, OPAT use for neonates is extremely limited due immediate hypersensitivity reaction or anaphylaxis, conditions
to a variety of clinical and technical factors, some of which are that can be life-threatening. Due to concerns about patient safety
unique to this vulnerable patient population. The absence of evi- and to ensure the appropriate management of anaphylaxis, the
dence about the safety and efficacy of OPAT using central catheters 2004 IDSA Practice Guidelines for OPAT recommended that
in neonates, especially for invasive infections such as meningitis, the first OPAT dose be administered in a supervised healthcare
remains an important research gap for pediatric investigators. setting before allowing OPAT administration at home [22].
There is increasing recognition that other considerations
ANTIMICROBIAL UTILIZATION must inform practice. For some patients (eg, elderly, disabled,
hospice), the potential benefit of first-dose observation in a
VI. Is it safe and appropriate to administer the first OPAT dose of a new
antimicrobial at home? healthcare facility is greatly outweighed by the inconvenience
Recommendation and cost of transport to the facility. The 2012 UK OPAT Good
6. In patients with no prior history of allergy to antimicrobials Practice Recommendations assert that the patient’s home may
in the same class, the first dose of a new parenteral antimicro- be a suitable setting if the first dose is administered in the pres-
bial may be administered at home under the supervision of ence of a person competent to manage anaphylaxis (eg, home
healthcare personnel who are qualified and equipped to care nurse) [70]. This practice has been adopted in some places
respond to anaphylactic reactions (weak recommendation, in the United States and in other countries around the world
very low-quality evidence). [71]. Reports related to this practice have not provided rea-
son to suggest that this has been an unsafe undertaking [72].
Evidence Summary There are no clear guidelines about how long a patient should
No studies have compared the outcomes of allergic reactions or be observed after administration of the first dose of a new anti-
other drug-related adverse events in patients treated with OPAT microbial. The usual practice is 30 minutes [73].
where the initial dose of an antimicrobial was administered Given the rarity of severe immediate type 1 allergic reactions,
outside the healthcare system environment (eg, in the patient’s it is reasonable to administer the first dose of an antimicro-
home) to outcomes when administered within the healthcare bial in a patient’s home under the supervision of a competent
system (eg, in the hospital inpatient service, ED, infusion center, healthcare worker in patients with no prior history of allergy to
or physician office). antimicrobials in the same class.
Reports of anaphylaxis related to administration of OPAT
VASCULAR ACCESS DEVICES
have been rare. No instances of anaphylaxis were reported in a
study examining allergic reactions in 770 patients who received For the purposes of uniformity and clarity in this guideline,
1000 courses of home OPAT with 25 different antimicrobials VADs are referred to as either central or noncentral. In OPAT,
[69]. Of note, in that study, 90% of antibiotics and virtually all the principal central devices are peripherally inserted central
prescribed beta lactam antibiotics or vancomycin were adminis- catheters (PICCs) and long-term central catheters (LTCCs), of
tered via continuous infusion, which may reduce the likelihood which there are 2 main types: tunneled central venous cathe-
of allergic reactions. In another study of 2009 OPAT episodes, ters (t-CVCs) and ports. Noncentral catheters include midline
0.2% of courses were complicated by anaphylaxis [49]. The tim- catheters (MCs) which are peripheral lines placed in the larger
ing of these reactions was not reported. It is recognized that veins of the upper arm with the catheter tip destination at or
serious adverse events from antimicrobials may occur on sub- below the axillary line, and short peripheral catheters (SPCs)
sequent administrations after the first dose has been tolerated. (Table 9).

VII. In patients needing short courses of OPAT, is it acceptable to use a 0% vs 0% [74]). More minor complications were found among
midline catheter (MC) instead of a central venous catheter? patients with MCs in 1 study (11.5% vs 1.5%, OR 8.76, 95% CI
Recommendation
2.84–37.21, P < .001 [76]) but not in another (19.9% vs 17.9%,
7. In adult patients needing short courses of OPAT (less than
RR 1.00, 95% CI 0.35–2.89, P = 1.0 [74]).
14 days), a MC may be used rather than a central catheter
Table 10 outlines the evidence from these studies. Taken
(weak recommendation, very low-quality evidence). No rec-
together, the available evidence provides insufficient infor-
ommendations can be made regarding the use of MCs in
mation to draw conclusions about the relative safety of MCs
pediatric patients.
vs PICCs.
Evidence Summary
Rationale for the Recommendation
Four studies comparing complications of MCs vs PICCs can be
Vascular access complications were considered the critical out-
used to address this question in OPAT patients [51, 74–76]. One
come. There was very low-quality evidence for increased risk
was a small, randomized, controlled trial (N = 54) that com-
of complications with MCs vs PICCs during OPAT. MCs may
pared outcomes in inpatients expected to be treated with up to
be preferred by some providers as they provide a longer dwell
6 days of vancomycin who were randomized to receive either
time compared to SPCs and a less invasive option compared to

a MC or a PICC [74]. The study was limited by its small size,
central lines, as well as faster placement and lower cost. In add-
short duration, and indirectness to OPAT patients since it was
ition, the fact that MC-associated bloodstream infections are not
an inpatient venue. The second was an observational study that
counted as central line–associated bloodstream infections may
examined vascular access complications in 328 adult patients
have increased the use of MCs for vascular access in hospitalized
with cystic fibrosis who received 231 MCs and 97 PICCs, 48%
patients. However, there are limited data on OPAT outcomes in
of whom were receiving home-based OPAT [75]. The mean in
patients with MCs, and the available studies provide insufficient
situ time for MCs was 22 days and that for PICCs was 14 days.
evidence with respect to outcomes for MCs vs PICCs.
A third inpatient observational study compared outcomes
A reasonable definition of a short duration of OPAT is a treat-
among 206 patients who had PICCs vs 200 patients who had
ment course that lasts less than 14 days. Using an expert con-
MCs for a variety of indications [76]. The fourth was a multi-
sensus method such as a modified Delphi approach (RAND/
variable analysis that examined factors associated with vascular
UCLA Appropriateness Method), appropriateness criteria for
access complications in a large OPAT cohort [51].
use and care of VADs were developed for hospitalized and SNF
A composite of catheter-related adverse events overall was
patients only [77]. Among patients receiving peripherally com-
reported in 3 studies [74–76]. An increased risk of adverse
patible infusates, this group recommended the use of a MC for
events among patients with MCs compared to patients with
infusions anticipated to last 14 or fewer days and preferential
PICCs (19.5% vs 5.8%, OR 3.90, 95% CI 1.92–8.48, P < .001)
use of a PICC for infusions anticipated to last 15 or more days
was found in 1 study [76], but no significant difference was
among hospitalized patients [77].
found in the other 2 studies (19.9% vs 17.9%, RR 1.00, 95% CI
On occasion, a MC may be selected for a course of ther-
0.35–2.89, P = 1.0 [74] and 14 vs 11 per 1000 VAD days, IRR
apy anticipated to be short but then extended for a longer
1.18, 0.62–2.22, P = .62 [75]) for MCs and PICCs, respectively.
period. Very limited data suggest that having a MC in place
Occurrence of major complications and minor complications
for more than 2 weeks is reasonably safe. In a retrospective
were reported in all 4 studies [51, 74–76]. Vascular catheter
cohort study of 92 patients in palliative home care with no
infections and deep venous thrombosis (DVT) were considered
comparator group, MCs had a median catheter dwell time
major complications. More DVTs were reported in MCs (5.96%
of 85 days (range 1–365 days) [78]. Premature MC removal
vs 0.0%) in 1 study [75], but it is not clear if this was a statisti-
was reported in 7.7% due to mechanical complications, which
cally significant difference. There were no line infections with
included obstruction (4.3%, N = 4), accidental dislodgement
either type of catheter in another study [51]. There was no dif-
(2.2%, N = 2), and catheter damage (1.1%, N = 1). There were
ference in the occurrence of major complications in the other 2
no reports of infectious complications. In the setting of a
studies (9.0% vs 4.9%, OR 1.94, 95% CI 0.87–4.47, P = .12 [76];
well-functioning catheter, there is no compelling argument
to exchange a MC for a PICC if an anticipated short OPAT
Table 9. Vascular Access Devices Commonly Used in Outpatient course requires extension.
Parenteral Antimicrobial Therapy Lack of evidence of harm when MCs are used for short periods
and the increasing willingness of the medical community to use
Central Catheters Noncentral Catheters
MCs warrants a weak recommendation that it is acceptable to use
• Peripherally inserted central catheters • Midline catheters
a MC instead of a CVC for patients requiring courses of OPAT
• Long-term central catheters • Short peripheral catheters
• Tunneled central vein catheters lasting fewer than 14 days. Studies are needed to examine the
• Ports safety of MCs used for OPAT courses lasting more than 14 days.
Table 10. Evidence Table: Vascular Access Complications During Outpatient Parenteral Antimicrobial Therapy: Comparison for Patients With Midline
Catheters Versus Peripherally Inserted Central Catheters
Factors That Alter

Quantity and Type Starting Level the Strength of Final Evidence
Outcome Conclusion Summary of Findings of Evidence of Evidence Evidence Strength
Vascular access Insufficient More complications overall with MCs (19.5% vs 1 RCT (n = 54) [74] High Risk of bias (–2) Very low
complications evidence 5.8%, OR 3.90,a 95% CI 1.92–8.48,a P < .001) in 1 2 cohort studies Inconsistency (–1)
overall study with high risk of bias [76] (n = 328, Indirectness (–1)
No difference (19.9% vs 17.9%, RR 1.00, 95% CI 406) [75, 76]
0.35–2.89,a P = 1.0 [74]; 14 vs 11 complications per
1000 vascular access device days, IRR 1.18, 95%
CI 0.62–2.22, P = .62 [75]) in 2 studies
Major Insufficient No difference in major complications (0% vs 0%) 1 RCT (n = 54) [74] High Risk of bias (–1) Very low
complications evidence [74]; 9.0% vs 4.9%, OR 1.94,a 95% CI 0.87–4.47a, 3 cohort studies Indirectness (–1)
P = .12 [76]) in 2 studies (n = 2766, 328, Imprecision (–1)
More DVT in MCs (5.9% vs 0.0%) reported in 1 406) [51, 75, 76]
study (tests of significance not reported [75]
MCs not associated with line infections compared to

PICCs (no line infections with either) in 1 study [51]
Minor Insufficient More minor complications among patients with MCs 1 RCT (n = 54) [74] High Risk of bias (–1) Very low
complications evidence (11.5% vs 1.5%, OR 8.76,a 95% CI 2.84–37.21,a 3 cohort studies Inconsistency (–1)
P < .001) in 1 study with high risk of bias [76], but (n = 2766, 328, Indirectness (–1)
not in another (19.9% vs 17.9%, RR 1.00, 95% CI 406) [51, 75, 76] Imprecision (–1)
0.35–2.89, P = 1.0) [74]
No difference in dislodgement (6.6% vs 14.2%, RR
0.39, 95% CI 0.06–2.33,a P = .40 [74]; 6.90 vs 2.89
per 1000 vascular access device days, IRR 2.24,
95% CI 0.91–5.56, P = .08) [75] in 2 studies
No difference in infiltration (10% vs 0%, RR 6.73,
95% CI 0.33–137.02,a P = .24) in 1 study [74]
No difference in leak (3.3% vs 0%, RR 2.68, 95% CI
0.01–68.66,a P = 1.00) in 1 study [74]
Higher odds of “other line events”b with MCs
compared to PICCs (OR 4.1, P = .03) in 1 study [51]
Abbreviations: CI, confidence interval; DVT, deep venous thrombosis; MC, midline catheter; OR, odds ratio; PICC, peripherally inserted central catheter; RCT, randomized, controlled trial;
RR, relative risk.
a
b
Other line events were a composite outcome of phlebitis, leakage, extravasation, and occlusion.
There are no published data in the pediatric population patients receiving vancomycin to all other antibiotics, found
addressing the use of MCs in children needing OPAT. MCs have that infiltration scores were significantly higher with vanco-
only recently been used for IV access in the inpatient pediatric mycin compared to other antibiotics (mean score 0.20 vs 0.06,
population, and experience is limited. P = .02) [79]. Of note, MCs, which may be less prone to infil-
tration than SPCs, were not used in this study. A second study
VIII. Should vesicant antimicrobials (medications associated with tissue
analyzed vascular device outcomes among 2766 OPAT patients
damage caused by extravasation) be administered via central catheters vs [51]. Because only 4 recipients of vancomycin were included,
noncentral catheters only? the use of vancomycin was not incorporated in multivariable
Recommendation analyses. The study did, however, find a significant association
8. Mandatory use of a central catheter over a noncentral catheter with the use of flucloxacillin (a presumptive vesicant not used
for OPAT with vancomycin is not necessary (weak recom- in the United States) and the occurrence of the composite of
mendation, very low-quality evidence). No recommendation various line events, when controlled for the type of catheter
can be made for choice of vascular catheter for OPAT with (MC, t-CVC, PICC), gender, presence of comorbidity, person
other vesicant antimicrobials such as nafcillin and acyclovir administering the OPAT, and duration of catheter use (OR 3.01,
(no recommendation, very low-quality evidence). 95% CI NR, P = .01) [51]. The evidence from these studies is
Evidence Summary summarized in Table 11. Because of a high risk of bias in 1 study
The first question when evaluating the use of vesicant anti- [79] and indirectness in the other [51], evidence from these
microbials is the safety of vesicant vs nonvesicant antimicro- studies is of too low quality to form a conclusion on the safety
bial administration via peripheral catheters. Two studies have of vesicant antimicrobials via a peripheral catheter.
addressed this question [51, 79]. The first, a retrospective A second issue is the safety of vesicant antimicrobial admin-
cohort study of 153 surgical inpatients with SPCs that compared istration via central vs noncentral catheters. One randomized,

controlled trial assessed vascular complications in patients drugs, of which only 4 antimicrobials were classified as vesi-
receiving the vesicant antimicrobial vancomycin via a noncen- cants: acyclovir, nafcillin, pentamidine, and vancomycin [81].
tral vs central catheter, specifically MCs vs PICCs, for fewer than Despite common perceptions, there is insufficient evidence
6 days (n = 54) [74]. No differences in rates of vascular access– to state that it is unsafe to administer vancomycin via a non-
related adverse events were found. The rate of adverse events central catheter. Of the 3 referenced studies, 1 used SPCs (not
was 19.9% among patients with MCs vs 17.9% among patients commonly used in OPAT) and found increased odds of infil-
with PICCs (P = 1.0) [74]. There were no instances of phlebitis tration with vancomycin [79]; a second had too few patients on
or thrombosis in either group. The study was limited by its small vancomycin to analyze this as a risk factor [51]; and the third
size and the very short duration of therapy. Its applicability to was a comparison of vancomycin vs other antimicrobials but
OPAT is restricted by the fact that participants were inpatients. was limited by its small size, very short duration of therapy, and
The evidence from this study is summarized in Table 12. There indirectness to the question of use for OPAT (it was an inpatient
have not been other comparisons of outcomes for other vesicant study) [74].
antimicrobials administered via central vs noncentral catheters. Given the lack of evidence for harm in administering van-
comycin via a MC, it is unnecessarily restrictive to mandate a

requirement of a central catheter for OPAT with vancomycin.
There is insufficient evidence to make a blanket catheter recom-
come. The evidence assessing harm from administering vancomy-
mendation for all vesicant antimicrobials.
cin via a MC rather than a central catheter was of very low quality.
The majority of antibiotics delivered in the OPAT setting
IX. Should patients with chronic kidney disease (CKD) requiring OPAT
are administered through central catheters (eg, PICCs), but have a tunneled central venous catheter (t-CVC) for vascular access rather
increasingly, noncentral catheters, particularly MCs, are used. than a PICC?
Therefore, it is important to understand the safety of vesicant Recommendation
antimicrobial agents in these settings. 9. For patients with advanced CKD requiring OPAT, a t-CVC is
Different groups have defined vesicants in different ways. recommended rather than a PICC (strong recommendation,
One systematic review of the literature sought to identify med- low-quality evidence).
ications associated with tissue damage caused by extravasa-
tion and, thus, characterized as vesicant drugs [80]. Cytotoxic Evidence Summary
medications (chemotherapy) were excluded. In the category Only 1 case-control study has examined the association between
of antimicrobials, 11 drugs were identified: acyclovir, ampho- a history of PICC use and absence of a functioning arteriovenous
tericin B, ampicillin, cloxacillin, gentamicin, metronidazole, fistula (AVF) for dialysis access [82]. A total of 120 patients with a
nafcillin, oxacillin, penicillin, tetracycline, and vancomycin. lack of a functioning AVF (cases) were compared to 162 patients
The review found 232 extravasation cases, including 21 anti- with a functioning AVF (controls). A history of having a PICC was
biotic events. Notably, except for nafcillin (9 reports), tetracy- found in 44.2% of cases but only in 19.7% of controls. A strong
cline (2 reports), and vancomycin (3 reports), the remainder of association was found between a history of PICC use and absence
the drugs included only a single citation. The Infusion Nurses of a functioning AVF for dialysis (OR 2.8, 95% 1.5–5.5, P = .002).
Society recently published a list of noncytotoxic vesicant The evidence from this study is summarized in Table 13.
Table 11. Evidence Table: Vascular Access Complications During Outpatient Parenteral Antimicrobial Therapy Via a Noncentral Line: Comparison for
Vesicants Versus Nonvesicant Antimicrobials
Quantity and Type Starting Level of Factors that Alter the Final Evidence
Outcome Conclusion Summary of Findings of Evidence Evidence Strength of Evidence Strength
Vascular access Insufficient evidence Higher infiltration scores with 2 cohort studies Low Large effect (+1) Very low
complications vancomycin than with other (N = 153, Indirectness (–1)
antibiotics administered via 2766) [51, 79] Imprecision (–1)
SPCs (0.20 vs 0.06, P = .02)
in 1 study [79]
Flucloxacillin (presumptive
vesicant) treatment was
associated with increase in
OLEa (OR 3.01, 95% CI NR,
P = .01) in 1 study [51]
Abbreviations: CI, confidence interval; NR, not reported; OLE, other line events; OR, odds ratio; SPC, short peripheral catheter.
a
Other line events were a composite outcome of phlebitis, leakage, extravasation, and occlusion.
Table 12. Evidence Table: Outpatient Parenteral Antimicrobial Therapy With Vesicant Antimicrobials: Comparison of Outcomes for Patients Treated via a
Midline Versus Those Treated via Central Line
Quantity and Type Starting Level of Factors That Alter the Final Evidence
Vascular access Insufficient evidence No difference in complica- 1 RCT (n = 54) [74] High Risk of bias (–2) Very low
complications tions overall (RR 1.00, Imprecision (–1)
95% CI 0.35–2.89, Indirectness (–1)
P = 1.0) [74]
No venous thrombosis or
line infection in either
group
Abbreviations: CI, confidence interval; RCT, randomized controlled trial; RR = relative risk.
Rationale for the Recommendation access assessment prior to placement of any VAD [98]. In the
The critical outcome was functioning AVF. There was low-qual- Michigan Appropriateness Guide for Intravenous Catheters

ity evidence for increased odds of a nonfunctioning fistula in study, a multidisciplinary panel of experts rated scenarios in
patients who had had a PICC in the past. Among patients with which PICCs might or might not be indicated [77]. For patients
CKD who currently need hemodialysis or may need hemo- with CKD stage 3b (eGFR of <45 mL/min/1.73 m2) or greater
dialysis in the future, vein preservation is paramount. The or receiving renal replacement therapy, panelists recommended
Centers for Medicare and Medicaid Services and the National CVCs over PICCs and MCs to maximize upper extremity vein
Kidney Foundation have collaborated through the Fistula First preservation.
Breakthrough Initiative (fistulafirst.org) and the National Kidney The ability to provide effective dialysis is critical to survival
Foundation’s Kidney Disease Outcomes Quality Initiative for patients with end-stage renal disease. It is important for
(KDOQI 2006 Clinical Practice Guidelines) to promote the all medical personnel to preserve options for hemodialysis in
prevalence of functioning AVFs in hemodialysis patients. These patients who may need renal replacement therapy in the near
AVFs have superior patency rates and decreased mortality, mor- future. In keeping with this goal and consistent with recom-
bidity, and cost compared to synthetic grafts and CVCs [82–96]. mendations from other societies [98], a strong recommenda-
Specifically, fistulas are favored over central venous dialysis tion that PICCs be avoided in patients with advanced CKD
catheters, which have been shown to promote a chronic inflam- requiring OPAT is warranted.
matory state, create an ongoing risk of bloodstream infection,
and increase both mortality and cost of chronic dialysis [83–89, X. Should patients requiring frequent OPAT courses have a long-term
central catheter (LTCC) inserted with the intention of leaving it in place
93–95, 97]. between courses?
To increase the likelihood that patent vessels are available Recommendation
for placement of AVFs, guidelines have recommended that 10. No recommendation can be made about whether patients who
PICCs be avoided in those with advanced kidney disease, on require frequent courses of OPAT should have a LTCC left in
dialysis, or with kidney transplants [98]. The CKD stage at place between courses (no recommendation, no evidence).
which PICCs should be avoided has been debated. According
to the American Society for Diagnostic and Interventional Evidence Summary
Nephrology/Association for Vascular Access Joint Clinical Neither clinical outcomes nor patient satisfaction have been
Practice Committee, patients with an estimated glomerular compared for a strategy of leaving a LTCC in place between
filtration rate (eGFR) of <60 mL/min/1.73 m2 or a serum cre- courses vs repeatedly placing a new VAD for repeated courses
atinine level ≥2.0 mg/dL should undergo an expert vascular of OPAT.
Table 13. Evidence Table: Comparison of Arteriovenous Fistula Failure Among Patients With and Without Prior Peripherally Inserted Central Catheters
Outcome Conclusions Summary of Findings Evidence Evidence Strength of Evidence Strength
AV fistula failure Higher odds of lack of Lack of a functioning AV fistula 1 case-control study Low Large effect (+1) Low
functioning AV fistula was associated with having (n = 282) [82] Imprecision (–1)
had a PICC in the past (OR
2.8, 95% CI 1.5–5.5,
P = .002) [82]
Abbreviations: AV, arteriovenous; CI, confidence interval; OR, odds ratio; PICC, peripherally inserted central catheter.

Rationale for the Recommendation [101, 102], and major bleeding occurred in 4% and 10% [101,
For patients who are known to require repeated courses of OPAT, 102]. The evidence from these studies is shown in Table 14. In
the options include leaving an LTCC such as an implanted port addition, 1 descriptive study found that only 3 of 83 cancer
or t-CVC in place between episodes or placing a new catheter, patients (4%) treated with catheter retention and anticoagula-
typically a PICC, for each event. There are no clinical outcomes tion developed catheter dysfunction while on rivaroxaban, and
data comparing these 2 options. 2 patients had major bleeding [103].
Two small studies suggest that if the decision is made to place
an LTCC for repeated courses of OPAT, patients may prefer a Rationale for the Recommendation
port rather than a tunneled catheter. In a follow-up to a rand- Catheter function, recurrent symptomatic thromboembo-
omized, controlled trial of acute leukemia patients with t-CVCs lism, and major bleeding were considered critical outcomes.
or implanted ports, 32 adult patients were periodically surveyed There was low-quality evidence for ability to preserve catheter
about their perceptions of vascular access strategies [99]. Overall, function and very low-quality evidence for risk of recurrent
patients were more satisfied with the ports. In another retrospec- thromboembolism and major bleeding with anticoagula-
tive cohort study of cystic fibrosis patients needing ongoing cen- tion. In addition, the population studied was that of cancer
patients, not OPAT patients. Overall, these amount to very

tral venous access for OPAT who had received ports, 28 of 30
patients preferred the ports to the SPCs or CVCs that they had low-quality evidence for a net benefit of catheter preserva-
used before [100]. However, both studies involved surveys and tion with anticoagulation in the setting of PICC thrombosis
only 1 involved OPAT patients, so the quality of the evidence during OPAT.
does not allow for the formulation of a recommendation. The International Society on Thrombosis and Haemostasis
[104], the Infusion Nurses Society [81], and the American
XI. Should the vascular access device be removed if a patient develops College of Chest Physicians [105] have suggested that the
symptomatic catheter-associated venous thromboembolism (CA-VTE) occurrence of CA-VTE is, by itself, not an absolute reason
while on OPAT?
to remove the catheter as long as the catheter remains well
Recommendation
positioned and arm pain and swelling decrease with anti-
11. It is not necessary to remove a vascular access device
coagulation. The practice of maintaining the VAD when
if CA-VTE develops during OPAT, as long as the cath-
patients develop CA-VTE while on OPAT is being increas-
eter remains well positioned and arm pain and swelling
ingly adopted by physicians; to date, this change in practice
decrease with anticoagulation (weak recommendation, very
has not led to complications that raise concern about patient
safety.
Evidence Summary Catheter retention and anticoagulation allow continued use
Two uncontrolled clinical trials have evaluated outcomes among of the catheter in most cases. The potential for major bleeding
patients with CA-VTE in cancer patients who were managed must be factored into a decision regarding catheter retention
with vascular catheter retention and anticoagulation [101, and anticoagulation. However, if a patient develops CA-VTE
102]. In the first study, patients were treated with dalteparin for while on OPAT and if there is continued need for a vascular
5–7 days, followed by warfarin, and were followed for 3 months catheter, the very low-quality evidence for a net benefit of cath-
[101]. In the second study, all patients were treated with rivar- eter preservation warrants a weak recommendation that it is not
oxaban for 12 weeks [102]. necessary to remove the catheter and place a new one as long as
Catheter function was 100% at 3 months in both studies [101, the catheter is functional and arm pain and swelling decrease
102]. Recurrent thromboembolism occurred in 0% and 1.4% with anticoagulation.
Table 14. Evidence Table: Outcomes for Vascular Access Retention in the Setting of Catheter-Associated Venous Thromboembolism
Quantity and Type Starting Level Factors That Alter the Overall Evidence
Outcome Conclusion Summary of Findings of Evidence of Evidence Strength of Evidence Strength
Preservation of line Line function can be 42/42a (100%) [101] and 2 clinical trials Low Large effect (+1) Low
function preserved 70/70 (100%) [102] of patients (N = 74, Indirectness (–1)
had a functional catheter at 70) [101, 102]
3 months
Recurrent symptomatic Insufficient evidence 0/74 (0%) [101] and 1 (1.43%) 2 clinical trials Low Risk of bias (–1) Very low
thromboembolism [102] had recurrent (N = 74, Indirectness (–1)
thromboembolism 70) [101, 102]
Major bleeding Insufficient evidence 3 (4%) and 7 (10%) had major 2 clinical trials Low Indirectness (–1) Very low
bleeding [101, 102] (N = 74,
70) [101, 102]
a
The remaining catheters were removed before the end of the study for other reasons (no longer needed, 21; infection, 2; other reasons not study endpoints, 9).
XII. Should patients with prior CA-VTE be treated with prophylactic anti- Seven case series have described the utilization of PICCs
coagulation while on OPAT?
in pediatric patients [112–118]. Reported rates of most cathe-
Recommendation
ter-related complications were low; line infections ranged from
12. No recommendation can be made regarding the need to
none to 7%, thrombosis ranged from none to 9%, mechanical
treat patients with a history of prior CA-VTE with prophy-
complications ranged from 7% to 28%, and catheter removal
lactic oral anticoagulation while on OPAT (no recommen-
ranged from 8% to 33%.
dation, no evidence).
Evidence Summary
Outcomes have not been compared for anticoagulation vs no
come. There was very low-quality evidence for increased risk of
anticoagulation for prevention of CA-VTE among patients with a
vascular access complications with PICCs compared to LTCCs
prior history of CA-VTE in either inpatient or outpatient settings.
in children.
Rationale for the Recommendation The available literature comparing outcomes of PICCs vs
Several groups have recommended against anticoagulation for LTCCs in children is very limited. Although the single reported
study comparing PICCs to LTCCs found more minor compli-

routine prophylaxis of CA-VTE in cancer patients [104, 106–
110]. Guidelines have not addressed other populations. Patients cations with PICCs [111], there are many reasons to consider
who have had CA-VTE in the past may be at increased risk of PICCs to be a safer option in children currently. The study was
CA-VTE with subsequent VADs. However, the use of oral anti- done at a time when use of PICCs in children was relatively
coagulation to reduce the risk of CA-VTE in such patients has new. Since then, PICCs have been used extensively in children,
not been examined. and with increasing use has come increasing comfort with their
use. The collective experience of pediatricians is that PICCs
XIII. Should children receive OPAT through a PICC or a LTCC? are much safer than appears to be the case from the findings
Recommendation in this study, and PICCs are much more convenient to place
13. For most children requiring OPAT, a PICC should be than LTCCs.
placed rather than a LTCC (strong recommendation, very Mechanical complications in children with PICCs have
low-quality evidence). decreased as experience with their use has accrued, resulting
in a decline in reported complication rates from >25% in ear-
Evidence Summary lier studies [111, 112, 114] to <10% in more recent studies [115,
One cohort study compared complications from PICCs vs 116, 118]. LTCCs require placement by an experienced sur-
LTCCs in children receiving OPAT [111]. Findings from this geon in the operating room under general anesthesia. In cur-
study are dated, and the evidence is all of low quality, as summa- rent practice, PICCs are typically placed by trained nurses with
rized in Table 15. These published data provide insufficient evi- the aid of ultrasound at the bedside, though they may also be
dence to draw conclusions about differences in complications placed by an interventional radiologist [119]. Given the relative
between the 2 catheter types. ease of placement of PICCs and declining complication rates
Table 15. Evidence Table: Comparison of Vascular Access Complications Among Pediatric Patients With Peripherally Inserted Central Catheters and
Long-Term Central Catheters
Outcome Conclusion Summary of Findings Quantity and Type of Starting Level Factors That Alter Overall Evidence
Evidence of Evidence the Strength of Strength
Evidence
Overall complications Insufficient evidence No difference in overall com- 1 cohort study Low Risk of bias (–1) Very low
plications (36% vs 24%, RR (N = 234, 104 PICC, Imprecision (–1)
1.49,a 95% CI 1.00–2.23,a 130 LTCC) [111]
P = .07) [111]
Major complications Insufficient evidence No difference in infectious 1 cohort study Low Risk of bias (–1) Very low
complications (details not (N = 234, 104 PICC, Imprecision (–1)
reported) [111] 130 LTCC) [111]
Minor complications Insufficient evidence More mechanical complica- 1 cohort study Low Risk of bias (–1) Very low
tions in PICCs (27% vs (N = 234, 104 PICC, Imprecision (–1)
15%, RR 1.84,a 95% CI 130 LTCC) [111]
1.09–3.11,a P = .03) [111]
Time to first Insufficient evidence Shorter time to first compli- 1 cohort study Low Risk of bias (–1) Very low
complication cation with PICCs (me- (N = 234, 104) PICC, Imprecision (–1)
dian 41 days vs 61 days, 130 LTCC) [111]
P = .003) (HR not reported)
[111]
Abbreviations: CI, confidence interval; HR, hazard ratio; LTCC, long-term central catheter; PICC, peripherally inserted central catheter; RR, relative risk.
a

associated with their use, PICCs have become the most com- OPAT [63, 124, 125]. Effective laboratory test monitoring entails
mon type of VAD selected for pediatric OPAT in the United the performance of laboratory tests and the availability of
States [118, 120] and other developed countries [121] in chil- results to the physician or team overseeing the OPAT course.
dren who do not have a preexisting LTCC in place. Given the One study compared readmission while on OPAT for patients
widespread adoption of PICCs in children, it is unlikely that any whose laboratory test results were available to the treatment
additional studies comparing PICCs and LTCCs in children will team vs those for whom they were not (total 400 patients) [63].
be done. The second study examined 60-day readmission and ED visits
Mechanical complications of PICCs have been noted more for patients who were seen by an ID transitions service (IDTS),
often in older children; the risk for these complications has been where laboratory test results were available to the treating phy-
reported to increase with longer dwell time and when the tip of the sicians. These patients were compared to those not followed by
catheter is not centrally located [114, 117, 118]. Newer anchoring the IDTS, where laboratory test results were usually not avail-
devices may reduce the risk of dislodgement [122, 123]. able (total 488 patients) [124]. The third study was an observa-
Giving due consideration to balancing benefits, harms, bur- tional cohort study of outcomes (including readmission while
dens, and utilization of resources for pediatric OPAT, a strong on OPAT) in 407 episodes of pediatric OPAT before and after

recommendation is warranted that insertion of PICCs (by implementation of a dedicated medical support team [125].
appropriately trained nursing teams or interventional radiol- The odds of readmission while on OPAT were lower with
ogists) is preferable to placement of LTCCs (in an operating effective monitoring (OR 0.40, 95% CI 0.21–0.74, P = .003) in
room under general anesthesia) in most circumstances. Some 1 adult study [63] and in the pediatric study (OR 0.45, 95% CI
pediatricians may prefer LTCCs over PICCs when the antici- 0.24–0.86, P = .014) [125], but a statistically significant reduc-
pated duration of OPAT is unusually long. tion in risk of readmission was not demonstrated in the other
adult study (OR 0.38, 95% CI 0.10–1.52, P NR for 30-day read-
MONITORING mission and OR 0.45, 95% CI 0.12–1.34, P NR for 60-day read-
mission) [124]. In all studies, residual confounders would have
XIV. Should patients receiving OPAT have laboratory test monitoring
while on therapy? If so, which tests should be done and how often? likely decreased the effect of monitoring in reducing odds of
Recommendation readmission. The evidence from these 3 studies is summarized
14. Serial laboratory testing should be monitored in patients in Table 16. With 2 studies demonstrating a large effect des-
receiving OPAT (strong recommendation, high-quality pite confounders that would have the effect of reducing the size
evidence). Data are insufficient to make evidence-based of the effect, this constitutes a high level of evidence strength
recommendations about specific tests and specific fre- that effective monitoring of OPAT is associated with reduced
quencies of monitoring for individual antimicrobials used readmission.
in OPAT. There are no published studies that directly address the question of
which laboratory tests should be followed and how often for patients
Evidence Summary receiving specific antibiotics. One study assessed eosinophilia as a
Two adult studies and 1 pediatric study have addressed the predictor of adverse events in a prospective cohort of 824 patients in
importance of laboratory test monitoring in patients receiving their OPAT program [126]; 25% of patients developed eosinophilia
Table 16. Evidence Table: Comparison of Hospital Readmission in the Presence Versus Absence of Effective Outpatient Parenteral Antimicrobial Therapy
Laboratory Test Result Monitoring
Quantity and Type Starting Level of Factors That Alter the Overall Evidence
Readmission Lower risk of Lower odds of readmission 3 cohort studies Low Large effect (+1) High
readmission while on OPAT with ef- (n = 400, 488, Confounding (+1)
fective monitoring (OR 407) [63, 124,
0.40a 95% CI 0.21–0.74, 125]
P = 0.003 [63]; OR 0.45,
95% CI 0.24 to 0.86,
P = .014 [125]) in 2 studies
No statistically significant
difference in 30-day read-
mission (OR 0.38, 95% CI
0.10–1.52, P NR) or 60-day
readmission (OR 0.45, 95%
CI 0.12–1.34, P NR) in 1
study [124]
Abbreviations: CI, confidence interval; NR, not reported; OPAT, outpatient parenteral antimicrobial therapy; OR, odds ratio.
a
over a median duration of therapy of 41 days. Treatment with van- XV. For patients receiving vancomycin as part of OPAT, should vancomycin
serum levels be measured regularly throughout the course of treatment?
comycin, penicillin, rifampin, and linezolid was significantly asso-
Recommendation
ciated with eosinophilia. In a multivariable analysis, eosinophilia
15. Vancomycin blood levels should be measured regularly
was found to be a predictor of subsequent hypersensitivity reactions
throughout the course of OPAT treatment (strong rec-
(HSRs; rash: HR 4.16, 95% CI 2.54–6.83, P < .0001; renal injury: HR
ommendation, very low-quality evidence). The optimal
2.13, 95% CI 1.36–3.33, P = .0009), although most patients (70%)
frequency of measurement is undefined, but the general
with eosinophilia did not develop any HSRs.
practice in the setting of stable renal function is once weekly.
Evidence Summary
Readmission and ED visits were considered the critical out-
No published studies have directly compared outcomes of
comes. There was high-quality evidence that effective monitor-
patients receiving vancomycin in OPAT settings who either did
ing of OPAT laboratory results was associated with reduced risk
or did not have serial monitoring of vancomycin levels.
of readmission. There were no data on ED visits.
A related question is whether it is necessary to follow vanco-
No comprehensive study has systematically explored the
mycin levels throughout the treatment course or whether this test
incidence of adverse drug events (ADEs) associated with anti-

may be avoided for patients who have stable renal function and
biotics used in OPAT. Not surprisingly, some antibiotics are
appropriate vancomycin levels in the early weeks of OPAT. This
used much more frequently than others in studies of OPAT
question can be informed by knowledge of when vancomycin
(eg, vancomycin, ceftriaxone, cefazolin, piperacillin/tazobac-
nephrotoxicity has been noted to occur during OPAT. In a US
tam). Consequently, more ADEs have been reported in associ-
retrospective cohort of 579 OPAT patients receiving vancomy-
ation with these agents. In addition, ADEs often develop while
cin (not continuous infusion), of the 154 patients who developed
patients are receiving multiple OPAT antibiotics, making it dif-
nephrotoxicity, 64 (42%) did so after 14 days [127], highlighting
ficult to accurately attribute such events to one drug vs another.
that vancomycin nephrotoxicity can occur at any time during the
Despite these limitations, evidence shows that adverse reactions
treatment course, even with previously stable renal function.
while on OPAT are common, occurring at a reported rate of
11.8% to 63.2% [35–37, 124, 127]. Rationale for the Recommendation
Many studies report following the monitoring table from the Given that vancomycin has a narrow therapeutic window, serum
IDSA guideline published in 2004, which generally advocates vancomycin levels should be monitored during therapy of more
for weekly testing for most antibiotics [1]. Serial surveys of the than a few days duration. Vancomycin for OPAT appears to be
IDSA/Centers for Disease Control and Prevention EIN demon- associated with more adverse events than comparator antibi-
strated that 98% [27] and 77% [28] of respondents followed the otics. In 1 propensity score-matched cohort study comparing
2004 IDSA guideline monitoring recommendations. vancomycin and daptomycin used in an OPAT setting, van-
Effective laboratory monitoring requires that appropriate comycin-treated patients had a higher incidence of rash and
monitoring tests be done and the results be made available to nephrotoxicity than daptomycin-treated patients (7.7 vs 3.2
the physician or team overseeing the OPAT course. Effective per 1000 OPAT days, respectively, IRR 2.63, 95% CI 1.16–6.67,
laboratory monitoring for OPAT appears to be facilitated in P = .002) and required a greater number of antimicrobial inter-
institutions by having a dedicated team for management of ventions (27.1 vs 5.6 per 1000 OPAT days, respectively, IRR
OPAT. Additional important outcomes noted by Keller et al 4.76, 95% CI 2.78–9.09, P < .001) [128]. The narrow therapeutic
following introduction of an IDTS for OPAT patients included margin of vancomycin in OPAT has been highlighted in 2 retro-
increased receipt of laboratory test results (increasing from spective studies of outpatients receiving continuous vancomycin
37.4% to 94.3%), improved attendance at outpatient follow-up infusion, where higher vancomycin levels were associated with
appointments (60.9% to 79.6%), and decreased antimicrobial nephrotoxicity [129, 130]. In both studies, vancomycin steady-
prescribing errors at discharge (18.1% to 1.4%) [124]. state levels were measured at least weekly. Among 102 patients in
In summary, the high-quality evidence that effective laboratory Singapore, nephrotoxicity was associated with serum concentra-
monitoring is associated with lower risk of readmission and the tions >28 mg/L (OR 21.2, 95% CI 2.7–167.8, P = .004) in a mul-
potential to identify problems before they become severe merit tivariable analysis [129]. In an Australian cohort of 155 OPAT
a strong recommendation that laboratory tests be monitored for episodes, nephrotoxicity was associated with a steady-state level
patients on OPAT. The tests required and the frequency of testing >30 mg/L (OR 8.7, 95% CI 3.1–29.6, P < .001) in multivariable
vary by the antimicrobial the patient is receiving. Short courses analysis [130]. It should be noted that continuous infusion of
of OPAT may not require laboratory monitoring. Tables 2 and 3 vancomycin is not commonly done in the United States.
outline the panel’s recommendations based on pharmacokinetic Ample published clinical data link nephrotoxicity to higher
properties of antimicrobials, common adverse effects, and impli- vancomycin trough levels that are now commonly utilized in
cations of potential adverse effects. the treatment of methicillin-resistant Staphylococcus aureus

infections, particularly deep-seated infections [131–133]. In patients after therapy, with more frequent visits as clinical needs
addition to vancomycin accumulation, other factors that could dictate [128]. Regarding nursing oversight, the most common
contribute to nephrotoxicity in OPAT patients include the con- reported site of OPAT is at home (90%) [27], where patients
comitant use of other nephrotoxins, a high Acute Physiology usually have at least weekly nursing visits. Patients who receive
and Chronic Health Evaluation (APACHE) score, and the use of OPAT at an infusion center are physically seen daily by nurses
vasopressors [133]. Based on 1 observational study that found who administer their antimicrobial therapy.
that nephrotoxicity is frequently noted more than 2 weeks into The potential benefits of frequent ID physician office visits
the course of treatment [127] and consistent with the clinical must be weighed against the practicalities of the patient being
experience of the members of the guideline panel, we recom- able to get to the clinic. For patients who are receiving OPAT in
mend that vancomycin drug levels be monitored throughout an infusion center, weekly physician visits are a typical compo-
the course of OPAT, not just during the initial phase of treat- nent of the oversight program. For patients who are receiving
ment. Whether serial measurement can be useful in averting OPAT at home or in SNFs, the physical condition of the patient
other manifestations of vancomycin toxicity (eg, leukopenia) or availability of transportation services (which may involve
remains uncertain due to lack of clinical data. traveling great distances) may render frequent ID physician vis-

In summary, vancomycin levels should be monitored through- its impractical. The frequency of ID physician visits for any indi-
out the OPAT course to ensure adequate and safe treatment. The vidual patient should be determined by the treating physician,
reader is referred to a previously published consensus statement giving due consideration to patient characteristics, the disease
for management of vancomycin that addresses appropriate dos- being treated, how the patient is tolerating the treatment, and
ing, timing, and monitoring of serum concentrations [134]. This the socioeconomic conditions associated with the OPAT course.
statement, which is widely followed, recommends vancomycin
dose adjustments based on serum trough levels. There is emerg- Monitoring While on Aminoglycosides
ing consensus that monitoring of the area under the curve/mini- The Monitoring Section of the Guidelines Committee also con-
mum inhibitory concentration ratio may allow more appropriate sidered the question of monitoring OPAT patients receiving
dosing than monitoring of serum vancomycin trough levels, but aminoglycoside antibiotics. Aminoglycoside use is generally
this practice has not yet gained widespread adoption. limited in most OPAT settings. There is no published literature
that would allow systematic evaluations of various aspects of
XVI. How frequently should patients on OPAT have scheduled physician aminoglycoside OPAT. The known toxicity of aminoglycosides
office visits for monitoring of treatment? warrants careful monitoring during OPAT, and the narrow ther-
Recommendation apeutic range warrants dose adjustments based on serum drug
16. No generalized recommendation on frequency of outpa- levels. However, important questions about frequency of serum
tient follow-up can be made for patients treated with OPAT drug level monitoring and the optimal schedule of monitor-
(no recommendation, no evidence). The treating physician ing for both renal and oto-vestibular toxicities (eg, serial audi-
should dictate the frequency of office visits, giving consid- ograms) are currently unanswerable based on the published
eration to patient characteristics, the nature of the infection, literature.
the patient’s tolerance of and response to therapy, and indi-
vidual patient social factors.
ANTIMICROBIAL STEWARDSHIP
Evidence Summary XVII. Should all patients have an infectious disease (ID) expert review
No published studies have compared outcomes in relation to prior to initiation of OPAT?
frequency of outpatient follow-up in patients receiving OPAT. Recommendation
17. All patients should have ID expert review prior to initia-
Rationale for the Recommendation tion of OPAT (strong recommendation, very low-quality
It is important to recognize that there are different models of evidence).
OPAT, each with unique patterns of nursing and physician
oversight and each with their own schedule of follow-up and Evidence Summary
observation. There is great variability in the frequency with Outcomes of OPAT with and without ID expert review were
which patients are seen by a physician who is overseeing OPAT. compared in 3 observational studies [125, 135, 136]. The first
Despite previous IDSA guidelines that recommended weekly compared outcomes in 407 episodes of pediatric OPAT before
outpatient visits for patients receiving OPAT [1], only 29% of and after implementation of a dedicated OPAT medical support
respondents in the 2006 EIN Survey of OPAT saw their patients team, which included a consultant pediatric ID physician and/
at least weekly [27]. Some programs report physician evaluation or a fellow [125]. The second assessed 100 adults discharged on
as frequently as every 1–2 weeks [8, 52]. Other programs see ertapenem, 60 of whom had ID expert review prior to discharge
[135]. The third included 210 pediatric patients, of whom 114 that consisted of ID specialists plus trained pharmacists and dis-
had ID consultation prior to discharge from hospital [136]. charge planners [124, 125, 139, 141]. A switch from IV to oral
Outcomes evaluated in these studies included clinical cure administration was achieved in 43 of 263 (16%) [138], 16 of 56
[135], readmissions [125, 135, 136], and ED visits [136]. Clinical (29%) [137], 66 of 250 (26.4%) [139], and 17 of 44 (39%) [140].
cure rates were not found to be different between patients with In a recently published pediatric report, a 24% reduction in the
and without ID consultation in 1 small study (78% vs 80%, OR rate of OPAT prescribing was realized by the institution of an
0.90, 95% CI 0.34–2.43, P = 1.00) [135]. A substantially lower ID-led OPAT stewardship program [141]. In addition, in vari-
odds of readmission (OR 0.45, 95% CI 0.24–0.86, P = .014) was ous studies, antibiotic therapy was not felt to be necessary at all
noted in the largest of these studies (n = 407) [125] but not in in a substantial proportion of patients: 6 of 573 (1%) [135], 1 of
the 2 smaller studies (15% vs 13%, OR 1.24, 95% CI 0.38–4.00, 44 (2.3%) [140], 38 of 415 (9.2%) [139], 28 of 263 (10.6%) [138],
P = .96 [131]; 5.3% vs 2.1%, OR 2.61, 95% CI 0.51–13.25, and 10 of 100 (10%) [135]. Other frequently described inter-
P = .41) [136]. The use of ED visits was no different (7.0% vs ventions included changes in the dose, duration, and choice
4.2%, OR 1.74, 95% CI 0.51–5.96, P = .56) among ID vs no ID of IV antimicrobial. ID team intervention was credited with
consultation patients in 1 of the small OPAT cohorts [136]. The enhanced coordination of care after hospital discharge [124].

evidence from these studies is summarized in Table 17. OPAT administration in nontraditional locations, such
as dialysis units, has not been well studied but appears to be
Rationale for the Recommendation particularly susceptible to overuse. One retrospective review
Readmission and ED visits were considered critical outcomes. of antimicrobial prescribing in hemodialysis units over a
There was moderate-quality evidence that OPAT with ID expert 12-month period noted that among 1003 antimicrobial doses
review was associated with lower risk of hospital readmission prescribed, 276 (29.8%) were classified as inappropriate, unnec-
than OPAT without ID expert review. There was very low-qual- essarily broad, or not needed at all [142].
ity evidence that ID expert review was associated with improve- Curtailment of antibiotic use after ID expert review prior to
ment in clinical cure or reduction in ED visits. These findings OPAT has not been associated with poor outcomes. In 2 obser-
amount to overall very low-quality evidence for a benefit of ID vational studies, adult patients for whom OPAT was denied did
expert review in OPAT. well, with none of the OPAT-denied patients having an ED visit
Inappropriate use of antimicrobials (unnecessary paren- or readmission related to infection within 30 days [140, 143].
teral treatment when oral therapy would have sufficed and In a third observational study, readmission rates for pediatric
the unnecessary use of antibiotic treatment entirely) has been patients discharged on oral antibiotics did not increase after
widely reported in the adult and pediatric literature. ID stew- implementation of enhanced OPAT stewardship that resulted
ardship, in the form of expert review, has been credited with in an estimated 24% of patients being discharged on no or
the curtailment of unnecessary OPAT in several observational oral antibiotics instead of IV antibiotics, suggesting that cur-
studies [124, 125, 137–141]. In these studies, consultations were tailment of OPAT by ID expert review did not cause harm
provided by either an ID specialist [137, 138, 140] or by “teams” [141]. In another study of 56 patients denied OPAT, 7 patients
Table 17. Comparison of Outcomes for Patients Who Had Infectious Diseases (ID) Expert Review Versus No ID Expert Review
Quantity and Type Starting Level of Factors That Alter the Final Evidence
Clinical cure Insufficient evidence No difference (78%a vs 80%,a 1 cohort study Low Risk of bias (–1) Very low
OR 0.90,a 95% CI 0.34–2.43,a (N = 100) [135] Imprecision (–1)
P =1.00a) [135]
Readmission Lower risk of Lower odds of readmission in ID 3 cohort studies Low Large effect (+1) Moderate
readmission intervention cohort (OR 0.45, (N = 407, 100, Imprecision (–1)
95% CI 0.24–0.86, P = .014) 210) [125, 135, Confounding (+1)
in 1 study (N = 407) with low 136]
risk of bias [125]
No difference (5.3%a vs 2.1%,a
OR 2.61,a 95% CI 0.51–
13.25,a P = .41a) [136];15%a
vs 13%,a OR 1.24,a 95% CI
0.38–4.00,a P = .96a [135] in 2
studies with high risk of bias
Emergency Insufficient evidence No difference (7.0%a vs 4.2%,a 1 cohort study Low Risk of bias (–1) Very low
Department visits OR 1.74,a 95% CI 0.51–5.96,a (N = 210) [136] Imprecision (–1)
P = .56a) in 1 study [136]
Abbreviations: CI, confidence interval; ID, infectious diseases; OR, odds ratio.

a

(12.5%) had treatment failure. Six of the 7 were noncompliant Antimicrobial resistance has been identified as a global health
with their oral medications, and the seventh had infections that emergency. It is widely recognized that there is large-scale inap-
were deemed incurable by the ID consult service based on the propriate antimicrobial prescribing. The current global crisis of
underlying disease processes, regardless of the route of anti- antimicrobial resistance demands better stewardship of our anti-
biotic administration [137]. biotic resources. The body of evidence showing substantial mis-
OPAT for pediatric patients remains a safe and effective alter- use of OPAT, reasonable control of antibiotic misuse when there
native to prolonged hospitalization for appropriately selected is ID expert review, and lack of patient harm when ID expert
patients to complete therapy for complicated infections such as review leads to limitation of antibiotic use and moderate-strength
bacteremia and endocarditis or for patients with cystic fibrosis. evidence that ID expert review is associated with a reduction in
The advantages of OPAT relative to prolonged hospitalization hospital readmissions warrants a strong recommendation that ID
are substantial. These include decreased medical costs and an expert review be obtained prior to initiation of OPAT.
earlier return to usual daily activities at home both for patients
and caregivers. For example, some school-aged children may FUTURE DIRECTIONS
return to school while receiving treatment at home. However,
The guideline panel identified areas of specific interest for

there is mounting evidence that oral therapy can be substituted
future research. Given the current opiate addiction crisis in
for OPAT without compromising cure rates. Safety is enhanced
the United States, an area of need is the development of newer
by avoiding OPAT-related complications for certain clinical
models of care for PWID, potentially expanding on nontradi-
conditions where OPAT has traditionally been the preferred
tional sites of care and newer technologies, perhaps including
treatment mode. The evidence supporting this practice includes
telemedicine. Also, in view of the burgeoning application of
studies comparing oral vs parenteral therapy for osteomyeli-
midline catheters, the safety of their use for OPAT courses of
tis [144, 145], perforated appendicitis [146], and complicated
longer than 2 weeks duration should be delineated. The safety
pneumonia [147, 148]. As a result, ensuring that OPAT is only
of vancomycin delivered through a peripheral catheter should
prescribed for patients where an equivalent oral therapy is not
be addressed. Additionally, data on the safety and efficacy of
available is a high priority for pediatric ID specialists and pedi-
OPAT in younger infants (<1 month) are needed. Finally, an
atric antimicrobial stewardship programs.
OPAT registry, following in the footsteps of the work of Tice
Estimated cost savings involve reductions in hospital
and others, should be reestablished in the United States [153].
expenses and avoidance of central lines. In the study by Conant
This would enable us to capitalize on the tremendous amount of
et al, the overall cost avoidance of averted OPAT in 56 patients
siloed data accumulating at large OPAT sites and answer these
was $3487 per patient [137]. In another retrospective review,
and other questions about the care of patients receiving OPAT.
after accounting for the cost of pharmacist time, the institu-
tion realized a net savings of $620 per OPAT referral [139]. In Supplementary Data
a report of 44 patients who underwent mandatory ID consult- Supplementary materials are available at Clinical Infectious Diseases online.
Consisting of data provided by the authors to benefit the reader, the posted
ation prior to OPAT, 17 patients were switched from IV to oral materials are not copyedited and are the sole responsibility of the authors,
therapy, resulting in a cost savings of $1550 per patient [140]. so questions or comments should be addressed to the corresponding author.
In addition to a demonstration of direct benefit of ID expert
review for OPAT, there is indirect evidence for the value of Notes
ID specialists in the management of infectious conditions. ID Acknowledgments. The expert panel expresses its gratitude for
thoughtful reviews of an earlier version by Drs Erika D’Agata, Donald
consultation for inpatients with suspected infection has been Poretz, and Susan Rehm. The expert panel expresses its appreciation for
shown to be associated with lower mortality and readmissions thoughtful research and advice by Christo Cimino, PharmD, and Marybeth
[149]. ID consultation has been shown to reduce mortality in Ruckelshaus, PharmD. The panel thanks Vita Washington for her guidance
and preparation of the manuscript.
patients with S. aureus bacteremia in several studies. Both a sys- Financial support. Support for these guidelines was provided by the
tematic review and a metaanalysis of these studies have been IDSA.
published [150, 151]. Potential conflicts of interest. The following list reflects what has been
reported to the IDSA. In order to provide thorough transparency, the IDSA
ID expert review may take different forms, depending on
requires full disclosure of all relationships, regardless of relevancy to the
the resources available. It may take the form of traditional ID guideline topic. Evaluation of such relationships as potential conflicts of
consultation [137, 138, 140], ID care transition team [124, 125, interest is determined by a review process that includes assessment by the
139], OPAT stewardship team [141], or an ID pharmacist– SPGC chair, the SPGC liaison to the development panel, and the board of
directors liaison to the SPGC, and, if necessary, the Conflicts of Interest
managed program in collaboration with an ID physician [152]. Task Force of the board. This assessment of disclosed relationships for pos-
Oversight of OPAT by ID physicians can be expected to pro- sible conflicts of interest will be based on the relative weight of the financial
vide value for the patient. Novel models need to be developed relationship (ie, monetary amount) and the relevance of the relationship
(ie, the degree to which an association might reasonably be interpreted by
to allow ID support of decision-making about antimicrobial use an independent observer as related to the topic or recommendation of con-
in dialysis units. sideration). The reader of this guideline should be mindful of this when
the list of disclosures is reviewed. G. M. A. has served as a consultant for 18. Antoniskis A, Anderson BC, Van Volkinburg EJ, Jackson JM, Gilbert DN.
Coram and received grants through other remuneration from Nuo, Aurix, Feasibility of outpatient self-administration of parenteral antibiotics. West J Med
Merck, and the National Institutes of Health (NIH). A. L. H. has received 1978; 128:203–6.
19. Poretz DM, Eron LJ, Goldenberg RI, et al. Intravenous antibiotic therapy in an
research grants from the Centers for Disease Control and Prevention
outpatient setting. JAMA 1982; 248:336–9.
(CDC), Agency for Healthcare Quality and Research, and Merck. L. A.
20. Rehm SJ, Weinstein AJ. Home intravenous antibiotic therapy: a team approach.
G. has received honoraria from BD, 3M, and Genetech; has received fees for Ann Intern Med 1983; 99:388–92.
speaker’s bureau participation for Genentech; and served as a consultant for 21. Tice AD. An office model of outpatient parenteral antibiotic therapy. Rev Infect
Ivwatch Telefelex and Baxter. J. A. B. has served as a consultant and received Dis 1991; 13 Suppl 2:S184–8.
fees for speaker bureau participation for Forest; has served a consultant for 22. Poretz DM. Evolution of outpatient parenteral antibiotic therapy. Infect Dis Clin
Cepheid, Waters, Theravance, and Mellinta; has received fees for speaker North Am 1998; 12:827–34.
bureau participation for Cubis; and has received research grants from 23. Wolter JM, Cagney RA, McCormack JG. A randomized trial of home vs hospital
Merck and the Medicines Company. M. H. R. has served as a consultant intravenous antibiotic therapy in adults with infectious diseases. J Infect 2004;
48:263–8.
for Cerexa and Sequiris and has received research grants from NIH, CDC,
24. Board N, Brennan N, Caplan GA. A randomised controlled trial of the costs of
Gilead, Cerexa, GSK, Hologic, and Pfizer. A. A. has received research grants
hospital as compared with hospital in the home for acute medical patients. Aust
from Merck, Astellas, and Melinta. A. S. has received fees for speaker bureau N Z J Public Health 2000; 24:305–11.
participation from Cubist, Merck, Theravance, Melinta, and the Medicines 25. Corwin P, Toop L, McGeoch G, et al. Randomised controlled trial of intravenous
Company. R. B. B. has served as a consultant for Express Scripts. All other antibiotic treatment for cellulitis at home compared with hospital. BMJ 2005;
authors: no reported conflicts. All authors have submitted the ICMJE Form 330:129.
for Disclosure of Potential Conflicts of Interest. Conflicts that the editors 26. Chary A, Tice AD, Martinelli LP, Liedtke LA, Plantenga MS, Strausbaugh LJ;

consider relevant to the content of the manuscript have been disclosed. Infectious Diseases Society of America Emerging Infections Network. Experience
of infectious diseases consultants with outpatient parenteral antimicrobial ther-
apy: results of an Emerging Infections Network survey. Clin Infect Dis 2006;
References 43:1290–5.
1. Tice AD, Rehm SJ, Dalovisio JR, et al.; IDSA. Practice guidelines for outpa- 27. Lane MA, Marschall J, Beekmann SE, et al. Outpatient parenteral antimicrobial
tient parenteral antimicrobial therapy. IDSA guidelines. Clin Infect Dis 2004; therapy practices among adult infectious disease physicians. Infect Control Hosp
38:1651–72. Epidemiol 2014; 35:839–44.
2. Guyatt GH, Oxman AD, Kunz R, et al.; GRADE Working Group. Going from 28. Woosley RL, Heise CW, Gallo T, Tate J, Woosley D, Romero KA. QTdrugs List.
evidence to recommendations. BMJ 2008; 336:1049–51. Oro Valley, AZ: AZCERT, Inc. Available at: https://www.crediblemeds.org.
3. Guyatt GH, Oxman AD, Kunz R, et al.; GRADE Working Group. Incorporating Accessed 26 October 2018.
considerations of resources use into grading recommendations. BMJ 2008; 29. Cunha CB, D’Agata EM. Implementing an antimicrobial stewardship program in
336:1170–3. out-patient dialysis units. Curr Opin Nephrol Hypertens 2016; 25:551–5.
4. Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schünemann HJ; 30. Hoffman-Terry ML, Fraimow HS, Fox TR, Swift BG, Wolf JE. Adverse effects of
GRADE Working Group. What is “quality of evidence” and why is it important to outpatient parenteral antibiotic therapy. Am J Med 1999; 106:44–9.
clinicians? BMJ 2008; 336:995–8. 31. Gomez M, Maraqa N, Alvarez A, Rathore M. Complications of outpatient paren-
5. Guyatt GH, Oxman AD, Vist GE, et al.; GRADE Working Group. GRADE: an teral antibiotic therapy in childhood. Pediatr Infect Dis J 2001; 20:541–3.
emerging consensus on rating quality of evidence and strength of recommenda- 32. Ceroni D, Regusci M, Pazos JM, Saunders CT, Kaelin A. Risks and complications
tions. BMJ 2008; 336:924–6. of prolonged parenteral antibiotic treatment in children with acute osteoarticular
6. OPAT eHandbook. In: Shah A, Norris A. (https://www.idsociety.org/opat-ehand- infections. Acta Orthop Belg 2003; 69:400–4.
book/) CRG Publishing and Infectious Diseases Society of America, 2016. 33. Pulcini C, Couadau T, Bernard E, et al. Adverse effects of parenteral antimicro-
Accessed 26 October 2018. bial therapy for chronic bone infections. Eur J Clin Microbiol Infect Dis 2008;
7. Rucker RW, Harrison GM. Outpatient intravenous medications in the manage- 27:1227–32.
ment of cystic fibrosis. Pediatrics 1974; 54:358–60. 34. Hale CM, Steele JM, Seabury RW, Miller CD. Characterization of drug-related
8. Petrak RM, Skorodin NC, Fliegelman RM, Hines DW, Chundi VV, Harting BP. problems occurring in patients receiving outpatient antimicrobial therapy. J
Value and clinical impact of an infectious disease-supervised outpatient paren- Pharm Pract 2017; 30:600–5.
teral antibiotic therapy program. Open Forum Infect Dis 2016; 3:ofw193. 35. Lee B, Tam I, Weigel B 4th, et al. Comparative outcomes of β-lactam antibiotics
9. Nguyen HH. Hospitalist to home: outpatient parenteral antimicrobial therapy at in outpatient parenteral antibiotic therapy: treatment success, readmissions and
an academic center. Clin Infect Dis 2010; 51:S220–3. antibiotic switches. J Antimicrob Chemother 2015; 70:2389–96.
10. Cox AM, Malani PN, Wiseman SW, Kauffman CA. Home intravenous antimicro- 36. Murphy JL, Fenn N, Pyle L, et al. Adverse events in pediatric patients receiving
bial infusion therapy: a viable option in older adults. J Am Geriatr Soc 2007; long-term oral and intravenous antibiotics. Hosp Pediatr 2016; 6:330–8.
55:645–50. 37. Muldoon EG, Snydman DR, Penland EC, Allison GM. Are we ready for an outpa-
11. Barr DA, Semple L, Seaton RA. Outpatient parenteral antimicrobial therapy tient parenteral antimicrobial therapy bundle? A critical appraisal of the evidence.
(OPAT) in a teaching hospital-based practice: a retrospective cohort study Clin Infect Dis 2013; 57:419–24.
describing experience and evolution over 10 years. Int J Antimicrob Agents 2012; 38. Tan SJ, Ingram PR, Rothnie AJ, et al. Successful outpatient parenteral antibiotic
39:407–13. therapy delivery via telemedicine. J Antimicrob Chemother 2017; 72:2898–901.
12. Gordon SM, Shrestha NK, Rehm SJ. Transitioning antimicrobial steward- 39. Forestier E, Gros S, Peynaud D, et al. Ertapenem administered intravenously or
ship beyond the hospital: the Cleveland Clinic’s community-based parenteral subcutaneously for urinary tract infections caused by ESBL producing enterobac-
anti-infective therapy (CoPAT) program. J Hosp Med 2011; 6:S24–30. teriacea. Med Mal Infect 2012; 42:440–3.
13. Madigan T, Banerjee R. Characteristics and outcomes of outpatient parenteral 40. Gauthier D, Schambach S, Crouzet J, Sirvain S, Fraisse T. Subcutaneous and intra-
antimicrobial therapy at an academic children’s hospital. Pediatr Infect Dis J 2013; venous ceftriaxone administration in patients more than 75 years of age. Med Mal
32:346–9. Infect 2014; 44:275–80.
14. Rentala M, Andrews S, Tiberio A, et al. Intravenous home infusion therapy insti- 41. Peeters O, Ferry T, Ader F, et al.; Lyon BJI Study Group. Teicoplanin-based anti-
tuted from a 24-hour clinical decision unit for patients with cellulitis. Am J Emerg microbial therapy in Staphylococcus aureus bone and joint infection: tolerance,
Med 2016; 34:1273–5. efficacy and experience with subcutaneous administration. BMC Infect Dis 2016;
15. Kayley J, Berendt AR, Snelling MJ, et al. Safe intravenous antibiotic therapy at 16:622.
home: experience of a UK based programme. J Antimicrob Chemother 1996; 42. Ho J, Archuleta S, Sulaiman Z, Fisher D. Safe and successful treatment of intrave-
37:1023–9. nous drug users with a peripherally inserted central catheter in an outpatient par-
16. Martone WJ, Lindfield KC, Katz DE. Outpatient parenteral antibiotic therapy with enteral antibiotic treatment service. J Antimicrob Chemother 2010; 65:2641–4.
daptomycin: insights from a patient registry. Int J Clin Pract 2008; 62:1183–7. 43. O’Toole TP, Conde-Martel A, Young JH, Price J, Bigelow G, Ford DE. Managing
17. Dalovisio JR, Juneau J, Baumgarten K, Kateiva J. Financial impact of a home intra- acutely ill substance-abusing patients in an integrated day hospital outpatient pro-
venous antibiotic program on a Medicare managed care program. Clin Infect Dis gram: medical therapies, complications, and overall treatment outcomes. J Gen
2000; 30:639–42. Intern Med 2006; 21:570–6.

44. Beieler AM, Dellit TH, Chan JD, et al. Successful implementation of outpatient diseases consultants: results of an Emerging Infections Network survey. J Pediatric
parenteral antimicrobial therapy at a medical respite facility for homeless patients. Infect Dis Soc 2014; 3:85–8.
J Hosp Med 2016; 11:531–5. 68. Rathore MH. The unique issues of outpatient parenteral antimicrobial therapy in
45. Hernandez W, Price C, Knepper B, McLees M, Young H. Oral parenteral anti- children and adolescents. Clin Infect Dis 2010; 51:S209–15.
microbial therapy administration in a homeless population. J Infus Nurs 2016; 69. Dobson PM, Boyle M, Loewenthal M. Home intravenous antibiotic therapy and
39:81–5. allergic drug reactions: is there a case for routine supply of anaphylaxis kits? J
46. Jaeschke R, Guyatt GH, Dellinger P, et al.; GRADE Working Group. Use of Infus Nurs 2004; 27:425–30.
GRADE grid to reach decisions on clinical practice guidelines when consensus is 70. Chapman AL, Seaton RA, Cooper MA, et al.; BSAC/BIA OPAT Project Good
elusive. BMJ 2008; 337:a744. Practice Recommendations Working Group. Good practice recommendations for
47. Schünemann HJ, Schünemann AH, Oxman AD, et al.; GRADE Working Group. outpatient parenteral antimicrobial therapy (OPAT) in adults in the UK: a con-
Grading quality of evidence and strength of recommendations for diagnostic tests sensus statement. J Antimicrob Chemother 2012; 67:1053–62.
and strategies. BMJ 2008; 336:1106–10. 71. Thiele H. First dose of intravenous antibiotics in outpatient parenteral antimicro-
48. Wells GA, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for bial therapy/hospital in the home—criteria for administration at home. Journal of
assessing the quality if nonrandomized studies in meta-analyses. Available at: Pharmacy Practice and Research 2017; 47:78–80.
http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm. Accessed 26 72. Ma G, Annaliese T, Paul T, Dorothy T, Susan M, Gerald E. The safety of first-dose
October 2018. home IV antibiotic therapy. Can J Hosp Pharm 2007; 60:106–13.
49. Matthews PC, Conlon CP, Berendt AR, et al. Outpatient parenteral antimicrobial 73. Gorski LA, Hadaway L, Hagle M, McGoldrick M, Meyer B, Orr M. Infusion
therapy (OPAT): is it safe for selected patients to self-administer at home? A ret- therapy policies and procedures. 5th ed. Norwood, MA: Infusion Nurses Society,
rospective analysis of a large cohort over 13 years. J Antimicrob Chemother 2007; 2016.
60:356–62. 74. Caparas JV, Hu JP. Safe administration of vancomycin through a novel midline
50. Seetoh T, Lye DC, Cook AR, et al. An outcomes analysis of outpatient parenteral catheter: a randomized, prospective clinical trial. J Vasc Access 2014; 15:251–6.

antibiotic therapy (OPAT) in a large Asian cohort. Int J Antimicrob Agents 2013; 75. Sharp R, Esterman A, McCutcheon H, Hearse N, Cummings M. The safety and
41:569–73. efficacy of midlines compared to peripherally inserted central catheters for adult
51. Barr DA, Semple L, Seaton RA. Self-administration of outpatient parenteral anti- cystic fibrosis patients: a retrospective, observational study. Int J Nurs Stud 2014;
biotic therapy and risk of catheter-related adverse events: a retrospective cohort 51:694–702.
study. Eur J Clin Microbiol Infect Dis 2012; 31:2611–9. 76. Xu T, Kingsley L, DiNucci S, et al. Safety and utilization of peripherally inserted
52. Bhavan KP, Brown LS, Haley RW. Self-administered outpatient antimicrobial central catheters versus midline catheters at a large academic medical center. Am
infusion by uninsured patients discharged from a safety-net hospital: a propensi- J Infect Control 2016; 44:1458–61.
ty-score-balanced retrospective cohort study. PLoS Med 2015; 12:e1001922. 77. Chopra V, Flanders SA, Saint S, et al.; Michigan Appropriateness Guide for
53. Kieran J, O’Reilly A, Parker J, Clarke S, Bergin C. Self-administered outpatient Intravenous Catheters (MAGIC) Panel. The Michigan Appropriateness Guide for
parenteral antimicrobial therapy: a report of three years experience in the Irish Intravenous Catheters (MAGIC): results from a multispecialty panel using the
healthcare setting. Eur J Clin Microbiol Infect Dis 2009; 28:1369–74. RAND/UCLA appropriateness method. Ann Intern Med 2015; 163:S1–40.
54. Pajarón M, Fernández-Miera MF, Allende I, et al.; Hospital Valdecilla Endocarditis 78. Giuliani J, Andreetta L, Mattioli M, et al. Intravenous midline catheter usage:
Study Group. Self-administered outpatient parenteral antimicrobial therapy which clinical impact in homecare patients? J Palliat Med 2013; 16:598.
(S-OPAT) for infective endocarditis: a safe and effective model. Eur J Intern Med 79. Roszell S, Jones C. Intravenous administration issues: a comparison of intrave-
2015; 26:131–6. nous insertions and complications in vancomycin versus other antibiotics. J Infus
55. Shrestha NK, Shrestha J, Everett A, et al. Vascular access complications during Nurs 2010; 33:112–8.
outpatient parenteral antimicrobial therapy at home: a retrospective cohort study. 80. Le A, Patel S. Extravasation of noncytotoxic drugs: a review of the literature. Ann
J Antimicrob Chemother 2016; 71:506–12. Pharmacother 2014; 48:870–86.
56. Mallon WK. Is it acceptable to discharge a heroin user with an intravenous line to 81. Gorski LA, Stranz M, Cook LS, et al.; Infusion Nurses Society Vesicant Task Force.
complete his antibiotic therapy for cellulitis at home under a nurse’s supervision? Development of an evidence-based list of noncytotoxic vesicant medications and
No: a home central line is too hazardous. West J Med 2001; 174:157. solutions. J Infus Nurs 2017; 40:26–40.
57. Riazati N. Is it acceptable to discharge a heroin user with an intravenous line to 82. El Ters M, Schears GJ, Taler SJ, et al. Association between prior peripherally
complete his antibiotic therapy for cellulitis at home under a nurse’s supervision? inserted central catheters and lack of functioning arteriovenous fistulas: a
Yes: supervised home care ensures continued treatment at lower cost. West J Med case-control study in hemodialysis patients. Am J Kidney Dis 2012; 60:601–8.
2001; 174:156. 83. Huber TS, Carter JW, Carter RL, Seeger JM. Patency of autogenous and polytet-
58. Duncan CJ, Barr DA, Ho A, Sharp E, Semple L, Seaton RA. Risk factors for fail- rafluoroethylene upper extremity arteriovenous hemodialysis accesses: a system-
ure of outpatient parenteral antibiotic therapy (OPAT) in infective endocarditis. J atic review. J Vasc Surg 2003; 38:1005–11.
Antimicrob Chemother 2013; 68:1650–4. 84. Oliver MJ, Rothwell DM, Fung K, Hux JE, Lok CE. Late creation of vascular
59. Pérez-López J, San José Laporte A, Pardos-Gea J, et al. Safety and efficacy of home access for hemodialysis and increased risk of sepsis. J Am Soc Nephrol 2004;
intravenous antimicrobial infusion therapy in older patients: a comparative study 15:1936–42.
with younger patients. Int J Clin Pract 2008; 62:1188–92. 85. Ortega T, Ortega F, Diaz-Corte C, Rebollo P, Ma Baltar J, Alvarez-Grande J. The
60. Allison GM, Muldoon EG, Kent DM, et al. Prediction model for 30-day hospital timely construction of arteriovenous fistulae: a key to reducing morbidity and
readmissions among patients discharged receiving outpatient parenteral anti- mortality and to improving cost management. Nephrol Dial Transplant 2005;
biotic therapy. Clin Infect Dis 2014; 58:812–9. 20:598–603.
61. Cramer S, Fonager K. Risk factors of 30-days re-hospitalization after Hospital at 86. Perera GB, Mueller MP, Kubaska SM, Wilson SE, Lawrence PF, Fujitani RM.
Home in a cohort of patients treated with parenteral therapy. Eur J Intern Med Superiority of autogenous arteriovenous hemodialysis access: maintenance of
2014; 25:895–9. function with fewer secondary interventions. Ann Vasc Surg 2004; 18:66–73.
62. Mujal A, Sola J, Hernandez M, et al. Safety and effectiveness of outpatient par- 87. Schon D, Blume SW, Niebauer K, Hollenbeak CS, de Lissovoy G. Increasing the
enteral antimicrobial therapy in older people. J Antimicrob Chemother 2016; use of arteriovenous fistula in hemodialysis: economic benefits and economic
71:1402–7. barriers. Clin J Am Soc Nephrol 2007; 2:268–76.
63. Huck D, Ginsberg JP, Gordon SM, Nowacki AS, Rehm SJ, Shrestha NK. 88. Woods JD, Turenne MN, Strawderman RL, et al. Vascular access survival among
Association of laboratory test result availability and rehospitalizations in an out- incident hemodialysis patients in the United States. Am J Kidney Dis 1997;
patient parenteral antimicrobial therapy programme. J Antimicrob Chemother 30:50–7.
2014; 69:228–33. 89. Allon M, Daugirdas J, Depner TA, Greene T, Ornt D, Schwab SJ. Effect of change
64. Ruh CA, Parameswaran GI, Wojciechowski AL, Mergenhagen KA. Outcomes and in vascular access on patient mortality in hemodialysis patients. Am J Kidney Dis
pharmacoeconomic analysis of a home intravenous antibiotic infusion program 2006; 47:469–77.
in veterans. Clin Ther 2015; 37:2527–35. 90. Lynch JR, Wasse H, Armistead NC, McClellan WM. Achieving the goal of the
65. Bradley JS, Ching DL, Wilson TA, Compogiannis LS. Once-daily ceftriaxone to Fistula First Breakthrough Initiative for prevalent maintenance hemodialysis
complete therapy of uncomplicated group B streptococcal infection in neonates. patients. Am J Kidney Dis 2011; 57:78–89.
A preliminary report. Clin Pediatr 1992; 31:274–8. 91. Vassalotti JA, Jennings WC, Beathard GA, et al.; Fistula First Breakthrough
66. Wagner CL, Wagstaff P, Cox TH, Annibale DJ. Early discharge with home anti- Initiative Community Education Committee. Fistula First Breakthrough
biotic therapy in the treatment of neonatal infection. J Perinatol 2000; 20:346–50. Initiative: targeting catheter last in fistula first. Semin Dial 2012; 25:303–10.
67. Banerjee R, Beekmann SE, Doby EH, Polgreen PM, Rathore MH, Hersh AL. 92. McGill RL, Marcus RJ, Healy DA, Brouwer DJ, Smith BC, Sandroni SE. AV fistula
Outpatient parenteral antimicrobial therapy practices among pediatric infectious rates: changing the culture of vascular access. J Vasc Access 2005; 6:13–7.
93. Wasse H, Kutner N, Zhang R, Huang Y. Association of initial hemodialysis vas- 118. Kovacich A, Tamma PD, Advani S, et al. Peripherally inserted central venous
cular access with patient-reported health status and quality of life. Clin J Am Soc catheter complications in children receiving outpatient parenteral antibiotic ther-
Nephrol 2007; 2:708–14. apy (OPAT). Infect Control Hosp Epidemiol 2016; 37:420–4.
94. Banerjee T, Kim SJ, Astor B, Shafi T, Coresh J, Powe NR. Vascular access type, 119. Nichols I, Doellman D. Pediatric peripherally inserted central catheter placement:
inflammatory markers, and mortality in incident hemodialysis patients: the application of ultrasound technology. J Infus Nurs 2007; 30:351–6.
Choices for Healthy Outcomes in Caring for End-Stage Renal disease (CHOICE) 120. Maraqa NF, Rathore MH. Pediatric outpatient parenteral antimicrobial therapy:
study. Am J Kidney Dis 2014; 64:954–61. an update. Adv Pediatr 2010; 57:219–45.
95. Solid CA, Carlin C. Timing of arteriovenous fistula placement and Medicare costs 121. Patel S, Abrahamson E, Goldring S, Green H, Wickens H, Laundy M. Good practice
during dialysis initiation. Am J Nephrol 2012; 35:498–508. recommendations for paediatric outpatient parenteral antibiotic therapy (p-OPAT)
96. Navuluri R, Regalado S. The KDOQI 2006 Vascular Access Update and Fistula in the UK: a consensus statement. J Antimicrob Chemother 2015; 70:360–73.
First Program synopsis. Semin Intervent Radiol 2009; 26:122–4. 122. Krenik KM, Smith GE, Bernatchez SF. Catheter securement systems for peripher-
97. Dhingra RK, Young EW, Hulbert-Shearon TE, Leavey SF, Port FK. Type of ally inserted and nontunneled central vascular access devices: clinical evaluation
vascular access and mortality in U.S. hemodialysis patients. Kidney Int 2001; of a novel sutureless device. J Infus Nurs 2016; 39:210–7.
60:1443–51. 123. Yamamoto AJ, Solomon JA, Soulen MC, et al. Sutureless securement device
98. Hoggard J, Saad T, Schon D, Vesely TM, Royer T; American Society of Diagnostic reduces complications of peripherally inserted central venous catheters. J Vasc
and Interventional Nephrology, Clinical Practice Committee; Association for Interv Radiol 2002; 13:77–81.
Vascular Access. Guidelines for venous access in patients with chronic kidney 124. Keller SC, Ciuffetelli D, Bilker W, et al. The impact of an infectious diseases tran-
disease. A position statement from the American Society of Diagnostic and sition service on the care of outpatients on parenteral antimicrobial therapy. J
Interventional Nephrology, Clinical Practice Committee and the Association for Pharm Technol 2013; 29:205–14.
Vascular Access. Semin Dial 2008; 21:186–91. 125. Mace AO, McLeod C, Yeoh DK, et al. Dedicated paediatric outpatient parenteral
99. Johansson E, Engervall P, Björvell H, Hast R, Björkholm M. Patients’ perceptions of hav- antimicrobial therapy medical support: a pre-post observational study. Arch Dis

ing a central venous catheter or a totally implantable subcutaneous port system—results Child 2017.
from a randomised study in acute leukaemia. Support Care Cancer 2009; 17:137–43. 126. Blumenthal KG, Youngster I, Rabideau DJ, et al. Peripheral blood eosinophilia
100. Rodgers HC, Liddle K, Nixon SJ, Innes JA, Greening AP. Totally implantable and hypersensitivity reactions among patients receiving outpatient parenteral
venous access devices in cystic fibrosis: complications and patients’ opinions. Eur antibiotics. J Allergy Clin Immunol 2015; 136:1288–94 e1.
Respir J 1998; 12:217–20. 127. Moh’d H, Kheir F, Kong L, et al. Incidence and predictors of vancomycin-associ-
101. Kovacs MJ, Kahn SR, Rodger M, et al. A pilot study of central venous catheter ated nephrotoxicity. South Med J 2014; 107:383–8.
survival in cancer patients using low-molecular-weight heparin (dalteparin) and 128. Shrestha NK, Mason P, Gordon SM, et al. Adverse events, healthcare interventions
warfarin without catheter removal for the treatment of upper extremity deep vein and healthcare utilization during home infusion therapy with daptomycin and
thrombosis (the Catheter Study). J Thromb Haemost 2007; 5:1650–3. vancomycin: a propensity score-matched cohort study. J Antimicrob Chemother
102. Davies GA, Lazo-Langner A, Gandara E, et al. A prospective study of rivaroxaban 2014; 69:1407–15.
for central venous catheter associated upper extremity deep vein thrombosis in 129. Ingram PR, Lye DC, Tambyah PA, Goh WP, Tam VH, Fisher DA. Risk factors
cancer patients (Catheter 2). Thromb Res 2017. for nephrotoxicity associated with continuous vancomycin infusion in outpatient
103. Laube ES, Mantha S, Samedy P, Wills J, Harnicar S, Soff GA. Treatment of cen- parenteral antibiotic therapy. J Antimicrob Chemother 2008; 62:168–71.
tral venous catheter-associated deep venous thrombosis in cancer patients with 130. Norton K, Ingram PR, Heath CH, Manning L. Risk factors for nephrotoxic-
rivaroxaban. Am J Hematol 2017; 92:E9–E10. ity in patients receiving outpatient continuous infusions of vancomycin in an
104. Debourdeau P, Farge D, Beckers M, et al. International clinical practice guidelines Australian tertiary hospital. J Antimicrob Chemother 2014; 69:805–8.
for the treatment and prophylaxis of thrombosis associated with central venous 131. Lodise TP, Lomaestro B, Graves J, Drusano GL. Larger vancomycin doses (at least
catheters in patients with cancer. J Thromb Haemost 2013; 11:71–80. four grams per day) are associated with an increased incidence of nephrotoxicity.
105. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antimicrob Agents Chemother 2008; 52:1330–6.
antithrombotic therapy and prevention of thrombosis, 9th ed: American College 132. Minejima E, Choi J, Beringer P, Lou M, Tse E, Wong-Beringer A. Applying new
of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; diagnostic criteria for acute kidney injury to facilitate early identification of
141: e419S–e96S. nephrotoxicity in vancomycin-treated patients. Antimicrob Agents Chemother
106. Schoot RA, Kremer LC, van de Wetering MD, van Ommen CH. Systemic treat- 2011; 55:3278–83.
ments for the prevention of venous thrombo-embolic events in paediatric cancer 133. Wong-Beringer A, Joo J, Tse E, Beringer P. Vancomycin-associated nephrotox-
patients with tunnelled central venous catheters. Cochrane Database Syst Rev icity: a critical appraisal of risk with high-dose therapy. Int J Antimicrob Agents
2013; 9:CD009160. 2011; 37:95–101.
107. Kirkpatrick A, Rathbun S, Whitsett T, Raskob G. Prevention of central venous 134. Rybak MJ, Lomaestro BM, Rotschafer JC, et al. Vancomycin therapeutic guide-
catheter-associated thrombosis: a meta-analysis. Am J Med 2007; 120:901 e1–13. lines: a summary of consensus recommendations from the Infectious Diseases
108. Lokich JJ, Bothe A Jr, Benotti P, Moore C. Complications and management of Society of America, the American Society of Health-System Pharmacists, and the
implanted venous access catheters. J Clin Oncol 1985; 3:710–7. Society of Infectious Diseases Pharmacists. Clin Infect Dis 2009; 49:325–7.
109. Mandala M, Falanga A, Roila F, Group EGW. Management of venous thrombo- 135. Bauer K, Mangino JE, Paolo-Holman D, Goff DA. Outpatient parenteral anti-
embolism (VTE) in cancer patients: ESMO Clinical Practice Guidelines. Ann microbial therapy and antimicrobial stewardship. Infect Dis Clin Pract 2016; 24:
Oncol 2011; 22: vi85–92. 328–31.
110. Guyatt GH, Akl EA, Crowther M, et al. Executive summary: antithrombotic ther- 136. Akar A, Singh N, Hyun DY. Appropriateness and safety of outpatient parenteral
apy and prevention of thrombosis, 9th ed: American College of Chest Physicians antimicrobial therapy in children: opportunities for pediatric antimicrobial stew-
Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: 7S–47S. ardship. Clin Pediatr 2014; 53:1000–3.
111. Hussain S, Gomez MM, Wludyka P, Chiu T, Rathore MH. Survival times and 137. Conant MM, Erdman SM, Osterholzer D. Mandatory infectious diseases approval
complications of catheters used for outpatient parenteral antibiotic therapy in of outpatient parenteral antimicrobial therapy (OPAT): clinical and economic
children. Clin Pediatr 2007; 46:247–51. outcomes of averted cases. J Antimicrob Chemother 2014; 69:1695–700.
112. Dubois J, Garel L, Tapiero B, Dubé J, Laframboise S, David M. Peripherally 138. Shrestha NK, Bhaskaran A, Scalera NM, Schmitt SK, Rehm SJ, Gordon SM.
inserted central catheters in infants and children. Radiology 1997; 204:622–6. Contribution of infectious disease consultation toward the care of inpatients
113. Thiagarajan RR, Ramamoorthy C, Gettmann T, Bratton SL. Survey of the use of being considered for community-based parenteral anti-infective therapy. J Hosp
peripherally inserted central venous catheters in children. Pediatrics 1997; 99:E4. Med 2012; 7:365–9.
114. Van Winkle P, Whiffen T, Liu IL. Experience using peripherally inserted central 139. Heintz BH, Halilovic J, Christensen CL. Impact of a multidisciplinary team review
venous catheters for outpatient parenteral antibiotic therapy in children at a com- of potential outpatient parenteral antimicrobial therapy prior to discharge from
munity hospital. Pediatr Infect Dis J 2008; 27:1069–72. an academic medical center. Ann Pharmacother 2011; 45:1329–37.
115. Le J, San Agustin M, Hernandez EA, Tran TT, Adler-Shohet FC. Complications 140. Sharma R, Loomis W, Brown RB. Impact of mandatory inpatient infectious dis-
associated with outpatient parenteral antibiotic therapy in children. Clin Pediatr ease consultation on outpatient parenteral antibiotic therapy. Am J Med Sci 2005;
2010; 49:1038–43. 330:60–4.
116. Hodgson KA, Huynh J, Ibrahim LF, et al. The use, appropriateness and outcomes 141. Hersh AL, Olson J, Stockmann C, et al. Impact of antimicrobial stewardship for
of outpatient parenteral antimicrobial therapy. Arch Dis Child 2016; 101:886–93. pediatric outpatient parenteral antibiotic therapy. J Pediatric Infect Dis Soc 2017.
117. Racadio JM, Doellman DA, Johnson ND, Bean JA, Jacobs BR. Pediatric peripher- 142. Snyder GM, Patel PR, Kallen AJ, Strom JA, Tucker JK, D’Agata EM. Antimicrobial
ally inserted central catheters: complication rates related to catheter tip location. use in outpatient hemodialysis units. Infect Control Hosp Epidemiol 2013;
Pediatrics 2001; 107:E28. 34:349–57.

143. Shrestha NK, Bhaskaran A, Scalera NM, Schmitt SK, Rehm SJ, Gordon SM. 148. Shah SS, Srivastava R, Wu S, et al. Intravenous versus oral antibiotics for postdis-
Antimicrobial stewardship at transition of care from hospital to community. charge treatment of complicated pneumonia. Pediatrics 2016; 138:e20161692.
Infect Control Hosp Epidemiol 2012; 33:401–4. 149. Schmitt S, McQuillen DP, Nahass R, et al. Infectious diseases specialty interven-
144. Keren R, Shah SS, Srivastava R, et al.; Pediatric Research in Inpatient Settings tion is associated with decreased mortality and lower healthcare costs. Clin Infect
Network. Comparative effectiveness of intravenous vs oral antibiotics for postdis- Dis 2014; 58:22–8.
charge treatment of acute osteomyelitis in children. JAMA Pediatr 2015; 169:120–8. 150. Paulsen J, Solligard E, Damas JK, DeWan A, Asvold BO, Bracken MB. The impact
145. Zaoutis T, Localio AR, Leckerman K, Saddlemire S, Bertoch D, Keren R. of infectious disease specialist consultation for Staphylococcus aureus blood-
Prolonged intravenous therapy versus early transition to oral antimicrobial ther- stream infections: a systematic review. Open Forum Infect Dis 2016; 3:ofw048.
apy for acute osteomyelitis in children. Pediatrics 2009; 123:636–42. 151. Vogel M, Schmitz RP, Hagel S, et al. Infectious disease consultation for
146. Rangel SJ, Anderson BR, Srivastava R, et al.; Pediatric Research in Inpatient Staphylococcus aureus bacteremia—a systematic review and meta-analysis. J
Settings (PRIS) Network. Intravenous versus oral antibiotics for the prevention of Infect 2016; 72:19–28.
treatment failure in children with complicated appendicitis: has the abandonment 152. Chung EK, Beeler CB, Muloma EW, Osterholzer D, Damer KM, Erdman SM.
of peripherally inserted catheters been justified? Ann Surg 2017; 266:361–8. Development and implementation of a pharmacist-managed outpatient paren-
147. Stockmann C, Ampofo K, Pavia AT, et al. Comparative effectiveness of oral ver- teral antimicrobial therapy program. Am J Health Syst Pharm 2016; 73:e24–33.
sus outpatient parenteral antibiotic therapy for empyema. Hosp Pediatr 2015; 153. Nathwani D, Tice A. Ambulatory antimicrobial use: the value of an outcomes
5:605–12. registry. J Antimicrob Chemother 2002; 49:149–54.

Ciy745 PDF

Uploaded by

Copyright:

Available Formats

Ciy745 PDF

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Ciy745 PDF

Uploaded by

Copyright:

Available Formats

Clinical Infectious Diseases

2018 Infectious Diseases Society of America Clinical

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

EXECUTIVE SUMMARY the recommendation and quality of evidence using Grading of

e2 • CID 2019:68 (1 January) • Norris et al

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

e4 • CID 2019:68 (1 January) • Norris et al

Who Performs Patient Training

e6 • CID 2019:68 (1 January) • Norris et al

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

e8 • CID 2019:68 (1 January) • Norris et al

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

Monitoring Frequencyd (Weekly)

Oral Liver profile: Torsades

e10 • CID 2019:68 (1 January) • Norris et al

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

Monitoring Frequencyd (Weekly)

Oral Liver profile: Torsades

the level of evidence available.

health sciences librarians performed literature searches.

met face-to-face 4 times and conducted numerous conference

Two to 3 panel members were assigned to each section with

evidence, as outlined in Figure 1. The strength assigned to a

calls to develop the guideline questions and literature search

siderations, antimicrobials, VADs, monitoring, and stewardship.

as “high” quality if it included randomized, controlled trials

ranted decreasing or increasing the rating of the quality of the

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

e12 • CID 2019:68 (1 January) • Norris et al

Cohort Study Domains

Subjects and Exposures Comparability Outcome Evaluation

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

e14 • CID 2019:68 (1 January) • Norris et al

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

Factors That Alter

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

Abbreviations: CI, confidence interval; HR, hazard ratio.

e16 • CID 2019:68 (1 January) • Norris et al

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

e18 • CID 2019:68 (1 January) • Norris et al

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

e20 • CID 2019:68 (1 January) • Norris et al

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

Factors That Alter

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

e22 • CID 2019:68 (1 January) • Norris et al

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

Abbreviations: CI, confidence interval; RCT, randomized controlled trial; RR = relative risk.

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

e24 • CID 2019:68 (1 January) • Norris et al

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

e26 • CID 2019:68 (1 January) • Norris et al

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023

Downloaded from https://academic.oup.com/cid/article/68/1/e1/5175018 by guest on 12 May 2023