Antimicrobial Stewardship

REVIEW
crossm
Philippe Morency-Potvin,a,b,c David N. Schwartz,a,b Robert A. Weinsteina,b

Division of Infectious Diseases, John H. Stroger, Jr. Hospital of Cook County, Chicago, Illinois, USAa; Rush
Medical College, Chicago, Illinois, USAb; Dpartement de Microbiologie, Infectiologie et Immunologie,
Universit de Montral, Montreal, Quebec, Canadac
SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
INTRODUCTION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 382
ANTIMICROBIAL STEWARDSHIP AT THE HELM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 382
THE LABORATORYS SEAT AT THE CAPTAIN=S TABLE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383
LOW-HANGING-FRUIT INTERVENTIONS OR TREASURES IN SHALLOW WATER . . . . . . . 386
Cumulative Antimicrobial Susceptibility Report . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387
Antimicrobial Susceptibility Reporting: beyond the Horizon. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 389
New Drug Testing and Changes in Interpretation Guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . 390
Guidance in the Preanalytic Phase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391
BIOMARKERS AND RAPID DIAGNOSTIC AND RAPID SUSCEPTIBILITY TESTING: NEW
TRADE WINDS MAY HELP YOU REACH YOUR DESTINATION . . . . . . . . . . . . . . . . . . . . . . 392
Biomarkers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 392
Rapid Diagnostic Testing (RDT) and Rapid Antimicrobial Susceptibility Testing . . . . . . . 393
Bacterial and Fungal Molecular Assays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 394
Viral Molecular Assays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395
MALDI-TOF MS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395
Old and New Antimicrobial Susceptibility Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395
RDT Bottom Line . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 396
PROVIDER EDUCATION: HOW TO TIE THE KNOTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 397
ALERT AND SURVEILLANCE SYSTEMS: SOUNDING THE ALL-HANDS-ON-DECK
ALARM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399
Critical Specimens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399
Resistant Pathogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 400
MICROBIOLOGY AT SEA: SAILING INTO THE SUNSET OR RETURNING TO
HARBOR?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401
AUTHOR BIOS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 406
Published 14 December 2016

Citation Morency-Potvin P, Schwartz DN,
Weinstein RA. 2017. Antimicrobial stewardship:
how the microbiology laboratory can right the
ship. Clin Microbiol Rev 30:381 407. https://
doi.org/10.1128/CMR.00066-16.
Copyright 2016 American Society for
Microbiology. All Rights Reserved.
Address correspondence to Philippe MorencyPotvin, [email protected].
Antimicrobial stewardship is a bundle of integrated interventions employed to optimize the use of antimicrobials in health care settings. While
infectious-disease-trained physicians, with clinical pharmacists, are considered
the main leaders of antimicrobial stewardship programs, clinical microbiologists
can play a key role in these programs. This review is intended to provide a comprehensive discussion of the different components of antimicrobial stewardship
in which microbiology laboratories and clinical microbiologists can make signicant contributions, including cumulative antimicrobial susceptibility reports, enhanced culture and susceptibility reports, guidance in the preanalytic phase,
rapid diagnostic test availability, provider education, and alert and surveillance
systems. In reviewing this material, we emphasize how the rapid, and especially
the recent, evolution of clinical microbiology has reinforced the importance of
clinical microbiologists collaboration with antimicrobial stewardship programs.
SUMMARY
KEYWORDS antimicrobials, antimicrobial stewardship, microbiologist, optimal use,

role, stewardship, rapid tests
January 2017 Volume 30 Issue 1
Clinical Microbiology Reviews
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Antimicrobial Stewardship: How the

Microbiology Laboratory Can Right the
Ship
Morency-Potvin et al.
INTRODUCTION
linical microbiology is a relatively new science. Van Leeuwenhoek, considered the
father of microbiology, wrote his rst letters on microscopy studies in the 17th
century (1), but the work by Pasteur and Koch (2), among others, that led to clinical
advances in the prevention and management of infectious diseases (ID) and associated
improvements of the human condition (3), was not performed until the late 19th
century. Once incurable and lethal infections have since become readily diagnosed and
easily treatable, contributing to todays lofty expectations of modern medicine in which
unsuccessful treatment of infections is considered a major failure.
Threats to these expectations loom, however. The emergence of antimicrobial
resistance, including readily transmissible genetic elements in major human bacterial
pathogens that confer resistance to most or all available antimicrobials, has foreshadowed the possible return of serious untreatable infection (4). Much of this is attributable
to suboptimal usually excessive use of antimicrobials in and out of hospital settings, which is estimated to occur in 30 to 50% of all prescriptions (5). Suboptimal
antimicrobial usage often stems from inappropriate interpretation or use of microbiological test results: lack of a microbiologically conrmed diagnosis, laboratory test
errors, failure to submit appropriate specimens for culture, misuse of microbiology
resources, and a general overreliance on empirical antimicrobial therapy with attendant
disregard of microbiological results. A comprehensive understanding of these issues
and a modern approach to their solution, though assembled as early as 1955 (6), has
been an elusive operational goal.
Microbiology laboratories and the physicians or scientists who lead them must avoid
a potentially paradoxical role in this dynamic. Their reports provide the primary basis
for determining the incidence of antimicrobial-resistant infections on which longitudinal assessments of the problems severity depend and for determining the prevalence
of resistance among clinical isolates of common bacterial species that crucially informs
empirical antimicrobial therapy strategies. Yet, microbiology input into the design and
execution of antimicrobial stewardship interventions is often minimal or absent. Despite recommendations for including clinical microbiologists in hospital antimicrobial
stewardship teams in prominent guidelines (7, 8), few if any of the interventions
recommended require laboratory input; i.e., the guidelines are often pharmacy centric.
This article will review the multiple avenues by which clinical microbiology laboratories can contribute to antimicrobial stewardship efforts and offer a roadmap for
clinical microbiologists to seize additional opportunities. It is intended not only for
clinical microbiologists but for all health care professionals who want to improve
laboratory collaboration in antimicrobial stewardship activities. We recognize that the
substantial and growing administrative and managerial responsibilities of clinical microbiologists may hinder their fuller participation in stewardship and other clinical
activities but argue here that the rapid pace of recent technological change and the
attendant needs for implementation and interpretive guidance described below have
produced a greater demand for clinical microbiologists expertise than at any time in
recent memory. Clinical microbiologists must collaborate closely with their clinician
colleagues if patients are to fully realize the benets of these advances.
ANTIMICROBIAL STEWARDSHIP AT THE HELM

Antimicrobial stewardship is a key instrument in working to improve the use of
microbiologic data in order to help facilitate the appropriate use of antimicrobials and
therefore to minimize antimicrobial resistance, as well as other unintended consequences, such as antimicrobial toxicity, adverse drug reactions, and Clostridium difcile
diarrhea (6, 7, 9).
Antimicrobial stewardship can be dened as a bundle of interventions to promote
and ensure the optimal use of antimicrobial treatment that results in the best clinical
outcome for the treatment or prevention of infection, with minimal toxicity to the
patient and minimal impact on subsequent resistance (10). The bundle and the key
cmr.asm.org 382
Antimicrobial Stewardship in Clinical Microbiology
role played in each step by microbiology laboratories can be summarized by the six Ds
of antimicrobial stewardship adapted from other sources (Table 1) (11, 12).
Antimicrobial stewardship programs have been shown to be benecial in numerous
health care settings, from small community health care centers to nursing homes and
academic urban hospitals (13, 14). Reported benets include, but are not limited to (15),
reduction of C. difcile infection incidence (1619), reduction of antimicrobial resistance
(2024), improving antimicrobial dosing in renally impaired patients (25, 26), improving
the use of surgical antimicrobial prophylaxis (2729), improved infection cure rates (30,
31), decreased mortality rates (14), more rapid administration of effective antimicrobial
therapy and appropriate de-escalation in critical infections (3235), and hospital cost
savings (3641).
Guidelines were published in 2007 by the Infectious Diseases Society of America
(IDSA) and the Society for Healthcare Epidemiology of America (SHEA) to enhance
antimicrobial stewardship activities (7) and updated in 2016 (42). In 2014, the Centers
for Disease Control and Prevention (CDC) proposed seven core elements for the success
of antimicrobial stewardship programs (Table 2) (5, 43).
In March 2015, the White House published a National Plan to Combat AntibioticResistant Bacteria (44). The ve goals of the plan are to slow the emergence of resistant
bacteria and prevent the spread of resistant infections; strengthen national One-Health
surveillance efforts to combat resistance; advance the development and use of rapid
and innovative diagnostic tests for the identication and characterization of resistant
bacteria; accelerate basic and applied research and development for new antibiotics,
other therapeutics, and vaccines; and improve international collaboration and capacities for antibiotic resistance prevention, surveillance, control, and antibiotic research
and development.
The plan aims to implement antimicrobial stewardship programs in every hospital
setting in the United States by 2020 and recognizes antimicrobial stewardship interventions as major elements of the ght against antimicrobial resistance. It addresses
antimicrobial resistance not only as a public health problem but also as a potential
national security threat (45, 46).
The Joint Commission recently established performance criteria for antimicrobial
stewardship for hospitals, critical-access hospitals, and nursing care centers that will
become effective in 2017 (47). Elsewhere, Accreditation Canada and the Australian
National Safety and Quality Health Service have had similar organizational requirements since 2013 and the National Institute for Health and Care Excellence published
quality standards in April 2016 (4850). Most recently, the issue of antimicrobial
resistance was the subject of an unprecedented United Nations meeting, only the
fourth health care issue to be accorded its own session of the United Nations General
Assembly (51).
THE LABORATORYS SEAT AT THE CAPTAIN=S TABLE
Because ID can affect all organ systems and encompass all medical disciplines,
clinical microbiologists must collaborate with a diverse range of health professionals.
Clinical microbiologists and ID physicians should naturally collaborate on a day-to-day
basis, and this is considered essential to a successful antimicrobial stewardship program
(7). Clinical pharmacists, especially those trained in ID, also play a major role in
antimicrobial stewardship programs. Their expertise in antimicrobial effectiveness,
toxicity, drug interactions, and pharmacodynamics and pharmacokinetics of antibiotics
inform multiple stewardship activities, including, but not limited to, development and
editing of order set, clinical pathways, and antibiotic usage policies; providing prior
authorization of selected antibiotics; tracking of antimicrobial use and resistance; and
interventions with feedback (52).
While medical practices combining both ID and medical microbiology are common
in many countries, there is extensive variation in the involvement of clinical microbiologists in antimicrobial stewardship programs around the world (53). In Europe, a large
observational study in 170 acute-care hospitals in 32 countries evaluated the role of
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TABLE 1 The six Ds of antimicrobial stewardship and associated key roles of microbiology laboratories
The 6 Ds of
antimicrobial
stewardship
Diagnosis
Examples of the key roles of microbiology laboratories

Provide guidance to clinicians in obtaining adequate and signicant specimens
(e.g., prefer tissues and uids in adequate volume to swabs)
Perform rapid testing for pathogens difcult to identify with standard
microbiology (e.g., Legionella urine antigen)
Perform rapid identication testing of critical specimens (e.g., rapid molecular
testing of positive blood cultures)
Perform timely biomarker testing (e.g., PCT) as indicated by institutional or
professional organization recommendations
Promptly send samples to reference laboratories for appropriate tests not
performed on site (e.g., Histoplasma urine antigen)
Advise clinicians about availability of advanced molecular diagnostic (e.g., 16S
rRNA) testing for culture-negative critical access tissues (e.g., brain or bone
biopsy specimens, cardiac valves) and provide timely access to reference lab
testing as clinically appropriate
Advise clinicians on the performance characteristics of conventional and
emerging RDT methods
Discard inadequate specimens (e.g., a urine specimen that has leaked from its
transport container, external drains, etc.)
Debridement/
drainage
Drainage of abscesses and removal of

necrotic tissue or foreign material
when required
Provide guidance for obtaining adequate and signicant specimens (e.g., uids
in adequate volume rather than just swabs)
Prioritize cultures of specimens from operating rooms and interventional
radiology (e.g., prepare slides and inoculate agar with specimens as soon as
specimens arrive in the laboratory)
Optimize routing and tracing of specimens to the laboratory (e.g., provide logs
to trace specimens from the operating room)
Drug
Use the right drug empirically

according to suspected or
conrmed diagnosis, risk factors for
resistant pathogens, allergy, or
major side effects
Participate in creating local guidelines for common infectious syndromes

Provide, revise, and publicize annual cumulative susceptibility reports to
clinicians (e.g., provide tables with local susceptibility patterns) and work with
ID physicians to interpret these data, e.g., to update recommended empirical
regimens
Provide supplementary testing for susceptibility to new drugs when appropriate
Use cascade reporting (e.g., do not report carbapenem susceptibility when a
pathogen is susceptible to narrower-spectrum drugs)
Repeat testing and promptly send to reference laboratory unusual susceptibility
proles (e.g., S. aureus resistant to vancomycin)
Contact clinicians directly and promptly in unusual cases and provide guidance
for testing and therapy (e.g., when carbapenem resistance is suspected in a
critical specimens and conrmation testing is pending)
Perform surveillance for emerging pathogens and resistance patterns and
inform clinicians and public health authorities as appropriate (e.g., reporting
to public health and memo to clinicians when multiple multiresistant
Acinetobacter spp. are identied at one institution)
Dose
Use right dose according to

diagnosis, site of infection, or renal
or hepatic dysfunction
Collaborate with pharmacists and ID physicians to improve reporting of MICs

for dosing based on pharmacokinetic targets
Duration
Use drugs for an appropriate duration
Perform biomarker testing and develop protocols to optimize their use for
informing therapy duration as indicated
De-escalation
Reevaluate diagnosis and therapy

routinely and de-escalate therapy
to narrow-spectrum and/or oral
agents when appropriate
Do not report skin contaminants in noncritical specimens and specify when

contamination of critical specimens is or is not suspected (e.g., report S.
epidermidis and other skin commensals exclusively from clinically signicant
specimens such as blood or prosthetic joints)
Leverage opportunities to append clinical guidance to microbiological reports,
e.g., preferred drugs, likelihood of polymicrobial infection by specimen source
(e.g., urine vs intra-abdominal wound), diagnostic follow-up (e.g., that repeat
blood cultures are usually required in cases of candidemia, links to respiratory
virus panel results in sputum culture reports)
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Description
Make and document the right
diagnosis
TABLE 2 The CDCs seven core elements of antimicrobial stewardship

Element
Leadership commitment
Accountability
Drug expertise
Action
Tracking
Reporting
Education
Description
Dedicating necessary human, nancial, and IT resources
Appointing a single leader responsible for program
outcomes
Appointing a single pharmacist leader responsible for
working to improve antibiotic use
Implementing at least one recommended action with the
goal of improving antimicrobial use
Monitoring antibiotic prescribing and resistance patterns
Regular reporting of information on antibiotic use and
resistance to doctors, nurses, and relevant staff
Educating clinicians about resistance and optimal prescribing
microbiology in antimicrobial stewardship programs. While there was some geographic

variation, a majority of microbiology laboratories participated in day-to-day antimicrobial stewardship activities ranging from advice outside business hours (71%) to daily
ward rounds (41%) and cascade reporting (67%) (54).
In many countries of the Commonwealth of Nations, clinical microbiologists assume
many clinical functions outside the laboratory because many are also trained in ID. For
example, clinical microbiologists were present in more than 90% of acute trust antimicrobial stewardship committees in England and Ireland, making microbiology the
most represented specialty in recent surveys (55, 56), perhaps reecting the clinical
roles that clinical microbiologists regularly have played in these countries, especially
when there were few clinically trained ID physicians.
In 2011, the Australian Commission on Safety and Quality in Healthcare promulgated multiple recommendations for antimicrobial stewardship programs, including
some pertaining to the role of microbiology services (9). The commission recommended that clinical microbiologists provide best practices for the rapid diagnosis of
common infections, notify clinicians when critical infections are detected, provide
regular patient-specic liaisons with clinicians in high-risk units, perform surveillance
for resistance, and run standard antimicrobial susceptibility testing with cascade reporting (described below). The commission emphasized that clinical microbiologists
should participate in pharmacy and therapeutics and antimicrobial stewardship committees, as their role is essential and integral to antimicrobial stewardship initiatives. A
survey that followed these recommendations in the State of Victoria demonstrated
large variations in the implementation of the proposed strategies, mainly depending on
the type of institutions (57). Another survey in Queensland found that clinical microbiologists were responsible for providing therapy advice and antimicrobial approval in
nearly 40% of the institutions surveyed, though half of the facilities did not have access
to in-house clinical microbiologists or ID specialists (58).
In the province of Quebec (Canada), a survey of 68 hospitals in 2008 found that
clinical microbiologists participated in 89% of antimicrobial stewardship surveillance
programs (59). In this province, as in some other countries, most microbiologists are
also trained and certied as ID specialists.
In the United States, clinical microbiologists training backgrounds can vary between
academic (Ph.D.) and medical (M.D.) training. In the latter, most will follow a pathology
track while some, more rarely, will additionally be trained in internal medicine and ID.
However, many microbiology laboratories focus on processing specimens and providing quality results without engaging in antimicrobial stewardship programs, which are
usually led by ID physicians and pharmacists (60). Studies performed in California and
Florida showed that microbiologists participated in antimicrobial stewardship activities
in 26% and 42% of the hospitals surveyed, respectively (61, 62). A nationwide electronic
survey, in which only half of the respondents reported having an institutional antimicrobial stewardship program, found similar results (63).
The 2007 IDSA/SHEA guidelines recommended that the core members of antimiJanuary 2017 Volume 30 Issue 1
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crobial stewardship programs should include an ID physician and a clinical pharmacist

with ID training. The participation of clinical microbiologists, along with information
system specialists, infection control professionals, and hospital epidemiologists, is
considered optimal (7). It is mentioned that the microbiology laboratory plays a critical
role in antimicrobial stewardship by providing patient-specic culture and susceptibility
data to optimize individual antimicrobial management and by assisting infection
control efforts in the surveillance of resistant organisms and in the molecular epidemiologic investigation of outbreaks (7). Other potential functions of microbiology
laboratories in antimicrobial stewardship programs mentioned in the guidelines include generating cumulative antimicrobial susceptibility reports (CASRs) to inform local
guidelines and clinical pathways, collaborating with infection control professionals in
outbreak investigations, and surveying for bacterial resistance.
In a 2016 guideline update, six to-do recommendations are listed for microbiology
laboratory collaboration with antimicrobial stewardship teams, all of which were weak
recommendations with low-to-moderate levels of evidence (42): use of stratied CASRs;
use of selective or cascade reporting in antimicrobial susceptibility reports, i.e., reporting of algorithm-selected antimicrobial susceptibilities according to local resistance,
treatment guidelines, and resistance patterns of a specic organism; use of rapid viral
testing for respiratory pathogens; use of rapid diagnostic assays for blood cultures; use
of procalcitonin (PCT) testing and algorithms for patients in the intensive care unit; and
use of non-culture-based fungal markers for patients with hematologic malignancies.
We believe that clinical microbiologists can play a vital role in clinical services in the
21st century and that antimicrobial stewardship can keep them closer to patient care
(64). More than 20 years ago, a survey by Thomson illustrated the changing role of
some microbiology laboratories, shifting from research, education, and clinical services
to management (65). There is also a worldwide trend in laboratory centralization with
stated goals of greater standardization for quality and cost savings. It may seem logical,
although unfortunate, that clinical microbiologists facing limited resources focus on
more managerial types of activities rather than educational activities. The presence of
an antimicrobial stewardship team whose members share responsibilities and in which
the laboratory is actively engaged can represent the missing link to reach prescribers
and perform the education perceived as missing by laboratorians and/or clinicians. The
ways in which the laboratory can contribute to education efforts will be detailed
further. In general, these activities should promote more uid communication between
clinicians and the laboratory to increase the clinical microbiologists visibility, knowledge of the players and issues, and contributions to antimicrobial stewardship. Participation of clinical microbiologists in antimicrobial stewardship committees is thus the
rst and probably most important step in enhancing collaboration between the
laboratory and other participants. Getting to know the current issues and objectives of
the program is essential to tailoring what the laboratory can offer.
Many current laboratory practices can be considered stewardship activities and
warrant recognition and credit as such. Table 3 presents some of the essential,
achievable, and aspirational elements that clinical microbiologists can bring to the
table of antimicrobial stewardship.
LOW-HANGING-FRUIT INTERVENTIONS OR TREASURES IN SHALLOW WATER
The timely availability of accurate and clinically signicant microbiology results is
critical for optimal antibiotic use and related clinical outcomes (7, 66). For example, a
positive blood culture Gram stain read as Gram-negative bacilli but later identied as
Listeria monocytogenes could signicantly delay the provision of effective therapy,
leading to an adverse outcome, even death (67). While microbiology laboratories
usually perform surveillance for sentinel events such as the one described, antimicrobial stewardship teams can assist in this effort, and pathways to report and analyze
these potential errors should be clearly dened. The World Health Organization (WHO),
the United States Food and Drug Administration (FDA), the CDC, and the Clinical and
Laboratory Standards Institute (CLSI) together developed a Laboratory Quality ManageJanuary 2017 Volume 30 Issue 1
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TABLE 3 Essential, achievable, and aspirational antimicrobial stewardship activities for the
microbiology laboratory
Stewardship
activity level
Essential
Achievable
Provide specic comments, drafted in collaboration with antimicrobial

stewardship team, to guide therapy on microbiology reports
Participate in establishing protocols on biomarker use
Use rapid diagnostic and antimicrobial susceptibility technologies for targeted
critical specimen types
Use rapid-detection platform for respiratory pathogens
Guide optimal use of diagnostic assays for C. difcile
Develop direct communication pathways with prescribers to help interpret
RDT results and discrepant results
Provide guidelines for the interpretation of microbiology test results
Collaborate in audit and feedback of antimicrobial therapies for specic
pathogens or syndromes where the role of lab test values is critical (e.g., C.
difcile, bloodstream infections)
Aspirational
Evaluate feasibility of and, where possible, perform testing for susceptibility to

new drugs
Broaden use of validated rapid diagnostic and rapid antimicrobial
susceptibility testing
Participate in education of patients and local population on antimicrobial
resistance
Participate in national and regional surveillance systems
Promote appropriate use of point-of-care microbiological tests, when available
Descriptiona
Provide timely, reliable, and reproducible identication and antimicrobial
susceptibility results
Actively participate in antimicrobial stewardship committee or work group
Collaborate in educating local health care workers on microbiology issues that
impact treatment and microbial resistance
Promptly report unusual patterns of resistance, test supplementary agents,
and provide advice on therapy for patients awaiting results
Optimize communication of critical test result values and alert systems
Provide, revise, and publicize annual CASR consistent with CLSI standards
Provide guidance for adequate collection of microbiology specimens
Develop alert systems for specic multidrug-resistant organisms
Use cascade or selective reporting
Collaborate with ID physicians and pharmacists on updating methods for
susceptibility testing
aCLSI,
Clinical and Laboratory Standards Institute; CASR, cumulative antimicrobial susceptibility report; RDT,
rapid diagnostic test.
ment Systems Handbook based on previous CLSI documents and International Organization for Standardization standard 15189 to pursue the goal of providing reliable,
timely, and accurate results (68, 69). Twelve quality essentials are described in this
document: organization, personnel, equipment, purchasing and inventory process
control, information management, documents and records, occurrence management,
assessment, process improvement, customer service, and safety. Thus, we believe that
a culture of quality in the microbiology laboratory and within antimicrobial stewardship
can be mutually reinforcing.
Cumulative Antimicrobial Susceptibility Report
CASRs, often referred to simply as antibiograms, have many uses, including, but
not limited to, helping prescribers select effective therapy when culture results are
pending, informing and updating local guidelines for empirical treatment of common
infection syndromes, updating periprocedural or perioperative prophylaxis recommendations, providing a rationale for antimicrobial formulary selection, surveying local
resistance and benchmarking, identifying targets for stewardship interventions and
best practices, and providing the context for new drug susceptibility testing results.
The CLSI rst published guidelines for the analysis and presentation of cumulative
susceptibility test data in 2002 and updated them most recently in 2014 (70). They
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TABLE 4 CLSI M39-A4 recommendations for CASRsa
Recommendationb
Analyze and present CASR at least annually
Include only nal, veried results
Include only species with results for 30 isolates
Include only diagnostic (not surveillance) isolates
Eliminate duplicate isolates by including only rst species isolate/patient/period of analysis
Include only routinely tested agents
Report % S and exclude % I
For Streptococcus pneumoniae, report data for both meningitis and nonmeningitis breakpoints
For viridans group streptococci, report both % S and % I
For S. aureus, report % S for all isolates and MRSA subset
aAdapted
bS,
from reference 70 with permission of the publisher.

susceptible; I, intermediate.
included 10 recommendations (Table 4). The clinical microbiologist is in an excellent

position to understand how these recommendations inuence the utility of the reports
and to contribute to antimicrobial stewardship programs on the basis of this expert
knowledge. Some institutions have also published their CASRs online, and they can be
consulted on the web (7173).
A 2004 national survey showed that among 474 responding laboratories (74%
response rate), 95% published a CASR and 60% published a summary report that was
distributed to infection control and medical staff and updated annually. Hospitals with
on-site susceptibility testing and greater numbers of laboratory personnel were more
likely to be compliant with the three survey elements previously (74).
Zapantis et al. (75) analyzed 209 CASRs from 2000 to 2002 and found that 14.3%
showed unusual results such as Enterococcus susceptible to cephalosporins or
Stenotrophomonas maltophilia susceptible to imipenem. Others have conrmed these
observations (76). More recently, Moehring et al. (77) specically looked at CASR quality
in community hospitals and found that adherence to CLSI guidelines was generally
poor. Only 8 (25%) microbiology laboratories excluded data for species with fewer than
30 isolates, while 20 (63%) reported data for nonrecommended pathogen-drug combinations. Only three microbiology laboratories (10%) were fully compliant. Both studies highlight that the rst step for microbiology laboratories contribution to antimicrobial stewardship programs must be to provide reliable data. CASRs benet from
multidisciplinary team interpretation and revision before publication to omit errors that
might promote antimicrobial misuse.
While CLSI guidelines provide criteria for standardizing and benchmarking CASR
data, challenges remain. Smaller microbiology laboratories may have difculty meeting
the recommended threshold of 30 isolates to report data in CASRs. Combining data at
the genus level, from a longer period, or from multiple institutions with shared
population characteristics might represent a reasonable option. On the other hand, if
the number of isolates is sufcient and results suggest signicant differences, data can
be stratied by service, unit, resistance mechanisms, body sites, or specimens. Combination therapy susceptibilities can be calculated to help prescribers choose the right
second agent for clinical situations, e.g., Gram-negative sepsis, where potentially
antibiotic-resistant pathogens may warrant the broadened coverage afforded by double therapy while susceptibility results for the specic pathogen are pending (70, 78).
Some pathogen-drug combinations that are not usually recommended for testing
can still be included in the CASR, especially when specic resistance phenotypes are
locally observed (and antibiotics are systematically tested) or to educate prescribers on
the usual nonsusceptibilities of certain pathogens. For example, entering R or 0%
susceptibility of S. maltophilia to piperacillin-tazobactam should be considered to
discourage its use.
Aggregated CASRs, i.e., the combination of strains from multiple institutions in one
CASR, have been attempted, using uniform methodology among hospitals with similar
patient populations and other characteristics (79). The State of Hawaii published a
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statewide antibiogram for selected bacteria of public health signicance (80). Though
obviously useful among small hospitals with insufcient numbers of specimens for
reliable reports, aggregation of hospital antibiograms can also uncover or conrm
newly emerging resistance phenotypes. For example, unusually high rates of resistance
to uoroquinolones, third-generation cephalosporins, and carbapenems identied
from aggregated susceptibilities of Gram-negative pathogens collected from our longterm and acute-care hospital spurred the development and acceptance of our comprehensive antimicrobial stewardship program (81). Such aggregation is facilitated
when hospitals already share some services (information technology [IT] systems,
administration, infection control services, etc.).
IT systems might present obstacles to obtaining cumulative susceptibility data. Most
available clinical microbiology management systems can extract data adequately.
However, some require substantial additional work to obtain the same information. The
CLSI also recommends an alternate manual data extraction method (70). In both
instances, careful review is mandatory to ensure data accuracy. In any event, the
participation of clinical microbiologists in antimicrobial stewardship programs is of
great value to ensure that laboratory IT systems are chosen with stewardship considerations in mind.
These challenges should not discourage microbiology laboratories from providing
CASRs, as their benets generally exceed the inconvenience. However, when microbiology laboratories use methods different from those provided by the CLSI, the alternative methods should be clearly stated.
With the adoption of clinical decision support systems in many hospitals, it is also
more and more common that CASRs are prepared by members of the antimicrobial
stewardship team without the input of the microbiologist. While information provided
by these systems can be accurate, errors in interpretation and reporting may lead to the
delivery of false information to prescribers. Laboratories should ensure that people who
prepare CASRs have received adequate training and have access to the most recent
CLSI guidelines. The clinical microbiologists input is also essential before the publication of the report.
Antimicrobial Susceptibility Reporting: beyond the Horizon
The nal step of reporting results is crucial in the process of susceptibility testing
(82). From the antimicrobial stewardship standpoint, the method by which the microbiology laboratory communicates results and the use of selective reporting and provision of instructions for how to interpret results can have a profound impact on
prescribing habits.
Cascade or selective reporting can be used to promote the judicious use of
antimicrobials (42, 83, 84). Cascades consist of algorithm-driven reports that provide
only a limited number of tested antimicrobial susceptibilities based on formulary
availability, local cumulative susceptibilities, and cost for isolates with no or low levels
of resistance and reporting of susceptibility to broader-spectrum drugs only when
isolates are resistant to drugs in the rst cascade. Examples include releasing only
gentamicin results when an organism is susceptible to all aminoglycosides, providing
only susceptibilities to narrow-spectrum urine agents such as nitrofurantoin and
trimethoprim-sulfamethoxazole when organisms isolated from midstream urine cultures are susceptible to these agents and releasing other agents such as quinolones or
cephalosporins only when resistance to the former is demonstrated and not releasing
non--lactam susceptibilities for Streptococcus agalactiae screening cultures if no
-lactam allergy is indicated in the patient chart. While some microbiology laboratories
prefer to release all of the information to clinicians, the cascade approach is recommended by the IDSA (42). Careful selection of reported susceptibilities and frequent
reevaluation are necessary to ensure the continued value and reliability of the cascade
and the quality of the reporting. Unreleased susceptibility data should also be readily
available upon clinician request. Some studies suggest an association between the
antibiotics listed in antimicrobial susceptibility reporting and the use of these antibiJanuary 2017 Volume 30 Issue 1
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otics by prescribers (85). For example, Cunney et al. found that antimicrobials were half
as likely to be prescribed when susceptibility results from noncritical cultures not
suggestive of infection were suppressed (86). Similarly, McNulty et al. showed that
reporting of cephalexin instead of amoxicillin-clavulanate in urine culture reports
resulted in dramatic modication of the use of these two agents in the intervention
period even when practitioners were not informed of the change (87). Unfortunately,
no guidelines on cascade reporting are currently available (88).
The benets and potential pitfalls of using comments or additional messages to
enhance microbiology reports have not been studied extensively, though this approach
is widely used on the basis of local experience. Clear and concise messages on patient
reports may be useful to guide therapy (84, 89). However, regulatory agencies may
require that some information be included and may overload the reports. The CLSI also
recommends few therapy-related comments (90). Some examples are listed in Table 5.
One important observation is that automated messages are easier to manage and less
likely to be forgotten than when such messages must be added manually. In general,
automated susceptibility reporting, available in many laboratory systems, reduces the
inherent complexity of managing this process (84, 91).
Phone calls remain the method of choice for rapid notication of critical results, but
other means of communication, such as paging, text messaging, electronic messaging,
and alerting, can be used to communicate with health care professionals in other
contexts. Though electronic reporting of microbiological data may improve workow
efciency, it may impact clinical decisions minimally (9, 92). Person-to-person communication optimally provides reliable transfer of information, increases collegiality, and
heightens appreciation of the clinical microbiologists value.
New Drug Testing and Changes in Interpretation Guidelines
Over the last few decades, a limited number of new antimicrobials have been
developed (93). However, new regulations were adopted to promote the development
and to speed up the availability of new drugs to patients (94). While new antibiotics
should be used with care and only when indicated, some clinicians might nd their use
urgent, especially when the new agents ll a void in the therapeutic arsenal. Microbiology laboratories should stay abreast of new drug development and assess the
laboratorys capacity to test the activity of new agents against appropriate pathogens.
Information on clinical breakpoints, quality control, and other drug particularities may
be limited when new drugs rst come to market or when older drugs, e.g., polymyxins,
reemerge as therapies of necessity. Materials for testing may sometimes be available
only through drug manufacturers with research use only status, and testing may be
limited to one or two methods. Thus, a laboratory that previously evaluated, experimented, or validated testing for a specic new drug may play a critical role in the
process of approval by a pharmacy and therapeutics committee.
The CLSI, European Committee for Antimicrobial Susceptibility Testing, and other
authoritative guidelines are updated frequently and are crucial to microbiology laboratories ability to provide quality results. Selecting the most appropriate breakpoint
guidelines can be challenging, as discussed elsewhere (95, 96). However, once reserved
for laboratorians, recommendations and criteria provided by these guidelines are now
used in day-to-day patient care by physicians and pharmacists. Interdisciplinary collaboration is essential in analyzing and implementing new breakpoint guidelines, especially in the case of the annual update of the performance standards for antimicrobial
susceptibility testing (90, 97). One example is the implementation of CLSI cephalosporin
breakpoints for Enterobacteriaceae, changed in 2010, that can impact the epidemiology
of resistance and consequently the use of carbapenems (89). New breakpoints should
therefore be evaluated for implementation in a timely manner. However, delays in the
adoption of these breakpoints by regulators like the FDA, and consequently by the
manufacturers of automated platforms, may represent signicant barriers to implementation (98). Similarly, as suggested by Heil and Johnson in their paper on clinical
breakpoint issues (89), changes in methods that impact identication, susceptibility
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TABLE 5 Examples of acceptable therapy-related comments added to patient clinical microbiology reports to improve prescribing of
antimicrobials
Category
CLSI-recommended comments (M100-S25)a
Diagnosis issues
Specialist consultation
Duration of therapy
Culture interpretation
Reference to documentation
Suggestions for alternatives
Selective or cascade susceptibility
reporting
Reference to antimicrobial stewardship
program services
Dosing recommendations
Probable contamination or colonization
Nonstandard methods or lack of
interpretation criteria
New interpretation criteria
Public health reporting
Infection control recommendations

Other potential comments
Enterobacter cloacae with AmpC-type -lactamase prole; cefepime is usually effective for infections
caused by this pathogen
Positive urine cultures should prompt targeted antimicrobial therapy only if the patient (i) has
symptoms of cystitis or pyelonephritis, (ii) is pregnant, or (iii) will soon undergo an invasive
urologic procedure; apart from these clinical indications, patients with asymptomatic bacteriuria
do not benet from antibiotic therapy
ID consultation is strongly recommended in S. aureus bacteremia
S. aureus bacteremia usually requires a minimum of 14 days of therapy; longer therapy is often
needed to treat or prevent complicated infections; expert consultation is advised
Gram stain and culture of this specimen represent normal skin ora
Refer to local guidelines for treatment recommendations of respiratory tract infections
In our institution, clindamycin is the preferred agent used to treat this pathogen in patients with
IgE-mediated allergy to penicillin
Only rst-line recommended antimicrobials appear in this report; contact the laboratory for
additional susceptibility testing if alternate agents are needed, e.g., due to allergy
Contact the antimicrobial stewardship team to choose the best agent to treat this infection (e.g.,
for unusual or multidrug-resistant pathogens)
Maximum dosing is recommended to treat severe infections caused by this agent; consider expert
consultation
Candida spp. are rarely pathogenic in respiratory tract or urine cultures
There are no validated susceptibility criteria for this agent; MICs are provided for information only
According to recent published standards, clinical breakpoints for this drug have changed; consult
with the laboratory for more information
Infection with this agent is a reportable disease that requires clinical information; this infection will
be reported to the public health department; you may be contacted if additional clinical
information is needed
Contact precautions are mandated in patients with MRSA infection or colonization; refer to
infection control procedures for more information
Cost of tested antimicrobials
Indication of preferred agents according to local guidelines in the report by highlighting or bolding
aAdapted
bTo
from reference 90 with permission of the publisher.

provide insight into agents to avoid or to consider on the basis of specic mechanisms of resistance.
testing, or simply reporting should also be promptly announced to clinicians to avoid

errors in interpretation. Clinical microbiologists, in conjunction with ID physicians and
pharmacists, are in the best position to rapidly identify such situations and to provide
timely insights and recommendations to antimicrobial stewardship programs.
Guidance in the Preanalytic Phase
Being able to make the right diagnosis is usually a prerequisite to providing effective
therapy. Recommendations for drug choice, dosing, or duration may be useless if the
diagnosis is wrong. Filice et al. assessed the accuracy of diagnosis and appropriateness
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Other potential comments

Resistance mechanism characterizationb
Examples
Cefazolin results predict results for oral agents cefaclor, cefdinir, cefpodoxime, cefprozil, cefuroxime,
cephalexin, and loracarbef when used for therapy of uncomplicated urinary tract infections due
to Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis
Rifampin should not be used alone for antimicrobial therapy in infections with Staphylococcus or
Streptococcus spp.
Use of penicillins or third-generation cephalosporins for pneumococcal meningitis requires therapy
with maximum doses
Dose of intravenous penicillin of at least 2 million units every 4 h in adult with normal renal
function (12 million U/day) can be used to treat nonmeningeal pneumococcal infections due to
strains with penicillin MICs of 2 g/ml; strains with an intermediate MIC of 4 g/ml may
require penicillin doses of 18 to 24 million U/day in adults with normal renal function
Penicillin- or ampicillin-intermediate isolates may require combined therapy with an
aminoglycoside for bactericidal action in streptococcal infections
Combination therapy with ampicillin, penicillin, or vancomycin (for susceptible strains) plus an
aminoglycoside is usually indicated for serious enterococcal infections such as endocarditis
unless high-level resistance to both gentamicin and streptomycin is documented; such
combinations are predicted to result in synergistic killing of the Enterococcus
of therapy from the medical records of 500 randomly selected hospitalized patients
who received antimicrobials. While prescribed antimicrobials were appropriate in the
majority (62%) of the cases when the diagnosis was considered accurate on the basis
of clinical, radiologic, and laboratory ndings, anti-infective appropriateness was abysmal (5%) when the diagnosis was incorrect (66).
One way microbiology laboratories can signicantly impact diagnostic accuracy and
the quality of antimicrobial prescribing is by providing guidance in the preanalytic
phase, i.e., guidance for selecting the appropriate test or culture according to the
patients syndrome, obtaining optimal collection of clinical specimens, and interpreting
microbiology test results. Because poorly collected specimens may result in the recovery of commensal or colonizing organisms and are often rejected (99, 100), clinicians
need instruction in the appropriate timing and technique of specimen collection.
Common problems in the preanalytic phase include contamination of blood cultures,
urine cultures in asymptomatic patients, and the failure to use specic testing in
specic clinical syndromes (e.g., Legionella urinary antigen in community-acquired
pneumonia) (9). The American Society for Microbiology and the IDSA produced detailed guidelines for the laboratory diagnosis of ID, and these are a useful tool for both
clinicians and laboratorians as part of antimicrobial stewardship programs (99). Collaborating with other laboratories to optimize the pathway of specimens, as well as
minimize superuous cultures, can also be considered. One example is collaboration
with the biochemistry laboratory to use algorithmic pathways between urinalysis and
urine cultures that have been shown to reduce antibiotic consumption (101, 102).
Nurses must be included among the recipients of guidance on microbiological test
selection and specimen collection, as they also perform diagnostic tests or collect
culture specimens, sometimes without or before the physicians evaluation of the
patient. Thus, the role of nursing in accurate and standardized specimen collection
should be emphasized (43, 103, 104).
BIOMARKERS AND RAPID DIAGNOSTIC AND RAPID SUSCEPTIBILITY TESTING:
NEW TRADE WINDS MAY HELP YOU REACH YOUR DESTINATION
Biomarkers
The quest to nd a highly sensitive and specic and readily available and interpretable ID biomarker has spanned decadesand such a marker is the object of recent
highly promoted prize competitions but the perfect biomarker has yet to be found.
Accurate biomarkers could be a boon to antimicrobial stewardship programs by
providing more accurate infection diagnosis, suggesting the class of infectious agent
(bacterial, fungal, viral, etc.), monitoring clinical responses, and guiding the duration of
treatment (105107).
C-reactive protein was one of the only commercially available biomarkers until a few
years ago. It is widely used to monitor the clinical response in bacterial infections, but
high intra- and interindividual variability makes it difcult to use for diagnostic purposes (106).
Newer bacterial infection biomarkers, such as PCT, are used more and more frequently in hospital settings. PCT, a prohormone of calcitonin, is secreted by a number
of organs in response to bacterial but not viralinvasion/infection (107). Serum PCT
is detectable as soon as 4 h and peaks between 12 and 48 h after infection onset. Most
studies have focused on its use for respiratory infections and sepsis (108110), and data
support its use more often as an indicator to stop, rather to start, therapy. A Cochrane
review in 2012 of the use of PCT algorithms in acute respiratory infections found that
the median exposure to antimicrobials was reduced from 8 to 4 days without any
adverse impact on the mortality rate (109). Similar data were found in patients with
sepsis in intensive care units (110).
Five commercial PCT assays are currently approved by the FDA. More detailed
reviews have been published elsewhere (108111). Other potential bacterial biomarkers
in development include, but are not limited to, amyloid A, interleukin-10, liposaccharide binding protein, and nCD64 (106).
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However useful PCT and other biomarkers may be now or in the future, they cannot
replace microbiology analysis. It has been suggested that antimicrobial stewardship
team recommendations on the interpretation of biomarker results are required for
optimal use (112). Other challenges to biomarker use include cost, turnaround time
(optimal with point-of-care testing), limited data in special populations such as immunocompromised patients, physician variability in modifying antibiotics based on available results, and interpretation of intermediate results (105, 113). While signicant
benets might result from using biomarkers to guide antimicrobial therapy, multidisciplinary input from antimicrobial stewardship programs that include clinical microbiologists seems essential when developing local protocols for biomarker use.
While biomarker testing may not fall under the responsibility of microbiology
laboratories in many institutions, clinical microbiologists involvement is desirable given
their close ties to and ability to integrate this testing with the workow for other
relevant analyses, for example, respiratory virus panels.
Rapid Diagnostic Testing (RDT) and Rapid Antimicrobial Susceptibility Testing
The delayed results of traditional bacterial cultures and antimicrobial susceptibility
testing, which may take up to several days to obtain, remain one of the major barriers
to providing optimal therapy (84). This is especially important for severe infections such
as sepsis and septic shock, for which a delay in initiating effective therapy is a strong
predictor of death (114, 115). Emerging RDT methods include a large variety of
technologies and vary greatly in terms of complexity, price, speed, and the ability to
identify single or multiple pathogens.
The key to successful RDT is the twinning of these technologies to an antimicrobial
stewardship team that can notify clinicians about test results and guide their use in
initiating or modifying antimicrobial therapy, for without this link between clinical
microbiologists and antimicrobial stewardship, the rapid results run the risk of oating
adrift at sea (116). A meta-analysis by Buehler et al. found that for patients with
bloodstream infections, only rapid diagnostic techniques coupled with direct communication led to signicant differences in the time to effective or optimal therapy (117).
Most published studies have been performed in larger tertiary-care centers with
multiple resources and direct communication of results with guidance on management
and therapy provided by clinical pharmacists and/or physicians trained in ID (117, 118).
As technologies simplify and become available in more diverse settings, clinical microbiologists will need to collaborate closely with antimicrobial stewardship teams to
rapidly communicate results and to interpret their meaning. In our experience, implementation of such technologies and protocols is a team effort. In addition to directing
the laboratory-specic steps required to implement a new test, clinical microbiologists
must collaborate with the rest of the antimicrobial stewardship team to achieve a
consensus on the rules of usage and the presentation and interpretation of the results.
Clinicians should receive appropriate information and training before microbiology
laboratories go live with RDT, especially when multiplex platforms are used as large
amounts of information are available at one time. Clinicians training should include at
least information specic to the RDT method and the technology used, chosen indications for testing in the institution and available alternative testing strategy, advantages and limitations, turnaround time, presentation of the report, and guidance for
interpretation. Online sessions provided by professional societies may provide instruction on such topics. While there are multiple advantages to having results faster, clinical
microbiologists must guide clinicians in nding the optimal balance between accuracy
and rapidity in interpreting rapid diagnostic results.
There is also an ongoing search for a better tool to diagnose ID. The Longitude Prize
(https://longitudeprize.org/challenge/antibiotics), launched in 2014 by the United Kingdom and afliated private partners, will reward with 10 million a team able to build
a diagnostic tool that can rapidly rule out the need for antibiotic use or help identify
an effective antibiotic to treat a patient (64).
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The following paragraphs will review some of the most frequently used assays; more
extensive review articles that focus on newer technologies have been published
elsewhere (116, 117, 119121).
Bacterial and Fungal Molecular Assays
Molecular assays have been the main focus in the development of rapid diagnostic
technologies in recent years. While methods vary, most bacterial assays focus on critical
specimens such as blood cultures.
Peptide nucleic acid uorescent in situ hybridization (PNA FISH) is a simple molecular assay that requires few instruments and therefore can be used in diverse laboratories. Four panels are available for blood cultures: Enterococcus, Gram-negative bacteria, Candida, and Staphylococcus, the latter being the only one with resistance gene
(mecA) detection (121). Laud and Knudsen observed a greater proportion (98% versus
89%) of early appropriate therapy when PNA FISH was used to detect Staphylococcus
bacteremia (122). Other studies also found that use of this test was associated with
shorter lengths of stay and decreased overall costs (119, 123125).
The two main multiplex molecular PCR assays currently available in clinical practice
are Biores FilmArray System and Nanospheres Verigene System (119). The FilmArray
System presently offers four panels: respiratory, gastrointestinal, blood cultures, and
meningitis/encephalitis. The Verigene system has ve panels: respiratory, enteric pathogens, C. difcile toxins, and Gram-positive and Gram-negative bacteria from blood
cultures. Both systems are relatively easy to use, with short hands-on time, excellent
performance, and results available in 1 to 2.5 h (35, 119, 126).
Multiple studies have demonstrated important benets when these technologies
are combined with antimicrobial stewardship interventions. A large randomized study
by Banerjee et al. evaluated the performance and impact of the FilmArray System Blood
Culture Identication (BCID) panel in addition to antimicrobial stewardship interventions performed by a clinical pharmacist or an ID physician. Reduced use of broadspectrum antibiotics and less frequent treatment of blood culture contaminants were
observed; de-escalation was signicantly more successful with antimicrobial stewardship guidance, and the mortality rates and overall costs were similar in all groups (35).
In another study, 152 causative agents of bacteremia were identied by conventional
methods over a 1-month period and 115 (80.4%) were also correctly identied by BCID
(127).
In a quasiexperimental study, Sango et al. showed a reduction of 23.4 to 31.1 h in
the time to appropriate therapy and signicant reductions in the length of stay and
hospital costs when the Verigene System was used to rapidly identify Enterococcus
bacteremia; there was no difference in the mortality rate (118). Similar results were
obtained in community settings (128).
One important concern with multiplex assays is that they are less accurate in
detecting polymicrobial infections; thus, clinical microbiologists should consider this
possibility when single organisms are reported (35, 129). Detected resistance genes are
also limited in number and may not always correlate with phenotypic antimicrobial
susceptibility. Thus, risk factor assessment for resistance cannot be dismissed. On the
other hand, these molecular assays are extremely sensitive and may detect organisms
that would not generally be detected or considered clinically signicant by the current
gold standards of traditional microbiology. Laboratorians have had to deal with similar
situations regularly since the beginning of molecular testing (130). A higher detection
of skin contaminants in critical specimens may be challenging in many situations,
especially with critically ill patients or when supplementary cultures are not possible,
for example, pediatric patients or specimens collected during surgery. Detection of
colonizing rather than pathogenic strains of C. difcile also occurs frequently with
newer PCR-based assays (131, 132). Microbiology laboratories may want to put in place
strategies to identify, track, and analyze discrepant results, especially in the implementation phase of new tests. Interpretation of individual results should always be done in
the light of a clinical evaluation of the patient and other available results. We recomcmr.asm.org 394
mend that clinical microbiologists contact prescribers or coordinate responses with

antimicrobial stewardship teams in these situations, especially when discrepant results
are found in critical specimens, to guide the most appropriate therapeutic strategy.
When suspicion for infection is low and the patient is stable, a wait-and-see strategy
may be the best option.
Viral Molecular Assays
Respiratory viral infections, including inuenza, are common mimics of bacterial

syndromes that can lead to increased bacterial resistance when inappropriately
treated with antibiotics (133, 134). Multiple testing platforms with different technologies are available on the market and are reviewed elsewhere (120, 135137).
While they are recommended in the latest IDSA guidelines (42), most of the
evidence supporting the use of these assays is from pediatric studies. As with other
rapid diagnostic assays, positive viral tests cannot exclude bacterial super- or
coinfection and so may not be sufcient to convince prescribers to discontinue
antibacterials. In a study in North Carolina, discontinuation of antibacterials within
48 h following respiratory viral testing with or without PCT was observed in only 10
to 20% of the cases studied (138). In another study, more than a third of the patients
with a positive inuenza PCR test result were continued on antibiotics more than 24
h after the availability of the test result, suggesting that additional diagnostic
toolsan evaluation of the host response that could indicate the presence of a
bacterial, viral, or combined infection or interventions may be required to convince clinicians that antibiotic discontinuation is safe for these patients (139). If
used, ease of availability, rapid turnaround time, and prompt notication of results
are essential for promoting appropriate antiviral therapy and timely discontinuation
of antibacterials when not otherwise indicated (140).
MALDI-TOF MS
Matrix-assisted laser desorption ionizationtime of ight mass spectrometry (MALDITOF MS) can accurately identify a large range of pathogens such as bacteria, yeasts,
lamentous fungi, and mycobacteria in as little as a few minutes (141143). Equipment
acquisition costs might be quite high, but the cost per individual test can be as low as
$0.41 per sample (144). While conceived for use on isolates grown in routine cultures,
protocols for testing specimens directly are commercially available and await FDA
clearance (143). Rapid identication with MALDI-TOF MS was also shown to reduce the
time to appropriate therapy in 11% to 44% of the cases (34, 145) and to increase the
Acinetobacter baumannii infection clinical cure rate by 19% (146). Given the fact it can
signicantly simplify workow, MALDI-TOF MS is a reasonable consideration for smaller
community institutions. A recent study reported average savings of $3,411 in hospital
costs along with a reduced time to appropriate therapy when MALDI-TOF was coupled
with a pharmacist intervention for bloodstream infections in two community hospitals
in Texas (147)nicely illustrating the results of successful collaboration between
clinical microbiology and antimicrobial stewardship.
Old and New Antimicrobial Susceptibility Testing
Currently available rapid susceptibility tests are limited to the detection of a few
specic genes associated with resistance or treatment failure (e.g., mecA in Staphylococcus aureus or blaKPC in Enterobacteriaceae). Therefore, MIC determination by
standard procedures is still often required. Rapid-result protocols using standard
technologies such as disk diffusion and microdilution have been described mostly
for critical specimens such as blood cultures (148151). These direct methods have
shown relatively high categorical agreement with standardized methods but usually require additional labor-intensive steps, with repeat standardized susceptibility
testing usually recommended when growth is sufcient (148). It is worth noting that
more rapid automated antimicrobial susceptibility tests may have pitfalls. For
example, the MICs of vancomycin for S. aureus were reported to be over- or
cmr.asm.org 395
FIG 1 Workow pathways for conventional microbiology and RDT. Implementation of RDT increases laboratory workow complexity
but can hasten the availability of results. Communication of results is a key factor. Blue arrows represent the conventional
microbiology pathway, orange arrows represent the RDT pathway, and green arrows represent opportunities for the laboratory and
antimicrobial stewardship teams to improve communication of results. AST, antimicrobial susceptibility testing.
underestimated by automated microdilution systems. Death, however, correlated

better with MICs determined by disk diffusion and gradient diffusion (91). While
controversial, higher vancomycin MICs may trigger prescribers to use alternative
drugs such as daptomycin, linezolid, or ceftaroline that can be more costly, more
toxic, and even less effective, depending on the clinical syndrome (152). Reex
protocols to conrm MICs coupled with specic comments, cascade reporting,
and/or therapeutic algorithms may lead to more appropriate use of vancomycin
and daptomycin and demonstrate cost savings (153).
Additional rapid antimicrobial susceptibility technologies are under development,
including automated digital microscopy in real time, ow cytometry, laser scatter, and
magnetic resonance (154, 155). An early study with automated digital microscopy in
real time speculated that the technology may impact therapies 40% of the time (155).
Whole-genome sequencing also has shown some promise, e.g., in Mycobacterium
tuberculosis (156, 157).
RDT Bottom Line
RDT evolves quickly, and many of the RDT methods discussed in this review may be
obsolete in as little as a few years. The multiplicity of newer diagnostic approaches,
tests, and platforms makes clinical microbiologist collaboration with antimicrobial
stewardship programs essential to determine which tests are right for an institution and
how best to implement and guide the interpretation of them, given the variation in the
tests performance characteristics and, just as likely, in clinicians perceptions of them.
Figure 1 summarizes the contributions and relationships of RDT in the workow
pathway. For the time being, the limitations of these tests mean that they can
supplement but not yet supplant conventional microbiological methods.
In the end, the complexity and all of the nuances of clinical microbiology testing
might make ordering testing by a xed combination of tests specic for each diagnoJanuary 2017 Volume 30 Issue 1
cmr.asm.org 396
sis e.g., a provider orders testing for community-acquired pneumonia rather than
list all of the specic tests easier for many providers. This new way of ordering tests
could represent a sea change in most hospitals and would require close cooperation of
clinical microbiologists, ID physicians, and pharmacy staff and careful monitoring for
changing susceptibility patterns.
PROVIDER EDUCATION: HOW TO TIE THE KNOTS

Informational interventions such as provider education have been found to be less
effective than coercive interventions in improving antibiotic prescribing in the short
term, but those differences become nonsignicant after interventions have been
implemented for many months (13). Because the sustainability of the effect of educational interventions is usually low, especially when work forces change over short
intervals, as in teaching hospitals, continuous education is considered essential to any
antimicrobial stewardship program (7, 42, 158). Clinical microbiologists are experts on
a multitude of subjects related to antimicrobial stewardship, such as resistance mechanisms, pathogen interaction with the environment, diagnostic testing, and interpretation of susceptibility reports (159). Their daily decisions as experts in laboratory
diagnostics impact clinicians interpretation of tests and inuence patient care. However, the tasks and purposes of clinical microbiologists may not always be fully
understood by clinicians (158). Thus, we strongly encourage the participation of clinical
microbiologists in designing and delivering antimicrobial stewardship-related teaching,
which is ideally multimodal, including rounds and conferences but also staff bulletins
and management guidelines (160, 161). To be maximally effective, the clinical microbiologist should visit the ward at least occasionally, in addition to providing educational
sessions at physician and staff conferences.
Clinical microbiologists collaboration with antimicrobial stewardship teams and
other clinicians can lead to benets that are multidirectional. Education sessions
provide excellent opportunities to gauge service satisfaction and suggest potential
avenues for improving laboratory services while teaching clinical microbiologists about
formularies, guidelines, order forms, and other tools in use or under development at
their institution, with resultant ideas for collaborating or for adjusting laboratory
services to better serve the needs of prescribers. For example, quinolones are no longer
recommended as rst-line agents for the treatment of uncomplicated urinary tract
infections, for which older agents such as nitrofurantoin and fosfomycin are now being
used, leading to the need to update urine susceptibility testing (162). Helpful changes
in reex or cascade reporting may also be triggered by feedback gleaned from such
interactions.
In addition to publishing the online and/or paper CASR, it also might be benecial
to provide a presentation letter or small conference on a yearly basis to highlight major
changes and indicate to prescribers how to use the CASR. The CLSI also suggests
supplementary methods for presenting the CASR, such as graphics and tables (70).
Different topics can be covered in education sessions. Some of the most relevant from
a clinical microbiology perspective are guidance in the preanalytic phase for optimal
specimen collection, antimicrobial resistance issues (mechanisms, laboratory testing,
therapies, etc.), interpretation of antimicrobial susceptibility reports, antimicrobial resistance surveillance and interpreting CASR annual updates (including infection control
and epidemiology), improving clinicians microbiologic literacy, pathogen-specic
diagnosis and management (including emerging pathogens), use of new technologies
and biomarkers in the institution, updates on testing and interpretation of clinical
microbiology testing, and research opportunities and collaborations.
The Cochrane Collaborative performed a meta-analysis of 89 studies on interventions to improve antibiotic practices for inpatients. They found that coercive interventions such as requiring preauthorization of restricted antibiotics or targeting certain
antibiotics for specic indications were more rapidly effective than informational
interventions such as prescriber education and audit and feedback (13). However, after
cmr.asm.org 397
6 months, the educational and audit/feedback interventions were as effective as the

up-front restrictive or targeted interventions (13).
Because lack of awareness and familiarity is an important factor that inuences
adherence to medical guidelines, education about the basis of the guidelines is a fairly
easy response to this problem (163). However, standard teaching methods focus mainly
on increasing the knowledge of participantswithout operationalizing that knowledgeand may not always translate to changes in behavior (158).
Antimicrobial stewardship currently receives relatively little attention in medical,
nursing, and pharmacy school curricula. Emerging programs are focused mostly
on advanced trainees like residents and fellows and practicing clinicians and
pharmacists (http://mad-id.org/antimicrobial-stewardship-programs/, http://www.sidp
.org/page-1442823). Many of these programs include rudimentary training in clinical
microbiology and antimicrobial resistance, but the participation of clinical microbiologists in such programs is limited. Recently published Doctor of Pharmacy student
elective curricula include teaching and/or laboratory skill sessions with a clinical
microbiologist (164, 165). The success of antimicrobial stewardship in a given institution
derives partly from the presence of a culture of antimicrobial stewardship, i.e., the
general impression that a better use of antimicrobials is necessary and benecial for all
of the participants of the institution. Clinical microbiologists have a great deal to offer
in developing and maintaining such a culture.
Multiple resources in diverse formats now exist to educate providers. In a world
where lack of time is the new normal, new ways to reach clinicians that offer more
exibility and interactivity might also help. Many states and hospitals provide
online antimicrobial stewardship toolkits with educational material that can be
used, for example, the California Department of Public Health (http://www.cdph
.ca.gov/programs/hai/Pages/AntimicrobialStewardshipProgramInitiative.aspx) and Nebraska Medicine (Omaha, NE). Massive online open courses (MOOC) and e-learning
tools may also be part of the solution (166). One example is the largely publicized
MOOC Antimicrobial Stewardship: Managing Antibiotic Resistance (http://www
.dundee.ac.uk/study/short/antimicrobial-stewardship/) offered by the University of
Dundee (Dundee, United Kingdom) and the British Society of Antimicrobial Chemotherapy (Birmingham, United Kingdom). This free 6-week online course provides participants the opportunity to develop skills and carry out interventions that underpin
antimicrobial stewardship, learning to promote responsible prescribing and to reduce
practice variation, waste, and harm from antibiotic overuse and misuse.
Communication methods have evolved quickly in recent years and are focused on
short and efcient messages. Facility with these new tools has the potential to reach a
maximum of prescribers and to trend some institutional messages. E-mail inboxes ll
quickly with information often unread by many. Social media, such as Facebook,
Instagram, YouTube, Snapchat, and Twitter, are now commonly used by clinicians,
hospitals, health agencies, and organizations to track diseases, raise awareness of the
public about health issues, quickly disseminate information, and engage health care
professionals (167). The CDC provides guidance and best practices on the use of social
media with a dedicated website (http://www.cdc.gov/socialmedia/index.html), and two
recent articles reviewed the power and potential of Twitter and Instagram for the
practice of microbiology and ID medicine and listed multiple accounts of interest (168,
169).
An important element of antimicrobial stewardship is how to effectively change
prescribers behavior to achieve positive and durable outcomes while respecting their
autonomy. The use of clinical guidelines was shown to have limited effects on prescribers behavior when no other interventions were coupled with them (163). Common
barriers include lack of knowledge, insufcient resources, adverse attitudes and beliefs,
and lack of time that may be specic to individuals or local practices or widespread
among prescribers (158, 163). The potential ability of microbiology laboratories to alter
this dynamic favorably is certainly worth exploring.
cmr.asm.org 398
ALERT AND SURVEILLANCE SYSTEMS: SOUNDING THE ALL-HANDS-ON-DECK

ALARM
Surveillance is dened as the ongoing and systematic collection, analysis, and interpretation of health data essential to the planning, implementation, and evaluation of public
health practice (170). Surveillance can be passive (with detection via normal laboratory
pathways or workow and alerting on an individual basis) or active (when specic targets
are followed by informatics models and processes and acted upon when thresholds are
crossed) (170). Most hospital laboratories already participate in some surveillance programs.
The Centers for Medicare & Medicaid Services requires reporting of multiple health careassociated infections, such as S. aureus bacteremia or C. difcile infections (171), on which
microbiology laboratories must collaborate with infection control teams on a regular basis.
Public health departments around the country also require laboratories to report certain
pathogens and outbreaks. In both instances, reporting can be complex and automatization
is not always seamless (91). While these surveillance systems are important for understanding the regional and national epidemiology of these pathogens and to dene national
objectives, we will focus on more local approaches for surveillance of resistant organisms
in the context of antimicrobial stewardship.
Microbiology laboratories deal with a large volume of information every day. Surveillance and alert systems need to be designed to digest the information and to make it easy
to interpret and analyze for antimicrobial stewardship personnel and clinicians (88). On the
other hand, if nobody analyzes or acts on the information generated, it is reasonable to
question the usefulness of the data. Therefore, microbiology laboratories, in collaboration
with other antimicrobial stewardship team members, must choose wisely what information
to report, when to report it, and what information it is no longer necessary to report.
Relevant microbiology information, appropriate for inclusion in antimicrobial stewardship
team alerts, includes positive results (stain[s], detection, culture, etc.) in critical specimens
such as normally sterile uids (blood, cerebrospinal uid, etc.); identication of specic
pathogens that require rapid intervention, such as C. difcile or M. tuberculosis; and specic
resistant patterns, such as carbapenem-resistant Enterobacteriaceae or vancomycinresistant Enterococcus spp. (172, 173).
Critical Specimens
As a patient safety measure, alerts to prescribers concerning positive results obtained with critical specimens are usually handled by protocols in microbiology laboratories. Antimicrobial stewardship interventions performed when these results become available may impact clinical outcomes (115). The value of such alerts has been
demonstrated with blood culture results in combination with RDT (35, 127) and for
specic pathogens such Candida spp. and S. aureus (174, 175). Pogue et al. evaluated
an automated alert system coupled with an antimicrobial stewardship intervention in
which pharmacists were alerted in real time when blood cultures turned positive during
business hours; they then reviewed charts and provided therapy recommendations.
Reviews and recommendations were delayed to the next weekday morning when
blood cultures turned positive at night or on weekends. Compared to historical controls
where only prescribers were alerted, they found a signicantly reduced time to
appropriate therapy, length of stay, and infection-related mortality rate in patients with
bacteremia (176). Similar results were also found in different settings without automated alert systems (177). Microbiology laboratories can and should participate in
developing enhanced alert protocols for high-risk infections that facilitate timely
treatment recommendations.
Of note, nurses because they frequently answer the phonesare often the rst
professionals to be aware of critical microbiology results in both outpatient and
inpatient settings, making them an essential link in the chain for the timely administration of optimal therapy (103, 104). Thus, antimicrobial stewardship teams and clinical
microbiologists should ensure that nurses are aware of, and educated about, the
meaning of these alerts and their implications.
cmr.asm.org 399
Resistant Pathogens
Detection of resistance mechanisms in clinical laboratories is controversial. For

example, the CLSI does not require screening for extended-spectrum -lactamases
since breakpoints for cephalosporins were lowered in 2010, unless it is required for
epidemiological purposes (89, 90). The CLSI lists intrinsic resistance and suggestions for
conrmation when uncommon or concerning phenotypes are detected (90). Unusual
resistance usually requires investigation and repeat testing to conrm results and
exclude clerical, technical, or contamination errors (90). Laboratories should send key
resistance isolates for conrmation and alert public health authorities promptly when
such results are suspected. It is also necessary to inform clinicians about possible delays
in result reporting and advise on alternative therapies while results are pending.
To stop or slow down the emergence of resistance is a goal of antimicrobial
stewardship activities. Tracking rates of resistance can also be useful to demonstrate
successes of antimicrobial stewardship programs; though antimicrobial consumption
metrics are preferred by recent guidelines, resistance trends provide evidence of
patient care impact (42). Antimicrobial resistance rates are impacted by multiple factors,
including population factors, immunosuppression, infection control measures, use of
antibiotics outside the inpatient setting, and others (178). Elligsen et al. (20), in a
controlled interrupted time series analysis of audit and feedback for the use of
broad-spectrum antibiotics in intensive care units, showed a modest but signicant
increase in meropenem susceptibility in Gram-negative isolates after the intervention
from 78.2 to 83.4% over a 1-year period. To do so, they included the rst isolate of each
patient in the study period but also included repeated inpatient isolates if patterns of
susceptibility to broad-spectrum agents varied, to avoid omitting hospital-acquired
strains. Others have focused on specic resistant pathogens, such as vancomycinresistant Enterococcus spp. and methicillin-resistant S. aureus (MRSA) (179) or specic
pathogen-antimicrobial combinations (21). Laxminarayan and Klugman developed a
drug resistance index that aggregated resistance to multiple antibiotics into an index
similar to stock markets and is intended for much larger populations than hospitals
(180). Such disparate efforts and the current absence of standardized methods illustrate
the challenges in assessing the impacts of antimicrobial stewardship interventions on
antimicrobial resistance (181).
IT systems used in microbiology laboratories are diverse, with multiple systems
often in use in a single facility. Some creative IT solutions for advanced clinical decision
support systems and reporting algorithms developed more than 20 years ago have
shown success (182). Along with electronic health records, multiple platforms are now
available to help antimicrobial stewardship teams and were reviewed recently (183).
These programs harness extensive information sources (patient information, pharmacy,
and microbiology and other laboratories, etc.) to support a large array of tasks from
clinical diagnosis to choice of therapy and may support antimicrobial stewardship
strategies, such as audit and feedback, formulary authorizations, clinical pathways, and
de-escalation protocols. Timely integration of results is thus extremely important to
ensure the attainment of their full potential. The popularity of these data mining tools
is increasing, especially in larger institutions, but complex and rapid evolution of
resistance patterns and clinical standards necessitates frequent evaluation and updating of these systems, whose high costs and resource intensity also impede widespread
use (91, 184). Using clinical decision support systems to their full potential may require
time to develop meaningful and actionable alerts, and the clinical microbiologist is
essential to the successful use of advanced IT applications for antimicrobial stewardship
programs. These alerts might be the most useful for critical results such as positive
blood cultures or when a mismatch between ongoing therapy and a susceptibility
report is detected. This may, however, require more complex programming and
interfacing, thus emphasizing the role of IT personnel in antimicrobial stewardship
teams.
cmr.asm.org 400
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MICROBIOLOGY AT SEA: SAILING INTO THE SUNSET OR RETURNING TO

HARBOR?
Clinical microbiology seems at a crossroads. On the one hand, questions about the
cost-effectiveness and clinical utility of traditional microbiological methods and the
pressure to cut costs have led to the outsourcing of many hospital microbiology
laboratories to off-site commercial or centralized laboratories, thereby increasing the
isolation of clinical microbiologists from their clinician colleagues and consigning them
to increasingly technical roles (64, 185). On the other, the crisis of antimicrobial
resistance and the resultant need to optimize clinical infection management, manifested by the widespread emergence of antimicrobial stewardship programs (186), and
the recent proliferation of innovative rapid diagnostic methodswith their attendant
uncertainties with respect to instrument selection, performance characteristics, deployment and work ow, costs, interpretive guidance, and rapid technological turnover
could boost the clinical relevance of clinical microbiologists to levels unseen since the
time of Koch and Pasteur. As clinicians long immersed in the practice and teaching of
ID and antimicrobial stewardship, we are certain that this distancing of microbiology
laboratories has deprived bedside medicine of a critical source of nuanced expertise,
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themselves in patient care. In part, this review is intended to offer a roadmap by which
this can occur as part of antimicrobial stewardship program development.
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Philippe Morency-Potvin obtained his medical

degree from the Universit Laval in Qubec City
in 2009. He completed his training in medical
microbiology and ID at the Universit de Montral, where he graduated in 2014. He is currently in a 2-year fellowship in antimicrobial
stewardship at the Rush University Medical
Center and the John H. Stroger, Jr. Hospital of
Cook County in Chicago under the supervision
of Dr. David Schwartz. Upon completion in
2017, he will return to the Centre Hospitalier de
lUniversit de Montral, where he will practice as a microbiologist and ID
physician and will lead the institutions antimicrobial stewardship team.
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David N. Schwartz, since completing his training in 1993, has worked as an attending physician at Cook County Hospital (now the John H.
Stroger, Jr. Hospital of Cook County) in Chicago, where he became the chair of the Division
of Infectious Diseases in 2008, and he has been
on the faculty of nearby Rush Medical College.
Dr. Schwartz has chaired the Cook County
Hospital Anti-Infective Committee and supervised its antimicrobial stewardship efforts since
1994. He and his colleagues have collaborated
on research with the U.S. CDC since 1999, focusing on the design and implementation of interventions to improve antimicrobial use and to refine
antimicrobial measurement in hospitals. He has presented research and spoken on these topics at national meetings and has served as a consultant to
antimicrobial stewardship collaboratives sponsored by the Illinois Department of Public Health since 2011.
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L, Nagel JL. 2013. Impact of an antimicrobial stewardship program
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Lpez-Corts LE, Del Toro MD, Glvez-Acebal J, Bereciartua-Bastarrica E,
Robert A. Weinstein is the C. Anderson Hedberg Professor of Medicine, Rush Medical Center, the Chairman of Medicine Emeritus, Cook
County Hospitals System, and the Founding
Chief Operating Officer, Ruth Rothstein CORE
Centerall in Chicago. Dr. Weinsteins research interests include healthcare-associated
infections, antimicrobial resistance, and infections in intensive care units. Dr. Weinstein is
past president of the SHEA and past chair of the
CDC Healthcare Infection Control Practices
Advisory Committee. Dr. Weinstein currently serves on the CDC Board of
Scientific Counselors and on the Presidential Advisory Council Combating
Antimicrobial-Resistant Bacteria.
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Philippe Morency-Potvin,a,b,c David N. Schwartz,a,b Robert A. Weinsteina,b

Published 14 December 2016

KEYWORDS antimicrobials, antimicrobial stewardship, microbiologist, optimal use,

Clinical Microbiology Reviews

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