The Febrile Infant 29 To 90 Days of Age Management UpToDate
The Febrile Infant 29 To 90 Days of Age Management UpToDate
The Febrile Infant 29 To 90 Days of Age Management UpToDate
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INTRODUCTION
The outpatient evaluation of febrile infants younger than 90 days of age; the
definition of fever in the young infant; the diagnosis, evaluation, and initial
management of fever and early-onset sepsis in neonates (younger than seven
days of age); and the approach to an ill-appearing infant are discussed
separately:
Fever — Rectal temperatures are the standard for detecting fever in infants
younger than three months of age, and most studies establishing the risk of
serious infections in febrile young infants have relied upon rectal temperatures.
We regard a rectal temperature of ≥38°C (100.4°F) as fever in infants ≤90 days of
age. (See "The febrile infant (younger than 90 days of age): Definition of fever",
section on 'Definition of fever'.)
Invasive bacterial infection — For this topic, invasive bacterial infection (IBI)
refers to bacteremia or meningitis.
MANAGEMENT
The age and the results of initial ancillary studies stratify the level of risk for
invasive bacterial infection (IBI; bacteremia or meningitis) and determine the
management of febrile young infants 29 to 90 days old.
Well-appearing
Infants 29 to 60 days old — In accordance with the 2021 American Academy of
Pediatrics Clinical Practice Guideline (AAP CPG), our approach is to manage well-
appearing febrile infants 29 to 60 days old without a focal infection on
examination based upon the level of risk for IBI (bacteremia or meningitis)
( algorithm 1). (See "The febrile infant (29 to 90 days of age): Outpatient
evaluation", section on '29 to 60 days old'.)
Because of the higher risk for IBI, infants 29 to 60 days of age with
significant comorbidities (eg, congenital disease, prematurity, or
technology dependence), CSF pleocytosis, or a finding on chest radiograph
(if obtained) suggesting a bacterial pneumonia require admission to a
hospital with nurses and staff experienced with young infants [2].
Many physicians may also prefer to admit infants with historical risk factors
( table 1) or abnormal inflammatory markers ( table 3) pending blood
and CSF culture results [1]. For patients with a single risk factor of antibiotic
therapy in the past three days, an alternative approach is to give a single
dose of intramuscular (IM) ceftriaxone (50 mg/kg) and discharge the patient
to home with ensured follow-up within 24 hours for a second IM dose of
ceftriaxone, pending culture results.
For patients who have positive and highly accurate CSF testing for
enterovirus (eg, reverse transcriptase polymerase chain reaction [RT-PCR])
and no other findings suggesting bacterial infection (including any
abnormal inflammatory markers), antibiotics may be discontinued [1]. (See
"Enterovirus and parechovirus infections: Clinical features, laboratory
diagnosis, treatment, and prevention", section on 'Laboratory diagnosis'.)
● Risk factors for IBI – For infants 29 to 60 days old, lumbar puncture for
testing (if not already performed), empiric parenteral antibiotics, and
hospital admission to a unit with nurses and other staff experienced with
young infants are warranted if any one of the following are present:
● Without risk factors for IBI – We suggest that otherwise low-risk, well-
appearing infants 29 to 60 days old with abnormal urine studies receive
oral antibiotics and close follow-up as an outpatient. These patients should
have normal inflammatory markers, and no other risk factors for IBI
( algorithm 1). Treatment is guided by local prevalence and patterns of
resistance to Escherichia coli. Some physicians may choose to give the first
dose of antibiotic parenterally prior to discharge. Some experts admit these
patients for parenteral antibiotics. (See "Urinary tract infections in infants
older than one month and young children: Acute management, imaging,
and prognosis", section on 'Oral therapy' and "Urinary tract infections in
infants older than one month and young children: Acute management,
imaging, and prognosis", section on 'Parenteral therapy'.)
Preliminary urine studies that suggest a UTI, such as a positive dipstick for
nitrites and leukocytes, uncentrifuged sample with a positive Gram stain or >10
WBCs/mm3, or centrifuged sample with >5 WBCs/high-power field, do not
necessarily indicate a higher risk for bacterial meningitis in well-appearing
infants [4-6]. In addition, sterile CSF pleocytosis (usually fewer than 20
cells/microliter), occurs in up to 29 percent of infants with a UTI, which may
complicate hospital management and lead to unnecessary and prolonged
antibiotic therapy for patients who undergo a lumbar puncture for this indication
[5,7,8]. Thus, many experts recommend not obtaining CSF in these patients if
they are otherwise at low risk and regardless of results of inflammatory markers
[6,9-11]. If the provider feels that CSF should be obtained, this should be a
shared decision with the family after discussing risks and benefits of the
procedure and incorporating their values and preferences. (See "The febrile
infant (29 to 90 days of age): Outpatient evaluation", section on '29 to 60 days
old'.)
Timely imaging to identify urinary tract abnormalities is also warranted in follow-
up for infants with a UTI. The type of study and timing for performance are
discussed separately. (See "Urinary tract infections in infants older than one
month and young children: Acute management, imaging, and prognosis",
section on 'Imaging'.)
Low risk for IBI — For low-risk, well-appearing febrile infants 29 to 60 days
old, we suggest close observation as an outpatient without antimicrobial therapy
( algorithm 1). Low-risk findings include:
Reliable follow-up must be arranged within 24 hours (by return visit to the
treating physician or primary care provider). If the social situation suggests that
follow-up within 24 hours is problematic (eg, transportation problems, no phone,
inability to assess severity of illness, or other concerns regarding parental
adherence), then the infant should be admitted to the hospital for observation.
Some experts suggest that infants who are followed as outpatients receive
empiric treatment with IM ceftriaxone (50 mg/kg in a single dose) pending
culture results. Observational evidence suggests that the risk of IBI in this
population is approximately 0.4 to 1.4 percent [2,12]. Thus, approximately 71 to
250 infants would need to receive empiric antibiotics to prevent delayed
treatment of one case of bacteremia or meningitis [2]. However, delayed
treatment is unlikely with automated blood culture techniques [1].
Because over 10 percent of ill-appearing young infants may have IBIs [3,21,22],
such infants should undergo the following treatment:
● Identify and treat septic shock – Many ill-appearing infants have sepsis
and require resuscitation according to the 2020 Surviving Sepsis Campaign
international guidelines ( algorithm 2). (See "Septic shock in children:
Rapid recognition and initial resuscitation (first hour)", section on 'Rapid
recognition' and "Septic shock in children: Rapid recognition and initial
resuscitation (first hour)", section on 'Resuscitation'.)
● Identify and treat other causes of ill appearance – Other causes of ill
appearance in addition to sepsis include congenital heart disease,
congenital adrenal hyperplasia, inborn errors of metabolism, malrotation
with volvulus, or a variety of causes. Infants with clinical manifestations
suggesting a diagnosis other than or in addition to serious infection
warrant additional studies based upon specific findings as discussed
separately. (See "Approach to the ill-appearing infant (younger than 90 days
of age)", section on 'Evaluation' and "Approach to the ill-appearing infant
(younger than 90 days of age)", section on 'Targeted Evaluation'.)
• 29 to 60 days of age:
- Add acyclovir for those infants with vesicular rash and/or laboratory
findings suggestive of HSV infection (eg, elevated liver enzyme
studies), which is unusual beyond four weeks of age and exceeding
unlikely beyond six weeks (see "Neonatal herpes simplex virus
infection: Clinical features and diagnosis", section on 'Clinical
manifestations' and "Neonatal herpes simplex virus infection:
Clinical features and diagnosis", section on 'Evaluation and
diagnosis')
• 61 to 90 days of age:
Viral infections
Herpes simplex virus — Febrile young infants with clinical findings that
suggest HSV infection ( table 6) or a maternal history of active genital lesions
at birth should undergo a full sepsis evaluation, receive empiric acyclovir and
antibiotics, and be admitted to the hospital. For an otherwise well-appearing
infant >28 days old with CSF pleocytosis (mononuclear cell predominant) and no
other risk factors or clinical findings for/signs of HSV infection, we typically do
not give acyclovir. (See "Neonatal herpes simplex virus infection: Management
and prevention", section on 'Initial antiviral therapy'.)
Appropriate testing for HSV should be obtained before the initiation of acyclovir,
whenever possible. Testing for HSV infection is discussed in greater detail
separately. (See "Neonatal herpes simplex virus infection: Clinical features and
diagnosis", section on 'Detection of HSV'.)
A positive blood PCR for enterovirus may also be associated with a reduced risk
of IBI in febrile young infants. For example, in a secondary analysis of a single-
center registry that included over 700 febrile infants ≤90 days old with blood PCR
testing for enterovirus, none of the 174 infants with a positive test had an IBI (0
percent, 95% CI 0-2.1 percent) compared with 2.6 percent (95% CI 1.5-4.4
percent) of infants with a negative test [25]. Approximately 25 percent of positive
blood PCR tests occurred outside of the typical enteroviral season. These findings
suggest that blood PCR for enterovirus along with clinical findings and other
tests may be helpful in determining the risk of IBI in febrile young infants and
guide management decisions. However, confirmation in a large multicenter
study is necessary before this testing becomes routine.
Other viruses — Testing panels for other viral pathogens such as human
rhinovirus, adenovirus, non-SARS-CoV-2 coronavirus, parainfluenza, and/or
human metapneumovirus exist but are not always readily available and may be
cost prohibitive depending upon the setting. Evidence suggests that IBI is less
common in febrile young infants with positive PCR testing for these respiratory
viruses but not to the extent that the evaluation or management should be
different after consideration of age, appearance, other risk factors, and, if
obtained, inflammatory markers. (See "The febrile infant (29 to 90 days of age):
Outpatient evaluation", section on 'PCR positive for other viral infections'.)
Focal bacterial infection (pneumonia, skin, breast, bone, or joint) — The
physician should tailor the diagnostic evaluation based upon the specific focal
infection. The evaluation of febrile young infants with focal infection is discussed
separately. (See "The febrile infant (29 to 90 days of age): Outpatient evaluation",
section on 'Focal infection'.)
Febrile young infants with a focal infection should receive an empiric antibiotic
regimen designed to cover perinatal pathogens and organisms commonly
associated with the specific focal infection and be hospitalized. For those not
familiar with the treatment of these infections in young infants, consultation with
a pediatric infectious disease specialist is encouraged.
Our suggested initial empiric regimens by type of focal infection are as follows:
Acute otitis media — Well- appearing febrile infants 29 to 90 days old with
acute otitis media should receive treatment based upon their age, risk for IBI,
and the results of the initial evaluation. (See "The febrile infant (29 to 90 days of
age): Outpatient evaluation", section on 'Acute otitis media'.):
● Elevated risk of IBI or suspected UTI – For patients with findings that
make them at elevated risk for IBI or who have abnormal urine results,
management is based upon age as described above for infants 29 to 60
days old (see 'Increased risk for invasive bacterial infection' above and
'Suspected urinary tract infection' above) and for infants 61 to 90 days old.
(See 'Infants 61 to 90 days old' above.)
● Low risk for IBI – For patients at low risk for IBI based upon lack of IBI risk
factors at all ages and, in infants 29 to 60 days old, results of initial studies,
we suggest outpatient management with oral antibiotics to treat otitis
media (eg, amoxicillin) with close follow-up pending culture results. (See
'Low risk for IBI' above and 'Infants 61 to 90 days old' above and "Acute
otitis media in children: Treatment".)
For all patients, outpatient treatment of young infants with acute otitis media
must include extensive parental counseling regarding warning signs of more
serious infection and close follow-up. The repeat evaluation should ensure that
the fever resolves by 48 hours and that the patient remains well appearing.
Special situations
Further management is based upon culture results and whether CSF was
obtained during initial evaluation:
After initial treatment, the infant with a traumatic lumbar puncture who has
done well and has negative blood, urine, and CSF cultures at 48 hours
typically does not require a repeat lumbar puncture. Infants receiving
acyclovir for possible HSV should receive treatment until all HSV cultures
and/or PCR are negative. (See "Neonatal herpes simplex virus infection:
Clinical features and diagnosis", section on 'Viral culture'.)
OUTPATIENT FOLLOW-UP
Well-appearing infants 29 to 90 days old who are sent home must have follow-up
in a clinical setting within 24 hours at which time preliminary culture results (if
available) are reviewed. Further treatment should be based upon clinical
presentation, laboratory features, and culture results.
Infants who are no longer febrile and a normal physical examination may
continue to be observed as an outpatient until culture results are final as can
well-appearing febrile infants who have a documented viral source (eg,
respiratory syncytial virus [RSV] bronchiolitis or influenza).
For an infant 29 to 90 days of age with a positive urine culture who is afebrile and
well-appearing less than 24 hours after parenteral ceftriaxone, options include a
second dose of parenteral ceftriaxone at 24 hours or initiation of oral antibiotics
and continued outpatient follow-up. (See "Urinary tract infections in infants older
than one month and young children: Acute management, imaging, and
prognosis", section on 'Antibiotic therapy'.)
Patients sent home before bacterial cultures have been negative for 48
hours must have follow-up within 24 hours either by phone or by visit, at
which time preliminary culture results are reviewed. If antibiotics were
given in the hospital and diagnostic testing does not identify a viral
etiology, then the child should receive an additional dose of antibiotics (eg,
ceftriaxone 50 mg/kg daily) until all cultures are final and negative.
● Febrile and well-appearing – For some admitted infants, fever may persist
after cultures are negative at 48 hours. For the patient whose clinical
condition has improved, a period of observation in the hospital off
antimicrobial therapy is a reasonable option. The child who remains ill or
who does not improve as expected should be carefully re-evaluated, and
further testing, consultation, and treatment options should be pursued.
Use of early discharge criteria has been associated with reduced length of stay
without an increase [13]. As an example, implementation of a care plan that
permitted discharge at 24 hours for infants 29 to 90 days old with positive viral
testing for enterovirus or respiratory viruses, other than rhinovirus (eg, RSV,
influenza), and negative bacterial cultures or discharge at 36 hours if both viral
testing and bacterial cultures were negative, resulted in a clinically significant
decrease in length of stay across a large hospital system without an increase in
readmissions for bacterial illness.
The 2021 American Academy of Pediatrics Clinical Practice Guideline (AAP CPG)
for evaluation and management of well-appearing febrile infants 8 to 60 days of
age provides a summary of the evidence and multidisciplinary consensus
guidance [1].
The use of evidence-based clinical practice guidelines (CPGs) can help
standardize care among individual physicians and various institutions. As an
example, outcomes for well-appearing febrile infants cared for in four hospitals,
including a children's hospital, were assessed before (over 4500 febrile episodes)
and after (almost 3000 febrile episodes) the implementation of an evidence-
based care process model (EB-CPM) that was derived from the Rochester Criteria
( table 11) [13,32]. EB-CPM implementation was associated with significantly
increased adherence to recommended diagnostic testing (13 percent increased
measurement of complete blood count, urinalysis, and blood and urine culture; 8
percent increase in viral testing for admitted infants) and recommended
antibiotic selection (15 percent increased use of recommended antibiotics), a 16-
hour decrease in hospital length of stay for admitted patients, and a significantly
lower cost per admitted infant.
However, when evidence is still evolving and not definitive, CPGs that promote
additional testing in febrile infants may not always have an associated clinical
benefit. For example, in a large administrative database study that evaluated the
outcomes of over 49,000 febrile infants 29 to 56 days of age, 65 percent of
infants treated in hospitals with CPGs recommending routine cerebrospinal fluid
(CSF) testing underwent lumbar puncture compared with 48 percent in hospitals
without such guidelines [16]. However, the increased CSF testing was not
associated with improved clinical outcomes for infants treated in hospitals with
CPGs, and adverse events (including delayed diagnosis of meningitis) were not
increased in hospitals where fewer lumbar punctures were performed
(approximately 3 percent unadjusted adverse events for both groups, adjusted
difference 0.3 percent [95% CI -0.2 to 0.9]). Thus, the CPGs that promoted
additional testing may have led to more costly care without clinical benefit.
UpToDate offers two types of patient education materials, "The Basics" and
"Beyond the Basics." The Basics patient education pieces are written in plain
language, at the 5th to 6th grade reading level, and they answer the four or five
key questions a patient might have about a given condition. These articles are
best for patients who want a general overview and who prefer short, easy-to-
read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th
grade reading level and are best for patients who want in-depth information and
are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can also
locate patient education articles on a variety of subjects by searching on "patient
info" and the keyword(s) of interest.)
● Basics topic (see "Patient education: Fever in babies younger than 3 months
(The Basics)")
● Beyond the Basics topic (see "Patient education: Fever in children (Beyond
the Basics)")
● Approach – The level of risk for invasive bacterial infection (IBI) determines
management of febrile young infants 29 to 90 days old. Admitted patients
should receive care in units with nurses and staff who are experienced with
young infants. (See 'Management' above and "The febrile neonate (28 days
of age or younger): Outpatient evaluation and initial management", section
on 'Management'.)
● Well-appearing
• Infants 29 to 60 days old – Well-appearing infants 29 to 60 days of age
without a focal bacterial infection on examination should be managed
based upon the level of risk for IBI identified by the initial evaluation
( algorithm 1) (see 'Infants 29 to 60 days old' above):
- Increased risk for IBI – For well-appearing febrile infants with a risk
factor for IBI ( table 1) or abnormal inflammatory markers
( table 3), we suggest empiric parenteral antibiotics (Grade 2C).
For these patients, we suggest ceftriaxone or, if available,
cefotaxime rather than other antibiotics (Grade 2C); selected
patients may need additional antibiotics ( table 4). The antibiotic
dose should be sufficient to treat meningitis. Most of these infants
warrant admission. (See 'Increased risk for invasive bacterial
infection' above.)
Patients with CSF pleocytosis and risk factors for herpes simplex
virus (HSV) infection ( table 6) should also receive acyclovir, as
discussed separately. (See "Neonatal herpes simplex virus infection:
Management and prevention", section on 'Initial antiviral therapy'.)
- Low risk for IBI – For well-appearing infants who have undergone
appropriate evaluation as summarized in the algorithm
( algorithm 1) and who lack the risk factors and laboratory
abnormalities discussed in the previous bullets, we suggest close
outpatient observation without antimicrobial therapy (Grade 2C),
provided that the infant is discharged to a reliable caregiver and
follow-up within 24 hours is ensured. (See 'Low risk for IBI' above.)
The evaluation should also identify and treat other causes of ill appearance
in young infants as discussed separately. (See "Approach to the ill-
appearing infant (younger than 90 days of age)".)
REFERENCES
1. Pantell RH, Roberts KB, Adams WG, et al. Evaluation and Management of
Well-Appearing Febrile Infants 8 to 60 Days Old. Pediatrics 2021; 148.
11. Dayan PS, Hanson E, Bennett JE, et al. Clinical course of urinary tract
infections in infants younger than 60 days of age. Pediatr Emerg Care 2004;
20:85.
12. Cruz AT, Mahajan P, Bonsu BK, et al. Accuracy of Complete Blood Cell Counts
to Identify Febrile Infants 60 Days or Younger With Invasive Bacterial
Infections. JAMA Pediatr 2017; 171:e172927.
13. Byington CL, Reynolds CC, Korgenski K, et al. Costs and infant outcomes
after implementation of a care process model for febrile infants. Pediatrics
2012; 130:e16.
14. Gomez B, Bressan S, Mintegi S, et al. Diagnostic value of procalcitonin in
well-appearing young febrile infants. Pediatrics 2012; 130:815.
18. Hsiao AL, Chen L, Baker MD. Incidence and predictors of serious bacterial
infections among 57- to 180-day-old infants. Pediatrics 2006; 117:1695.
19. Bonadio WA, Hennes H, Smith D, et al. Reliability of observation variables in
distinguishing infectious outcome of febrile young infants. Pediatr Infect Dis
J 1993; 12:111.
20. Bachur RG, Harper MB. Predictive model for serious bacterial infections
among infants younger than 3 months of age. Pediatrics 2001; 108:311.
21. Baker MD, Avner JR, Bell LM. Failure of infant observation scales in detecting
serious illness in febrile, 4- to 8-week-old infants. Pediatrics 1990; 85:1040.
22. Gómez B, Mintegi S, Benito J, et al. Blood culture and bacteremia predictors
in infants less than three months of age with fever without source. Pediatr
Infect Dis J 2010; 29:43.
23. Paret M, Lighter J, Pellett Madan R, et al. Severe Acute Respiratory Syndrome
Coronavirus 2 (SARS-CoV-2) Infection in Febrile Infants Without Respiratory
Distress. Clin Infect Dis 2020; 71:2243.
26. Rogers S, Gravel J, Anderson G, et al. Clinical utility of correction factors for
febrile young infants with traumatic lumbar punctures. Paediatr Child
Health 2021; 26:e258.
27. Rogers S, Gravel J, Anderson G, et al. Erratum to: Clinical utility of correction
factors for febrile young infants with traumatic lumbar punctures. Paediatr
Child Health 2021; 26:260.
28. Hanson AL, Schunk JE, Corneli HM, Soprano JV. A Randomized Controlled
Trial of Positioning for Lumbar Puncture in Young Infants. Pediatr Emerg
Care 2016; 32:504.
29. Nigrovic LE, Kuppermann N, Neuman MI. Risk factors for traumatic or
unsuccessful lumbar punctures in children. Ann Emerg Med 2007; 49:762.
30. McGowan KL, Foster JA, Coffin SE. Outpatient pediatric blood cultures: time
to positivity. Pediatrics 2000; 106:251.
31. Garcia-Prats JA, Cooper TR, Schneider VF, et al. Rapid detection of
microorganisms in blood cultures of newborn infants utilizing an automated
blood culture system. Pediatrics 2000; 105:523.
32. Pantell RH. Febrile infants: aligning science, guidelines, and cost reduction
with quality of individualized care. Pediatrics 2012; 130:e199.
Topic 106744 Version 36.0
GRAPHICS
IMs: inflammatory markers; SPA: suprapubic aspiration; LP: lumbar puncture; CSF: cerebros
key action statement; CRP: C-reactive protein; ANC: absolute neutrophil count; HSV: herpes
PCR: polymerase chain reaction.
* Key action statement references are shown in parentheses. To see the statements, refer t
Academy of Pediatrics Clinical Practice Guideline: Evaluation and management of well-appe
infants 8 to 60 days old.
Δ Send CSF for cell count, Gram stain, glucose, protein, bacterial culture, and enterovirus PC
if CSF pleocytosis is present and during periods of increased local enterovirus prevalence. A
this age group, HSV should be considered when there is a maternal history of genital HSV l
infants with vesicles, seizures, hypothermia, mucous membrane ulcers, CSF pleocytosis in t
positive Gram stain result, leukopenia, thrombocytopenia, or elevated alanine aminotransf
further discussion, see the current Red Book. Recommended HSV studies are CSF PCR; HSV
of mouth, nasopharynx, conjunctivae, and anus for HSV culture (if available) or PCR assay; a
aminotransferase; and blood PCR. If CSF is unobtainable or uninterpretable, there are insuf
make a specific recommendation. Options include the following: observe without treatmen
time and, depending on infant clinical condition, repeat LP and/or laboratory markers; beg
antimicrobial agents and reassess in 24 hours on the basis of infant response and results o
if CSF is bloody or antimicrobial agents have previously been started, analysis by multiplex
additional information; consult with local a pediatric infectious disease specialist.
◊ Infant may be managed at home if parent and clinician agree that the following are prese
phone and transportation, parent willingness to observe and communicate changes in con
agreement to the infant being reevaluated in 24 hours.
§ Most 29- to 60-day-old infants with negative IMs and urinalysis results may be observed a
However, hospital observation is an option for infants when there are barriers to follow-up.
Reproduced with permission from Pediatrics, Vol. 148, Page e2021052228, Copyright © 2021 by the AAP.
Ill appearance
Maternal risk for early-onset sepsis (neonates <14 days only, any one of the
following):
Peripartum fever
Prolonged rupture of membranes
Vaginal culture positive for group B Streptococcus
Focal infection ◊
Patient
Studies
characteristics
For patient characteristics that indicate an elevated risk for invasive bacterial
infection and the need for a full sepsis evaluation, refer to UpToDate content on the
outpatient evaluation of neonates and febrile young infants 7 to 90 days old.
CBC: complete blood count; CSF: cerebrospinal fluid; HSV: herpes simplex virus;
COVID-19: coronavirus disease 2019; PCR: polymerase chain reaction; PT:
prothrombin time; aPTT: activated partial thromboplastin time; INR: international
normalized ratio; ALT: alanine aminotransferase; AST: aspartate aminotransferase;
RSV: respiratory syncytial virus.
Δ Do not use RSV or influenza test results to determine the need for antibiotics or
antiviral agents to treat influenza in ill-appearing febrile young infants.
Blood inflammatory marker values above these thresholds suggest an increased risk
of invasive bacterial illness (IBI) in febrile young infants 22 to 60 days old.
Procalcitonin has the best ability to identify IBI in well-appearing febrile young
infants if it is rapidly available (ie, within 1 to 2 hours). When applying these
thresholds, ensure concordance with units and range in use by the laboratory
performing the test. For additional information regarding the utility of blood
inflammatory markers in febrile young infants, refer to UpToDate topics on the
outpatient evaluation and management of infants 29 to 90 days old.
* These thresholds are derived from two different decision models. An elevated
absolute neutrophil count is useful for identifying elevated risk for invasive bacterial
infection but is not as accurate as procalcitonin or C-reactive protein. The threshold
of 4000/mm 3 is most appropriate to use with procalcitonin results. The threshold of
5200/mm 3 is most appropriate to use with height of fever ≥38.6°C (101.5°F) when
procalcitonin results are not available.
Reference:
1. Pantell RH, Roberts KB, Adams WG, et al. Evaluation and Management of Well-Appearing Febrile
Infants 8 to 60 Days Old. Pediatrics 2021; 148.
2. Kuppermann N, Mahajan P, Dayan PS. Fever, absolute neutrophil count, procalcitonin, and the
AAP Febrile Infant Guidelines. Pediatric 2023; 151.
Δ Acyclovir is indicated in asymptomatic infants ≤28 days but at risk due to exposure
(maternal active genital lesions); those with ill appearance, mucocutaneous vesicles,
seizures, or cerebrospinal fluid pleocytosis; and in older infants with clinical findings
of HSV infection.
Special circumstances
Amikacin 15 to 22.5
mg/kg/day IV in 3 divided
doses (maximum 1.5
g/day)
Patients treated Some experts suggest adding The rationale for adding
with adjunctive rifampin to the regimen in Box rifampin is based on the
dexamethasone A: concern that the entry of
Rifampin 20 mg/kg/day vancomycin into the CSF may
IV in 2 divided doses be reduced by adjunctive
(maximum 900 mg/day) dexamethasone.
Ceftazidime 150
mg/kg/day IV in 3 divided
doses (maximum 6
g/day)
OR
Meropenem 120
mg/kg/day IV in 3 divided
doses (maximum 6
g/day)
PLUS an aminoglycoside:
Gentamicin 7.5
mg/kg/day IV in 3 divided
doses
OR
Amikacin 15 to 22.5
mg/kg/day IV in 3 divided
doses (maximum 1.5
g/day)
Ceftazidime 150
mg/kg/day IV in 3 divided
doses (maximum 6
g/day)
OR
Meropenem 120
mg/kg/day IV in 3 divided
doses (maximum 6
g/day)
An aminoglycoside is added if
CSF Gram stain shows GNR
IV: intravenous; Hib: Haemophilus influenza type B; GBS: group B streptococcus; GNR:
gram-negative rod; S. aureus: Staphylococcus aureus; CSF: cerebrospinal fluid; H.
influenzae: Haemophilus influenzae; P. aeruginosa: Pseudomonas aeruginosa.
Diagnostic testing fo
Viral Viral
Proportion Clinical culture culture or
Bloo
of cases manifestations or HSV HSV PCR
plasm
PCR of of skin
PC
surface lesion
swabs ¶ scrapings Δ
* All of these diagnostic tests should be performed in any neonate with suspected
HSV infection.
Δ DFA permits rapid detection of HSV antigens in skin lesion scrapings; however,
DFA is not as sensitive as culture or PCR and therefore viral culture and/or PCR
should also be performed.
◊ The dose of acyclovir must be adjusted for neonates with renal impairment and/or
weight <1 kg. Refer to Lexicomp for additional dosing information. If IV acyclovir is
not available, ganciclovir is an alternative. Refer to the UpToDate's topic on
management of neonatal HSV infection for additional information. Oral acyclovir
dosing is based on BSA, which is calculated as follows: square root
(height [cm] × weight [kg]/3600). The oral suppressive acyclovir dose should be
adjusted each month to account for growth.
1 to 6 months
C. trachomatis Azithromycin
≥6 months
This table is meant for use with UpToDate content on the treatment of CAP in
children. Refer to related UpToDate content for details regarding complete Hib and
S. pneumoniae immunization, criteria for severe pneumonia, and pneumonia
requiring ICU admission. Consultation with a specialist in infectious diseases for
children is suggested for children with severe hypersensitivity to beta-lactam
antibiotics (eg, penicillins and cephalosporins).
Data from:
1. McIntosh K. Community-acquired pneumonia in children. N Engl J Med 2002; 346:429.
2. Bradley JS, Byington CL, Shah SS, et al. The management of community-acquired pneumonia in
infants and children older than 3 months of age: Clinical practice guidelines by the Pediatric
Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis 2011;
53:e25.
* A clinical diagnosis of severe sepsis or septic shock is made in children who have signs of
infection, inadequate tissue perfusion, and two or more age-based criteria for the systemic
syndrome (SIRS). The SIRS is present when a child has an abnormality of temperature (feve
specific abnormality of the white blood cell count and one of the following: tachycardia, bra
distress, or pulmonary condition requiring mechanical ventilation. Systematic screening is
with early recognition. Refer to UpToDate content on signs and symptoms of SIRS and reco
septic shock.
Δ Fluid volume should be calculated based upon ideal body weight (eg, 50 th percentile for a
develops signs of fluid overload (eg, rales, worsening respiratory distress, new or worsenin
gallop rhythm, hepatomegaly, or has cardiomegaly or pulmonary edema on chest radiogra
be omitted or reduced (eg, 5 to 10 mL/kg given over 15 minutes).
◊ Consultation with an expert in pediatric infectious disease is strongly encouraged for all c
Empiric antimicrobial treatment should consist of broad-spectrum antibiotics and, for susce
and antiviral agents. Refer to UpToDate topics on recognition and initial resuscitation of sep
specific regimens.
Reference: Weiss SL, Peters MJ, Alhazzani W, et al. Surviving Sepsis Campaign International Guidelines for the Ma
Sepsis-Associated Organ Dysfunction in Children. Pediatr Crit Care Med 2020; 21:e52.
Inhaled zanamivir May have shorter time Requires twice per day
to alleviation of administration for 5
symptoms than other days
agents Δ Requires inspiratory
flow sufficient to
mobilize and
aerosolize the
medication
Should be avoided in
people with a history
of:
Underlying lung
disease (eg,
asthma)
Allergy to lactose
or milk protein
Adverse effects:
Sinusitis, dizziness
Antiviral therapy for influenza should be initiated as soon as possible. It should not
be delayed pending results of viral testing, including testing for SARS-CoV-2 virus.
The agents listed above are active against influenza A and B. However, clinical trials
of peramivir included a limited number of subjects with influenza B virus. Refer to
related UpToDate content for dosing information.
Δ Clinical trials directly comparing the antiviral agents listed above with 1 another in
children are generally lacking (with the exception of 2 trials comparing oseltamivir
and baloxavir [2,3] ). However, in a network meta-analysis that estimated the relative
efficacy of different antiviral agents (oseltamivir, zanamivir, peramivir, and baloxavir)
based upon indirect comparisons from placebo-controlled and oseltamivir-
controlled trials (most trials involved adult patients managed in the outpatient
setting), zanamivir therapy was associated with the shortest duration of symptoms
and baloxavir therapy was associated with the lowest risk of complications [4] . The
certainty of these findings is low. The network meta-analysis did not include one of
the trials that compared baloxavir and oseltamivir [3] .
References:
1. Centers for Disease Control and Prevention. Influenza antiviral medications: Summary for
clinicians. Available at: https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm
(Accessed on October 14, 2021).
2. Ison MG, Portsmouth S, Yoshida Y, et al. Early treatment with baloxavir marboxil in high-risk
adolescent and adult outpatients with uncomplicated influenza (CAPSTONE-2): A randomised,
placebo-controlled, phase 3 trial. Lancet Infect Dis 2020; 20:1204.
3. Baker J, Block SL, Matharu B, et al. Baloxavir marboxil single-dose treatment in influenza-infected
children: A randomized, double-blind, active controlled phase 3 safety and efficacy trial
(miniSTONE-2). Pediatr Infect Dis J 2020; 39:700.
4. Liu JW, Lin SH, Wang LC, et al. Comparison of antiviral agents for seasonal influenza outcomes in
healthy adults and children: A systematic review and network meta-analysis. JAMA Netw Open
2021; 4:e2119151.
Time to
Test Comments
results
Recommended tests
Additional tests
Viral culture
References:
1. Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical practice guidelines by the Infectious Diseases
Society of America: 2018 update on diagnosis, treatment, chemoprophylaxis, and institutional
outbreak management of seasonal influenza. Clin Infect Dis 2019; 68:895.
2. United States Centers for Disease Control and Prevention. Influenza virus testing methods.
Available at: https://www.cdc.gov/flu/professionals/diagnosis/table-testing-methods.htm
(Accessed on August 31, 2021).
PCR: polymerase chain reaction; UTI: urinary tract infection; LE: leukocyte
esterase; WBCs: white blood cells; HPF: high-power field.
Parenteral
Infants ≤28 days Infants >28 days
antibiotics
Gram-positive cocci
CA-MRSA a concern
Refer to UpToDate content on mastitis and breast abscess in infants for additional
information. The doses in this table are intended for patients with normal renal
function. The doses of many of these agents must be adjusted in the setting of renal
insufficiency; refer to the Lexicomp drug-specific monographs for renal dose
adjustments. Unless otherwise specified, "age" refers to postnatal age.
‡ Intravenous ceftriaxone should be avoided in infants who are also receiving or are
expected to receive intravenous calcium in any form, including parenteral nutrition.
References:
1. Capparelli EV, Lane JR, Romanowski GL, et al. The influences of renal function and maturation on
vancomycin elimination in newborns and infants. J Clin Pharmacol, 2001; 41:927.
2. Nelson's Pediatric Antimicrobial Therapy, 27 rd ed, Bradley JS, Nelson JD, Barnett ED, et al (Eds),
American Academy of Pediatrics, Itasca, IL 2021. p.100.
3. Radu L, Bengry T, Akierman A, et al. Evoluation of empiric vancomycin dosing in a neonatal
population. J Perinatol 2018; 38:1702.
Data adapted from: American Academy of Pediatrics. Tables of antibacterial drug dosages. In: Red Book:
2021-2024 Report of the Committee on Infectious Diseases, 32 nd ed, Kimberlin DW, Barnett ED, Lynfield
R, Sawyer MH (Eds), American Academy of Pediatrics, Ithasca, IL 2021. p.876.
Milwaukee Philadelphia R
Boston criteria
criteria criteria
ABC: absolute band count; C: Celsius; CSF: cerebrospinal fluid; hpf: high-power field;
UA: urinalysis; WBC: white blood cells.
* The evaluation algorithms rate patients as normal/low risk versus high/not low
risk for serious bacterial infection based on information in each of these domains.
The example values in the table represent low risk.
Reproduced from: Hui C, Neto G, Tsertsvadze A, et al. Diagnosis and management of febrile infants (0-3
months). Evid Rep Technol Assess 2012; (205):1. Available at:
https://effectivehealthcare.ahrq.gov/products/febrile-infants-diagnosis-management/research (Accessed
March 23, 2021).
Graphic 106307 Version 6.0
Contributor Disclosures
Hannah F Smitherman, MD No relevant financial relationship(s) with ineligible
companies to disclose. Charles G Macias, MD, MPH No relevant financial relationship(s)
with ineligible companies to disclose. Morven S Edwards, MD Grant/Research/Clinical
Trial Support: Pfizer [Group B Streptococcus]. Other Financial Interest: Texas State
University personal services agreement [Chagas disease]. All of the relevant financial
relationships listed have been mitigated. Stephen J Teach, MD,
MPH Grant/Research/Clinical Trial Support: Novartis [Pediatric asthma]. All of the relevant
financial relationships listed have been mitigated. James F Wiley, II, MD, MPH No
relevant financial relationship(s) with ineligible companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When
found, these are addressed by vetting through a multi-level review process, and through
requirements for references to be provided to support the content. Appropriately
referenced content is required of all authors and must conform to UpToDate standards of
evidence.