The Febrile Infant 29 To 90 Days of Age Management UpToDate

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The febrile infant (29 to 90 days of age):

Management
AUTHORS: Hannah F Smitherman, MD, Charles G Macias, MD, MPH
SECTION EDITORS: Morven S Edwards, MD, Stephen J Teach, MD, MPH
DEPUTY EDITOR: James F Wiley, II, MD, MPH
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Mar 2023.

This topic last updated: Feb 21, 2023.
INTRODUCTION
The management of febrile infants younger than 90 days of age is discussed in

this topic.
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:
● (See "The febrile infant (29 to 90 days of age): Outpatient evaluation".)

● (See "The febrile infant (younger than 90 days of age): Definition of fever".)
● (See "Clinical features, evaluation, and diagnosis of sepsis in term and late
preterm neonates", section on 'Evaluation and initial management'.)
● (See "Approach to the ill-appearing infant (younger than 90 days of age)".)
TERMINOLOGY
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'.)
Interpretation of other means of temperature measurement and caregiver

reports of fever in young infants are discussed in detail separately. (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.
Well-appearing — There is no consensus definition for what constitutes a "well-

appearing" febrile young infant. The distinction between "well" and "ill" may not
be clear cut, and an infant's appearance may change rapidly. Because of the
difficulties in assessing well appearance, the clinical practice guideline (CPG) for
well-appearing, febrile infants 29 to 60 days with which this topic is in general
accord should not be applied when clinicians are uncertain as to whether an
infant is well appearing [1]. Furthermore, clinicians should adapt their approach
if an infant's appearance deteriorates.
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'.)
Increased risk for invasive bacterial infection — In otherwise well-

appearing febrile infants 29 to 60 days old without a focal infection,
management of those with an increased risk for IBI ( table 1) includes a full
evaluation for sepsis ( table 2). Further management depends upon the results
of the evaluation:
● Risk factors for IBI or abnormal inflammatory markers – For febrile

infants with known risk factors for IBI ( table 1) or abnormal
inflammatory markers ( table 3) but no obvious source of infection, we
suggest empiric parenteral antibiotics (eg, ceftriaxone or, if available,
cefotaxime) ( table 4). Cerebrospinal fluid (CSF) should be obtained for
testing, if not already performed, prior to antibiotic administration in these
patients whenever possible. However, antibiotics should not be delayed if
lumbar puncture cannot be accomplished in a timely manner. The initial
dose of empiric antibiotics should be sufficient to treat meningitis until the
results of CSF testing are available.
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.
These recommendations are based upon observational studies that provide

test characteristics for combined clinical features and laboratory tests [2].
Based upon studies that include febrile infants evaluated prior to
widespread use of conjugate vaccines, the range of positive predictive
values is wide for clinical features, basic laboratory tests alone, or a
combination of the two (3 to 71 percent). More recent evidence indicates
that the estimated baseline prevalence for IBI is low (approximately 1 to 2
percent for bacteremia and 0.25 percent for meningitis) [1]. In a multicenter
study of over 900 febrile infants, IBI occurred in approximately 3 percent of
infants with an elevated C-reactive protein or absolute neutrophil count and
in 8 percent of patients with an elevated procalcitonin [3].
● CSF pleocytosis – In patients who undergo lumbar puncture, those with

CSF pleocytosis require empiric treatment for bacterial meningitis
( table 5) and admission to a hospital with nurses and staff experienced
in caring for young infants. Although central nervous system herpes virus
infection is rare in this age group, patients with a history of active maternal
genital herpes lesions at birth or signs of herpes virus infection ( table 6)
should also receive acyclovir. (See "Neonatal herpes simplex virus infection:
Management and prevention", section on 'Initial antiviral therapy'.)
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'.)
Suspected urinary tract infection — The approach to well-appearing

infants 29 to 60 days old who have abnormal urine studies (ie, positive dipstick
for nitrites or leukocytes, uncentrifuged sample with a positive Gram stain or >10
white blood cells [WBCs]/mm3, or centrifuged sample with >5 WBCs/high-power
field) varies by degree of fever and risk status:
● 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:
• Any risk factors for IBI ( table 1)

• Any abnormal inflammatory marker ( table 3)
Because the risk of meningitis in well-appearing infants 29 to 60 days old

with a urinary tract infection (UTI) is low, the choice to obtain cerebrospinal
fluid (CSF) studies should be a shared decision with the family after
discussing risks and benefits of the procedure and incorporating the
caregivers' values and preferences [1]. For otherwise healthy infants with
elevated inflammatory markers, we suggest not obtaining CSF (see "The
febrile infant (29 to 90 days of age): Outpatient evaluation", section on 'Low-
risk, well-appearing infants'). The suggested empiric antibiotic regimens for
treatment of a UTI in infants younger than 60 days of age are discussed
separately. (See "Urinary tract infections in infants older than one month
and young children: Acute management, imaging, and prognosis", section
on 'Parenteral therapy'.)
Alternatively, these patients may receive a single dose of IM ceftriaxone (50

mg/kg) and can be discharged to home with ensured follow-up within 24
hours for a second IM dose of ceftriaxone, pending culture results, if all of
the following criteria are met:
• Lumbar puncture completed and CSF shows no pleocytosis and a

negative Gram stain
• No neutropenia (absolute neutrophil count >500/mm3)
• Chest radiograph (if obtained because of respiratory findings) shows no
infiltrate suggesting a bacterial pneumonia
Additional 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'.)
● 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
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'.)
Limited evidence from retrospective observational studies supports outpatient

management of low-risk, well-appearing infants 29 to 60 days old [10,11]. Such
infants are unlikely to have progression of illness after treatment. This alternative
approach may be offered to families of infants who meet these additional
criteria.
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:
● No risk factors for IBI ( table 1)

● Normal inflammatory markers ( table 3)
● Normal urine dipstick or urinalysis
● If obtained, no findings of pneumonia on chest radiograph
● If obtained, CSF with no pleocytosis and a negative Gram stain (although
CSF studies are not required to classify the patient as low risk)
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].
In addition to ensured follow-up within 24 hours, caregivers must understand

that worsening respiratory distress, ill appearance, or inability to feed warrant
emergency return for medical care. As an example, rapidly progressive
Staphylococcus aureus pneumonia has been described in infants and children
with influenza and should be suspected if other members of the family have had
or have S. aureus infection. (See "Methicillin-resistant Staphylococcus aureus
infections in children: Epidemiology and clinical spectrum", section on 'Clinical
spectrum' and "Seasonal influenza in children: Clinical features and diagnosis",
section on 'S. pneumoniae or S. aureus coinfection'.)
The risk of IBI (bacteremia or bacterial meningitis) in well-appearing febrile

infants 29 to 60 days of age with a temperature <38.6°C (101.5°F) and a normal
evaluation is approximately 0.4 percent [2]. Multiple prospective studies that
included over 11,000 febrile infants have reported that patients who are at low
risk of serious bacterial infection (SBI; bacteremia, meningitis, and other
infections such as UTI, pneumonia, or bacterial gastroenteritis) based upon
history, physical examination, and whatever laboratory testing has been
performed can be safely managed as outpatients [13-15]. In several
observational studies, CSF studies were not obtained at the initial evaluation in
most febrile infants with no major adverse events reported. In a large
administrative database study that evaluated the outcomes of over 49,000 febrile
infants 29 to 56 days of age and compared risk of adverse events in hospitals
with more versus less CSF testing, there was no increase in adverse events,
including delayed diagnosis of meningitis, among the hospitals with less CSF
testing (approximately 3 percent unadjusted adverse events for both groups,
adjusted difference 0.3 percent [95% CI -0.2 to 0.9]) [16].
Infants 61 to 90 days old — The management of well-appearing infants 61 to

90 days old without focal infection depends upon whether other risk factors for
IBI ( table 1) are present:
● Risk factors for IBI – For infants who have comorbidities (eg,
tracheostomy, in-dwelling central line, or significant congenital anomalies)
that raise the risk of IBI, we suggest urine testing, blood inflammatory
markers, blood culture, and, if respiratory symptoms are present, chest
radiograph.
For patients in whom any blood inflammatory markers are abnormal

( table 3), we suggest parenteral antibiotics and admission to the
hospital.
Patients with findings of bacterial pneumonia warrant empiric antibiotic

therapy ( table 7) and hospital admission as discussed separately. (See
"Pneumonia in children: Inpatient treatment".)
● No risk factors for IBI – The suggested evaluation for well-appearing

febrile infants 61 to 90 days old without risk factors for IBI includes urine
dipstick or microscopic urinalysis and urine culture. Management varies by
the results of initial urine studies:
• For previously healthy and well-appearing febrile infants 61 to 90 days of

age with no risk factors for IBI who have normal preliminary urine
testing (negative dipstick for leukocytes and nitrites, <5 WBCs/high-
power field on spun urine, or <10 WBCs/mm3 and negative Gram stain
of unspun urine), we suggest outpatient observation with close follow-
up with their primary care provider.
Patients who have preliminary urine findings indicative of a UTI warrant

oral antibiotics and close follow-up as an outpatient. Blood or CSF
studies need not be obtained prior to initiating antibiotics. Additional
imaging to identify urinary tract abnormalities is warranted in infants
with urine cultures results demonstrating 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'.)
This approach acknowledges the low prevalence of bacteremia and
meningitis and the possible low utility of further studies in these
patients as discussed below. (See "Urinary tract infections in infants
older than one month and young children: Acute management, imaging,
and prognosis", section on 'Oral therapy'.)
Some contributors to this topic also recommend blood inflammatory

markers and blood culture in selected patients, primarily when there is
concern about the caregiver's ability to identify progression of illness or
when close follow-up is not possible. If obtained, then it is reasonable to
treat patients with abnormal urine testing and elevated blood
inflammatory markers with parenteral antibiotics either as an outpatient
when close follow-up is ensured or in the hospital while awaiting blood
culture results. (See "The febrile infant (29 to 90 days of age): Outpatient
evaluation", section on '61 to 90 days old' and "Urinary tract infections in
imaging, and prognosis", section on 'Parenteral therapy'.)
The risk of bacteremia for well-appearing febrile infants 61 to 90 days of age is

estimated at 0.4 to 1 percent with a risk for meningitis of <0.1 percent [2,17]. This
risk is similar to that of older infants. As an example, in a prospective
observational study (conducted after the initiation of routine immunization of
infants with conjugated pneumococcal vaccine) describing febrile infants 57 to
180 days of age, there was no significant difference in the incidence of
bacteremia between those who were 57 to 89 days of age and those who were
older (0.9 percent for both) [18]. At this threshold, the measurement of a WBC
count, inflammatory markers (eg, C-reactive protein or procalcitonin), and blood
culture have limited utility and may lead to unnecessary treatment. For example,
the risk of blood culture contamination (approximately 2 percent) exceeds the
frequency of bacteremia. However, some experts think the risk of bacteremia in
well-appearing infants 61 to 90 days of age is high enough to warrant routine
blood culture [17].
Ill-appearing — Regardless of age or degree of highest measured temperature,
infants who are ill-appearing, have a weak cry, or have other abnormal behaviors
have a higher risk of IBI with sepsis and, from birth through about six weeks of
age, herpes simplex virus (HSV) infection [19,20]. In addition, infants who are ill
appearing but have normal or low temperature are also at significant risk for
infection.
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'.)
● Ancillary studies – Ill-appearing infants warrant a full and rapid evaluation

for sepsis ( table 2).
● Empiric antimicrobial – Empiric antimicrobial therapy using dosing for

severe infections, meningitis, or sepsis should be given as soon as possible
regardless of the initial laboratory results. Some ill-appearing infants may
be too unstable from a respiratory or hemodynamic standpoint to undergo
a lumbar puncture; in such cases, antimicrobial therapy should not be
withheld or delayed.
Initial empiric therapy for immunocompetent patients varies by age as

follows (see "Septic shock in children: Rapid recognition and initial
resuscitation (first hour)", section on 'Empiric regimens'):
• 29 to 60 days of age:
- Ceftriaxone or, if available, cefotaxime and
- Ampicillin (to cover group B Streptococcus [GBS], Enterococcus

species, and Listeria monocytogenes) and
- Vancomycin (to cover Streptococcus pneumoniae or S. aureus that is

not susceptible to cefotaxime or ceftriaxone)
- 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:
- Ceftriaxone or cefotaxime and
- Vancomycin (to cover S. pneumoniae or S. aureus that is not

susceptible to cefotaxime or ceftriaxone)
In addition to these regimens, suggested antibiotics in individuals with a

suspected genitourinary or gastrointestinal source or who are
immunosuppressed are discussed separately. (See "Septic shock in children:
Rapid recognition and initial resuscitation (first hour)", section on 'Empiric
regimens'.)
● Hospital admission – Ill-appearing febrile infants are at higher risk of

decompensation and may have early or established septic shock that
requires acute and ongoing resuscitation. They typically warrant admission
to a pediatric-capable intensive care facility. (See "Septic shock in children:
Rapid recognition and initial resuscitation (first hour)", section on
'Resuscitation' and "Septic shock in children: Ongoing management after
resuscitation".)
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'.)
Among young infants undergoing outpatient evaluation with clinical findings of

HSV infection, the overall prevalence of HSV infection is approximately 1 percent
but peaks in the second week of life and declines significantly after four weeks of
age. Despite the low prevalence of HSV in febrile infants >28 days old in this
setting, testing and empiric treatment for HSV is warranted in those with
findings suspicious for HSV because early treatment has been shown to improve
survival and reduce long-term sequelae. (See "Neonatal herpes simplex virus
infection: Clinical features and diagnosis", section on 'Incidence and prevalence'
and "Neonatal herpes simplex virus infection: Clinical features and diagnosis",
section on 'Clinical suspicion'.)
Respiratory syncytial virus bronchiolitis or influenza — Febrile infants 29 to

90 days of age with respiratory syncytial virus (RSV) bronchiolitis or influenza
have a markedly reduced risk of IBI that permits modification of their evaluation
and treatment (see "The febrile infant (29 to 90 days of age): Outpatient
evaluation", section on 'Patients with recognizable viral infections'):
● RSV bronchiolitis – Febrile infants 29 to 90 days of age with RSV

bronchiolitis and normal urine testing should receive care according to the
severity of their bronchiolitis ( algorithm 3). They do not require empiric
antibiotics. (See "Bronchiolitis in infants and children: Treatment, outcome,
and prevention".)
Patients 29 to 60 days of age with abnormal initial urine testing warrant

additional laboratory evaluation and management as described separately
(see "The febrile infant (29 to 90 days of age): Outpatient evaluation",
section on '29 to 60 days old' and 'Suspected urinary tract infection' above).
● Influenza – Febrile infants 29 to 90 days of age with influenza by highly

accurate testing (eg, polymerase chain reaction [PCR]) during a period of
high seasonal prevalence warrant antiviral therapy ( table 8) and, as
determined by the results of urine testing, treatment for UTI ( table 9 and
algorithm 4). (See "Seasonal influenza in children: Management", section on
'Antiviral therapy'.)
Otherwise, they should be managed according to appearance and age as

described above. (See 'Ill-appearing' above and 'Well-appearing' above.)
Coronavirus disease 2019 — In young infants, severe acute respiratory

syndrome coronavirus 2 (SARS-CoV-2) can cause fever without any other
manifestations, including respiratory symptoms and signs [23,24]. Thus,
coronavirus disease 2019 (COVID-19) testing of young infants who require
hospital admission for possible IBI is warranted to prevent transmission in the
hospital setting. (See "COVID-19: Clinical manifestations and diagnosis in
children", section on 'Criteria for COVID-19 testing'.)
The treatment of COVID-19 in infants is discussed in detail separately. (See

"COVID-19: Management in children".)
Enterovirus — RT-PCR for enterovirus in cerebrospinal fluid distinguishes viral

from bacterial meningitis in febrile young infants and, for patients with a positive
test, permits shorter duration of antibiotic administration and hospitalization.
(See "Viral meningitis in children: Clinical features and diagnosis", section on
'Cerebrospinal fluid studies' and "Viral meningitis in children: Clinical features
and diagnosis", section on 'Distinguishing viral from bacterial meningitis'.)
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:
● Abscess, cellulitis, osteomyelitis, or bacterial arthritis – Vancomycin and

ceftazidime or, if available, cefotaxime.
Drainage and culture of any abscesses and, in ill-appearing infants with

septic shock, surgical source control should accompany empiric antibiotic
therapy. (See "Techniques for skin abscess drainage" and "Septic shock in
children: Ongoing management after resuscitation", section on 'Eradicate
infection'.)
● Omphalitis – Vancomycin and gentamicin or, in regions with substantial

(>10 percent) gentamicin-resistant E. coli, ceftazidime or (if available)
cefotaxime; add metronidazole or clindamycin to cover anaerobic infection
in infants with foul-smelling umbilical discharge or those born to mothers
with amnionitis. (See "Care of the umbilicus and management of umbilical
disorders", section on 'Omphalitis'.)
● Mastitis – Febrile infants warrant empiric parenteral antibiotics tailored to

the prevalence of methicillin-resistant S. aureus (MRSA) isolates in the
community. Drainage of the abscess should accompany antibiotic
treatment. Suggested regimens for infants with uncomplicated mastitis are
similar to treatment of abscesses and are provided in the table ( table 10).
Antimicrobial therapy for patients with severe complications (eg, extensive
cellulitis, fasciitis, osteomyelitis, and/or shock) are discussed separately.
(See "Mastitis and breast abscess in infants younger than two months",
section on 'Antimicrobial therapy'.)
● Pneumonia – The treatment regimen is determined by age, clinical

findings, and MRSA isolates in the community. In regions with high MRSA
prevalence (generally considered to be >10 percent of isolates), the
preferred regimens include:
• Infants 29 to 90 days of age with uncomplicated pneumonia –

Ceftriaxone or cefotaxime (see "Pneumonia in children: Inpatient
treatment", section on 'Uncomplicated bacterial pneumonia')
• Infants 29 to 90 days of age with complicated pneumonia – Vancomycin

and ceftriaxone provide appropriate coverage in most cases, but the
choice of antibiotic regimen is determined by severity of illness and
potential for hospital-associated infection (see "Pneumonia in children:
Inpatient treatment", section on 'Empiric therapy')
Use of oxacillin, nafcillin, or clindamycin instead of vancomycin where specified

above is appropriate only in well-appearing infants cared for in regions with low
prevalence of MRSA. However, some physicians may wish to administer
vancomycin instead of alternative antistaphylococcal antibiotics despite a
regional prevalence of MRSA that is <10 percent.
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
Traumatic or dry lumbar puncture — A traumatic lumbar puncture can cause

small amounts of bleeding into the CSF that can interfere with interpretation of
the CSF cell count. Certain formulas have been used to aid in the interpretation
of the cell count when the lumbar puncture is traumatic. When the CSF is not
grossly bloody, we subtract 1 WBC for every 1000 red blood cells (RBCs)/microL in
young infants [26,27]. However, none of the formulas to "correct" the CSF WBC
can be used with total confidence to exclude meningitis when the lumbar
puncture is traumatic (see "Cerebrospinal fluid: Physiology and utility of an
examination in disease states", section on 'Predicted WBC count after traumatic
tap'). A dry tap occurs when no CSF is obtained.
If interpretable CSF cannot be obtained in febrile infants 29 to 90 days of age,

then the patient should receive meningitic doses of parenteral antibiotics, and if
indicated (eg, active maternal genital lesions at birth or clinical findings of HSV
infection ( table 6)), acyclovir while awaiting culture results. Most of these
patients also warrant admission. However, for well-appearing infants who do not
require empiric acyclovir treatment, close observation at home with ensured
follow-up for repeated parenteral antibiotics with 24 hours is a reasonable option
because, despite abnormal blood inflammatory markers, the risk of meningitis is
low ( algorithm 1) [1]. (See 'Increased risk for invasive bacterial infection' above
and "Bacterial meningitis in children older than one month: Clinical features and
diagnosis", section on 'Interpretation'.)
Further management is based upon culture results and whether CSF was
obtained during initial evaluation:
● Traumatic lumbar puncture – Patients with positive blood culture, CSF

culture, or HSV testing warrant further care as discussed separately. (See
"Bacterial meningitis in children older than one month: Treatment and
prognosis" and "Neonatal herpes simplex virus infection: Management and
prevention".)
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'.)
● CSF not obtained – Repeat lumbar puncture is required in infants in whom

CSF was not obtained and who have positive blood culture, urine culture, or
HSV testing because the presence of CSF pleocytosis may necessitate a
prolonged course of parenteral antibiotics or acyclovir. (See "Bacterial
meningitis in children older than one month: Treatment and prognosis",
section on 'Treatment duration' and "Neonatal herpes simplex virus
infection: Management and prevention", section on 'Duration of therapy'.)
Management of infants with negative blood and urine cultures at 48 hours

and, if indicated, other testing for HSV depends upon the patient's clinical
course during observation. Well-appearing patients who defervesce and
whose inflammatory markers normalize may be candidates for additional
observation off antibiotics either in the hospital or at home.
Once the physician decides to perform a lumbar puncture, every reasonable
attempt should be made to obtain interpretable CSF for studies and culture.
However, this task frequently cannot be accomplished in infants ≤90 days old [1].
For example, success rates for obtaining CSF with <10,000 RBCs/mm3 on the first
attempt in children range from 45 to 74 percent [28,29], and age <90 days is an
important risk factor for not obtaining CSF despite multiple lumbar puncture
attempts [29]. If the lumbar puncture is traumatic, the tube in which the CSF is
clearest should be sent for a cell count.
Receiving antibiotics — Based upon the half-life of oral antibiotics in young

infants, a well-appearing, febrile young infant 29 to 60 days old on prophylactic
antibiotics or who has received antibiotics within the previous three days, usually
for a urinary tract abnormality, may have an IBI masked by negative culture
results. In these patients, we prefer to perform a complete sepsis evaluation with
the understanding that, regardless of the results, these patients cannot be
classified as "low risk" for IBI. (See "The febrile infant (29 to 90 days of age):
Outpatient evaluation", section on 'Definition and risk factors'.)
Further management depends upon the results:
● Abnormal CSF, urine testing, and/or elevated blood inflammatory markers

(eg, procalcitonin or C-reactive protein) – Manage as previously described
(see 'Increased risk for invasive bacterial infection' above)
● Normal results – Admit to the hospital for observation that includes

repeated vital signs and clinical reassessment off antibiotics
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).
Any of the following circumstances warrants additional evaluation and

hospitalization for empiric antibiotic therapy (see 'Management' above):
● Any deterioration in clinical status (eg, no longer well appearing or

increasing height of fever from prior evaluation)
● A positive blood culture not thought to be a contaminant
● A positive urine culture in an infant who remains febrile
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'.)
DISCHARGE CRITERIA FOR ADMITTED PATIENTS
Early discharge at 24 to 36 hours is feasible in hospitals with continuously

monitored blood culture instruments [1]. These systems identify between 77 and
87 percent of all cultures with pathogens [30,31] and 95 percent of critical
pathogens (eg, S. pneumoniae, Salmonella and other Enterobacteriaceae, Neisseria
meningitidis, groups A and B Streptococcus) within 24 hours [30]. The length of
hospitalization for admitted infants whose cultures remain negative depends
upon the clinical course of the patient:
● Afebrile and well-appearing – Admitted patients who remain well-

appearing during hospitalization and become afebrile are eligible for
discharge at 36 hours of negative cultures [13]. In addition, 24-hour
discharge may be appropriate for well-appearing patients who have
positive viral testing (eg, respiratory syncytial virus [RSV], influenza, or
enterovirus) regardless of the presence of fever [1].
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.
CLINICAL PRACTICE GUIDELINES
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.
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries

and regions around the world are provided separately. (See "Society guideline
links: Febrile young infants (younger than 90 days of age)".)
INFORMATION FOR PATIENTS
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)")
SUMMARY AND RECOMMENDATIONS
● 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.)
- Cerebrospinal fluid (CSF) pleocytosis – Infants with CSF pleocytosis

require empiric treatment for bacterial meningitis ( table 5) and
hospital admission, as discussed separately. (See "Bacterial
meningitis in children older than one month: Treatment and
prognosis", section on 'Empiric therapy'.)
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'.)
- Abnormal urine studies – For infants 29 to 60 days old with

abnormal urine studies and any one of the following: other risk
factors for IBI, or temperature ≥38.6°C (101.5°F); we suggest empiric
parenteral antibiotics and hospital admission (Grade 2C). Such
patients warrant a lumbar puncture, if not already performed. (See
'Suspected urinary tract infection' above and "Urinary tract
infections in infants older than one month and young children:
Acute management, imaging, and prognosis", section on 'Inpatient
parenteral therapy'.)
For infants 29 to 60 days of age with abnormal urine studies who
are at low risk for IBI, we suggest oral antibiotics and home
observation (Grade 2C). (See "Urinary tract infections in infants
older than one month and young children: Acute management,
imaging, and prognosis", section on 'Oral 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.)
• Infants 61 to 90 days old – For previously healthy and well-appearing

febrile infants 61 to 90 days of age with no risk factors for IBI and who
have normal preliminary urine testing, we suggest outpatient
observation with close follow-up with their primary care provider (Grade
2C). (See 'Infants 61 to 90 days old' above.)
Patients who have preliminary urine findings indicative of a urinary tract

infection (UTI) warrant oral antibiotics and close follow-up as an
outpatient, as discussed separately. (See "Urinary tract infections in
imaging, and prognosis", section on 'Oral therapy'.)
For infants who have comorbidities (eg, tracheostomy, in-dwelling

central line, or significant congenital anomalies) that raise the risk of IBI,
treatment depends upon results of the evaluation as described
separately (see "The febrile infant (29 to 90 days of age): Outpatient
evaluation", section on '61 to 90 days old'). For patients in whom any
blood inflammatory marker is abnormal ( table 3), we suggest
parenteral antibiotics and admission to the hospital (Grade 2C).
● Ill-appearing – Ill-appearing febrile infants 29 to 90 days old require a full
sepsis evaluation ( table 2) and treatment for sepsis and septic shock, as
summarized in the figure ( algorithm 2) and discussed in detail
separately. (See "Septic shock in children: Rapid recognition and initial
resuscitation (first hour)", section on 'Empiric regimens'.)
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)".)
● Recognizable infections – For infants with a recognizable viral infection

(eg, HSV, bronchiolitis, influenza) or evidence of a focal bacterial infection,
the extent of evaluation depends upon the specific infection, as discussed
separately. (See "The febrile infant (29 to 90 days of age): Outpatient
evaluation", section on 'Patients with recognizable viral infections' and "The
febrile infant (29 to 90 days of age): Outpatient evaluation", section on
'Focal infection'.)
Detailed management of these conditions is provided in separate topic

reviews:
• (See "Neonatal herpes simplex virus infection: Management and

prevention".)
• (See "Bronchiolitis in infants and children: Treatment, outcome, and
prevention".)
• (See "Seasonal influenza in children: Management".)
• (See "COVID-19: Management in children".)
• (See "Pneumonia in children: Inpatient treatment" and "Community-
acquired pneumonia in children: Outpatient treatment".)
• (See "Suspected Staphylococcus aureus and streptococcal skin and soft
tissue infections in children >28 days: Evaluation and management".)
• (See "Acute otitis media in children: Treatment".)
• (See "Hematogenous osteomyelitis in children: Management".)
Use of UpToDate is subject to the Terms of Use.
REFERENCES
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Well-Appearing Febrile Infants 8 to 60 Days Old. Pediatrics 2021; 148.
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ants (0-3 months). Evidence Report/Technology Assessment No. 205 (Prepar
ed by the University of Ottawa: Evidence-based Practice Center under Contra
ct No. HHSA 290-2007-10059-I). AHRQ Publication No. 12-E004-EF. Rockville,
MD: Agency for Healthcare Research and Quality. March 2012. Available at h
ttp://www.ahrq.gov/research/findings/evidence-based-reports/febrinftp.htm
l (Accessed August 3, 2015)
3. Gomez B, Mintegi S, Bressan S, et al. Validation of the "Step-by-Step"

Approach in the Management of Young Febrile Infants. Pediatrics 2016; 138.
4. Wang ME, Biondi EA, McCulloh RJ, et al. Testing for Meningitis in Febrile Well-
Appearing Young Infants With a Positive Urinalysis. Pediatrics 2019; 144.
5. Nugent J, Childers M, Singh-Miller N, et al. Risk of Meningitis in Infants Aged

29 to 90 Days with Urinary Tract Infection: A Systematic Review and Meta-
Analysis. J Pediatr 2019; 212:102.
6. Mahajan P, VanBuren JM, Tzimenatos L, et al. Serious Bacterial Infections in
Young Febrile Infants With Positive Urinalysis Results. Pediatrics 2022; 150.
7. Schnadower D, Kuppermann N, Macias CG, et al. Sterile cerebrospinal fluid

pleocytosis in young febrile infants with urinary tract infections. Arch Pediatr
Adolesc Med 2011; 165:635.
8. Thomson J, Cruz AT, Nigrovic LE, et al. Concomitant Bacterial Meningitis in

Infants With Urinary Tract Infection. Pediatr Infect Dis J 2017; 36:908.
9. Velasco R, Benito H, Mozún R, et al. Febrile young infants with altered

urinalysis at low risk for invasive bacterial infection. a Spanish Pediatric
Emergency Research Network's Study. Pediatr Infect Dis J 2015; 34:17.
10. Schnadower D, Kuppermann N, Macias CG, et al. Febrile infants with urinary
tract infections at very low risk for adverse events and bacteremia. Pediatrics
2010; 126:1074.
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;
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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.
15. Milcent K, Faesch S, Gras-Le Guen C, et al. Use of Procalcitonin Assays to

Predict Serious Bacterial Infection in Young Febrile Infants. JAMA Pediatr
2016; 170:62.
16. Chua KP, Neuman MI, McWilliams JM, et al. Association between Clinical
Outcomes and Hospital Guidelines for Cerebrospinal Fluid Testing in Febrile
Infants Aged 29-56 Days. J Pediatr 2015; 167:1340.
17. Bonilla L, Gomez B, Pintos C, et al. Prevalence of Bacterial Infection in Febrile

Infant 61-90 Days Old Compared With Younger Infants. Pediatr Infect Dis J
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19. Bonadio WA, Hennes H, Smith D, et al. Reliability of observation variables in
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J 1993; 12:111.
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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
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24. Nathan N, Prevost B, Corvol H. Atypical presentation of COVID-19 in young

infants. Lancet 2020; 395:1481.
25. Pintos C, Mintegi S, Benito J, et al. Blood enterovirus polymerase chain
reaction testing in young febrile infants. Arch Dis Child 2021; 106:1179.
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.
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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.
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with quality of individualized care. Pediatrics 2012; 130:e199.
Topic 106744 Version 36.0
GRAPHICS
Evaluation and management of the low-risk, well-appearing febrile

60 days of age
2021 American Academy of Pediatrics Clinical Practice Guideline: Algorithm for 29- to 60-da
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.
¶ If available, procalcitonin should be obtained along with ANC or CRP. If procalcitonin is un

ANC and CRP should be obtained, and a temperature >38.5°C is considered abnormal. IMs
abnormal at the following levels: (1) temperature >38.5°C, (2) procalcitonin >0.5 ng/mL, (3)
(4) ANC >4000 to 5200/mm 3 .
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.
Graphic 132301 Version 4.0

Risk factors for invasive bacterial illness* in febrile infants
younger than 90 days of age
Age <28 days
Ill appearance
Rectal temperature ≥38.6°C (101.5°F; infants 22 to 60 days old only) ¶
Prematurity (gestational age <37 weeks)
Received antibiotics within:

Neonates: 7 days of presentation
Infants 29 to 60 days old: 3 days of presentation
Comorbidities or chronic illness (any one of the following):

Perinatal course complicated by surgery or infection
Medically fragile (technology dependent or require specific therapies to sustain
life) Δ
Documented or suspected immune compromise
Congenital or chromosomal abnormality
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 ◊
* Invasive bacterial illness (IBI) primarily refers to bacteremia and meningitis.
¶ For well-appearing neonates 22 to 28 days old and infants 29 to 60 days old in

settings where procalcitonin measurements are not readily available, a temperature
≥38.6°C may also be used as an inflammatory marker that raises the risk of IBI
along with absolute neutrophil count, or C-reactive protein (refer to UpToDate
content on evaluation and management of the febrile neonate and the febrile infant
29 to 60 days of age).
Δ Examples include home ventilator, home oxygen, or total parenteral nutrition.

◊ Focal infections associated with an increased risk of IBI in febrile young infants
include cellulitis, abscess, pneumonia, osteomyelitis, bacterial arthritis, and
omphalitis.

Recommended sepsis evaluation for febrile young infants 7 to
90 days old at elevated risk for invasive bacterial infection
Patient
Studies
characteristics
All patients CBC with differential

Blood or serum glucose (to permit comparison with CSF
glucose)
Procalcitonin or C-reactive protein (optional)
Blood culture
Urinalysis
Urine culture (by bladder catheterization or suprapubic
aspiration)
COVID-19 PCR (nasal swab)
Chest radiograph (if respiratory signs or symptoms present)
Stool culture (if diarrhea or stool containing blood or
mucus)
CSF cell count with differential
CSF glucose and protein
CSF for bacterial culture and Gram stain
CSF PCR as indicated based upon clinical risk:
Enterovirus studies during time of high prevalence or in
patients with CSF pleocytosis
HSV in infants with clinical findings or increased risk of
maternal HSV transmission
CSF for viral culture if there is pleocytosis; if there is a
limited CSF sample, we prioritize PCR over viral culture
Signs of septic Add:

shock* PT, aPTT, INR
Fibrinogen and D-dimer
Serum lactate
Serum total bilirubin and ALT
Ionized calcium
Findings of HSV Add:

infection or at risk
due to exposure Surface viral cultures from the conjunctivae, mouth,
(maternal active nasopharynx, and rectum
genital lesions) Swab or scraping from skin vesicles or mucous
membrane lesions for direct immunofluorescence assay
and viral culture
Blood PCR for HSV
Serum AST and ALT ¶
Findings of Add rapid RSV test Δ

bronchiolitis
High regional Add influenza PCR Δ

prevalence of
influenza
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.
* Other causes of ill appearance in addition to sepsis include congenital heart

disease, congenital adrenal hyperplasia, inborn errors of metabolism, malrotation
with volvulus, and a variety of other conditions. Refer to UpToDate content on
approach to the ill-appearing infant younger than 90 days of age.
¶ Serum alanine transaminase and aspartate transaminase to identify elevation in

association with HSV-associated hepatitis; although these studies can also be
elevated in patients with disseminated enteroviral infection or in septic shock.
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 threshold values for well-
appearing, febrile infants 22 to 60 days of age
Inflammatory marker Abnormal value
Procalcitonin >0.5 ng/mL
C-reactive protein >20 mg/L
Absolute neutrophil count >4000/mm 3 or 5200/mm 3 *
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.

Empiric antimicrobial regimens for febrile young infants
younger than 90 days of age without focal infections*
Age Common pathogens Empiric treatment
Neonate (≤28 Common: Group B Ampicillin

days) Streptococcus, E. coli and
Less common: Listeria ceftazidime or cefepime or
monocytogenes, Enterococcus, S. cefotaxime (if available) or
aureus, other Gram negative gentamicin ¶
organisms, HSV Add acyclovir when
indicated Δ
Add vancomycin when
indicated ◊
Infant (29 to Common: Group B Ceftriaxone or cefotaxime (if

60 days) Streptococcus, E. coli, S. available)
pneumoniae, H. influenzae, N. Add ampicillin, when
meningitidis, S. aureus coverage for Enterococcus or
Less common: Enterococcus, Listeria monocytogenes
Listeria monocytogenes, infection is indicated or
Pseudomonas sp., other Gram when meningitis is
negative organisms suspected
Add vancomycin, when
indicated ◊
Add gentamicin, when
broader coverage for Gram
negative pathogens is
indicated
Add acyclovir when
indicated Δ
Infant (61 to Common: S. pneumoniae, H. Ceftriaxone or cefotaxime (if

90 days) influenzae, N. meningitidis available)
Less common: Group B Add vancomycin when
Streptococcus, E. coli, S. aureus, indicated ◊
Enterococcus, Listeria
monocytogenes, Pseudomonas
sp., other Gram negative
organisms
HSV: herpes simplex virus.
* Broad-spectrum coverage is prudent until an organism is identified. For specific

drug dosing, refer to Lexicomp drug monographs available by searching UpToDate,
or while in an UpToDate topic, clicking on the drug name. Refer to UpToDate topics
on management of febrile infants younger than 90 days of age.
¶ The choice of regimen should be based on local susceptibility patterns of E. coli

and likelihood of L. monocytogenes infection or Enterococcus infection. Per the
American Academy of Pediatrics Clinical Practice Guidelines, selected well-appearing
neonates 22 to 28 days old with normal inflammatory markers may be eligible for
intramuscular ceftriaxone and discharge home to reliable caregivers as long as a
follow-up visit within 12 to 24 hours for physical examination, review of culture
results, and a repeated dose of ceftriaxone is assured.
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.
◊ Vancomycin is warranted for coverage of methicillin-resistant S. aureus infection in

regions with high prevalence (>10% of isolates) and for coverage of resistant S.
pneumoniae in infants older than 28 days of age who are ill appearing or have
findings of bacterial meningitis.

Empiric antibiotic regimens for bacterial meningitis in infants
(age 1 to 12 months) and children
Suggested regimens Comments
Usual empiric Box A This regimen covers

regimen pneumococcus and
Vancomycin 60
meningococcus (the two
mg/kg/day IV in 4 divided
most common causes of
doses (maximum 4
bacterial meningitis in infants
g/day)
and children), Hib, and GBS.
PLUS one of the following:
Ceftriaxone 100
doses (maximum 4
g/day)
OR
Cefotaxime (if available)

300 mg/kg/day IV in 3 or
4 divided doses
(maximum 12 g/day)
Special circumstances
CSF Gram stain Add an aminoglycoside to the

shows GNR regimen in Box A:
Gentamicin 7.5
doses
OR
Amikacin 15 to 22.5
doses (maximum 1.5
g/day)
If there is concern for resistant

GNR infection, meropenem
should be substituted for
ceftriaxone/cefotaxime:
Meropenem 120
mg/kg/day in 3 divided
doses (maximum 6
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.
Neutropenic Box B S. aureus and gram-negative

patients with organisms are potential
Vancomycin 60
malignancy pathogens (in addition to
usual pathogens such as
doses (maximum 4
pneumococcus and
g/day)
meningococcus).
Cefepime 150 mg/kg/day
IV in 3 divided doses
(maximum 6 g/day)
OR
Ceftazidime 150
doses (maximum 6
g/day)
OR
Meropenem 120
doses (maximum 6
g/day)
PLUS an aminoglycoside:
Gentamicin 7.5
doses
OR
Amikacin 15 to 22.5
doses (maximum 1.5
g/day)
Impaired cell- Add high-dose ampicillin to Listeria is a potential

mediated the regimen in Box A: pathogen (in addition to
immunity (eg, Ampicillin 300 to 400 usual pathogens such as
renal transplant mg/kg/day IV in 4 or 6 pneumococcus and
recipients) divided doses (maximum meningococcus).
12 g/day)
Recent The regimen in Box A is Coagulase-negative

neurosurgery adequate for most patients staphylococci, S. aureus, and
and/or medical enteric gram-negative rods
Alternative regimens:
device in place are potential pathogens (in
Vancomycin 60
(CSF drain, CSF addition to usual pathogens
shunt, or like pneumococcus).
doses (maximum 4
cochlear
g/day)
implant)
Cefepime 150 mg/kg/day
IV in 3 divided doses
(maximum 6 g/day)
OR
Ceftazidime 150
doses (maximum 6
g/day)
OR
Meropenem 120
doses (maximum 6
g/day)
An aminoglycoside is added if
CSF Gram stain shows GNR
Optimal management also

includes removal/replacement
of the CSF drain or shunt, if
present
Basilar skull The regimen in Box A is Pneumococcus is the most
fracture/CSF adequate for most patients likely pathogen in this
leak setting; H. influenzae is
another potential pathogen.
Penetrating Same as in Box B S. aureus, coagulase-negative

head trauma staphylococci, and aerobic
gram-negative bacilli
(including P. aeruginosa) are
potential pathogens (in
addition to usual pathogens
like pneumococcus).
Anatomic The regimen in Box A is Coagulase-negative

defects (eg, adequate for most patients staphylococci, S. aureus, and
dermal sinus) enteric gram-negative rods
An aminoglycoside is added if are potential pathogens.
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.

Summary of clinical, laboratory, and radiographic findings and
treatment of neonatal herpes simplex virus infection
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
SEM disease 35 to 45% Characteristic Positive Positive in Positive

vesicular in >90% >90% approxi
lesions 75%
Conjunctivitis,
excessive
tearing
Ulcerative
lesions of the
mouth, palate,
and tongue
CNS disease 30 to 35% Seizures Positive Positive in Positive

Lethargy in >90% >90% if approxi
Irritability lesions are 65%
Tremors present;
Poor feeding however,
skin lesions
Skin lesions are
are often
present in 60
not present
to 70%
at the onset
of disease
Disseminated 25 to 30% Sepsis Positive Positive in Positive

disease syndrome in >90% >90% if 100%
Fever or lesions are
hypothermia present;
however,
Hepatitis
skin lesions
Respiratory
are often
distress
not present
DIC at the onset
Skin lesions are of disease
present in 60
to 80%
CNS
involvement
occurs in 60 to
75%
HSV: herpes simplex virus; PCR: polymerase chain reaction; CSF: cerebrospinal fluid;
SEM: skin, eyes, mouth; CNS: central nervous system; EEG: electroencephalogram;
LPD: lateralized periodic discharges (previously known as PLEDs [periodic lateralized
epileptiform discharges]); DIC: disseminated intravascular coagulopathy; DFA: direct
immunofluorescence assay; IV: intravenous; BSA: body surface area.
* All of these diagnostic tests should be performed in any neonate with suspected
HSV infection.
¶ Surface swabs are performed on specimens collected from the conjunctivae,

mouth, nasopharynx, and rectum. Some experts suggest these be obtained with a
single swab, starting with eyes and ending with the rectum, and placed in 1 viral
transport media tube. Alternatively, they may be collected with multiple swabs.
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.
§ Idoxuridine (iododeoxyuridine) is not available in the United States.

Parenteral empiric antibiotics for inpatient treatment of
pediatric community-acquired pneumonia [1,2]
Age group and Suggested parenteral

Comments
suspected pathogens empiric agent(s)
1 to 6 months
Bacterial (not One of the following: If CA-MRSA is

Chlamydia trachomatis Ceftriaxone suspected, ADD one of
or Staphylococcus Cefotaxime the following:
aureus) Vancomycin or
clindamycin
Ceftaroline*
(alternative)
C. trachomatis Azithromycin
≥6 months
Uncomplicated One of the following: Cefotaxime and

bacterial (not Ampicillin or ceftriaxone are
Mycoplasma penicillin G reserved for:
pneumoniae, Chlamydia (preferred) Children with
pneumoniae, or S. Cefotaxime incomplete Hib or
aureus) Streptococcus
Ceftriaxone
pneumoniae
immunizations, or
Communities with
substantial
prevalence of
penicillin-resistant
S. pneumoniae (eg,
≥25%)
M. pneumoniae or C. One of the following:

pneumoniae Azithromycin
Erythromycin
Levofloxacin
Clinical syndrome Suggested empiric
Comments
(any age) parenteral agent(s)
Severe pneumonia Combination therapy with Children with severe

one of the following: infection may benefit
Ceftriaxone from broad-spectrum
Cefotaxime therapy that addresses
PLUS one of the following: both typical and
atypical pathogens
Azithromycin
If S. aureus is a
Erythromycin
consideration, either:
Doxycycline
ADD vancomycin or
clindamycin, OR
Provide therapy
with ceftaroline*
PLUS azithromycin
Severe pneumonia Combination therapy with: If S. aureus is likely:

requiring ICU admission Vancomycin ADD nafcillin ¶ , OR
PLUS one of the following: SUBSTITUTE
Ceftriaxone linezolid for
Cefotaxime vancomycin and
PLUS: nafcillin, OR
Azithromycin Use ceftaroline*

PLUS azithromycin
PLUS:
PLUS antiviral
Antiviral treatment
treatment for
for influenza if the
influenza if the
child is hospitalized
child is hospitalized
during influenza
during influenza
season
season
Complicated pneumonia Combination therapy with Potential pathogens

(eg, effusion/empyema, one of the following: include S. pneumoniae,
necrotizing process, Ceftriaxone S. aureus, and
abscess Δ ) Cefotaxime Streptococcus pyogenes
PLUS: Vancomycin is an
Clindamycin if S. alternative to
aureus or anaerobic clindamycin for
children with allergy to
infection is a clindamycin or high
consideration prevalence of
clindamycin resistance
in the community ◊
Monotherapy with
ceftaroline is an
alternative if S. aureus
is a consideration
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).
CA-MRSA: community-associated methicillin-resistant S. aureus; Hib: Haemophilus

influenzae type b; ICU: intensive care unit; CAP: community-acquired pneumonia;
MSSA: methicillin-susceptible S. aureus; MRSA: methicillin-resistant S. aureus.
* Ceftaroline is a fifth-generation cephalosporin. It is available in the United States

for the treatment of pediatric CAP due to S. pneumoniae, MSSA, and H. influenzae in
children ≥2 months of age. Although ceftaroline has in vitro activity against MRSA,
experience in children with documented MRSA CAP is limited.
¶ Nafcillin is added if S. aureus is likely because MSSA is more rapidly killed by

nafcillin than by vancomycin.
Δ Ampicillin-sulbactam alone may be effective if lung abscess is thought to be

secondary to aspiration.
◊ The threshold prevalence of clindamycin-resistant MRSA (constitutive plus

inducible) for choosing vancomycin varies from center to center, usually ranging
from 10 to 25%, in an effort to balance the benefit of definitive therapy for the
patient with the risk of increasing vancomycin resistance in the community.
Additional considerations in the decision to choose vancomycin include the
prevalence of MRSA in the community, the severity of illness, and the turn-around
time for susceptibilities.
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.

Initial resuscitation of children with septic shock in setting with in
capability*
ICU: intensive care unit; IV: intravenous; BP: blood pressure; ECHO: echocardiography.
* 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.
¶ A trial of noninvasive ventilation, such as continuous positive airway pressure ventilation

pressure ventilation, may avoid the need for endotracheal intubation in selected patients. P
hemodynamic instability should receive appropriate interventions to achieve hemodynamic
during intubation. When performing rapid sequence intubation in children with septic shoc
and not contraindicated (ie, patients younger than three months of age or with psychosis),
Etomidate is not recommended unless ketamine is not available or contraindicated. Infants
may receive IV fentanyl 1 to 2 mcg/kg slowly.
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.
§ For recommended dosing and administration of dextrose or calcium infusion, refer to Up

hypoglycemia or hypocalcemia.
¥ For recommended dosing and administration of vasoactive infusions in children, refer to

resuscitation of septic shock in children.
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.

Evaluation and management of well-appearing,
otherwise healthy febrile infants ≤90 days of age
with bronchiolitis
RSV: respiratory syncytial virus; UTI: urinary tract infection; LE:

leukocyte esterase; WBCs: white blood cells; HPF: high-power field.
* Rapid RSV testing is not required to make the diagnosis of

bronchiolitis.
¶ Urine tests should be obtained by bladder catheterization or

suprapubic aspiration. Some experts also recommend a complete
blood count with differential, a blood culture, and, for patients with
abnormal inflammatory markers, intravenous antibiotics and
hospital admission.
Δ Empiric antibiotics should be adjusted based upon susceptibility of

organisms in the region. Although risk of bacteremia is low in well-
appearing febrile infants who are 29 to 90 days of age with a UTI,
some clinicians may choose to perform a complete blood count with
differential, a blood culture, and, especially for patients with
abnormal inflammatory markers or those who have not received
conjugate vaccines (infants 42 days of age and older), intravenous
antibiotics and hospital admission. Refer to UpToDate content on
treatment of UTI in infants and children.
◊ Refer to UpToDate content on treatment of bronchiolitis in infants

for indications for hospitalization. Young infants with non-severe
bronchiolitis who are hydrated and have adequate oral intake may
be discharged home with close follow-up in 24 to 48 hours.

Choice of antiviral therapy for children with suspected or
confirmed influenza [1]
Choice of agent according to clinical characteristics
Patient group Preferred agent(s) Alternative agent
Children with severe illness
Any of the following: Oral oseltamivir* IV peramivir (for those

Hospitalization ≥6 months of age)
Serious
complications (eg,
lower respiratory
tract
complications,
myocarditis,
encephalitis)
Progressive
clinical
deterioration
Children with nonsevere illness
Age 2 weeks Oral oseltamivir* IV peramivir (for those

through 4 years ≥6 months)
Age 5 through 6 Oral oseltamivir* IV peramivir (for those

years Oral baloxavir ≥6 months)
Age ≥7 years Oral oseltamivir*

Inhaled zanamivir
Oral baloxavir
IV peramivir
Considerations in choice of agent in children with nonsevere illness
Agent Advantages Disadvantages
Oral oseltamivir* Best-studied agent in Requires twice per day

children and agent administration for 5
days
with most clinical Emergence of escape
experience mutants, particularly in
Greater experience immunocompromised
with this agent in patients ¶
patients with severe Adverse effects:
illness Nausea, vomiting,
diarrhea, headache
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
Oral baloxavir Given as a single one- Emergence of escape

time dose mutants ◊
Compared with other Adverse effects:
agents, may reduce Vomiting, diarrhea
risk of influenza
complications Δ
Compared with
oseltamivir, may result
in shorter duration of
symptoms Δ
Appears to reduce
duration and amount
of viral shedding
IV peramivir Given as a single one- Requires IV
time dose administration
Uncertain efficacy for
treating infections due
to influenza B virus
Adverse effects:
Diarrhea, vomiting
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.
IV: intravenous; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; OG:

orogastric; NG: nasogastric.
* May be administered via OG or NG tube, although pharmacokinetics may differ

from oral administration, resulting in decreased concentrations.
¶ Oseltamivir resistance has been reported among children and

immunocompromised patients during treatment with oseltamivir, predominantly
among immunocompromised patients with influenza A(H1N1)pdm09 virus infection.
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] .
◊ Baloxavir has been associated with treatment-emergent resistance, particularly

when influenza A(H3N2) viruses were circulating. In clinical trials, escape mutants
(virus with mutations with decreased susceptibility to baloxavir) were detected in
approximately 15 to 20% of young patients (ie, <12 years old) treated with baloxavir
and approximately 5 to 10% of older baloxavir recipients.
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.

Influenza diagnostic tests for respiratory specimens [1,2]
Time to
Test Comments
results
Recommended tests
Conventional molecular 1 to 8 hours High sensitivity and very

assays, including real-time high specificity
RT-PCR and multiplex PCR Can differentiate influenza A
(nucleic acid detection) and B, as well as influenza A
subtypes
Multiplex PCR detects other
respiratory viruses and
bacterial pathogens
Rapid molecular assays 15 to 30 High sensitivity and

(nucleic acid detection) minutes specificity
Can differentiate influenza A
and B, but cannot not
differentiate influenza A
subtypes
Additional tests
Rapid influenza diagnostic <15 minutes Low to moderate sensitivity;

tests (antigen detection) high specificity
Direct and indirect 1 to 4 hours Moderately high sensitivity;

immunofluorescence high specificity
(antigen detection)
Viral culture
Shell viral culture 1 to 3 days Moderately high sensitivity;

highest specificity
Not useful for timely clinical
3 to 10 days management
Isolation in cell culture
Used for public health
surveillance
Refer to UpToDate content on diagnosis of influenza in adults and children for
additional details about the choice and interpretation of influenza tests. Refer to the
United States Centers for Disease Control and Prevention information on influenza
testing methods for additional details.
RT-PCR: reverse-transcriptase polymerase chain reaction.
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).

Evaluation and management of well-appearing, otherwise
healthy febrile infants ≤90 days of age with influenza
PCR: polymerase chain reaction; UTI: urinary tract infection; LE: leukocyte
esterase; WBCs: white blood cells; HPF: high-power field.
* For recommended tests, refer to UpToDate content on outpatient evaluation

of febrile young infants.
¶ Urine tests should be obtained by bladder catheterization or suprapubic

aspiration. Some experts also recommend a complete blood count with
differential and a blood culture, and, for patients with abnormal inflammatory
markers, intravenous antibiotics and hospital admission.
Δ Empiric antibiotics should be adjusted based upon susceptibility of organisms

in the region. Although risk of bacteremia is low in febrile infants who are 29 to
90 days of age with a UTI, some experts also recommend a complete blood
count and a blood culture, and, for patients with an elevated WBC or absolute
neutrophil count, intravenous antibiotics and hospital admission. Refer to
UpToDate content on treatment of UTI in infants and children.
◊ Refer to UpToDate content on treatment of seasonal influenza in children.

Infants who are hydrated, have adequate oral intake, and do not have
significant respiratory distress may be discharged home with close follow-up
within 24 to 48 hours.

Suggested parenteral antibiotic regimens for mastitis or breast
abscess in infants without severe complications,* according to
most frequent gram stain findings
Parenteral
Infants ≤28 days Infants >28 days
antibiotics
Gram-positive cocci
CA-MRSA not a concern (one of the following)
Nafcillin or oxacillin GA ≤34 weeks: 100 to 200 mg/kg IV

Age ≤7 days: 25 per day in 4 to 6 doses
mg/kg IV every 12
hours
Age >7 days: 25
mg/kg IV every 8
hours
GA >34 weeks:
Age ≤7 days: 25
mg/kg IV every 8
hours
Age >7 days: 25
mg/kg IV every 6
hours
CA-MRSA a concern (one of the following)
Clindamycin ¶ PMA ≤32 weeks: 5 20 to 40 mg/kg IV per

mg/kg IV every 8 hours day in 3 or 4 doses
PMA 33 to 40 weeks: 7
mg/kg IV every 8 hours
PMA >40 weeks: 9
mg/kg IV every 8 hours
Vancomycin Δ Loading dose: 20 Refer to UpToDate

mg/kg IV content related to
Maintenance dosing alternative methods of
according to GA and dosing vancomycin for
serum creatinine as children older than 28
indicated below. The days ◊
interval between the
loading dose and the
first maintenance dose
should be the same as
the dosing interval for
the maintenance
regimen. This dosing
regimen was designed
with a target trough
concentration of 5 to
10 mg/L [1] .
GA ≤28 weeks:
<0.5 mg/dL: 15
mg/kg IV every
12 hours
0.5 to 0.7
mg/dL: 20
mg/kg IV every
24 hours
0.8 to 1 mg/dL:
15 mg/kg IV
every 24 hours
1.1. to 1.4
mg/dL: 10
mg/kg IV every
24 hours
>1.4 mg/dL: 15
mg/kg IV every
48 hours
GA >28 weeks:
<0.7 mg/dL: 15
mg/kg IV every
12 hours
0.7 to 0.9
mg/dL: 20
mg/kg IV every
24 hours
1 to 1.2 mg/dL:
15 mg/kg IV
every 24 hours
1.3 to 1.6
mg/dL: 10
mg/kg IV every
24 hours
>1.6 mg/dL: 15
mg/kg IV every
48 hours
Gram-negative organisms (one of the following)
Gentamicin § GA <30 weeks: 6 to 7.5 mg/kg IV per

Age ≤14 days: 5 day in 3 doses, or
mg/kg IV every 48 5 to 7.5 mg/kg IV per
hours day once daily
Age >14 days: 5
mg/kg IV every 36
hours
GA 30 to 34 weeks:
Age ≤10 days: 5
mg/kg IV every 36
hours
Age >10 days: 5
mg/kg IV every 24
hours
GA ≥35 weeks:
Age ≤7 days: 4
mg/kg IV every 24
hours
Age >7 days: 5
mg/kg IV every 24
hours
Amikacin § GA <30 weeks: 15 to 22.5 mg/kg IV

Age ≤14 days: 15 per day in 2 or 3 doses
mg/kg IV every 48 or once daily
hours
Age >14 days: 15
mg/kg IV every 24
hours
GA 30 to 34 weeks:
Age ≤10 days: 15
mg/kg IV every 36
hours
Age >10 days: 15
mg/kg IV every 24
hours
GA ≥35 weeks:
Age ≤7 days: 15
mg/kg IV every 24
hours
Age >7 days: 18
mg/kg IV every 24
hours
Cefotaxime ¥ (if Age <7 days: 50 mg/kg 150 to 180 mg/kg IV

available) IV every 12 hours per day in 3 doses
Age ≥7 days: 50 mg/kg 200 to 225 mg/kg IV

IV every 8 hours per day in 4 doses for
meningitis
Ceftazidime ¥ (if Age <7 days: 50 mg/kg 90 to 150 mg/kg IV per

cefotaxime not IV every 12 hours day in 3 doses
available) Age ≥7 days: 50 mg/kg 200 to 300 mg/kg IV
IV every 8 hours per day in 3 doses for
suspected
Pseudomonas (severe
infection)
Ceftriaxone ¥ ‡ (if 50 mg/kg IV every 24 50 to 75 mg/kg IV per

cefotaxime not hours day
available) 100 mg/kg IV per day
in 1 or 2 doses for
meningitis
Gram stain not available or no organisms seen
CA-MRSA not a concern
Nafcillin or oxacillin, Dosing regimens provided above

plus one of the
following:
Gentamicin §
Amikacin §
Cefotaxime ¥
Ceftazidime ¥
Ceftriaxone ¥
CA-MRSA a concern
Clindamycin ¶ or Dosing regimens provided above

vancomycin, plus
one of the
following:
Gentamicin §
Amikacin §
Cefotaxime ¥
Ceftazidime ¥
Ceftriaxone ¥
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.
CA-MRSA: community-acquired methicillin-resistant Staphylococcus aureus; GA:

gestational age; IV: intravenously; PMA: postmenstrual age; PNA: postnatal age;
AUC: area under the curve.
* Severe complications include extensive cellulitis, necrotizing fasciitis,

osteomyelitis, and shock. Refer to UpToDate content on mastitis and shock in
infants.
¶ Clindamycin should not be used if central nervous system infection is a concern.

Monitor carefully when used if more than 15% of local community-associated S.
aureus isolates are resistant to clindamycin.
Δ Serum creatinine concentration will take approximately 5 to 7 days after birth to

reasonably reflect neonatal renal function. Cautious use of creatinine-based dosing
strategy with frequent assessment of renal function and vancomycin serum
concentrations are recommended in neonates ≤7 days old [2] . A vancomycin dosing
method based upon PMA and PNA is provided as an alternative to the serum
creatinine-based method listed above and may be useful in some clinical
situations [3] . The regimen was designed with a target trough concentration of 10 to
20 mg/L.
PMA ≤29 weeks
PNA ≤21 days: 15 mg/kg IV every 18 hours
PNA >21 days: 15 mg/kg IV every 12 hours
PMA 30 to <37 weeks
PMA 37 to <45 weeks
◊ The approach to vancomycin dosing is generally determined at the institutional
level. Refer to UpToDate content on invasive staphylococcal infections in children for
details of trough-guided and AUC-guided vancomycin dosing for infants ≥28 days of
age.
§ Initial aminoglycoside dosing is provided. The optimal, individualized dose of

amikacin and gentamicin should be based on determination of serum
concentrations. Doses may differ from those recommended by the package insert.
¥ Cefotaxime (if available), ceftazidime, or ceftriaxone is recommended if

cerebrospinal fluid is abnormal.
‡ 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.

Traditional strategies for the evaluation of febrile young infant
s (younger than 90 days of age)
Milwaukee Philadelphia R
Boston criteria
criteria criteria
Age range 28 to 89 days 28 to 56 days 29 to 60 days ≤6
Temperature ≥38.0°C ≥38.0°C ≥38.2°C ≥3
History* No Not defined Not defined Te

immunizations No
within last 48 an
hours No
No antimicrobial dis
within 48 hours No
Not dehydrated lon
m
Physical Well appearing Well Well appearing We

examination* No sign of focal appearing Unremarkable No
infection (middle (normal examination inf
ear, soft tissue, breathing, ea
bone/joint) alert, active, bo
normal
muscle tone)
Not
dehydrated
No sign of
focal
infection
(middle ear,
soft tissue,
bone/joint)
Laboratory CSF <10/mm 3 CSF <10/mm 3 CSF <8/mm 3 CS

parameters* WBC WBC WBC lum
<20,000/mm 3 <15,000/mm 3 <15,000/mm 3 is
UA <10 UA <5 to 10 UA <10 W
WBCs/hpf WBCs/hpf (no WBCs/hpf <1
Chest bacteria, Urine Gram stain AB
radiograph: no negative negative UA
infiltrate (if LE/nitrite) CSF Gram stain W
obtained) Chest negative Sto
radiograph: Chest W
no infiltrate radiograph: no (if
(if obtained) infiltrate
Stool: no blood,
few or no WBCs
on smear (if
indicated)
Band-neutrophil
ratio <0.2
Management Home/outpatient Reliable Home/outpatient Ho

strategy for Empiric caretaker No antibiotics No
low risk antibiotics followup Followup Fo
Follow-up required required re
required IM
ceftriaxone
50 mg/kg
followed by
re-evaluation
within 24
hours
Management Hospitalize Not defined Hospitalize Ho

strategy for Empiric Empiric Em
high risk antibiotics antibiotics an
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).
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.
Conflict of interest policy

The Febrile Infant 29 To 90 Days of Age Management UpToDate

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The febrile infant (29 to 90 days of age):

Literature review current through: Mar 2023.

The management of febrile infants younger than 90 days of age is discussed in

● (See "The febrile infant (29 to 90 days of age): Outpatient evaluation".)

Interpretation of other means of temperature measurement and caregiver

Well-appearing — There is no consensus definition for what constitutes a "well-

Increased risk for invasive bacterial infection — In otherwise well-

● Risk factors for IBI or abnormal inflammatory markers – For febrile

These recommendations are based upon observational studies that provide

● CSF pleocytosis – In patients who undergo lumbar puncture, those with

Suspected urinary tract infection — The approach to well-appearing

• Any risk factors for IBI ( table 1)

Because the risk of meningitis in well-appearing infants 29 to 60 days old

Alternatively, these patients may receive a single dose of IM ceftriaxone (50

• Lumbar puncture completed and CSF shows no pleocytosis and a

Limited evidence from retrospective observational studies supports outpatient

● No risk factors for IBI ( table 1)

In addition to ensured follow-up within 24 hours, caregivers must understand

The risk of IBI (bacteremia or bacterial meningitis) in well-appearing febrile

Infants 61 to 90 days old — The management of well-appearing infants 61 to

For patients in whom any blood inflammatory markers are abnormal

Patients with findings of bacterial pneumonia warrant empiric antibiotic

● No risk factors for IBI – The suggested evaluation for well-appearing

• For previously healthy and well-appearing febrile infants 61 to 90 days of

Patients who have preliminary urine findings indicative of a UTI warrant

Some contributors to this topic also recommend blood inflammatory

The risk of bacteremia for well-appearing febrile infants 61 to 90 days of age is

● Ancillary studies – Ill-appearing infants warrant a full and rapid evaluation

● Empiric antimicrobial – Empiric antimicrobial therapy using dosing for

Initial empiric therapy for immunocompetent patients varies by age as

- Ceftriaxone or, if available, cefotaxime and

- Ampicillin (to cover group B Streptococcus [GBS], Enterococcus

- Vancomycin (to cover Streptococcus pneumoniae or S. aureus that is

- Ceftriaxone or cefotaxime and

- Vancomycin (to cover S. pneumoniae or S. aureus that is not

In addition to these regimens, suggested antibiotics in individuals with a

● Hospital admission – Ill-appearing febrile infants are at higher risk of

Among young infants undergoing outpatient evaluation with clinical findings of

Respiratory syncytial virus bronchiolitis or influenza — Febrile infants 29 to

● RSV bronchiolitis – Febrile infants 29 to 90 days of age with RSV

Patients 29 to 60 days of age with abnormal initial urine testing warrant

● Influenza – Febrile infants 29 to 90 days of age with influenza by highly

Otherwise, they should be managed according to appearance and age as

Coronavirus disease 2019 — In young infants, severe acute respiratory

The treatment of COVID-19 in infants is discussed in detail separately. (See

Enterovirus — RT-PCR for enterovirus in cerebrospinal fluid distinguishes viral

● Abscess, cellulitis, osteomyelitis, or bacterial arthritis – Vancomycin and

Drainage and culture of any abscesses and, in ill-appearing infants with

● Omphalitis – Vancomycin and gentamicin or, in regions with substantial

● Mastitis – Febrile infants warrant empiric parenteral antibiotics tailored to

● Pneumonia – The treatment regimen is determined by age, clinical

• Infants 29 to 90 days of age with uncomplicated pneumonia –

• Infants 29 to 90 days of age with complicated pneumonia – Vancomycin

Use of oxacillin, nafcillin, or clindamycin instead of vancomycin where specified

Traumatic or dry lumbar puncture — A traumatic lumbar puncture can cause

If interpretable CSF cannot be obtained in febrile infants 29 to 90 days of age,

● Traumatic lumbar puncture – Patients with positive blood culture, CSF

● CSF not obtained – Repeat lumbar puncture is required in infants in whom

Management of infants with negative blood and urine cultures at 48 hours

Receiving antibiotics — Based upon the half-life of oral antibiotics in young

Further management depends upon the results:

● Abnormal CSF, urine testing, and/or elevated blood inflammatory markers