FOD EN NIOS MENORES DE 3 MESES

EVALUATION AND MANAGEMENT A cautious approach to neonates (0 to 28 days) and young

infants (29 to 90 days) with fever is prudent, given the risk and potentially adverse consequences of
unrecognized and/or untreated serious bacterial infection (SBI). Multiple approaches to the evaluation
of these infants, with varying inclusion and exclusion criteria, have been proposed and studied,
including protocols from Boston, Philadelphia, and Rochester [9-11]. While these approaches have a
high negative predictive value (ability to remove patients with SBI from the low-risk group), each
suffers from a relatively low positive predictive value, resulting in many infants undergoing
unnecessary laboratory testing, hospitalization, and exposure to unnecessary antibiotics.
(See "Strategies for the evaluation of fever in neonates and infants (less than three months of age)".)
The predictors of SBI used to classify febrile infants into risk subsets aid in the assessment of risk, but
they do not eliminate risk. There is a lack of definitive data to guide patient evaluation, and some
categories that define high-risk groups such as age and white blood cell (WBC) count are arbitrary.
Consequently, each patient and each clinical situation must be evaluated individually.
(See "Strategies for the evaluation of fever in neonates and infants (less than three months of age)".)
However, the use of evidence-based guidelines could help standardize care among, not only
individual physicians, but various institutions as well. As an example, outcomes for well-appearing
febrile infants cared for in four hospitals, including a childrens hospital, were assessed before (4524
febrile episodes) and after (2987 febrile episodes) the implementation of an evidence-based care
process model (EB-CPM) that was derived from the Rochester criteria [31,32]. EB-CPM
implementation was associated with significantly increased adherence to recommended diagnostic
testing (13 percent increased measurement of complete blood count, urinalysis, blood and urine
culture; 8 percent increase in viral testing for admitted infants), 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.
Neonates (0 to 28 days) The available guidelines and approaches to fever in young infants do not
perform well in neonates 28 days of age and younger compared with older infants [1]. Consequently,
most experts recommend that all neonates with a rectal temperature 38C have blood, urine, and
CSF cultures performed regardless of clinical appearance [33,34]. A chest radiograph should be
obtained in those with any sign or symptom of pulmonary disease. These neonates should be
admitted to the hospital and treated with empiric antibiotics (table 2). (See "Strategies for the
evaluation of fever in neonates and infants (less than three months of age)", section on 'Limitations in
neonates'.)
Antibiotic therapy Serious bacterial illness is present in approximately 12 percent of febrile
neonates [35]. Group B Streptococcus, a common pathogen in this age group, causes high rates of
meningitis (39 percent) and sepsis (9 percent). Prior to routine antibiotic administration to intrapartum
mothers and to febrile neonates, the case fatality rate approached 50 percent in babies with early
onset group B Streptococcal infection [36]. Other organisms that cause SBI in neonates include
Escherichia coli and other gram negative rods, enterococcus, and Listeria monocytogenes [37,38]. In
addition, Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis cause
disease in the slightly older neonate.
Because of the high rates of serious bacterial infection and high risk of mortality if untreated, we
recommend empiric treatment with antibiotics. Ampicillin and cefotaximeor ampicillin
and gentamicin are potential regimens that will provide empiric coverage for these organisms until
culture results are available (table 2). The combination of ampicillin and cefotaxime is preferred in
regions where there are high rates of gentamicin-resistant organisms [39]. (See "Definition and
etiology of fever in neonates and infants (less than three months of age)".)
Acyclovir Although acyclovir should not be used routinely in the management of febrile neonates,
those who are ill-appearing, have mucocutaneous vesicles, have a maternal history of genital
herpesvirus (HSV) infection, or have seizures should be treated with acyclovir (60 mg/kg per day
divided three times daily). In addition, elevated liver enzymes may be an early indicator of
disseminated HSV in neonates less than two weeks of age. Controversy exists regarding the use of
empiric acyclovir in neonates who have CSF pleocytosis without other clinical features suggestive of
HSV. We suggest that such patients receive acyclovir empirically pending the results of bacterial CSF
culture and CSF HSV DNA polymerase chain reaction (PCR). (See "Neonatal herpes simplex virus
infection: Management and prevention", section on 'Acyclovir therapy' and "Neonatal herpes simplex
virus infection: Clinical features and diagnosis", section on 'Clinical manifestations'.)
Cultures of skin vesicles (if present), oropharynx, conjunctivae, urine, blood, stool, and cerebrospinal
fluid for HSV should be obtained before the initiation of acyclovir. HSV antigen may be detected using
direct fluorescent antibody (DFA) tests of scrapings from the base of vesicles. In addition, CSF should
be sent for HSV DNA polymerase chain reaction (PCR). (See "Definition and etiology of fever in
neonates and infants (less than three months of age)".)
Ill-appearing infants (29 to 90 days) Infants who are ill-appearing, have an abnormal cry, or
temperatures 38.5C have a higher risk of SBI [40,41]. Because up to 45 percent of ill-appearing
young infants may have SBI [1], such infants should undergo the following treatment:
Full laboratory evaluation including blood, urine, and CSF.
Chest radiograph if signs or symptoms of pulmonary disease are present (respiratory rate
>50 breaths/min, rales, rhonchi, retractions, wheezing, coryza, grunting, stridor, nasal flaring, or
cough).
Empiric antibiotic therapy (with cefotaxime or ceftriaxone), regardless of the initial laboratory
results. Empiric therapy should also be adjusted based on specific clinical findings as follows:
Ampicillin (to cover Listeria up to six to eight weeks of age).
Vancomycin should be given to those infants with evidence of soft tissue infection.
(See "Evaluation and management of suspected methicillin-resistant Staphylococcus
aureus skin and soft tissue infections in children", section on 'Severe SSTI'.)
Vancomycin should be given to those infants with CSF pleocytosis to treat meningitis
caused by S. pneumoniae that is not susceptible to cefotaxime orceftriaxone, and in infants
29 to 60 days of age, ampicillin should also be given to cover Listeria monocytogenes
(table 2). (See "Treatment, prognosis, and prevention of Listeria monocytogenes
infection".)
Hospital admission
Well-appearing infants
29 to 60 days For well-appearing infants with a rectal temperature 38.0C, laboratory testing is
necessary to help determine which patients may be at high risk for a serious bacterial infection (SBI)
[11]. A complete history and physical examination with appropriate laboratory evaluation including
CBC, blood culture, urinalysis and culture, and CSF for cell count and culture should be performed in
most patients. Infants without CSF pleocytosis, a WBC count 5000 to 15,000/microL, and a normal
urinalysis are at low risk for a SBI.
Some clinicians may elect to perform fewer laboratory tests. There are, however, no guidelines for the
minimal evaluation of fever in well-appearing infants ages 29 to 60 days. The following factors should
be considered:
Urinary tract infections (UTIs) are common in this age group, particularly in uncircumcised boys
and in girls [26]. Consideration always should be given to performing a urinalysis with culture.
A WBC count 5000 to 15,000/microL with less than 1500 bands/microL suggests a lower risk of
SBI.
A stool culture should be performed if diarrhea is present.
Lumbar puncture may not be necessary in some well-appearing infants who have
knowledgeable caregivers, reliable transportation, and well-established follow up. However, a
lumbar puncture should always be performed whenever empiric antibiotics are prescribed.
A chest radiograph should be obtained in infants with at least one clinical sign of pulmonary
disease (respiratory rate >50 breaths/min, rales, rhonchi, retractions, wheezing, coryza,
grunting, stridor, nasal flaring, or cough) [29,42].
Infants 29 to 60 days of age with CSF pleocytosis or a peripheral WBC 20,000/microL should be
admitted to the hospital for treatment with empiric parenteral antibiotics. Many clinicians may also
prefer to admit infants with WBC 5000/microL and WBC 15,000/microL. We also suggest that those
with an abnormal urinalysis be treated with parenteral antibiotics as inpatients. (See "Strategies for
the evaluation of fever in neonates and infants (less than three months of age)".)
However, some experts treat well-appearing infants with an abnormal urinalysis with parenteral
antibiotics as outpatients [43,44]. Limited data from a retrospective review of the hospital course of
febrile infants <60 days of age with UTI demonstrated that progression of illness was unlikely and
lends some support to this strategy as long as the infant is well-appearing, does not have a high risk
past medical history, and has normal peripheral band and absolute neutrophil counts [44,45].
Multiple prospective studies have reported that infants who are at low risk of SBI based on history,
physical examination, and whatever laboratory testing has been performed can be safely managed as
outpatients. Reliable follow up must be arranged within 24 hours (either by phone or by return visit to
the clinician). If the social situation suggests that follow up within 24 hours is problematic (eg,
transportation problems or other concerns regarding parental adherence), then the infant should be
admitted to the hospital. (See "Strategies for the evaluation of fever in neonates and infants (less than
three months of age)", section on 'Traditional strategies'.)
Infants who are followed as outpatients may be treated presumptively with ceftriaxone (50 mg/kg in a
single dose), pending culture results. In making the decision whether or not to prescribe empiric
antibiotic therapy, the clinician must consider both the potentially severe risk of not treating a SBI as
well as the more common but typically less severe risks associated with parenteral antibiotic
administration. We recommend that CSF for culture be obtained if antibiotics are given empirically.
61 to 90 days Data regarding the incidence of serious bacterial infection (SBI) among infants 61 to
90 days of age with fever (as compared with younger infants) on which to base definitive guidelines
are limited. The risk of SBI for this age group may be similar to that for older febrile infants. 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 SBI between those who were 57 to 89 days of age and those
who were older [46]. (See "Fever without a source in children 3 to 36 months of age".)
Since infants less than three months of age have not yet been fully immunized against pneumococcus
and Haemophilus influenzae type b, most experts recommend a CBC, urinalysis, and cultures of
blood and urine be obtained in those who are well-appearing (see "Fever without a source in children
3 to 36 months of age", section on 'Well-appearing'). Those who have signs of pulmonary disease
should have a chest radiograph as well.
Despite its poor ability to identify young infants with bacteremia or meningitis, a WBC outside of the
normal range of 5000 to 15,000/microL suggests the need for lumbar puncture followed by treatment
with parenteral antibiotics until all cultures are final (table 2). For outpatient therapy in patients with
normal cerebrospinal fluid (CSF) and urinalysis, ceftriaxone (50 mg/kg) is the preferred drug because
of its antimicrobial spectrum and long duration of action. (See 'WBC count' above.)
Ill-appearing infants with an abnormal urinalysis should receive parenteral antibiotics after obtaining
CSF and be admitted to the hospital. However, well-appearing infants, over two months of age, can
be treated orally as long as oral intake is tolerated without obtaining CSF. The choice of antibiotic is
discussed in more detail separately. (See "Urinary tract infections in infants and children older than
one month: Acute management, imaging, and prognosis", section on 'Oral therapy'.)
As with infants 29 to 60 days of age, the clinician must consider the risk of not treating a SBI as well
as the risks associated with parenteral antibiotic administration in deciding whether or not to prescribe
empiric antibiotic therapy (ceftriaxone 50 mg/kg in a single dose). We suggest that CSF be obtained if
empiric antibiotics are prescribed. (See 'Cerebrospinal fluid studies' above.)
Follow up for outpatient treatment Well-appearing infants ages 29 to 90 days who are sent
home must have follow up within 24 hours either by phone or by visit, at which time preliminary
culture results (if obtained) are reviewed. Patients who received parenteral antibiotics at the initial visit
should return for a second intramuscular dose (eg, ceftriaxone 50 mg/kg) pending final culture results.
Any of the following circumstances warrants extensive evaluation and hospitalization for empiric
antibiotic therapy with cefotaxime, ceftriaxone, or other antibiotics, as indicated:
Any deterioration in clinical status or worsening of fever
A positive blood culture not thought to be a contaminant
A positive urine culture in an infant who remains febrile
For an infant with a positive urine culture who is afebrile and well-appearing less than 24 hours after
parenteral ceftriaxone, it may be reasonable to give a second dose of parenteral ceftriaxone at 24
hours and continue outpatient follow-up. (See "Urinary tract infections in newborns".)
Discharge criteria for admitted patients The length of hospitalization depends upon the clinical
course of the patient and the type of culture system in use. Early discharge is feasible in hospitals
with continuously monitored blood culture instruments, These systems identify between 77 and 87
percent of all cultures with pathogens [47,48] and 95 percent of critical pathogens (eg, S.
pneumoniae, Salmonella and other Enterobacteriaceae, N. meningitidis, groups A and B
streptococcus) within 24 hours [47].
Admitted patients over 28 days of age, who remain well-appearing during hospitalization and become
afebrile are eligible for discharge at 36 hours of negative cultures [31]. In addition, 24 hour discharge
may be appropriate for well-appearing patients who have positive viral testing regardless of the
presence of fever. 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 do not identify a viral etiology,
then the child should receive two additional doses of antibiotics (eg,ceftriaxone 50 mg/kg daily) until
all cultures are final and negative.
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 reevaluated, and further testing, consultation, and treatment options should be pursued.
Of note, neonates (0 to 28 days of age) by definition are not low risk and would not be eligible for
early discharge. These patients typically receive inpatient care and parenteral antibiotics until all
cultures are negative for at least 48 hours. Furthermore, initial treatment with acyclovir implies
significant clinical concern for herpes infection. It would seem prudent then to continue to treat the
infant with acyclovir until the PCR result of CSF specimen is available. (See "Neonatal herpes simplex
virus infection: Management and prevention", section on 'Acyclovir therapy'.)
Use of early discharge criteria has been associated with reduced length of stay. As an example,
implementation of a care plan that allowed discharge at 24 hours for infants with positive viral testing
for enterovirus or respiratory viruses, other than rhinovirus, (eg, respiratory syncytial virus, influenza)
and negative bacterial cultures ordischarge 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 [31].
DIFFICULT CLINICAL SITUATIONS Some clinical situations arise that do not fit neatly into
treatment guidelines. Until more definitive information becomes available, these circumstances should
be considered on an individual basis, using clinical judgment.
Dry or traumatic lumbar puncture When the decision is made to perform a lumbar puncture (LP),
every reasonable attempt should be made to obtain cerebrospinal fluid (CSF) for studies and culture.
However, this cannot always be accomplished and either no CSF (dry LP) or bloody CSF (traumatic
LP) may be obtained. In this circumstance, at a minimum, cultures of blood and urine should be
obtained.
If the LP is traumatic, the tube in which the CSF is clearest should be sent for a cell count. For
patients with a peripheral white blood cell (WBC) count that is in the normal range, one rule of thumb
is to subtract one WBC for every 500 to 1500 red blood cells. A predicted CSF WBC count can also
be used and its calculation is discussed in detail separately. (See "Cerebrospinal fluid: Physiology and
utility of an examination in disease states", section on 'Predicted WBC count after traumatic tap'.)
The possibility of meningitis cannot be excluded when the CSF cell count is not available or is not
interpretable. In this situation, the infant should be admitted and treated with meningitic doses of
antibiotics until the CSF culture is negative at 48 hours or the clinical picture warrants discharge.
When no CSF culture is obtained, negative blood and urine culture results in a baby who does well
would be reassuring, although the true incidence of meningitis in patients who have negative blood
and urine cultures is not known. A repeat lumbar puncture after admission, or observing the infant in
the hospital off antibiotics after the cultures are negative at 48 hours, are two acceptable approaches,
especially in infants under 29 days of age.
In contrast, the infant with a traumatic LP who has done well and has negative blood, urine, and CSF
cultures at 48 hours typically does not require a repeat lumbar puncture. In selected instances, infants
over 28 days of age may be discharged without a repeat LP or observation off antibiotics if they are
well-appearing and afebrile in addition to having negative blood and urine cultures.
However, a repeat lumbar puncture should be performed if either the blood or urine culture is positive
in patients with a dry LP because the finding of CSF pleocytosis may necessitate a prolonged course
of parenteral antibiotics, depending upon the organism isolated. (See "Bacterial meningitis in children
older than one month: Treatment and prognosis", section on 'Duration of therapy' and "Bacterial
meningitis in children older than one month: Clinical features and diagnosis", section on 'Diagnosis'.)
Patient on antibiotics A young infant on prophylactic antibiotics, usually for a urinary tract
abnormality, may have a serious bacterial illness masked by negative culture results. CBC, UA, CSF
cell count, and cultures of blood, urine, and CSF should be obtained with the understanding that
regardless of the laboratory evaluation, these patients cannot be classified as "low risk" for serious
bacterial infection (SBI), since they have an underlying condition that places them at risk for SBI.
Neonates should be admitted to the hospital and treated empirically with ampicillin and gentamicin or
ampicillin and cefotaxime, at least until cultures have been negative for 48 hours. For well-appearing
infants 29 days, it would be reasonable to consider admission to the hospital and empiric antibiotic
therapy, or at least observation in the hospital off of antibiotics.
Concomitant viral infections Despite the concern for SBI, most young infants with fever have a
viral illness. The presence of upper respiratory symptoms does not rule in a viral etiology, nor
conversely rule out a SBI. However, infants with a "recognizable viral syndrome," such as
bronchiolitis, croup, varicella, or stomatitis, have a markedly lower risk for bacteremia, although UTI
remains a significant concomitant infection in those with bronchiolitis and influenza [49,50].
Influenza Rapid diagnostic tests for the detection of viral neuraminidase are commercially
available for influenza A and B viruses and can be used for rapid point of care testing. However, test
performance is variable. False positive results occur and are of particular concern if rapid influenza
testing is used to limit further laboratory evaluation in young febrile infants. As a result, rapid influenza
testing should only be relied upon for clinical management during the time of regional high prevalence
for influenza infection, since high prevalence will raise the positive predictive value. (See "Seasonal
influenza in children: Clinical features and diagnosis", section on 'Laboratory diagnosis'.)
In a multicenter trial of 844 febrile infants 60 days of age who were tested for influenza, a
significantly lower rate of serious bacterial infection (SBI) was noted in the 123 infants who were
influenza-positive compared with the 721 infants who were influenza-negative (2.5 percent versus
11.7 percent, relative risk 0.19 [95% CI 0.06-0.59]) [51]. The three infants with SBI in the influenza-
positive group all had a urinary tract infection (UTI); none had bacteremia or meningitis. In contrast,
SBIs in influenza-negative patients included 77 with UTIs, 16 with bacteremia, and 6 with meningitis.
Although bacteremia was not identified in any of the 123 febrile infants with influenza, we suggest that
a complete blood count (CBC) with differential, blood culture, urinalysis, urine culture, and, in children
with clinical signs of pneumonia, a chest radiograph be obtained. If the CBC and urinalysis do not
suggest bacterial infection, lumbar puncture can be omitted in well-appearing febrile infants who are
older than 28 days of age, have a positive rapid influenza test, and no evidence of bacterial infection
on physical examination. This approach should only be considered if the rapid influenza test in use
has high specificity and is obtained during a time of high prevalence of influenza infection in the
region, thereby maximizing the positive predictive value.
Parents of infants more than 28 days of age who are discharged home from the emergency
department should understand that worsening respiratory distress, ill appearance, or inability to feed
warrant emergent return for medical care. In addition, these patients should have assured follow-up
with their primary care provider within 24 hours for possible worsening disease. 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 "Seasonal influenza in children: Clinical features and diagnosis", section on 'Bacterial
coinfection' and "Methicillin-resistant Staphylococcus aureus infections in children: Epidemiology and
clinical spectrum", section on 'Clinical spectrum'.)
Current evidence is insufficient to identify the risk of SBI in febrile neonates 28 days of age with
influenza infection, as only 36 such patients were in the above trial [51]. Extrapolation from studies of
febrile neonates with concomitant RSV infection suggests that those with influenza infection may
remain at high risk for a SBI and should undergo a full evaluation followed by inpatient observation
with antibiotic therapy. (See 'Bronchiolitis' below.)
Bronchiolitis Multiple retrospective and prospective observational studies demonstrate that the
incidence of SBI is 1.1 to 7 percent among febrile infants with bronchiolitis as opposed to 10 to 17
percent in high risk febrile infants without bronchiolitis [49,52-63]. However, the risk of SBI among
neonates (0 to 28 days of age) is substantial and does not appear to be altered by the presence of
RSV infection [49,63].
UTI is the most common SBI seen in febrile infants with bronchiolitis [62]. Bacteremia may be found in
up to 1 percent of these patients [49]. No cases of meningitis have been described in febrile infants
with concomitant clinical bronchiolitis [62].
These findings suggest that it may be reasonable to limit laboratory testing in well-appearing febrile
infants older than 28 days of age with bronchiolitis to CBC, blood culture, urinalysis, and urine culture.
If the CBC and urinalysis do not suggest bacterial infection, then these children may be managed
without antibiotics according to the degree of illness caused by their bronchiolitis. (See "Bronchiolitis
in infants and children: Treatment; outcome; and prevention", section on 'Indications for
hospitalization'.)
Febrile neonates (0 to 28 days) with bronchiolitis remain at high risk for a SBI and should have a full
evaluation and inpatient observation with antibiotic therapy.
Otitis media Acute otitis media (AOM) is diagnosed infrequently in neonates and young infants.
Nevertheless, the infant who presents with otitis media, with or without fever, can present a diagnostic
and management challenge. (See "Acute otitis media in children: Diagnosis", section on
'Diagnosis' and "Acute otitis media in children: Epidemiology, microbiology, clinical manifestations,
and complications", section on 'Clinical manifestations'.)
The Rochester [11] and Boston criteria [9] specifically exclude patients with ear infections from low-
risk groups, and the Philadelphia protocol only considers low-risk those cases with an "unremarkable
exam" [8]. On the other hand, one study found that none of the 13 infants excluded from the low-risk
group for only otitis media had systemic infections [12], and in a second report no infant excluded
from the low-risk group because of otitis media had a systemic infection [11]. (See "Strategies for the
evaluation of fever in neonates and infants (less than three months of age)".)
Similarly, a report of 130 patients 60 days and younger with AOM confirmed by tympanocentesis
found that the presence of AOM did not predict a higher risk for SBI in either febrile or afebrile
patients [64]. None of the afebrile infants with AOM or the febrile infants who were otherwise
determined to be at low risk developed a SBI. On the other hand, 14 percent of high-risk infants with
AOM also had a serious bacterial illness.
Finally, in a study of 40 infants zero to eight weeks of age with isolated otitis media who underwent a
full sepsis evaluation and tympanocentesis, all afebrile infants had negative cultures of blood, urine,
and CSF [65]. Two febrile infants had a SBI.
These findings suggest that febrile infants with AOM should be evaluated and managed similarly to
febrile infants without AOM. The decision to forego a full sepsis evaluation in afebrile infants with
AOM should be made with caution. The practitioner must consider the possibility of masking a SBI
and the difficult situation that will arise if the infant becomes febrile and ill-appearing.
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Beyond the Basics topic (see "Patient information: Fever in children (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS Given the risk and potentially adverse consequences of
unrecognized and/or untreated serious bacterial infection (SBI), a cautious approach to neonates (0 to
28 days) and young infants (29 to 90 days) with fever (T 38C or 100.4F) is prudent.
(See "Definition and etiology of fever in neonates and infants (less than three months of age)".)
Definitive data to guide patient evaluation are lacking, and some categories that define high-risk
groups such as age and white blood cell (WBC) count are arbitrary. (See"Strategies for the evaluation
of fever in neonates and infants (less than three months of age)".)
Consequently, each patient and each clinical situation must be evaluated individually. Bearing in mind
that the predictors of SBI used to classify febrile infants into risk subsets aid in the assessment of risk,
but do not eliminate risk, we offer the following recommendations:
Neonates (0 to 28 days)
We recommend that all neonates with a rectal temperature 38C have blood, urine, and
cerebrospinal fluid (CSF) cultures performed regardless of clinical appearance. We recommend
a chest radiograph be obtained in those with any sign or symptom of pulmonary disease. We
recommend that these neonates be admitted to the hospital (Grade 1B). Because of the high
rates of serious bacterial infection and high risk of mortality if untreated, we recommend empiric
treatment with antibiotics (Grade 1B) (table 2). (See 'Neonates (0 to 28 days)' above.)
Ampicillin and cefotaxime or ampicillin and gentamicin are potential regimens that will provide
empiric coverage for these organisms until culture results are available (table 2). The
combination of ampicillin and cefotaxime is preferred in regions where there are high rates of
gentamicin-resistant organisms. (See 'Neonates (0 to 28 days)' above.)
Infants 28 days who are ill-appearing and lethargic, demonstrate mucocutaneous vesicles,
have had seizures, display a CSF pleocytosis, or exhibit elevated liver transaminases may have
a CNS or disseminated herpes simplex virus (HSV) infection. In this select population of infants,
we suggest initiating treatment withacyclovir (60 mg/kg per day divided three times daily) (Grade
2B). For patients who are not initially treated with acyclovir, we suggest adding it if the bacterial
cultures remain negative at 48 to 72 hours, and the patient has not improved clinically (Grade
2C). Routine use of acyclovir is not indicated in the management of febrile neonates. Laboratory
studies to confirm the diagnosis of HSV should be sent prior to the initiation of acyclovir.
(See 'Neonates (0 to 28 days)' above.)
Ill-appearing infants (29 to 90 days)
We recommend that infants who are ill-appearing have a full laboratory evaluation including
blood, urine, and CSF cultures and receive parenteral antibiotics. Those who have signs of
pulmonary disease should also receive a chest radiograph. We recommend that these patients
receive empiric antibiotic therapy with cefotaximeor ceftriaxone and be admitted to the hospital
for ongoing parenteral antibiotic therapy (Grade 1B). (See 'Ill-appearing infants (29 to 90
days)' above.)
Empiric antibiotic therapy should also be adjusted based on specific clinical findings as follows
(see 'Ill-appearing infants (29 to 90 days)' above):
Vancomycin should be given to those infants with evidence of soft tissue infection.
(See "Evaluation and management of suspected methicillin-resistant Staphylococcus
aureus skin and soft tissue infections in children", section on 'Severe SSTI'.)
Vancomycin should be given to those infants with CSF pleocytosis to treat meningitis
caused by S. pneumoniae that is not susceptible to cefotaxime orceftriaxone and, in infants
29 to 60 days of age, ampicillin should also be given to cover Listeria monocytogenes
(table 2). (See "Treatment, prognosis, and prevention of Listeria monocytogenes
infection".)
Well-appearing
Infants 29 to 60 days of age
We suggest that well-appearing infants 29 to 60 days of age with a rectal temperature 38.0C
undergo a complete history and physical examination with appropriate laboratory evaluation
including CBC, blood culture, urinalysis and culture, and CSF for cell count and culture.
Although lumbar puncture may not be necessary in some well-appearing infants, including those
with bronchiolitis or a positive rapid test for influenza, we recommend that lumbar puncture be
performed if empiric antibiotics are prescribed, including in infants who have an abnormal
urinalysis or otitis media. A stool culture is suggested if diarrhea is present. (See '29 to 60
days' above.)
We suggest that a chest radiograph be obtained only in infants with at least one clinical sign of
pulmonary disease (respiratory rate >50 breaths/minute, rales, rhonchi, retractions, wheezing,
coryza, grunting, stridor, nasal flaring, or cough). (See '29 to 60 days' above.)
Infants who have an abnormal urinalysis, CSF pleocytosis, or an abnormal chest radiograph
require presumptive antibiotic therapy (table 2). Infants with pneumonia or meningitis should be
admitted to the hospital. We suggest that infants under 60 days of age with an abnormal
urinalysis also be admitted for a period of observation (Grade 2C). (See '29 to 60 days' above.)
Infants 29 to 60 days of age who are well-appearing and have a normal laboratory evaluation
and chest radiograph, when one is performed, can be sent home as long as reliable follow up
within 24 hours can be arranged (either by phone or by return visit to the clinician). We suggest
treatment with parenteral antibiotics (Grade 2C). Ceftriaxone (50 mg/kg in a single dose) is
preferred because of its antimicrobial spectrum and long duration of action. This
recommendation emphasizes the small but potentially severe risk of not treating a SBI as
opposed to the more common but typically less severe risks associated with parenteral antibiotic
administration. We suggest that CSF be obtained if antibiotics are given empirically. (See '29 to
60 days' above.)
Infants 61 to 90 days of age
We suggest that a CBC, urinalysis, and cultures of blood and urine be obtained in well-
appearing infants. Those who have signs of pulmonary disease should receive a chest
radiograph as well. In addition, WBC outside of the normal range of 5000
to 15,000/microL suggests the need for lumbar puncture followed by treatment with parenteral
antibiotics until all cultures are final (table 2). We suggest that CSF be obtained when empiric
antibiotics are prescribed. (See 'Cerebrospinal fluid studies'above and '61 to 90 days' above.)



Fiebre nios entre 3-36 meses

INITIAL APPROACH The evaluation and management of the febrile child 3 to 36 months of age
without a source of infection must balance the consequences of not diagnosing a SBI with the
decreasing prevalence of occult infection and the potential adverse effects of excessive testing and
treatment [41]. Burdens of testing and expectant antibiotic therapy include false-positive results,
adverse reactions to antibiotics, and, possibly, the effect of widespread antibiotic use on patterns of
antibiotic resistance. The likelihood of SBI varies significantly by clinical appearance, age, and
immunization status. (See 'Occult sources of infection' above.)
Well-appearing children 3 to 36 months of age, with fever 39C (102.2F), who have no underlying
medical condition that would alter susceptibility to infection, and no focus of infection identified by a
complete physical examination, are hereafter referred to as children with FWS.
Ill-appearing Children who are ill-appearing or have unstable vital signs should be fully evaluated
for serious infection with cultures of blood, urine, and, when meningitis is suspected, CSF. Those with
tachypnea or leukocytosis (>20,000/microL) should have a chest radiograph. These patients should
receive parenteral antibiotic therapy targeting the likely pathogens in this age group (S. pneumoniae,
S. aureus, N. meningitidis, H. influenzae type b) and be admitted to the hospital.
Well-appearing
Immunization incomplete The risk of occult bacteremia in incompletely immunized children is
estimated to be as high as 5 percent (ie, what it was during the preconjugate vaccine era); the actual
risk is probably somewhat lower because of "herd immunity." (See 'Immunization status' above
and 'Impact of vaccines' above.)
Strategies for the evaluation and management of these children reflect the increased risk of
bacteremia compared with completely immunized children and are drawn from experience and
guidelines developed during the preconjugate vaccine era [4,30,31,33,44,50,63,64].
We suggest the following approach to evaluation of these children:
CBC with differential.
Blood culture should be obtained if the WBC is 15,000/microL. As a practical matter, the
blood culture may be drawn with the CBC and sent if the WBC is15,000/microL. Recognizing
that WBC is not an ideal screening tool, some clinicians may prefer to always send a blood
culture in these patients [33,39,42].
Urinalysis, and urine culture by bladder catheterization or in exceptional cases (eg, tight
phimosis), suprapubic aspiration.
Chest radiograph in children with WBC 20,000/microL.
Children with an abnormal urinalysis should be treated for a urinary tract infection, although in
questionable cases awaiting results of urine culture represents a reasonable alternative. (See "Urinary
tract infections in infants and children older than one month: Acute management, imaging, and
prognosis", section on 'Overview'.)
We recommend that children with FWS who are incompletely immunized who have a
WBC 15,000/microL receive parenteral antibiotic therapy pending blood and urine cultures
[4,42]. Ceftriaxone (50 mg/kg, intramuscularly) is preferred because of its antimicrobial spectrum and
prolonged duration of action. Clindamycin (10 mg/kg,intravenously followed by oral clindamycin eight
hours later) is one alternative for patients allergic to cephalosporins. Outpatient follow-up should occur
within 24 hours. Patients in whom outpatient follow-up is uncertain should be admitted.
This strategy of selective treatment of high-risk children with FWS and WBC 15,000/microL is in
agreement with the practice guidelines of the American Academy of Pediatrics and the American
College of Emergency Physicians for children with FWS [4,65,66].
Support for treating patients 3 to 36 months of age with FWS and significant risk of bacteremia with
empiric parenteral antibiotics is derived from meta-analyses and randomized trials performed before
the routine availability of Hib, PCV7, and PCV13 conjugate vaccines [23,24,30].
A meta-analysis of four randomized controlled trials of 7899 children, age 3 to 36 months, who
had a fever 39C (102.2F), found that treatment of occult bacteremia with
IM ceftriaxone reduced the chance of serious bacterial infections by approximately 75 percent
(Number needed to treat (NNT) 17; OR 0.25; 95% CI 0.07-0.89) and that oral antibiotics were
not effective [67].
A meta-analysis of prospective and retrospective studies of children age 3 to 36 months with
fever without a source and bacteremia found that the mean probability of subsequent meningitis
was 8.2 percent (all H. influenzae, type b) in patients treated with oral antibiotics and 0.3 percent
in patients treated with parenteral antibiotics versus 9.8 percent in untreated children. No child
treated with ceftriaxone developed culture-positive meningitis (0.3 percent; 95% CI 0.0-1.5
percent). The authors concluded that antibiotic therapy is effective in preventing meningitis [8].
A randomized, double blind, placebo controlled trial of 955 children between the ages of 3 to
36 months with fever 39C (102.2F) demonstrated no difference in major infectious morbidity
between bacteremic children receiving oral amoxicillin (2 of 19) or placebo (1 of 8). The
incidence of diarrhea was 15 percent in children receiving amoxicillin versus 11 percent in the
placebo group (p = 0.10) [24]. The overall rate of bacteremia was 2.8 percent in this study.
An unblinded, randomized controlled trial of 6733 children between the ages of 3 to 36 months
with fever 39C (102.2F) also described an overall rate of bacteremia of 2.8 percent (195 of
6733) [30]. Five definitive focal infections (three meningitis, one pneumonia, and one sepsis)
developed in the 3347 children receiving amoxicillin versus none in those treated with
IM ceftriaxone (OR 0.0, 95% CI 0.0-0.5).
An unblinded, randomized trial of 96 children, between 6 and 24 months of age with a
temperature >40C (104F), found that 4.3 percent of untreated patients (2 of 46) developed
pneumococcal meningitis versus none of the 50 children treated with intramuscular
aqueous penicillin G at the initial visit followed by oral penicillin for 10 days. Bacteremia was
identified in 10.4 percent of all children [23].
Possible dermatologic adverse reactions were more commonly seen in the ceftriaxone group (8.7
versus 4.9 percent), but gastrointestinal complaints, such as diarrhea, were not different (14.5 versus
15.0 percent). No anaphylaxis was seen in either group.
Taken together, these studies indicate that unimmunized children with FWS avoid progression of
bacteremia to focal infections, especially meningitis, when treated with parenteral antibiotics. Given
the increasing prevalence of penicillin resistant S. pneumoniae, intramuscular ceftriaxone remains a
preferred parenteral agent.
Immunization complete A child with FWS who is completely immunized has a risk of bacteremia
that is <1 percent. Decision analysis suggests that at this low risk, laboratory evaluation and empiric
antibiotic therapy do not significantly alter the likelihood of progression to focal bacterial infection and
are not indicated [42,68]. (See 'Immunization status' above and 'Impact of vaccines' above.)
However, the risk of UTI as an occult source of infection remains substantial in fully immunized
children, depending on age, gender, and circumcision status [41]. This risk guides recommendations
for evaluation and treatment in these patients [67].
For children over six months of age with FWS who are completely immunized, we suggest that
girls less than 24 months of age and uncircumcised boys less than 12 months receive a
urinalysis and urine culture. Urine for culture should be collected by catheterization or, in
exceptional cases (eg, tight phimosis or severe labial adhesions), suprapubic aspiration. Bag
specimens should not be sent for culture because they are frequently contaminated. (See "Urine
collection techniques in children" and 'Urinary tract infection' above.)
For girls >24 months of age, uncircumcised boys >12 months of age and circumcised boys >6
months of age, all of whom have been completely immunized, we do not suggest routine
laboratory evaluation or presumptive treatment with antibiotics. However, urinalysis and urine
culture should be obtained in those with signs or symptoms of UTI, which must be specifically
sought (eg, dysuria, frequency, abdominal pain, back pain, new onset incontinence). In addition,
children with a prior history of UTI, urogenital anomalies, or prolonged fever (>48 hours) warrant
urinalysis and urine culture. (See 'Urinary tract infection' above.)

Some experts suggest that a high fever without a source (>39C [102.2F]) is sufficient
justification for urine culture on the first visit in uncircumcised boys 12 to 24 months of age
(algorithm 1). (See "Urinary tract infections in infants and children older than one month: Clinical
features and diagnosis", section on 'Decision to obtain'.)
Children with FWS who are completely immunized against Hib and either PCV7 or PCV13,
meet criteria for urine testing, and have an abnormal urinalysis should be treated for UTI.
Appropriate follow-up should be arranged. (See "Urinary tract infections in infants and children
older than one month: Acute management, imaging, and prognosis", section on 'Overview'.)
Despite the high risk for UTI and low risk for bacteremia among fully immunized children, evidence
suggests that some emergency department (ED) clinicians may not utilize laboratory testing and
antibiotic therapy appropriately when caring for these patients. As an example, between 2006 and
2008, estimates regarding laboratory testing and antibiotic treatment extrapolated from 1600 ED visits
by fully immunized febrile children 6 to 36 months of age in the United States were as follows [69]:
No testing was performed in 59 percent
Complete blood counts were obtained in 21 percent
Urine testing was not performed in an estimated 60 percent of girls with high fever
Antibiotics were prescribed in an estimated 20 percent of patients in whom no testing was
performed
These estimates suggest that urine testing may be underutilized while measurement of complete
blood count and antibiotic treatment may be overutilized in these patients.
FOLLOW-UP Follow-up should be arranged within 24 hours for those children with FWS who have
received parenteral antibiotics. Patients who are not treated with antibiotics should be instructed to
seek medical attention within 48 hours if they have persistent fever.
Careful instructions should be given to caretakers to return immediately if fever becomes higher, the
patient looks sicker, or local symptoms or signs develop (eg, cough, diarrhea, cellulitis).
Positive blood cultures An organism may not be identified definitively for 24 to 48 hours after the
blood culture becomes positive, making management decisions difficult. The clinical appearance of
the child and the Gram stain of the organism can be useful in deciding whether or not the child should
be admitted to the hospital. Consultation with the microbiology laboratory personnel and/or an
infectious disease consultant may be helpful in narrowing the list of potential organisms and the
likelihood that the findings represent a pathogen. Patients with a positive culture that is felt to be a
pathogen should be reevaluated and managed according to appearance, persistence of fever, and
specific isolate (algorithm 2).
The main goal is to identify and avoid progression to serious bacterial infection, especially meningitis:
S. pneumoniae
Febrile In a retrospective observational study prior to PCV7 availability, 548 children with a
blood culture positive for S. pneumoniae had outcomes examined. Children who were well, but
persistently febrile at the revisit and did not receive antibiotics at the initial visit had a 33 to 42
percent chance of infection (primarily persistent bacteremia) and a 4.4 percent chance of
meningitis [64]. Meningitis developed despite initial oral antibiotic therapy in 2 of 49 children (4
percent). Because of this high risk of SBI, patients with a blood culture positive for S.
pneumoniae who are febrile on revisit should undergo a full sepsis evaluation (including lumbar
puncture). They should also receive parenteral antibiotics tailored to the isolate's susceptibility or
to the community susceptibility pattern for S. pneumoniae if the culture susceptibility is not yet
available.

These children may receive continued antibiotic therapy as an outpatient for 7 to 10 days with
close follow-up if CSF findings show no evidence of meningitis. Antibiotic regimens should
provide coverage for resistant S. pneumoniae. Possibilities include high dose
oral amoxicillin (30 mg/kg per dose, three times daily; maximum dose: 3 grams daily),
oral amoxicillin-clavulanate 45 mg/kg per dose twice daily (maximum dose of amoxicillin: 3
grams daily), or clindamycin 10 mg/kgper dose three times daily in penicillin allergic patients.
Afebrile Well-appearing, afebrile children who did not receive antibiotics at the initial visit and
who have a blood culture positive for S. pneumoniae have an approximately 9 percent risk of
persistent bacteremia [64]. These patients can be managed with antibiotics as an outpatient with
close follow-up. Another blood culture should be drawn before further antibiotic therapy is
initiated. Antibiotic regimens should provide coverage for resistant S. pneumoniae. Possibilities
include high dose oral amoxicillin (30 mg/kg per dose, three times daily; maximum dose: 2 to 3
grams daily), oral amoxicillin-clavulanate (45 mg/kg per dose, twice daily; maximum dose: 3
grams total daily dose of amoxicillin), or clindamycin (10 mg/kg per dose, three times daily) in
penicillin allergic patients.
Other pathogens The limited data for bacteremia caused by organisms other than S. pneumoniae
suggests that outpatient therapy with oral antibiotics does not prevent serious bacterial infection, even
in well-appearing, afebrile children. In addition, the risk of meningitis is presumed to be high for
patients with N. meningitidis bacteremia.
For these reasons, hospital admission and parenteral antibiotic therapy is suggested for children with
a blood culture that is positive for N. meningitidis, H. influenzae type b, S. aureus, gram negative rods,
or other pathogens. A lumbar puncture should be performed if meningitis is clinically suspected. CSF
evaluation is also recommended for patients with blood culture positive for N. meningitidis and for
young infants (three to six months of age) with Group B Streptococcus bacteremia. Well children over
three months of age with a blood culture positive for E. coli or S. aureus do not need a lumbar
puncture.
Probable blood culture contaminant With the decline in the prevalence of occult bacteremia, it is
now more likely that a blood culture will be positive for a contaminant than for a pathogen [31-33,50].
Certain microbiologic features, such as slow growth or Gram stain, showing either gram-positive rods
or gram-positive cocci that are coagulase negative, suggest a contaminant. Consultation with the
microbiology laboratory and/or an infectious disease specialist may be useful when preliminary results
are unclear.
Molecular assays can help rapidly detect Staphylococcus aureus, including methicillin-resistant
strains in blood cultures positive for gram-positive cocci in clusters. (See"Rapid detection of
methicillin-resistant Staphylococcus aureus", section on 'Blood cultures'.)
The child who is well on follow-up, afebrile, and has an isolate from blood culture that is a likely
contaminant can be followed without antibiotic treatment, pending the final identification of the
organism.
Children who are not well on follow-up or continue to have fever should be reevaluated and the
assumption that the positive blood culture represents a contaminant should be reevaluated (algorithm
2). (See 'Positive blood cultures' above.)
Positive urine culture Children with a positive urine culture should be treated for UTI.
(See "Urinary tract infections in infants and children older than one month: Acute management,
imaging, and prognosis", section on 'Overview'.)
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 5
th
to 6
th
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 10
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to 12
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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 information: Fever in children (The Basics)")
Beyond the Basics topic (see "Patient information: Fever in children (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
General issues
The following recommendations apply to well-appearing children 3 to 36 months of age, with
fever 39C (102.2F), who have no underlying medical condition that would alter susceptibility
to infection, and no focus of infection identified by a complete physical examination, hereafter
referred to as children with FWS. (See'Background' above.)
The majority of children with fever have either a self-limited viral infection or a recognizable
source of bacterial infection. (See 'Occult sources of infection' above.)
Serious bacterial infections that occur in children 3 to 36 months of age include meningitis,
pneumonia, and focal skin infections.
Subtle sources of infection, such as pneumonia or osteomyelitis, can sometimes be
identified with a careful history and physical examination.
Relatively common occult sources of infection include pneumonia and urinary tract
infections (UTIs), with occasional cases of bacteremia.
A thorough history, including immunization status and complete physical examination, should
be performed in all febrile children to identify obvious and subtle focuses of infection.
(See 'History' above and 'Physical examination' above.)
Ill-appearing child
Children who are ill-appearing or have unstable vital signs require full evaluation for serious
infection with cultures of blood, urine, and when meningitis is suspected, CSF. A chest
radiograph should be obtained in patients who have tachypnea or respiratory distress and is
warranted for those with WBC 20,000/microL, even in the absence of physical findings of
pneumonia. (See 'Ill-appearing' above.)
Children who are ill-appearing or have unstable vital signs should receive parenteral antibiotic
therapy targeting the likely pathogens in this age group (S. pneumoniae, S. aureus, N.
meningitidis, H. influenzae type b) and be admitted to the hospital. (See 'Ill-appearing' above.)
Well-appearing child
Incompletely immunized
For children with FWS who have not been completely immunized, we suggest the following
tests:
CBC with differential: A blood culture should be sent for those with
WBC 15,000/microL. Some clinicians may choose to send a blood culture for all patients.
(See 'Immunization incomplete' above.)
Urinalysis and urine culture by bladder catheterization or, in exceptional cases (eg, tight
phimosis or severe labial adhesions), suprapubic aspiration. (See'Urine tests' above
and 'Immunization incomplete' above.)
Chest radiograph when WBC 20,000/microL. (See 'Immunization incomplete' above.)
We recommend that incompletely immunized children with FWS and
WBC 15,000/microL receive parenteral antibiotic therapy pending culture results (Grade 1B). A
single dose of intramuscular ceftriaxone (50 mg/kg) is preferred because of its antimicrobial
spectrum and duration of action. (See 'Immunization incomplete'above.)
These patients should be seen for follow-up by their primary care provider within 24 hours. An
alternative is to follow-up in the emergency department if a regular source of primary care is
unavailable. (See 'Follow-up' above.)
Completely immunized
For children >6 months of age with FWS who are completely immunized, we suggest that girls
<24 months of age and uncircumcised boys <12 months receive a urinalysis and urine culture.
Urine for culture should be collected by catheterization or, in exceptional cases (eg, tight
phimosis or severe labial adhesions), suprapubic aspiration. Bag specimens should not be sent
for culture because they are frequently contaminated. (See 'Urinary tract infection' above
and "Urine collection techniques in children".)
For girls >24 months of age, uncircumcised boys >12 months of age and circumcised boys >6
months of age with FWS, all of whom have been completely immunized, we do not suggest
routine laboratory evaluation. In addition, these children should not receive presumptive
treatment with antibiotics (Grade 1B). However, urinalysis and urine culture should be obtained
in those at high risk for UTI. (See 'Urine tests' above and 'Immunization complete' above.)
Completely immunized children with fever 39C (102.2F) and an abnormal urinalysis should
be treated for a urinary tract infection. (See 'Immunization complete'above and "Urinary tract
infections in infants and children older than one month: Acute management, imaging, and
prognosis", section on 'Antibiotic therapy'.)
Clinical follow-up
We recommend that children with fever that persists for more than 48 hours or with a
deterioration in clinical condition undergo repeat medical evaluation.
Culture follow-up
Urine cultures
Patients with a positive urine culture require treatment tailored to the identified organism and
their clinical status. (See "Urinary tract infections in infants and children older than one month:
Acute management, imaging, and prognosis", section on 'Overview'.)
Blood cultures
Children of 3 to 36 months of age with a positive blood culture for a presumed pathogen
require reevaluation and management based on their appearance, persistence of fever, and
specific isolate (algorithm 2). (See 'Positive blood cultures' above.)
We suggest that the child who is well on follow-up, afebrile, and has an isolate from a
preliminary report of a blood culture that is a likely contaminant, be followed on a daily basis as
an outpatient without antibiotic treatment, pending the final identification of the organism (Grade
2C). (See 'Probable blood culture contaminant'above.)