pediatrics
Fever in Infants and Children
Testing for Acute Fever
Foracute fever,testing for infectious causes is directed by the age of the child. Typically, children < 36 months, even those who do not appear very ill and those who have an apparent source of infection (eg, otitis media), require a thorough search to rule out serious bacterial infections (eg, meningitis, sepsis/bacteremia, urinary tract infection). In this age group, early follow-up (by phone and/or outpatient visit) is important for all those managed at home. All febrile children<1 month of age require a white blood cell (WBC) count with a manual differential, blood cultures, urinalysis and urine culture (obtained by catheterization, not an external bag), and cerebrospinal fluid (CSF) evaluation with culture and appropriate polymerase chain reaction (PCR) testing (eg, for herpes simplex, enterovirus) as indicated by historical risk factors. Inflammatory marker levels (C-reactive protein, procalcitonin, or both) may be measured to assist with risk assessment. Chest x-ray is done in neonates with respiratory manifestations. Stool is sent for culture or enteric PCR stool test in neonates with diarrhea. Neonates are hospitalized and given empiric IV antibiotic coverage for the most common neonatal pathogens (eg, usingampicillinandgentamicinorampicillinandcefotaxime); antibiotics are continued until a serious bacterial infection is ruled out by negative blood, urine, and CSF cultures or a specific diagnosis is made.Acycloviralso should be given if neonates are ill-appearing, have mucocutaneous vesicles, have a maternal history of genital herpes simplex virus (HSV) infection, or have seizures, hypothermia, leukopenia, thrombocytopenia, or elevated alanine aminotransferase (ALT);acycloviris stopped if CSF HSV PCR testing and mucocutaneous vesicle HSV culture (if done) results are negative. Febrile children between 1 month and 3 months of age require a different approach, which has evolved over the last few decades because the number of children in this age group who turn out to have a potentially serious bacterial infection has been markedly reduced by routine immunization againstH. influenzaetype b andS. pneumoniae. Clinicians must nonetheless maintain vigilance because, although serious bacterial infections have been reduced, they have not been eliminated. Therefore, clinicians who choose to observe without treatment or send home under parental observation need to have a greater certainty regarding that child's low-risk status than that of a child who is tested, admitted, and treated. Infants in this 1- to 3-month age group are differentiated based on Temperature Clinical appearance (ill- or well-appearing, as below) Laboratory results Febrile infants between 1 month and 3 months of age who are ill-appearing (eg, abnormal cry, lethargy, rectal temperature > 38.5° C) or who have risk factors for serious bacterial infection (eg, significant congenital anomalies, prematurity, technology dependence, unvaccinated) should be admitted to the hospital and have a WBC count with a manual differential, blood cultures, urinalysis and urine culture (obtained by catheterization, not an external bag), and lumbar puncture with CSF evaluation, including culture and, if available, PCR panel. Inflammatory marker levels (C-reactive protein [CRP], procalcitonin, or both) may be measured to assist with risk assessment. Chest x-ray and a respiratory PCR panel should be done in those with respiratory manifestations, and stool is sent for stool culture or enteric PCR stool test in those with diarrhea. These infants should be given age-specific empiric parenteral antibiotic therapy (eg,ceftriaxone) until serious bacterial infection is ruled out by negative cultures or a specific diagnosis is made. Well-appearing febrile infantsbetween 29 days and 60 days of agewith all of the following are at low risk of serious bacterial infections: Rectal temperature ≤ 38.5° C Normal WBC count (5,000 to 15,000/mcL [5 to 15 × 109/L] and an absolute neutrophil count ≤ 4000/mcL [≤ 4 × 109/L]) Normal inflammatory marker levels (procalcitonin ≤ 0.5 ng/mL [≤ 0.5 mcg/L] and/or CRP ≤ 2 mg/dL [≤ 20 mg/L]) Normal urinalysis (and CSF analysis and chest x-ray, if done) Blood and urine cultures should be obtained. Some experts defer lumbar puncture in these infants who meet the above criteria, but guidelines regarding minimum necessary testing in this age group continue to evolve based on changing bacteriology and advances in testing (eg, inflammatory markers, pathogen identification with rapid PCR testing) ( Testing for acute fever reference ). In addition, well-appearing febrile infants in this age group with a respiratory syncytial virus (RSV), influenza, or other viral infection documented by PCR testing during a period of high seasonal prevalence and who have a normal urinalysis seem to have a markedly reduced risk of serious bacterial infection, which some experts believe permits modifications to the above recommendations, meaning the infants might not necessarily require blood or CSF studies. These infants can be managed as outpatients if reliable follow-up is arranged within 24 to 36 hours either by telephone or by return visit, at which time preliminary culture results are reviewed. If the family's social situation suggests that follow-up within 24 to 36 hours is problematic, infants should be admitted to the hospital and observed. If infants are sent home, any deterioration in clinical status or worsening of fever, a positive blood culture not thought to be a contaminant, or a positive urine culture in an infant who remains febrile warrants immediate hospitalization with repeat cultures and age-specific empiric antibiotic therapy (eg,ceftriaxone) until serious bacterial infection is ruled out by repeat culture results or a specific diagnosis is made. In well-appearing febrile infantsbetween 61 days and 90 days of agewithout risk factors for serious bacterial infection, many experts defer blood and CSF studies pending urinalysis results. When testing is done in well-appearing infants between 1 month and 3 months of age, infants who have any of the following should be admitted to the hospital for treatment with age-specific empiric parenteral antibiotics as described above: CSF pleocytosis An abnormal urinalysis or chest x-ray A peripheral WBC count ≤ 5,000/mcL (≤ 5 × 109/L) or ≥ 15,000/mcL (≥ 15 × 109/L) An absolute neutrophil count > 4000/mcL (> 4 × 109/L) Abnormal inflammatory marker levels (procalcitonin > 0.5 ng/mL [> 0.5 mcg/L] and/or CRP > 2 mg/dL [> 20 mg/L]) If empiric antibiotics are to be given, lumbar puncture with CSF analysis should be strongly considered if not previously done, especially in infants 29 to 60 days of age. Some experts believe that well-appearing infants between 1 month and 3 months of age with an abnormal urinalysis but otherwise reassuring examination and laboratory results can be safely managed with antibiotics at home if close follow-up is assured within 24 hours ( Testing for acute fever reference ). Febrile children between 3 months and 36 months of age who have an apparent source of fever on examination and who do not appear ill or toxic can be managed based on the clinical diagnosis. Children in this age group who are ill-appearing should be fully evaluated for serious bacterial infection with WBC count and cultures of blood, urine, and, when meningitis is suspected, CSF. Those with tachypnea or a WBC count > 20,000/mcL (> 20 × 109/L) should have a chest x-ray. These children should be given parenteral antibiotic therapy (usually usingceftriaxone) targeting the likely pathogens in this age group (S. pneumoniae,Staphylococcus aureus,Neisseria meningitidis,H. influenzaetype b) and be admitted to the hospital pending culture results. Well-appearing children in this age group who have a temperature > 39° C and no identifiable source on examination (fever without source) and who are not fully immunized have a risk of occult bacteremia as high as 5% (equal to the risk before the pneumococcal andH. influenzaeconjugate vaccines came into use). These children should have a complete blood count with differential, blood culture, and urinalysis and urine culture. A chest x-ray should be done if the WBC count is ≥ 20,000/mcL (≥ 20 × 109/L) . Children who have a WBC count ≥ 15,000/mcL (≥ 15 × 109/L) should be given parenteral antibiotics pending blood and urine culture results.Ceftriaxone(50 mg/kg IM) is preferred because of its broad antimicrobial spectrum and prolonged duration of action. Children who received parenteral antibiotics should have follow-up within 24 hours by telephone or by return visit, at which time preliminary culture results are reviewed. If the social situation suggests that follow-up within 24 hours is problematic, children should be admitted to the hospital. Children who are not treated with antibiotics should be brought for reevaluation if they are still febrile (≥38°C) after 48 hours or earlier if they become sicker or if new symptoms or signs develop. Well-appearing children in this age group who have a temperature > 39° C and fever without identifiable source and who are completely immunized have a risk of bacteremia < 0.5%. At this low-risk level, most laboratory testing and empiric antibiotic therapy are neither indicated nor cost-effective. However, because urinary tract infection (UTI) can be an occult source of infection in fully immunized children in this age group, girls < 24 months, circumcised boys < 6 months, and uncircumcised boys < 12 months should have a urinalysis and urine culture (obtained by catheterization, not an external bag) and be appropriately treated if UTI is detected. For other completely immunized children, urine testing is done only when they have symptoms or signs of UTI, they have a prior history of UTI or urogenital anomalies, or fever has lasted > 48 hours. For all children, caregivers are instructed to return immediately if fever becomes higher, the child looks sicker, or new symptoms or signs develop. For febrile children>36 months of age, testing is directed by history and examination. In this age group, a child's response to serious illnesses is sufficiently developed to be recognized clinically (eg, nuchal rigidity is a reliable finding of meningeal irritation), so empiric testing (eg, screening WBC counts, urine and blood cultures) is not indicated. For acute recurrent or periodic fever, laboratory tests and imaging should be directed toward likely causes based on findings from the history and physical examination. PFAPA Syndrome should be considered in young children who have periodic high fever at intervals of about 3 to 5 weeks with aphthous ulcers, pharyngitis, and/or adenitis. Between episodes and even during the episodes, the children appear healthy. Diagnosis requires 6 months of stereotypic episodes, negative throat cultures during episodes, and exclusion of other causes (eg, specific viral infections). In patients with attacks of fever, arthralgia, skin lesions, mouth ulcers, and diarrhea, IgD levels should be measured to look for hyperimmunoglobulinemia D syndrome (HIDS). Laboratory features of HIDS include elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) and markedly elevated IgD (and often IgA). Genetic testing is available for familial Mediterranean fever (FMF), TNF receptor–associated periodic syndrome (TRAPS), and HIDS. 1.Pantell RH, Roberts KB, Adams WG, et al: Evaluation and management of well-appearing febrile infants 8 to 60 days old.Pediatrics148(2):e2021052228, 2021. doi: 10.1542/peds.2021-052228 