22.2 Serious Neonatal, Congenital, Vector-Borne & Vaccine-Preventable Acute Infections
Key Takeaways
For eligible, well-appearing febrile infants aged 8–21 days, obtain catheterized or suprapubic urine for urinalysis, blood culture and CSF, then admit and start parenteral therapy. At 22–60 days, age and inflammatory markers help guide the need for LP and hospital observation.
Vesicles, seizures or otherwise unexplained hepatitis, coagulopathy or sepsis-like illness warrant assessment for neonatal HSV. Start IV acyclovir promptly when disease is suspected while obtaining PCR samples and assessing renal function.
Suspected RMSF warrants empiric doxycycline at any pediatric age. The rash can be absent early, and early serology can be negative.
In a young infant with apnea and rapidly rising leukocytosis, consider critical pertussis and evaluate for pulmonary hypertension. Constipation with descending bulbar weakness points toward infant botulism and prompt program-directed BabyBIG.
In a young infant with fever, age and appearance help determine whether to use a well-infant pathway or stabilize and treat immediately. For a child with suspected measles, start isolation at first contact. For suspected neonatal herpes simplex virus (HSV) or Rocky Mountain spotted fever (RMSF), collect specimens when feasible and begin treatment while results are pending.
Well-appearing febrile infants aged 8–60 days
The 2021 American Academy of Pediatrics (AAP) guideline applies to well-appearing infants born at 37 to less than 42 weeks who are now aged 8–60 days, are at home after nursery discharge or home birth, and have a rectal temperature of at least 38.0°C at home within the preceding 24 hours or in a clinical setting. Use a separate assessment for infants who appear ill, those younger than 8 days, or those with prematurity, a neonatal course complicated by surgery or infection, suspected HSV, a focal bacterial infection, clinical bronchiolitis, immunocompromise, medical fragility, congenital abnormalities or vaccination within the past 48 hours. Also exclude infants under 2 weeks whose perinatal course included maternal fever, infection or antimicrobial use. Base management on the reason for exclusion. A poorly perfused or ill-appearing infant needs urgent sepsis assessment and treatment. AAP febrile infant guideline
For eligible infants aged 22–60 days, obtain procalcitonin (PCT) with an absolute neutrophil count (ANC) or C-reactive protein (CRP). Abnormal markers include PCT >0.5 ng/mL, CRP >20 mg/L, or ANC >4,000/mm³ when using the PCT and ANC approach. If PCT is unavailable, use both ANC and CRP and count a temperature >38.5°C as an abnormal marker. The AAP discusses ANC cutoffs from 4,000 to 5,200/mm³ across strategies. A no-PCT strategy uses >5,200/mm³ with CRP and temperature. Use the thresholds from the same pathway. A rectal temperature of 38.0°C still qualifies as fever.
| Age | Initial evaluation | CSF, therapy and disposition |
|---|---|---|
| 8–21 days | Catheterized or suprapubic urine for urinalysis (UA) and culture if positive, blood culture and CSF studies. | Admit and start parenteral therapy. Normal inflammatory markers cannot justify skipping CSF evaluation. The AAP table uses ampicillin plus ceftazidime for suspected bacterial meningitis. |
| 22–28 days | UA, catheterized or suprapubic urine culture if UA is positive, blood culture and inflammatory markers. | Obtain CSF if any marker is abnormal. With normal markers, CSF may be deferred under the inpatient observation pathway after obtaining blood and urine cultures. Hospitalize if CSF is unavailable or uninterpretable, UA is positive or CSF suggests bacterial meningitis. Home monitoring is an option when UA and markers are normal, CSF is normal or enterovirus-positive and safe follow-up is arranged. Give parenteral therapy before home monitoring with normal CSF, as in AAP KAS 12d. |
| 29–60 days | UA, catheterized or suprapubic urine culture if UA is positive, blood culture and inflammatory markers. | Consider CSF if any marker is abnormal. With normal markers, LP is generally unnecessary. Admit for abnormal CSF and use parenteral meningitis therapy if indicated. Treat a positive UA with oral UTI therapy when markers are normal and CSF, if obtained, is normal. When UA and markers are normal and CSF, if obtained, is normal, home observation without antibiotics is appropriate if reliable follow-up is in place. |
Choose empiric therapy by age and suspected site. If considering ceftriaxone in a neonate, first check postmenstrual age, bilirubin, IV calcium exposure and institutional eligibility. Home observation depends on caregiver teaching, reliable communication and transport, access to urgent reassessment and reevaluation within 24 hours. For an eligible 25-day-old with normal markers whose parents decline LP, discuss inpatient monitoring. An eligible 41-day-old with normal markers and a positive UA may receive oral treatment with a properly collected urine culture and close follow-up. In either age group, clinical deterioration supersedes the low-risk pathway. AAP key action statements and antimicrobial table · UCSF neonatal ceftriaxone safety criteria
Perform lumbar puncture when indicated and safe
In an eligible, stable febrile infant aged 8–21 days, cerebrospinal fluid (CSF) helps identify meningitis and direct therapy. If shock, significant respiratory compromise, findings concerning for herniation or a clinically important bleeding risk make the procedure unsafe, defer it and reassess after stabilization. In suspected bacterial meningitis, obtain blood cultures promptly when feasible and start empiric antibiotics without waiting for an unsafe or delayed puncture.
Explain the purpose and risks, prepare analgesia and monitoring, and use an assistant to hold the child sitting or lateral with the lower back flexed. Avoid overflexing an infant's neck because this can obstruct breathing. Identify the lumbar interspace using the iliac crests and use a low lumbar site, such as L4–L5, below the spinal cord. With sterile preparation and a styleted spinal needle, collect CSF into sterile, numbered tubes for cell count, glucose, protein, Gram stain and bacterial culture. Obtain a paired blood glucose and order other studies, such as HSV PCR, when indicated. A traumatic tap can make interpretation difficult. Reassess the need for another attempt with an experienced clinician. Other risks include post-puncture headache and rare infection or bleeding. AAP febrile infant guideline · RCH pediatric lumbar puncture technique
Neonatal HSV
Consider skin, eye and mouth disease, CNS encephalitis, and disseminated disease. Clues include vesicles or mucosal ulcers, seizures, unexplained hepatitis or coagulopathy, thrombocytopenia, hypothermia or a sepsis-like illness. CNS or disseminated disease can occur without vesicles. Maternal genital lesions or a first episode around delivery matter even if an exposed newborn has no symptoms. Use the perinatal-exposure algorithm for that infant.
When neonatal HSV disease is suspected, begin IV acyclovir promptly. The usual term-neonatal dose is 20 mg/kg every 8 hours with interval or dose review for prematurity or renal impairment. Obtain lesion or mucosal samples, blood HSV PCR, CSF HSV PCR when safe and serum ALT. Avoid delaying treatment for LP or PCR results. AAP febrile infant HSV considerations · UCSF neonatal HSV pathway
Congenital and late-onset neonatal infection
| Infection | Findings that narrow the differential | Diagnostic and treatment priorities |
|---|---|---|
| Congenital CMV | Sensorineural hearing loss, periventricular calcifications, microcephaly, petechiae or thrombocytopenia, hepatosplenomegaly or chorioretinitis. | Collect urine for CMV PCR or confirm a positive saliva PCR with urine within 21 days of birth. For moderate-to-severe disease, the 2026 AAP report recommends valganciclovir 16 mg/kg per dose twice daily for six months, starting by 13 weeks of age. For isolated sensorineural hearing loss, six weeks may be offered within that initiation window with specialist input. Arrange hearing follow-up and monitor blood counts and organ function during therapy. |
| Congenital toxoplasmosis | Chorioretinitis, hydrocephalus and scattered intracranial calcifications are classic. | Arrange reference-laboratory serology, with PCR where appropriate, eye exam and neuroimaging. The usual treatment course is 12 months of pyrimethamine, sulfadiazine and leucovorin, with blood count monitoring. |
| Congenital syphilis | Rhinitis, rash involving palms or soles, hepatosplenomegaly and bone disease with apparent limb weakness from pain. | Compare infant serum and maternal quantitative nontreponemal titers using the same test. An infant titer at least fourfold higher supports highly probable disease. Maternal treatment history and the infant exam also guide classification even with a lower titer. For confirmed or highly probable disease, evaluate CSF, blood count and long bones and use a 10-day parenteral penicillin G regimen. |
| Late-onset group B streptococcal disease | Age 7–89 days. Consider bacteremia, meningitis and focal disease such as bone or joint infection. | Intrapartum prophylaxis targets early-onset disease. Obtain blood culture and CSF when indicated and safe, give age- and site-appropriate empiric therapy, and narrow confirmed susceptible GBS to penicillin G or ampicillin. Arrange audiology after meningitis. |
AAP congenital CMV report · CDC congenital CMV testing · AAP congenital toxoplasmosis report · CDC congenital syphilis · AAP GBS report
Vector-borne emergencies
- RMSF. Rickettsia rickettsii infects vascular endothelium and can cause systemic vascular leak, thrombocytopenia, hyponatremia and organ injury. Consider it with fever, severe headache, myalgia or gastrointestinal symptoms after possible tick exposure. Macules may appear first on the wrists and ankles after several days of fever, spread centrally, and later become petechial. Palms and soles can be involved. Rash can be absent at presentation and serology is often negative in the first week. Start doxycycline 2.2 mg/kg per dose every 12 hours up to 100 mg per dose in children of all ages, with IV therapy for severe disease or when oral therapy is unsuitable. The short courses used for RMSF have not been shown to stain permanent teeth. CDC rickettsial guidance · CDC RMSF treatment
- Lyme carditis. Syncope, presyncope, palpitations or changing AV conduction after possible Ixodes exposure can indicate Lyme disease even without a recalled rash. CDC classifies symptomatic disease, first-degree block with PR ≥300 ms, and second- or third-degree block as severe. Admit, monitor continuously and start IV ceftriaxone. Use temporary pacing if symptomatic bradycardia requires it. Once symptoms and high-grade block resolve, consider oral therapy to complete 14–21 days total. CDC Lyme carditis guidance
- Lyme neuroborreliosis. Facial palsy, lymphocytic meningitis and radicular pain are clues. For meningitis, cranial neuropathy or radiculoneuropathy without brain or spinal cord parenchymal involvement, oral doxycycline and appropriate IV regimens are options. Consider severity, oral tolerance and whether alternative diagnoses require initial IV treatment. Use IV therapy for parenchymal brain or spinal cord involvement. IDSA/AAN/ACR Lyme guideline
- Ehrlichiosis and anaplasmosis. Fever, headache, leukopenia, thrombocytopenia and elevated transaminases suggest these infections. Rash occurs more often in children with ehrlichiosis and is uncommon with anaplasmosis. Morulae may be visible but their absence is unhelpful. Send whole blood for PCR early if feasible and start doxycycline on clinical suspicion at any age. CDC rickettsial guidance
Pertussis, measles, varicella and infant botulism
- Critical infant pertussis. Young infants may present with apnea, cyanosis, bradycardia and feeding difficulty with little cough and no whoop. Rapidly rising leukocytosis with pulmonary hypertension or shock prompts PICU escalation and early expert consultation. A multicenter cohort linked leukocytosis and pulmonary hypertension with severe outcomes. Evidence for exchange transfusion or leukapheresis is limited, so discuss these as individualized rescue options. Use Droplet Precautions and start azithromycin promptly when pertussis is suspected in a high-risk infant. For infants under 6 months, CDC dosing is 10 mg/kg once daily for five days. Azithromycin is preferred even under 1 month of age because of the risk of severe pertussis. Monitor for infantile hypertrophic pyloric stenosis after macrolide exposure. CDC pertussis treatment · CDC dosing guideline · Multicenter critical pertussis cohort
- Measles. Fever, cough, coryza, conjunctivitis, Koplik spots and a descending maculopapular rash should prompt immediate Airborne Precautions, public health notification, and respiratory RT-PCR plus serum IgM testing. Pneumonia and encephalitis can complicate infection. Maintain airborne isolation through four days after rash onset, or for the duration of illness in immunocompromised patients. Give hospitalized children supervised oral vitamin A at diagnosis and the next day. Doses are 50,000 IU under 6 months, 100,000 IU at 6–11 months and 200,000 IU at 12 months or older. Clinical vitamin A deficiency warrants a third age-specific dose 2–4 weeks later. CDC measles overview · CDC Yellow Book
- Severe varicella. Use IV acyclovir for severe disease such as pneumonia or encephalitis and for varicella in immunocompromised patients. Use Airborne and Contact Precautions until lesions have crusted. Continue them for the duration of illness in an immunocompromised patient with varicella pneumonia. For lesions that do not crust, use absence of new lesions for 24 hours. Give VariZIG promptly, within 10 days after exposure, to eligible susceptible high-risk patients who cannot receive vaccine. A newborn whose mother develops varicella from 5 days before through 2 days after delivery is a priority exposure. CDC varicella clinical guidance · CDC healthcare isolation table · CDC varicella surveillance and isolation
- Infant botulism. Ingested spores, including from honey or environmental dust, can colonize the infant gut. Neurotoxin blocks presynaptic acetylcholine release. Constipation followed by weak suck and cry, ptosis, poor head control and descending weakness suggests infant botulism. Assess respiratory and bulbar function and contact the Infant Botulism Treatment and Prevention Program immediately. Give program-directed IV BabyBIG on clinical suspicion without waiting for stool toxin testing or EMG. FDA specifies 20 mg/kg (0.4 mL/kg) once IV for Lots 7 and 8, with the supplied 0.2-micron filter for Lot 8. Confirm the lot at dispensing. Antibiotics do not treat intestinal infant botulism. Seek specialist advice if a separate bacterial infection requires therapy because aminoglycosides can worsen weakness. Equine heptavalent antitoxin is used for foodborne or wound botulism. The syndrome and exposure guide product selection. FDA Lot 7 · FDA Lot 8 · CDC infant botulism · CDC botulism guideline
A previously healthy, well-appearing, term 16-day-old has a rectal temperature of 38.4°C and meets the AAP febrile infant pathway criteria. What is the appropriate evaluation and initial treatment?
Obtain urinalysis, blood culture, and procalcitonin; discharge home without antibiotics if procalcitonin is below 0.5 ng/mL
Obtain catheterized or suprapubic urine for urinalysis and culture if positive, blood culture and CSF. Admit and start source-appropriate parenteral antibiotics.
Administer a single IM dose of ceftriaxone 50 mg/kg after obtaining blood and urine cultures, deferring lumbar puncture unless inflammatory markers rise
Perform a respiratory viral panel and observe in the emergency department for 6 hours without lumbar puncture if the viral panel is positive
A 6-year-old boy from North Carolina presents in June with 3 days of fever to 39.5 degrees C, severe frontal headache, myalgias, nausea, sodium 129 mEq/L, platelets 88,000/uL, and faint blanching macules emerging on his wrists and ankles. Serologic testing for rickettsial antibodies is drawn. What is the most critical immediate management step?
Wait for acute IgG/IgM serology results and petechial progression before starting tetracyclines to prevent permanent dental enamel staining
Start IV ceftriaxone monotherapy for presumed meningococcemia and hold doxycycline until age 8 years
Initiate empiric doxycycline immediately without waiting for serology or rash progression
Administer oral amoxicillin for 14 days while awaiting tick-borne PCR panels
A 3-month-old previously healthy infant presents with 4 days of constipation, poor feeding, weak cry, bilateral ptosis, sluggishly reactive pupils, loss of head control, and shallow respirations. The mother reports giving chamomile tea sweetened with honey for colic. Temperature is 36.8 degrees C. While preparing for airway support and sending stool for toxin testing, which combination of action and medication safety rule is essential?
Wait for mouse bioassay stool confirmation before giving antitoxin, and administer IV gentamicin for aspiration prophylaxis
Administer equine heptavalent botulinum antitoxin after EMG confirmation and start ampicillin plus gentamicin for sepsis coverage
Administer oral metronidazole to eradicate Clostridium botulinum spores and avoid macrolides
Administer program-directed BabyBIG on clinical suspicion and avoid aminoglycosides when feasible because they can worsen weakness
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