Overview

Definition:
-Fever in infants less than 60 days of age is defined as a rectal temperature of 38°C (100.4°F) or higher
-This age group is particularly vulnerable due to an immature immune system, increasing the risk of serious bacterial infections (SBIs).
Epidemiology:
-Fever is a common presentation in neonates, with approximately 5-10% of febrile infants under 60 days having an SBI
-Common SBIs include urinary tract infections, bacteremia, meningitis, and pneumonia
-Group B Streptococcus (GBS) and Escherichia coli are the most frequent pathogens
-Prematurity, prolonged rupture of membranes (>18 hours), maternal fever, and chorioamnionitis are risk factors.
Clinical Significance:
-Prompt and accurate triage of febrile infants under 60 days is critical as SBIs can rapidly progress to severe illness, sepsis, or death
-Early identification and appropriate management of these infants are paramount for preventing morbidity and mortality, a key focus in pediatric residency and DNB/NEET SS examinations.

Clinical Presentation

Symptoms:
-Fever (rectal temp ≥38°C)
-Lethargy or irritability
-Poor feeding or vomiting
-Apnea or respiratory distress
-Hypotonia or unusual cry
-Seizures
-Jaundice
-Petechial or purpuric rash (less common but highly concerning).
Signs:
-Vital sign abnormalities: Tachycardia, tachypnea, hypothermia, or shock
-Signs of dehydration: Sunken fontanelle, decreased skin turgor, dry mucous membranes
-Signs of localized infection: Umbilical redness, pustules, pneumonia findings on auscultation, meningeal signs (irritability with neck stiffness, bulging fontanelle).
Diagnostic Criteria:
-There are no specific diagnostic criteria for fever itself, but the diagnostic approach is guided by the age and clinical suspicion of serious bacterial infection
-Current guidelines from organizations like the American Academy of Pediatrics (AAP) and Indian Academy of Pediatrics (IAP) emphasize a systematic approach focusing on risk stratification and empirical management.

Diagnostic Approach

History Taking:
-Detailed birth history: Gestational age, maternal fever, chorioamnionitis, prolonged rupture of membranes
-History of current illness: Onset and duration of fever, feeding pattern, presence of vomiting or diarrhea, changes in activity, recent sick contacts
-Pre-existing medical conditions or congenital anomalies
-Immunization status (though less relevant in this age group for acute infection)
-Red flags: Neonatal jaundice, poor feeding, lethargy, any signs of respiratory distress, recurrent fevers, or known immunodeficiency.
Physical Examination:
-Comprehensive physical examination focusing on the infant's general appearance, vital signs (including axillary, rectal temperature if safe and feasible, and peripheral perfusion)
-Perform a thorough assessment of all body systems: Skin (rashes, pustules, umbilical stump), HEENT (fontanelle, ears, throat), Cardiopulmonary (auscultation, perfusion), Abdomen (tenderness, hepatosplenomegaly), Neurological (activity, tone, reflexes, irritability), and Genitourinary (meatus).
Investigations:
-Complete Blood Count (CBC) with differential: Elevated WBC count (>15,000/µL) or neutropenia (<1,500/µL) may suggest infection
-C-reactive protein (CRP): Elevated CRP (>0.5 mg/dL) is a sensitive marker for inflammation
-Blood culture: Essential for identifying bacterial pathogens
-requires adequate volume (1-2 mL) and proper technique
-Urine analysis and culture: Urinalysis may show pyuria or bacteriuria
-urine culture is definitive
-Lumbar puncture for cerebrospinal fluid (CSF) analysis and culture: Indicated in infants with suspicion of meningitis (pleocytosis, low glucose, high protein)
-requires adequate CSF volume
-Chest X-ray: If respiratory symptoms are present to rule out pneumonia
-Other investigations based on clinical suspicion: e.g., stool culture for diarrhea, viral respiratory panel.
Differential Diagnosis:
-Serious Bacterial Infections (SBIs): Sepsis, meningitis, UTI, pneumonia, osteomyelitis, omphalitis
-Viral infections: Common viral illnesses can present with fever, but SBIs must be ruled out
-Non-infectious causes: Post-vaccination fever (rare in this age group due to few vaccines given), heat stroke, drug fever (rare)
-Neonatal Abstinence Syndrome (NAS) can mimic fever and irritability.

Management

Initial Management:
-Immediate assessment and stabilization
-For infants <60 days with fever, a low threshold for hospital admission and full sepsis workup is recommended, especially if risk factors are present or clinical suspicion is high
-Empirical antibiotic therapy should be initiated promptly after obtaining necessary cultures
-Fluid resuscitation if signs of shock or dehydration are present.
Medical Management:
-Empirical antibiotic therapy is guided by likely pathogens and local resistance patterns
-Common regimens include: Ampicillin (50-100 mg/kg/dose IV q6-8h) plus a third-generation cephalosporin (e.g., Cefotaxime 50 mg/kg/dose IV q8-12h or Ceftriaxone 50 mg/kg/dose IV q12-24h for infants >7 days)
-Vancomycin may be added if MRSA is suspected or prevalent
-Duration of therapy depends on the identified pathogen and clinical response, typically 7-14 days for bacteremia/pneumonia, 10-21 days for meningitis, and 7-10 days for UTI
-Antipyretics (e.g., Paracetamol 10-15 mg/kg/dose PO/PR q4-6h) can be used cautiously for comfort, but are not a substitute for antimicrobial therapy.
Surgical Management:
-Surgical intervention is rarely required for initial fever workup, but may be indicated if a localized collection develops, such as an abscess secondary to osteomyelitis or omphalitis requiring drainage
-Definitive surgical management is dependent on the underlying cause if identified as a surgical emergency.
Supportive Care:
-Close monitoring of vital signs, cardiorespiratory status, hydration, and neurological status
-Maintain adequate fluid balance
-Provide adequate nutrition
-Administer antipyretics for comfort
-Manage any complications such as respiratory distress or seizures
-Strict adherence to infection control protocols.

Complications

Early Complications:
-Sepsis-induced hypotension and shock
-Disseminated intravascular coagulation (DIC)
-Respiratory failure
-Seizures
-Neurological sequelae (e.g., developmental delay, hearing impairment) from meningitis
-Necrotizing enterocolitis (NEC)
-Renal failure
-Death.
Late Complications:
-Long-term neurological deficits from meningitis or hypoxic-ischemic injury
-Developmental delay
-Hearing loss
-Visual impairment
-Recurrent infections due to damaged immune system.
Prevention Strategies:
-Maternal health and hygiene during pregnancy
-Prompt diagnosis and treatment of maternal infections
-Aseptic delivery techniques
-Postnatal care emphasizing hygiene and avoiding unnecessary exposure to sick individuals
-Timely and appropriate vaccination of older siblings and caregivers to reduce transmission risks.

Prognosis

Factors Affecting Prognosis:
-The most critical factor is the presence and extent of serious bacterial infection
-Early diagnosis and prompt, appropriate antibiotic treatment significantly improve outcomes
-Gestational age at birth (preterm infants have poorer prognosis), host immune status, and specific pathogen virulence also play a role.
Outcomes:
-With prompt diagnosis and treatment, the prognosis for most febrile infants without SBIs is excellent
-For infants with SBIs, outcomes vary widely
-Neonatal sepsis and meningitis carry significant risks of mortality and long-term morbidity
-Early identification and aggressive management improve survival rates and reduce sequelae.
Follow Up:
-Infants treated for SBIs require close follow-up to monitor for resolution of infection and assess for potential long-term complications
-This may include serial developmental assessments, hearing and vision screening, and neurological examinations
-Infants discharged after a sepsis workup without identified infection also require vigilant parental education on recognizing worsening symptoms.

Key Points

Exam Focus:
-Fever in infants <60 days is a medical emergency
-Assume SBI until proven otherwise
-ALWAYS obtain blood, urine, and consider CSF cultures
-Empirical antibiotics are crucial after cultures are drawn
-Differentiate between low-risk and high-risk infants based on clinical status and risk factors
-Common pathogens: GBS, E
-coli, Listeria monocytogenes
-Management of meningitis and sepsis is a frequent high-yield topic.
Clinical Pearls:
-Always use rectal temperature for definitive fever assessment in neonates if possible and safe
-A seemingly minor rash can be petechial/purpuric and highly concerning for meningococcemia
-Do not delay antibiotics while awaiting all culture results
-start empirically
-A thorough neurological exam is vital in febrile neonates
-Understand the rationale behind combination antibiotic therapy (e.g., ampicillin + cephalosporin).
Common Mistakes:
-Underestimating the severity of fever in neonates
-Delaying empirical antibiotic treatment
-Inadequate blood or CSF volume for cultures
-Failing to consider meningitis in the differential diagnosis
-Relying solely on clinical signs without a systematic workup
-Discharging a febrile infant without a thorough evaluation and risk stratification.