Overview
Definition:
Fever without source (FWS) in infants aged 29 to 60 days refers to a rectal temperature of ≥38°C (100.4°F) in an infant who does not have an apparent focus of infection on initial clinical examination.
Epidemiology:
This age group represents a critical window for serious bacterial infections (SBIs), with an incidence of SBIs ranging from 3-15% in febrile infants without a source
Bacterial meningitis and sepsis are the most concerning diagnoses, carrying significant morbidity and mortality.
Clinical Significance:
Accurate risk stratification is paramount to identify infants requiring aggressive diagnostic workup and management for potential SBIs while avoiding unnecessary hospitalizations and antibiotic exposure in low-risk infants
This is a high-yield topic for DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
Fever (rectal ≥38°C)
Irritability or lethargy
Poor feeding
Vomiting
Diarrhea
Respiratory distress
Seizures.
Signs:
Fever
Tachycardia
Tachypnea
Signs of dehydration
Pallor
Jaundice
Mottling of skin
Poor perfusion
Meningeal signs (irritability, nuchal rigidity - often subtle in this age group).
Diagnostic Criteria:
No clear source of infection identified on initial history and physical examination
Rectal temperature ≥38°C.
Diagnostic Approach
History Taking:
Detailed birth history (gestational age, prolonged rupture of membranes, maternal fever)
Duration and height of fever
Feeding pattern changes
Vomiting or diarrhea
Respiratory symptoms
Urinary symptoms (fussiness during urination)
Exposure to sick contacts
Vaccination status (e.g., pneumococcal, Hib)
Use of antipyretics prior to presentation
Red flags: prematurity, congenital anomalies, recent hospitalization.
Physical Examination:
Complete physical examination, including thorough assessment of all organ systems
Vital signs: temperature, heart rate, respiratory rate, blood pressure, oxygen saturation
Assess for signs of distress, dehydration, and sepsis
Careful examination of skin for rashes or lesions
Gentle palpation of abdomen
Neurological assessment for lethargy or irritability
Otoscopic and oropharyngeal examination.
Investigations:
Complete Blood Count (CBC) with differential (WBC count >15,000/µL or <5,000/µL, absolute neutrophil count >10,000/µL)
C-reactive protein (CRP) >20 mg/L
Urinalysis and urine culture (suprapubic aspiration or catheterization preferred for young infants)
Blood culture (at least two sets from different sites)
Chest X-ray if respiratory symptoms present
Lumbar puncture for cerebrospinal fluid (CSF) analysis (cell count, protein, glucose, Gram stain, culture) if any suspicion of meningitis or high risk of SBI.
Differential Diagnosis:
Serious Bacterial Infections (SBIs): Sepsis, meningitis, urinary tract infection (UTI), pneumonia, osteomyelitis, cellulitis
Viral infections: Enteroviruses, RSV, influenza
Non-infectious causes: Heat exposure, over-bundling, post-vaccination fever (less common in this age group without a clear source)
Necrotizing enterocolitis (NEC) in premature infants.
Risk Stratification
Low Risk Criteria:
Well-appearing infant
No signs of respiratory distress or dehydration
No significant laboratory abnormalities (WBC 5,000-15,000/µL, ANC <10,000/µL, negative urinalysis, negative chest X-ray)
Clinical judgment based on established protocols (e.g., Boston, Rochester criteria).
Intermediate Risk Criteria:
Infant with some concerning features but not meeting criteria for high risk
May include mild lethargy, slight dehydration, or borderline lab values
Requires careful consideration and often further observation.
High Risk Criteria:
Infant appearing ill
Significant laboratory abnormalities (e.g., markedly elevated WBC count, positive inflammatory markers)
Positive blood or urine culture
Suspicion of meningitis based on CSF findings or clinical signs
Prematurity (<37 weeks gestation)
Congenital anomalies
Known immunodeficiency.
Management Based On Risk:
Low-risk infants may be managed as outpatients with close parental education and follow-up
Intermediate-risk infants may require brief observation and repeat examinations
High-risk infants require hospitalization, prompt empiric antibiotic therapy, and comprehensive workup for SBIs.
Management
Initial Management:
Assess and stabilize the infant
Obtain vital signs
Perform thorough physical examination
Initiate appropriate diagnostic workup based on risk stratification
Administer antipyretics (acetaminophen or ibuprofen) if indicated and without masking signs of infection.
Medical Management:
Empiric antibiotic therapy is crucial for infants with high-risk features or those who appear ill
Common regimens include ampicillin plus a third-generation cephalosporin (e.g., ceftriaxone or cefotaxime) to cover common pathogens like *Streptococcus pneumoniae*, *Escherichia coli*, and *Listeria monocytogenes*
Dosage and duration depend on the suspected diagnosis and culture results
Intravenous fluids for dehydration.
Supportive Care:
Close monitoring of vital signs, fluid balance, and clinical status
Oxygen therapy if hypoxic
Nutritional support as needed
Comfort measures and parental reassurance.
Complications
Early Complications:
Sepsis with shock
Meningitis leading to neurological sequelae (hydrocephalus, seizures, developmental delay)
Pneumonia with respiratory failure
Osteomyelitis leading to joint damage
Bacteremia with metastatic infection.
Late Complications:
Long-term neurological deficits from meningitis
Hearing impairment
Developmental delays
Chronic renal insufficiency from recurrent UTIs.
Prevention Strategies:
Prompt diagnosis and effective treatment of SBIs
Universal newborn screening for hearing impairment
Immunizations against common bacterial pathogens (e.g., pneumococcal conjugate vaccine, Hib vaccine).
Prognosis
Factors Affecting Prognosis:
The causative organism
Promptness of diagnosis and treatment
Presence of complications (e.g., meningitis, sepsis with shock)
Infant's underlying health status.
Outcomes:
With timely and appropriate management, most infants with FWS recover fully
Infants with meningitis or severe sepsis have a higher risk of long-term sequelae
A significant proportion of febrile infants without a source do not have SBIs and can be managed safely without hospitalization.
Follow Up:
Close follow-up is essential for all infants treated for FWS, especially those managed as outpatients
Parents should be educated on warning signs requiring immediate medical attention
Infants with confirmed SBIs require follow-up to monitor for complications and ensure complete recovery.
Key Points
Exam Focus:
Differentiating between low, intermediate, and high-risk infants is critical for management decisions in DNB/NEET SS
Understand the classic presentation and workup of sepsis, meningitis, and UTI in this age group
Know the empiric antibiotic choices and indications for lumbar puncture.
Clinical Pearls:
Always use rectal temperature for accuracy in infants
A seemingly minor infection can escalate rapidly in this age group
Trust your clinical judgment – an infant who looks ill requires thorough investigation regardless of lab values
Educate parents thoroughly on red flags.
Common Mistakes:
Underestimating the severity of fever in young infants
Relying solely on laboratory tests without considering clinical presentation
Delaying empiric antibiotics in high-risk infants
Inadequate follow-up for outpatients with fever.