What is the recommended approach to antibiotic stewardship in patients with central fever, particularly those with neurological conditions or post-neurosurgical patients?

Antibiotic Stewardship in Central Fever

Primary Recommendation

In neurocritical care patients with fever, recognize that approximately 50% of fevers are noninfectious (central fever), and antibiotics should be withheld or discontinued when specific clinical indicators predict central rather than infectious etiology. 1, 2

Understanding Central Fever in Neurologic Patients

Central fever occurs in approximately 25% of neurocritical care patients, with nearly half of all fevers in this population being noninfectious in origin 1. This high prevalence of noninfectious fever creates a critical opportunity for antibiotic stewardship, as inappropriate antibiotic use contributes to resistance development and patient harm 2, 3.

Key Predictors of Central Fever

A validated model identifies central fever with 90% probability when the following criteria are present: 2

• Negative cultures
• Absence of infiltrate on chest radiograph
• Diagnosis of subarachnoid hemorrhage, intraventricular hemorrhage, or tumor
• Fever onset within 72 hours of hospital admission

Additional strong indicators of central fever include: 2

• Persistent fever lasting >6 hours for ≥2 consecutive days (OR 1.42)
• Recent blood transfusion (OR 3.06)
• Younger age (mean 53.5 vs 57.4 years for infectious fever)

Diagnostic Algorithm for Fever Evaluation

Step 1: Initial Assessment (All Febrile Patients)

Obtain CSF analysis when: 1

• Altered consciousness or unexplained focal neurologic signs are present
• Patient has an intracranial device (ventriculostomy, VP shunt, Ommaya reservoir)
• New fever develops in any patient without clear alternative source

Critical caveat: In patients with focal neurologic findings suggesting disease above the foramen magnum, obtain non-contrast CT before lumbar puncture to exclude mass lesions or obstructive hydrocephalus 1. However, if bacterial meningitis is suspected and imaging delays the LP, start empirical antibiotics for rapidly fatal etiologies (e.g., S. pneumoniae) immediately after obtaining blood cultures 1.

Step 2: CSF Analysis Protocol

For patients with intracranial devices: 1

• Aspirate CSF from the reservoir or catheter directly
• If CSF flow to subarachnoid space is obstructed, also obtain lumbar CSF
• Remove and culture ventriculostomy catheters in patients developing stupor or meningitis signs

Essential CSF tests: 1

• Cell count with differential
• Glucose and protein concentrations
• Gram stain and bacterial culture
• Additional tests based on clinical suspicion (fungal, viral PCR, cytology)

CSF findings essentially excluding bacterial meningitis in immunocompetent hosts: 1

• Normal opening pressure
• ≤5 white blood cells/μL
• Normal CSF protein concentration

Step 3: Risk Stratification for Antibiotic Decision

HIGH probability of central fever (consider withholding/discontinuing antibiotics): 2

• SAH, IVH, or tumor diagnosis
• Fever within 72 hours of admission
• Negative cultures at 48 hours
• Clear chest radiograph
• Recent blood transfusion
• Persistent fever pattern (>6 hours for ≥2 days)

HIGH probability of infectious fever (continue/initiate antibiotics): 2, 4

• Positive cultures
• Infiltrate on chest radiograph
• Central venous catheter in place
• Prolonged mechanical ventilation
• Older age
• Fever onset >72 hours after admission

Antibiotic Management Strategy

When to Start Empirical Antibiotics

Initiate antibiotics immediately if: 1

• Suspected bacterial meningitis (even before LP if imaging required)
• Positive CSF Gram stain
• CSF findings consistent with bacterial meningitis (glucose <35 mg/dL, CSF:blood glucose ratio <0.23, protein >220 mg/dL, >2000 WBC/μL, or >1180 neutrophils/μL)
• Clinical deterioration or sepsis signs
• Immunocompromised state

When to Discontinue Antibiotics

Stop antibiotics after 48 hours if: 2, 3

• Cultures remain negative
• Clinical indicators strongly suggest central fever (≥90% probability using validated model)
• Patient remains hemodynamically stable
• No evidence of infection on imaging

Common pitfall: Clinicians often continue antibiotics unnecessarily in neurosurgical patients with central fever, contributing to antimicrobial resistance and adverse effects 2, 3. The recognition of central fever patterns is essential to avoid inappropriate antimicrobial therapy 3.

Duration for Documented Infections

For proven CNS infections: 1

• Continue antibiotics for the full treatment course appropriate to the organism and site
• Maintain therapy at least until neutrophil recovery if applicable
• Most bacterial CNS infections require 10-14 days of appropriate therapy

Special Considerations

Patients with Intracranial Devices

These patients require heightened vigilance: 1, 5

• CSF should almost always be obtained when fever develops
• Coagulase-negative staphylococci (predominantly methicillin-resistant) are the most common pathogens
• Acinetobacter baumannii represents a major challenge with limited effective antimicrobials
• All MRCoNS isolates remain susceptible to vancomycin, linezolid, rifampin, and amoxicillin-clavulanate 5

Temperature Management

Regardless of fever etiology, control temperature aggressively: 1

• Target controlled normothermia (36.0-37.5°C) for neurogenic fever
• Uncontrolled fever (neurogenic or infectious) precipitates secondary brain injury
• Use automated feedback-controlled temperature management devices when available
• Acute phase TBI patients require urgent temperature management regardless of source

Critical distinction: While determining infectious vs. central etiology guides antibiotic decisions, temperature control itself is essential for all febrile neurocritical care patients to prevent secondary brain injury 1.

Monitoring and Reassessment

Continuous monitoring requirements: 1

• Daily assessment of fever patterns
• Serial cultures if fever persists or recurs
• Chest radiography if respiratory symptoms develop
• Repeat neurologic examination for new focal findings
• Consider repeat CSF analysis if clinical deterioration occurs despite appropriate management

Reassess antibiotic necessity daily using the validated central fever indicators, particularly in patients with SAH, IVH, or tumor who develop fever within 72 hours of admission 2.