What is the recommended management for pyrexia?

Management of Pyrexia

The management of pyrexia depends critically on the clinical context: in febrile neutropenia, immediate broad-spectrum antibiotics are mandatory; in BRAF inhibitor-related fever, drug discontinuation with antipyretics is first-line; in neurogenic fever from brain injury, aggressive temperature control targeting 36.0-37.5°C with automated devices is essential; and in pyrexia of unknown origin, the approach is guided by risk stratification and systematic investigation before empiric therapy. 1, 2

Context-Specific Management Algorithms

Febrile Neutropenia (ANC <0.5 × 10⁹/L)

This represents a medical emergency requiring same-day intervention 1, 3:

• Immediate empiric broad-spectrum antibacterial therapy must be initiated within hours, before culture results return 1, 3
• Obtain blood cultures (at least two sets, 60 mL total) before starting antibiotics, but do not delay treatment 1
• Perform chest imaging if respiratory symptoms present 1
• Clinical assessment frequency: every 2-4 hours in unstable patients 2

48-Hour Reassessment Protocol 2:

• If afebrile and ANC ≥0.5 × 10⁹/L:

  • Low-risk patients: consider switching to oral antibiotics 2, 1
  • High-risk patients on dual therapy: aminoglycoside may be discontinued 2, 1
  • When pathogen identified: continue targeted therapy 2

• If still febrile at 48 hours:

  • Clinically stable: continue initial antibacterial therapy 2
  • Clinically unstable: rotate antibiotics or broaden coverage; seek infectious disease consultation urgently 2
  • Persistent fever >4-6 days: initiate antifungal therapy (voriconazole or liposomal amphotericin B for suspected aspergillosis) 2, 1

Duration of therapy 2:

• If ANC ≥0.5 × 10⁹/L, afebrile for 48 hours, and blood cultures negative: discontinue antibiotics 2
• If ANC <0.5 × 10⁹/L but afebrile for 5-7 days: discontinue except in acute leukemia or post-high-dose chemotherapy (continue 10 days or until ANC ≥0.5 × 10⁹/L) 2

BRAF/MEK Inhibitor-Related Pyrexia

Fever occurs in the majority of patients on BRAF-targeted therapy, typically 2-4 weeks after initiation 2:

• Immediately discontinue or hold BRAF/MEK inhibitor therapy at onset of pyrexia 2
• Administer antipyretics: acetaminophen and/or NSAIDs 2
• Monitor for associated complications: chills, night sweats, rash, dehydration, electrolyte abnormalities, hypotension 2
• After fever resolution, resume treatment at reduced dose 2
• Critical caveat: Hold BRAF/MEK inhibitors 3 days before and after fractionated radiation, or 1 day before and after stereotactic radiosurgery to avoid increased toxicity 2

Neurogenic Fever in Traumatic Brain Injury

Fever (>37.5°C) in severe TBI precipitates secondary brain injury and must be aggressively managed 2, 4:

• Target temperature: 36.0-37.5°C using controlled normothermia 2, 4
• Use automated feedback-controlled temperature management devices for rapid induction and precise maintenance 2, 4
• Antipyretics (acetaminophen/NSAIDs) have limited efficacy in severe TBI and should not be relied upon as monotherapy 2, 4
• Continuous central temperature monitoring (bladder catheter, esophageal thermistor, or pulmonary artery catheter) is preferred over peripheral measurements 4
• Maintain temperature stability with minimal variation (≤±0.5°C per hour, ≤1°C per 24 hours) 4

Do not delay temperature control while investigating fever source - the duration of fever correlates with worse outcomes regardless of etiology (infectious vs. neurogenic) 2, 4

Pyrexia of Unknown Origin (Classical PUO)

Systematic investigation before empiric therapy 1, 5:

Initial diagnostic workup 1:

• Comprehensive blood cultures before any antimicrobial therapy 1
• Complete blood count with differential to assess for neutropenia 1
• Chest imaging (X-ray or CT) for respiratory symptoms or persistent fever 1

Advanced imaging for persistent fever 1:

• FDG-PET/CT has high sensitivity and specificity for detecting infections and inflammatory processes in prolonged unexplained fever 1
• High-resolution chest CT if invasive fungal disease suspected (look for nodules with haloes or ground-glass changes) 1
• Bronchoalveolar lavage if infiltrates found on imaging 1

Empiric therapy considerations (only after adequate investigation) 1:

• Suspected aspergillosis: voriconazole or liposomal amphotericin B 1
• Suspected viral encephalitis: high-dose aciclovir after sampling 1
• Suspected bacterial meningitis: ceftazidime plus ampicillin (for Listeria coverage) or meropenem 1

Pediatric Community-Acquired Pneumonia with Pyrexia

Families managing children at home need specific guidance 2:

• Antipyretics and analgesics to keep child comfortable and facilitate coughing 2
• Prevent dehydration 2
• Review by general practitioner if deteriorating or not improving after 48 hours on treatment 2
• Admission indicators: oxygen saturation <92%, respiratory rate >70 breaths/min (infants) or >50 breaths/min (older children), difficulty breathing, grunting, not feeding, inadequate family supervision 2

Critical Pitfalls to Avoid

• Never delay antibiotics in febrile neutropenia while awaiting culture results - mortality increases significantly with delayed treatment 1, 3
• Do not attribute fever to "central" causes in brain injury without first investigating infectious sources (chest X-ray, blood cultures, consider CT if post-surgical) 4
• Avoid relying on antipyretics alone in severe TBI - automated temperature control devices are necessary 2, 4
• Do not continue BRAF/MEK inhibitors through pyrexic episodes - drug discontinuation is essential for fever resolution 2
• Inadequate follow-up in severe neutropenia can be fatal - close monitoring required until resolution 3