How should I assess and treat a fever, including red‑flag criteria, antipyretic dosing, and indications for further work‑up?

Assessment and Treatment of Fever in Adults

Initial Temperature Measurement

Use central temperature monitoring methods (bladder catheter, esophageal thermistor, or pulmonary artery catheter thermistor) when accurate measurements are critical for diagnosis and management. 1 For patients without these devices, obtain oral or rectal temperatures rather than less reliable methods like axillary, tympanic, temporal artery, or chemical dot thermometers. 1

Red-Flag Criteria Requiring Immediate Action

Initiate empiric antimicrobial therapy within 1 hour when any of the following are present: 2, 3

• Sepsis or septic shock (hemodynamic instability, organ dysfunction, clinical deterioration)
• Procalcitonin ≥0.5 ng/mL suggesting bacterial infection 4
• Neutropenia with fever (absolute neutrophil count <0.5 × 10⁹/L)
• Immunocompromised state with fever
• Critically ill or deteriorating patient regardless of culture results

Critical pitfall: Delaying antimicrobial therapy in septic patients increases mortality—treat empirically while diagnostic evaluation proceeds. 2, 4, 3

Diagnostic Work-Up Algorithm

Step 1: Obtain Cultures Before Antibiotics

• Draw 3-4 blood culture sets within first 24 hours from separate sites before initiating antimicrobials 1
• One set from peripheral venipuncture plus one through any indwelling catheter if present 1
• Use 2% chlorhexidine gluconate in 70% isopropyl alcohol for skin disinfection (30 seconds drying time) 1
• Collect 20-30 mL blood per culture set 1

Step 2: Determine Fever Category

Assess whether this represents:

• Initial fever onset → Proceed with full infectious work-up
• Persistent unexplained fever (>4-7 days) → Consider non-infectious causes and invasive diagnostics 2
• Recurrent fever → Reassess for inadequately treated infection or non-infectious etiology

Step 3: Source Identification

Obtain imaging and site-specific cultures based on clinical suspicion: 1

Respiratory symptoms:

• Chest radiograph (upright PA/lateral or CT if immunocompromised) 1
• Lower respiratory tract sample (sputum, tracheal aspirate, or bronchoscopic lavage) for Gram stain and culture 1

Diarrhea:

• Test for Clostridium difficile if antibiotic exposure within 60 days 1

Catheter-related:

• Blood cultures through catheter and peripherally 1
• Remove catheter if tunnel infection, persistent bacteremia, or candidemia 1

Urinary symptoms:

• Urinalysis and urine culture

CNS symptoms:

• Lumbar puncture mandatory if meningitis/encephalitis suspected 1

Step 4: Biomarker Assessment

Procalcitonin is the most reliable biomarker for distinguishing infectious from non-infectious fever: 4

• ≥0.5 ng/mL: Bacterial infection likely
• 2-10 ng/mL: Severe sepsis range
• >10 ng/mL: Septic shock range
• <0.5 ng/mL in stable patient: Consider non-infectious causes (drug fever, inflammatory conditions)

Non-Infectious Causes to Consider

Always maintain broad differential including: 1, 4, 3

• Drug fever (mean onset 21 days after drug initiation, resolves 1-7 days after discontinuation)
• Venous thromboembolism
• Acute myocardial infarction
• Malignancy
• Thyroid storm
• Withdrawal syndromes (alcohol, benzodiazepines, opiates)
• Blood transfusion reactions
• Adrenal insufficiency

Drug fever diagnosis: Temporal relationship to medication + procalcitonin <0.5 ng/mL + defervescence within 1-7 days of stopping suspected agent. 4 Never delay antibiotics in unstable patients to pursue drug fever diagnosis. 4

Empiric Antimicrobial Therapy

Direct therapy against likely pathogens based on: 2

• Suspected infection source
• Patient risk factors for multidrug-resistant organisms
• Local antimicrobial susceptibility patterns

Specific scenarios:

Neutropenic fever: Hospitalize and initiate vancomycin plus antipseudomonal antibiotics (e.g., ceftazidime, meropenem, or piperacillin-tazobactam). 1, 2 Add empiric antifungal therapy if fever persists >4-6 days. 1

Community-acquired pneumonia (mild): Amoxicillin, azithromycin, or fluoroquinolones 1

Severe illness: Broad-spectrum coverage for both resistant Gram-positive cocci and Gram-negative bacilli 2

Antipyretic Dosing

When temperature >38.5°C (101.3°F): 1

• Ibuprofen 600 mg orally every 4-6 hours (maximum 4 times per 24 hours)
• Paracetamol 1000 mg is equally effective 5
• Paracetamol 500 mg/Ibuprofen 150 mg combination may be more effective for bacterial fever within first hour 5

Important caveat: Temperature below 38°C may not be conducive to antiviral treatment—fever has beneficial effects in fighting infection. 1, 2

Duration and De-escalation

Discontinue antibiotics when: 1

• Neutrophil count ≥0.5 × 10⁹/L AND
• Afebrile for 48 hours AND
• Blood cultures negative AND
• Patient asymptomatic

Narrow therapy once cultures available: Treat based on antimicrobial susceptibilities of isolated organisms. 2 Most bacterial skin/soft tissue infections require 7-14 days treatment. 2

Persistent fever at 48 hours: 1

• If clinically stable: Continue initial therapy
• If clinically unstable: Broaden coverage and obtain infectious disease consultation
• Consider antifungal therapy if fever persists >4-6 days

Common Pitfalls to Avoid

• Never rely on axillary or tympanic temperatures for critical decisions 1, 3
• Don't assume absence of fever excludes infection in elderly or immunocompromised patients 3, 6
• Don't draw single blood cultures—always obtain paired sets 1
• Don't delay source control measures (abscess drainage, infected catheter removal) 3
• Don't use empiric antibiotics for fever of unknown origin in stable, immunocompetent patients—this has not been shown effective 7