How should fever be evaluated and treated in an otherwise healthy adult (≥18 years), including indications for urgent assessment and choice of antipyretics?

Management of Fever in Adults

Fever in an otherwise healthy adult should trigger a focused clinical assessment rather than automatic testing, with treatment prioritized for patient comfort rather than temperature normalization, and urgent evaluation reserved for signs of sepsis or severe illness. 1

Fever Definition and Measurement

• Fever is defined as a single temperature ≥38.3°C (101°F) in most clinical contexts, though some sources use ≥38.0°C (100.4°F) as the threshold. 2, 1

• Use oral or rectal temperature measurements for accurate assessment in otherwise healthy adults, avoiding unreliable methods like tympanic membrane, temporal artery, or axillary measurements. 2, 1, 3

• Central temperature monitoring (bladder catheter thermistors, esophageal probes) is preferred only when these devices are already in place or when precise temperature measurement is critical to diagnosis. 2

Initial Clinical Evaluation

Perform a targeted assessment focusing on:

• Respiratory rate, hydration status, and mental status changes as these indicate severity. 2

• Examination of the oropharynx, conjunctiva, skin (including pressure areas), chest, heart, abdomen, perineum, and perirectal area to identify potential infection sources. 2

• Review of recent medications, procedures, surgeries, and indwelling devices within the past 60 days, as drug-induced fever is common with antibiotics and chemotherapy. 3

• Assessment for underlying conditions that predispose to specific infections: diabetes (skin infections, UTI), COPD (pneumonia), poor swallowing (aspiration), chronic immobility (pressure ulcers). 2

Indications for Urgent Assessment

Seek immediate evaluation if the patient exhibits:

• Signs of sepsis or septic shock (hypotension, altered mental status, tachycardia, tachypnea, evidence of organ dysfunction). 2

• Severe illness or clinical deterioration despite initial management. 2

• Temperature ≥38.3°C with neutropenia or immunocompromise (though this guideline focuses on immunocompetent adults). 2

When infection is suspected in an unstable patient, empirical antimicrobial therapy should begin within 1 hour after obtaining cultures, as delayed treatment increases mortality. 2

Diagnostic Workup Algorithm

For all febrile adults without an obvious source:

• Obtain a chest radiograph as initial imaging, since pneumonia is the most common serious infection causing fever. 1, 3

• Draw at least two sets of blood cultures (ideally 60 mL total) from different anatomical sites simultaneously if septic shock is present or if results will change management. 1, 3

• Complete blood count, comprehensive metabolic panel, and urinalysis are recommended as baseline studies. 1

When bacterial infection probability is low-to-intermediate:

• Measure procalcitonin (PCT) or C-reactive protein (CRP) in addition to clinical evaluation to help rule out bacterial infection. 2, 3

When bacterial infection probability is high:

• Do not rely on PCT or CRP to rule out bacterial infection; proceed with empirical treatment based on clinical suspicion. 2, 3

For suspected respiratory infection:

• Test for viral pathogens using nucleic acid amplification panels if upper respiratory symptoms (cough, rhinorrhea) are present. 2, 3

• Test for SARS-CoV-2 by PCR based on community transmission levels. 2

If initial workup fails to identify a source:

• Consider 18F-FDG PET/CT if transport risk is acceptable, with sensitivity of 85-100% for identifying occult infection or inflammation. 3, 4

Antipyretic Therapy

The primary goal of treating fever is patient comfort, not temperature normalization. 1

• Avoid routine antipyretic use specifically for temperature reduction, as fever may serve beneficial immunologic functions and aggressive treatment does not improve mortality. 1, 5, 6

• If the patient values comfort and temperature reduction, use pharmacologic antipyretics (acetaminophen or ibuprofen) rather than nonpharmacologic cooling methods (ice packs, cooling blankets). 1

• Antipyretics work primarily by inhibiting cyclooxygenase and reducing prostaglandin E2 levels in the hypothalamus. 6

• There is no substantial difference in safety and effectiveness between acetaminophen and ibuprofen for fever management in healthy adults. 7

Critical Pitfalls to Avoid

• Do not implement automatic order sets with reflexive laboratory and imaging tests; let clinical assessment guide the workup to avoid unnecessary testing, patient discomfort, and resource waste. 2, 3

• Do not aggressively treat fever with antipyretics or cooling devices unless for patient comfort, as this does not improve outcomes and may impair immune response. 1, 5

• Do not use unreliable temperature measurement methods (tympanic, temporal artery, axillary) for diagnostic decisions. 1, 3

• Do not routinely culture urine in catheterized patients without pyuria or UTI symptoms, as asymptomatic bacteriuria is common and does not require treatment. 3

• Recognize that fever can have many noninfectious etiologies including drug reactions, thromboembolism, acute myocardial infarction, pancreatitis, gout, adrenal insufficiency, thyroid storm, and malignancy. 2, 8, 4

Empirical Antibiotic Therapy

When clinical evaluation suggests infection as the cause:

• Administer empirical antimicrobial therapy as soon as possible after cultures are obtained, especially if the patient is seriously ill or deteriorating. 2

• Direct initial therapy against likely pathogens based on suspected source, patient risk factors for multidrug-resistant organisms, and local antimicrobial susceptibility patterns. 2

• For suspected resistant pathogens, use broad-spectrum coverage against both resistant Gram-positive cocci (including MRSA) and Gram-negative bacilli, potentially requiring multiple agents. 2