Step-by-Step Evaluation of Fever in Adults

Define and Measure Temperature Accurately

Fever is defined as a single temperature ≥ 38.3°C (101°F), and accurate measurement is the essential first step. 1

Use oral or rectal thermometry for reliable temperature assessment in most patients; these methods provide clinically acceptable accuracy. 1
Central temperature monitoring (bladder catheter thermistor, esophageal probe, or pulmonary artery catheter thermistor) is preferred when these devices are already in place or when precise core temperature is critical to diagnosis and management. 1
Avoid unreliable methods: tympanic membrane, temporal artery, axillary, and chemical dot thermometers should not be used for diagnostic decisions because they often differ by 1–2 degrees from actual core temperature. 1
Recognize that absence of fever does not exclude serious infection; elderly patients, those with open wounds, burns, heart failure, end-stage liver or renal disease, and patients receiving anti-inflammatory drugs or renal replacement therapy may be euthermic or hypothermic despite life-threatening infection. 1

Perform Immediate Clinical Assessment for Severity

Assess for signs of sepsis or septic shock immediately, as these mandate empirical antimicrobial therapy within 1 hour after obtaining cultures. 2

Identify High-Risk Features Requiring Urgent Intervention

Hemodynamic instability: systolic blood pressure < 90 mm Hg or mean arterial pressure < 65 mm Hg. 2
Altered mental status or confusion. 2
Tachycardia (heart rate > 90 bpm) or tachypnea (respiratory rate > 20/min) or hypoxemia. 2
Evidence of organ dysfunction: oliguria, elevated lactate, coagulopathy, or thrombocytopenia. 2
If any of these are present, obtain cultures immediately and initiate empirical antimicrobial therapy within 1 hour; delays increase mortality. 2

Stable Patients Without Sepsis Criteria

In hemodynamically stable, immunocompetent patients without signs of sepsis or organ dysfunction, do not reflexively start antibiotics; proceed with systematic diagnostic evaluation. 2

Obtain Focused History and Physical Examination

Direct your history and examination toward high-yield infection sources and predisposing factors, not a generic review of systems. 2

Critical History Elements

Recent procedures, surgeries, or hospitalizations within the past 60 days. 2
All medications started within the past 3 weeks, because drug-induced fever has a mean lag time of 21 days and is common with antibiotics and chemotherapy. 2, 3
Indwelling devices: urinary catheters, central venous lines, prosthetic joints, or other foreign bodies increase risk of device-associated infections. 2
Travel history within the past 3 weeks to endemic areas for enteric fever, malaria, or rickettsial infections. 3
Tick exposure or outdoor activities in wooded areas, raising suspicion for tickborne rickettsial diseases. 3
Underlying conditions: diabetes mellitus (predisposes to skin/soft-tissue infections and UTI), COPD (pneumonia), dysphagia or impaired gag reflex (aspiration), chronic immobility (pressure ulcers). 2

Targeted Physical Examination

Oropharynx and conjunctiva: look for pharyngitis, dental abscesses, or conjunctival petechiae. 2
Skin: inspect all pressure areas, IV sites, and surgical wounds for erythema, warmth, or purulence. 2
Chest: auscultate for crackles, consolidation, or pleural rubs. 2
Heart: listen for new murmurs suggesting infective endocarditis. 2
Abdomen: palpate for tenderness, organomegaly, or peritoneal signs. 2
Perineal and perirectal regions: examine for abscesses, especially in diabetic or immunocompromised patients. 2
Search for "silent sources": otitis media, hidden decubitus ulcers, or retained foreign bodies that can be occult foci. 2

Initiate Diagnostic Workup Based on Clinical Probability

When no obvious source is identified, obtain a chest radiograph first, as pneumonia is the most common serious infection causing fever. 2

Blood Cultures

Collect at least two sets of blood cultures (total ≈ 60 mL) from separate anatomical sites simultaneously when septic shock is present or when results are likely to change management. 1, 2
Do not obtain blood cultures reflexively in hemodynamically stable patients without clinical suspicion of bacteremia. 2
In patients with indwelling central venous catheters, sample at least two lumens. 1

Baseline Laboratory Studies

Complete blood count with differential: look for leukocytosis, leukopenia, bandemia ≥ 10%, or thrombocytopenia. 2
Comprehensive metabolic panel: assess renal function, electrolytes, and liver enzymes. 2
Urinalysis: obtain in all patients; if pyuria is present and UTI is suspected, replace the urinary catheter and culture urine from the newly placed catheter. 1, 2

Biomarker Use (Procalcitonin and C-Reactive Protein)

When bacterial infection probability is low to intermediate, measure procalcitonin (PCT) or C-reactive protein (CRP) in addition to bedside clinical evaluation to aid in ruling out bacterial etiology. 1, 2
When bacterial infection probability is high, do not rely on PCT or CRP to exclude infection; proceed with empirical therapy based on clinical judgment. 1, 2

Respiratory Pathogen Testing

If upper respiratory symptoms (cough, rhinorrhea) are present, perform nucleic acid amplification test panels for viral pathogens. 1, 2
Test for SARS-CoV-2 by PCR when community transmission levels justify testing. 1, 2
Do not routinely test for herpesviruses or adenovirus in immunocompetent patients; insufficient evidence supports this practice. 1

Advanced Imaging

If the initial workup fails to locate a source, consider ¹⁸F-FDG PET/CT (provided transport risk is acceptable); this modality has a sensitivity of 85–100% for detecting occult infection or inflammation. 2

Initiate Empirical Antimicrobial Therapy When Indicated

Start empirical antibiotics as soon as possible after cultures are obtained in patients with suspected infection who are seriously ill or deteriorating. 2

Indications for Immediate Empirical Therapy

Sepsis or septic shock (any of the high-risk features listed above). 2
Clinical deterioration despite initial supportive measures. 2
Severe immunocompromise with fever ≥ 38.3°C. 2
Suspected meningitis or cholangitis. 3

When NOT to Initiate Empirical Antibiotics

Hemodynamically stable patients who lack sepsis criteria. 2
Fever as the sole abnormality with no infectious source identified. 2

Selection of Empirical Regimen

Choose agents based on the suspected infection source (pneumonia, urinary tract, intra-abdominal) and patient risk factors for multidrug-resistant organisms (recent hospitalization, prior antibiotics, healthcare exposure). 2
Incorporate local antimicrobial susceptibility patterns into regimen selection. 2
For suspected resistant organisms, provide broad-spectrum coverage that includes resistant Gram-positive cocci (e.g., MRSA) and Gram-negative bacilli, potentially using multiple agents. 2

Consider Non-Infectious Causes of Fever

Fever arises from numerous non-infectious causes; maintain a broad differential when the infectious workup is negative. 2

Drug-Related Fever

Medication-related fevers from antibiotics, chemotherapy, or other drugs are common; review all medications started within the past 3 weeks. 2, 3

Vascular Events

Venous thromboembolism, pulmonary infarction, myocardial infarction, or stroke can present with fever. 2

Inflammatory Conditions

Gout, pancreatitis, pericardial injury syndrome, or transplant rejection are additional non-infectious etiologies. 2

Endocrine Emergencies

Thyroid storm or adrenal insufficiency may manifest as fever. 2

Malignancy

Tumor fever or cytokine release syndrome should be part of the differential in appropriate contexts. 2

Other Causes

Acalculous cholecystitis, fat embolism, heterotopic ossification, or non-convulsive status epilepticus. 2

Manage Fever for Patient Comfort, Not Routine Temperature Reduction

Treat fever primarily for patient comfort, not routinely to normalize temperature, as fever may serve beneficial immunologic functions. 2, 4

Avoid routine antipyretic use specifically for temperature reduction in critically ill patients. 2
If patients value comfort and temperature reduction, use pharmacologic antipyretics (acetaminophen 1000 mg orally every 4–6 hours, maximum 4 g/day) rather than nonpharmacologic cooling methods. 2, 3
Do not aggressively treat fever with antipyretics or cooling devices unless for patient comfort, as this does not improve mortality and may impair immune response. 2, 4

Critical Pitfalls to Avoid

Do not employ automatic order sets that reflexively trigger laboratory and imaging studies without clinical justification; individualized assessment prevents unnecessary testing and resource waste. 1, 2
Do not use unreliable temperature measurement methods (tympanic, temporal artery, axillary) for diagnostic decision-making. 1, 2
Do not routinely culture urine in catheterized patients lacking pyuria or urinary tract infection symptoms, because asymptomatic bacteriuria is common and does not require treatment. 2
Do not overlook silent infection sources such as otitis media, hidden pressure ulcers, perianal abscesses, or retained foreign bodies, as they may be the hidden focus of fever. 2
Recognize that fever may be absent in high-risk populations (elderly, immunocompromised, those on anti-inflammatory drugs) despite serious infection; use other clinical signs (hypotension, tachycardia, altered mental status, leukocytosis, bandemia, thrombocytopenia) to guide evaluation. 1

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