What is the best approach to identify the cause of fever?

Approach to Identifying the Cause of Fever

A systematic, focused physical examination and targeted diagnostic testing based on clinical suspicion is the most effective approach to identify the cause of fever. 1

Definition of Fever

• Fever is defined as a temperature of ≥38°C/100.4°F 1
• In elderly patients, especially those in long-term care facilities, lower thresholds may be more appropriate:
  • A single temperature reading of ≥37.8°C (100°F) has 70% sensitivity and 90% specificity for infection 1
  • An increase in temperature of at least 1.1°C (2°F) over baseline 1
  • Rectal temperature measurements are more accurate than oral or axillary methods 1

Initial Diagnostic Approach

Physical Examination

Focus examination on these key areas:

• Mental status (altered mental status may indicate CNS infection or sepsis) 1
• Oropharynx (look for signs of infection) 1
• Chest (assess for pneumonia - tachypnea >25 breaths/min has 90% sensitivity and 95% specificity for pneumonia in elderly) 1
• Heart (evaluate for endocarditis) 1
• Abdomen (assess for intra-abdominal infection) 1
• Skin (including turning patient to examine for pressure ulcers) 1
• Perineum and perirectal area (check for abscesses) 1
• Indwelling devices (catheters, IV lines) 1
• "Silent sources" of infection (otitis media, decubitus ulcers, perineal/perianal abscesses, retained foreign bodies) 1

Laboratory Testing

• Complete blood count with differential 2, 3
• Basic metabolic panel and liver function tests 4
• Blood cultures (at least two sets, with at least one from peripheral venipuncture) 1
• Urinalysis and urine culture 1
• Serum procalcitonin (PCT) - levels >0.5 ng/mL suggest bacterial infection 1, 4
  • PCT levels correlate with infection severity: 0.6-2.0 ng/mL for SIRS, 2-10 ng/mL for severe sepsis, >10 ng/mL for septic shock 1, 4
  • High negative predictive value (98.6%) for Gram-negative infection 1, 4

Imaging Studies

• Chest radiography - portable films are generally adequate for initial evaluation 1
  • Unilateral air bronchograms have best predictive value for pneumonia, though no single finding is highly predictive 1
  • Consider CT imaging for higher resolution if clinical suspicion remains high despite negative chest X-ray 1
• Abdominal imaging based on clinical findings:
  • Ultrasound for patients with abdominal symptoms, abnormal physical examination, or elevated liver enzymes 4
  • CT scan for patients with recent abdominal surgery or when source remains unclear 4

Specific Clinical Scenarios

Fever in Critically Ill Patients

• Examine intravascular catheters daily for inflammation or purulence 1
• Any purulence from catheter insertion sites should be Gram stained and cultured 1
• For suspected catheter-related infection with signs of tunnel infection, embolic phenomena, vascular compromise, or septic shock, remove the catheter and insert a new one at a different site 1
• For respiratory symptoms, obtain respiratory secretions via appropriate technique (expectoration, deep tracheal suctioning, bronchoscopy) 1
• Consider CT imaging for immunocompromised patients to detect small nodular or cavitary lesions 1

Fever in Neutropenic Patients

• Empiric antibiotic therapy is indicated (e.g., cefepime 2g IV every 8 hours) 5
• Continue therapy for 7 days or until resolution of neutropenia 5
• For patients at high risk for severe infection (recent bone marrow transplant, hypotension, underlying hematologic malignancy, severe/prolonged neutropenia), monotherapy may not be appropriate 5

Noninfectious Causes of Fever

• Drug-induced fever (may take up to 21 days after administration to develop and 1-7 days to resolve after discontinuation) 1, 4
• Malignant hyperthermia and neuroleptic malignant syndrome (especially with very high fevers) 1, 4
• Atelectasis (particularly in postoperative patients, though this should be a diagnosis of exclusion) 6
• Thromboembolism 3, 7
• Malignancy 8, 3
• Autoimmune/inflammatory conditions 8, 3

Common Pitfalls to Avoid

• Failing to examine "silent sources" of infection such as pressure ulcers, perineal abscesses, or retained foreign bodies 1
• Relying solely on typical signs and symptoms of infection in elderly patients, as presentations are often atypical 1
• Delaying empiric antibiotic therapy in critically ill patients while awaiting diagnostic results 4
• Attributing fever to atelectasis without excluding other causes 6
• Using a "shotgun" approach to testing rather than a focused, clue-directed evaluation 9, 7
• Failing to re-evaluate patients with persistent fever 4, 3