What are the guidelines for diagnosing and managing fever?

Guidelines for Diagnosing and Managing Fever

Fever should be promptly evaluated with appropriate diagnostic measures and treated based on the underlying cause, with empiric antimicrobial therapy initiated when infection is suspected, especially in critically ill or deteriorating patients. 1

Definition and Diagnosis of Fever

• Fever is defined as a clinically documented temperature of 101°F (38.3°C) or higher on several occasions 2
• In healthcare settings, axillary measurement using a digital thermometer is recommended for infants <4 weeks; for older children, either axillary (digital) or tympanic (infrared) measurement is appropriate 3
• Children reported to have had fever by caregivers should be considered febrile even if afebrile during examination 3
• Fever may be the first sign of serious infection, especially in critically ill patients, and requires thorough evaluation 1

Initial Evaluation

• Comprehensive physical examination focusing on:

  • Skin (rashes, lesions, eschar) 1
  • Mucous membranes (oral lesions) 1
  • Lymphadenopathy 1
  • Hepatosplenomegaly 1
  • Neurological status 1

• Initial laboratory investigations should include:

  • Complete blood count (noting thrombocytopenia, lymphopenia, or eosinophilia) 1
  • Liver function tests (elevated in up to 85% of certain infections) 1
  • Blood cultures (at least two sets before antibiotic therapy) 1
  • Urinalysis and urine culture 1
  • C-reactive protein and erythrocyte sedimentation rate 2

• Consider biomarkers to distinguish infectious from non-infectious causes:

  • Serum procalcitonin (levels >0.5 ng/mL suggest bacterial infection) 1
  • Endotoxin activity assay (high negative predictive value for Gram-negative infection) 1

Management Approach

Infectious Causes

• When infection is suspected, empirical antimicrobial therapy should be administered as soon as possible after cultures are obtained 1
• Antibiotic therapy should begin within 1 hour after diagnosis of sepsis is considered 1
• Initial empirical antibiotic therapy should target likely pathogens based on:
  • Suspected source of infection
  • Risk for multidrug-resistant pathogens
  • Local antimicrobial susceptibility patterns 1
• For neutropenic fever, hospitalization and empiric therapy with vancomycin plus antipseudomonal antibiotics (cefepime, carbapenem, or piperacillin-tazobactam) is recommended 1
• For persistent fever in neutropenic patients (>4-5 days), consider adding empiric antifungal therapy 1

Non-Infectious Causes

• Consider common non-infectious causes of fever including:
  • Drug fever (may take up to 21 days to develop after drug initiation) 1
  • Blood product transfusion 1
  • Venous thromboembolism 1
  • Malignancy 2
  • Autoimmune/inflammatory conditions 1
  • Neuroleptic malignant syndrome (associated with antipsychotic medications) 1
  • Serotonin syndrome (associated with serotonin reuptake inhibitors) 1
  • Drug withdrawal (alcohol, opiates, barbiturates, benzodiazepines) 1

Special Populations

Critically Ill Patients

• Perform thorough evaluation for "silent" sources of infection (otitis media, decubitus ulcers, perineal/perianal abscesses) 1
• Consider invasive diagnostic procedures (tissue biopsy) if non-invasive tests are unrevealing 2
• If no source is identified after initial evaluation, consider advanced imaging such as 18F-FDG PET/CT scan 2

Returning Travelers

• Obtain detailed travel history including geographical locations visited 1
• Most tropical infections become symptomatic within 21 days of exposure 1
• Consider malaria testing for all patients who have visited tropical countries within 1 year of presentation 1
• Three thick films/RDTs over 72 hours should be performed to confidently exclude malaria 1

Neutropenic Patients

• Determine whether current fever is initial episode, persistent, or recurrent 1
• Aggressively determine etiology through aspiration/biopsy of skin and soft tissue lesions 1
• For persistent or recurrent fever, consider fungal infections (Candida, Aspergillus) 1

Treatment Considerations

• The primary goal of treating fever should be to address the underlying cause rather than simply normalizing body temperature 4, 5
• Routine antipyretic therapy should be avoided as fever may benefit host defense mechanisms 6, 5
• Consider antipyretics only when fever is associated with significant discomfort or in patients with underlying cardiovascular or neurological disorders 6, 3
• When using antipyretics, dose should be based on weight rather than age 3
• Empiric antimicrobial therapy has not been shown effective for fever of unknown origin and should be avoided except in neutropenic, immunocompromised, or critically ill patients 2

When to Seek Emergency Care

• Fever with signs of sepsis (hypotension, altered mental status, tachypnea) 1
• Rapidly spreading rash or worsening oral lesions with fever 7
• Difficulty breathing or swallowing 7
• Signs of anaphylaxis 7
• High fever with muscle rigidity (possible malignant hyperthermia or neuroleptic malignant syndrome) 1