What is the appropriate evaluation and treatment for a patient with symptoms but no fever?

Evaluation and Management of Patients with Symptoms but No Fever

The absence of fever does not exclude serious infection, and evaluation should proceed based on clinical presentation, risk factors, and other signs of infection rather than relying on temperature alone. 1

Critical Concept: Fever Absence Does Not Equal Infection Absence

Not all patients with infection manifest fever, and the absence of fever in patients with infection is actually associated with worse outcomes. 2, 1 This is a fundamental principle that should guide your entire approach.

Patient Populations at High Risk for Afebrile Infection

• Elderly patients: Often have blunted fever responses and may not mount typical febrile reactions to serious infections 1
• Immunocompromised patients: Including solid organ transplant recipients, may have severe infections without fever, cough, sputum production, or leukocytosis 2, 1
• Patients on immunosuppressive medications: Corticosteroids, anti-inflammatory drugs, and antipyretics can mask fever 1
• Patients with specific comorbidities: End-stage liver disease, chronic renal failure, and congestive heart failure can affect fever response 1
• Patients receiving external cooling: Those on continuous renal replacement therapy, ECMO, or with large burns/open abdominal wounds may have altered temperature regulation 1
• Patients who received antibiotic pre-treatment: May have a blunted fever response 3

Systematic Evaluation Approach

Step 1: Identify Alternative Signs of Infection

When fever is absent, actively search for these clinical markers of infection: 1

• Hemodynamic instability: Unexplained hypotension, tachycardia
• Respiratory changes: Tachypnea out of proportion to clinical status
• Mental status changes: New confusion or altered consciousness
• Laboratory abnormalities:
  • Leukocytosis or leukopenia
  • Elevated band count (>1500/mm³ has highest likelihood ratio of 14.5 for bacterial infection) 2
  • Left shift (>16% bands) or elevated neutrophil percentage (>90%) 2
  • Thrombocytopenia

Step 2: Obtain Inflammatory Markers

For patients with suspected infection but no fever, measure procalcitonin (PCT) or C-reactive protein (CRP) to help rule out bacterial infection. 2, 1

• If probability of bacterial infection is deemed low to intermediate, PCT or CRP measurement is suggested to rule out bacterial infection 2
• Elevated inflammatory markers support pursuing further diagnostic workup 1

Step 3: Directed Physical Examination

Focus on high-yield examination findings based on symptoms: 4

Respiratory System

• Examine for cough, rales, tachypnea, or respiratory distress
• Obtain chest radiography if: cough present, rales detected, respiratory symptoms present, or tachycardia/tachypnea out of proportion to clinical status 4
• Consider thoracic ultrasound when expertise available to identify pleural effusions or parenchymal pathology 2

Abdominal System

• Do NOT routinely obtain abdominal imaging without abdominal symptoms, signs, or liver function abnormalities 2, 4
• DO obtain abdominal ultrasound if: recent abdominal surgery, abdominal pain/tenderness, elevated alkaline phosphatase or bilirubin, or abnormal physical examination 2

Neurological System

• For altered consciousness or focal neurologic signs, consider lumbar puncture unless contraindicated 2
• Obtain imaging before lumbar puncture if focal findings suggest disease above foramen magnum 2

Surgical Sites

• Carefully examine any recent surgical incisions for signs of infection 2
• Consider CT imaging of operative area if etiology not identified by initial workup 4

Step 4: Obtain Appropriate Cultures and Specimens

Base specimen collection on clinical suspicion, not fever presence: 2

Blood Cultures

• Obtain before antibiotics if bacterial infection suspected
• Particularly important in patients with indwelling devices (39-fold increased risk of bacteremia with urinary catheters) 2

Respiratory Specimens

• For intubated patients: deep endotracheal suctioning without saline if possible 2
• For non-intubated patients: expectorated sputum or nasotracheal aspirate usually sufficient initially 2
• Consider bronchoscopy for immunocompromised patients or when specific pathogens suspected (Pneumocystis, Aspergillus, Cryptococcus) 2

Urine Studies

• Urinalysis is useful primarily to EXCLUDE UTI: negative urinalysis for WBCs and negative leukocyte esterase dipstick have ~100% negative predictive value 2
• Positive pyuria has low predictive value due to high prevalence of asymptomatic bacteriuria (15-50% in non-catheterized patients, 100% in long-term catheterized patients) 2
• Only pursue urine culture if urinalysis suggests infection AND patient has localizing urinary symptoms 2

Step 5: Advanced Imaging When Initial Workup Unrevealing

If source remains unclear after initial evaluation: 4

• Consider 18F-FDG PET/CT if transport risk acceptable (sensitivity 85-100% for identifying source) 2, 4
• CT imaging has advantages over ultrasound for comprehensive evaluation but requires transport 2

Critical Pitfalls to Avoid

The most dangerous error is dismissing serious infection based solely on absence of fever, particularly in elderly, immunocompromised, or antibiotic-pretreated patients. 3, 1

• Do NOT wait for fever to develop before initiating workup in high-risk populations 1
• Do NOT obtain routine abdominal ultrasound without abdominal symptoms or liver function abnormalities 2, 4
• Do NOT dismiss elevated band count or left shift even with normal total WBC count (<10,000 cells/mm³) 2
• Do NOT start empiric antibiotics for fever of unknown origin unless patient is neutropenic, immunocompromised, or critically ill 4, 5
• Do NOT interpret positive urine culture as diagnostic without pyuria and localizing symptoms due to high prevalence of asymptomatic bacteriuria 2

Special Considerations for Specific Populations

Long-Term Care Facility Residents

When calling the clinician, report: 2

• Vital signs (even if afebrile)
• Acute or subacute changes in functional status
• Presence of urinary catheter or other indwelling devices
• Respiratory symptoms
• Bowel patterns and urinary symptoms
• Directed review of systems based on presenting symptoms

Post-Surgical Patients

• Examine surgical site carefully regardless of fever status 2
• Consider CT imaging of operative area if clinical concern exists 4
• Risk factors for surgical site infection include diabetes, obesity, prolonged/emergency surgery, and improper antimicrobial prophylaxis 2

Patients with Severe Pharyngitis

Maintain high suspicion for Lemierre syndrome in adolescents and young adults with severe pharyngitis, even without fever. 3

• Look for neck pain/swelling, tender lymph nodes, difficulty swallowing, drooling 3
• This is a life-threatening condition that can present without fever in elderly or immunocompromised patients 3