Diagnostic Tests for Differentiating Upper Respiratory Tract Infections
C-reactive protein (CRP) testing is the most valuable first-line test for differentiating between viral and bacterial upper respiratory tract infections, with levels <20 mg/L making bacterial infection highly unlikely and >100 mg/L strongly suggesting bacterial etiology. 1
Clinical Assessment for Differentiation
Signs and Symptoms to Evaluate
- Presence of focal chest signs
- Dyspnea
- Tachypnea (elevated respiratory rate)
- Pulse rate >100 beats/minute
- Fever lasting >4 days 1
Key Diagnostic Tests
First-Line Testing
C-reactive protein (CRP)
- <20 mg/L: Viral infection likely
100 mg/L: Bacterial infection likely
- 20-100 mg/L: Indeterminate, consider additional testing 1
Nucleic acid amplification tests (NAATs)
Chest radiography
- Indicated when pneumonia is suspected based on clinical findings
- Essential for confirming lower vs. upper respiratory tract involvement
- Should be performed if CRP results are indeterminate and symptoms persist 1
Second-Line Testing
Microbiological studies
- Gram staining and culture of expectorated sputum
- Particularly valuable in patients with severe illness or treatment failure 1
Specific pathogen testing
- For influenza A/B, RSV, and parainfluenza viruses as priority pathogens
- Specimens should be taken from the site of clinical involvement 1
- Pooled swabs for upper respiratory tract infections
- BAL for lower respiratory tract infections when indicated
Diagnostic Algorithm
Initial assessment: Evaluate for signs of pneumonia (focal chest signs, dyspnea, tachypnea, pulse >100, fever >4 days)
CRP testing:
- If <20 mg/L: Likely viral infection, supportive care
- If >100 mg/L: Likely bacterial infection, consider antibiotics
- If 20-100 mg/L: Proceed to additional testing
Respiratory virus testing:
- Multiplex PCR for influenza A/B, RSV, and parainfluenza as priority pathogens
- Consider testing for other viruses based on local epidemiology or if first-line testing is negative
Chest radiography:
- If pneumonia is suspected based on clinical findings
- If CRP is indeterminate and symptoms persist
- To differentiate between upper and lower respiratory tract involvement
Special Considerations
Specimen Collection
- Upper respiratory tract: Pooled nasopharyngeal and throat swabs preferred
- Lower respiratory tract: BAL preferred over tracheal aspirates 1
Testing Technology Comparison
- NAATs (PCR): Highest sensitivity, can detect multiple pathogens, results in <24 hours
- Direct antigen detection: Good specificity, rapid (<4 hours), but lower sensitivity
- Virus isolation by cell culture: High specificity but slower (2-5 days) and less sensitive than NAATs 1
Common Pitfalls
Overreliance on clinical signs alone: Physical examination to detect rales or bronchial breath sounds is neither sensitive nor specific for detecting pneumonia 1
Inappropriate antibiotic use: Up to 56% of patients with upper respiratory infections receive antibiotics, though only a small percentage actually require them 3
Specimen quality issues: Poor specimen collection technique can lead to false-negative results, particularly with nasopharyngeal swabs
Timing of testing: Viral shedding may decrease after the first few days of symptoms, potentially leading to false-negative results if testing is delayed
By following this evidence-based approach to diagnostic testing, clinicians can more accurately differentiate between viral and bacterial upper respiratory tract infections, leading to more appropriate treatment decisions and improved antibiotic stewardship.