A 22-year-old male student presents with acute pharyngitis, fever, and bilateral tonsillar enlargement with exudate. Rapid antigen detection test (RADT) for Group A Streptococcus is negative. The clinical suspicion for streptococcal pharyngitis remains high. Which is the most appropriate next investigation?

## Investigation of Choice When RADT is Negative but GAS Suspected **Key Point:** Throat culture on blood agar is the gold standard confirmatory test for Group A Streptococcus (GAS) pharyngitis when RADT is negative but clinical suspicion remains high. RADT has 90–95% sensitivity; culture has near 100% sensitivity. ### Why Throat Culture is the Gold Standard | Investigation | Sensitivity | Specificity | Turnaround Time | When to Use | |---------------|-------------|-------------|-----------------|-------------| | **RADT** | 90–95% | 95–99% | 5–10 min | Initial screening | | **Throat culture** | 95–100% | 99–100% | 48–72 hrs | Gold standard; negative RADT | | **Monospot** | 80–90% | 95–98% | 5 min | Suspected EBV (atypical lymphocytes) | | **Repeat RADT** | Same as first | Same as first | 5–10 min | Not recommended; wastes time | | **Viral serology** | Variable | Variable | Days | Retrospective diagnosis | **High-Yield:** Current guidelines (American Academy of Pediatrics, Infectious Diseases Society of America) recommend: 1. If RADT is **positive** → treat for GAS 2. If RADT is **negative** but clinical suspicion is high → perform throat culture for confirmation 3. Do NOT repeat RADT; it will not improve diagnostic accuracy ### Clinical Pearl **Clinical Pearl:** The negative RADT in this patient does not exclude GAS pharyngitis. RADT sensitivity is 90–95%, meaning 5–10% of true GAS infections are missed. Throat culture on blood agar is essential to: - Definitively confirm or exclude GAS - Identify the organism and guide antibiotic therapy - Detect penicillin-resistant strains (rare but important) - Provide epidemiological data ### Throat Culture Technique - **Medium:** Blood agar (5% sheep blood) - **Incubation:** 35–37°C, 5% CO₂, 24–48 hours - **Identification:** Beta-hemolytic colonies, bacitracin-sensitive (CAMP test positive) - **Sensitivity:** Increased by culturing both tonsillar surfaces and posterior pharynx **Mnemonic:** **RADT-Negative → Culture** = **R**emember **A**RADT **D**oesn't **T**ell the whole story; **C**ulture **O**ffers **N**ew **F**indings **I**n **R**esolution **M**issed **E**vents **Warning:** Do NOT treat empirically based on clinical suspicion alone if RADT is negative and culture is pending. However, in high-risk populations (rheumatic fever endemic areas, immunocompromised), empirical treatment may be justified while awaiting culture results. [cite:Harrison 21e Ch 140]