## GAS Pharyngitis in Penicillin-Allergic Patients ### Clinical Scenario Group A Streptococcus (GAS) pharyngitis is confirmed by: - Rapid antigen test positivity (high specificity) - Throat culture isolation (gold standard, but slower) - Penicillin allergy documented → β-lactams contraindicated ### Why Azithromycin is First-Line in Penicillin Allergy **Key Point:** In penicillin-allergic patients with GAS pharyngitis, macrolides (azithromycin) are the preferred alternative because: 1. Excellent efficacy against GAS (bacteriostatic, but sufficient for pharyngitis) 2. Oral bioavailability — convenient outpatient therapy 3. Avoids cross-reactivity risk with β-lactams 4. Superior compliance due to shorter course (5 days) 5. Lower cost than vancomycin or fluoroquinolones **High-Yield:** GAS remains universally susceptible to macrolides in most regions; resistance is <5% in India and developed nations. Azithromycin is preferred over erythromycin due to better tolerability and shorter duration. ### Treatment Algorithm for GAS Pharyngitis ```mermaid flowchart TD A[GAS pharyngitis confirmed]:::outcome --> B{Penicillin allergy?}:::decision B -->|No| C[Penicillin V or Amoxicillin]:::action B -->|Yes| D{Type of allergy?}:::decision D -->|Non-anaphylactic<br/>rash, mild| E[Cephalexin<br/>1st gen cephalosporin]:::action D -->|Anaphylaxis,<br/>Stevens-Johnson| F[Macrolide:<br/>Azithromycin]:::action C --> G[7-10 day course]:::action E --> G F --> H[5-day course]:::action ``` ### Dosing & Duration - **Azithromycin:** 500 mg on day 1, then 250 mg daily for 4 days (total 5-day course) - **Alternative (if macrolide allergy):** Clindamycin 300 mg TID × 10 days **Clinical Pearl:** Cephalosporins (cephalexin) carry a ~1–3% cross-reactivity risk with penicillins, particularly in anaphylaxis-type reactions. First-generation cephalosporins are safer than third-generation agents. However, in true anaphylaxis or severe delayed hypersensitivity, macrolides are preferred. ### Why Other Options Are Suboptimal | Drug | Reason | |------|--------| | **Amoxicillin** | Contraindicated due to documented penicillin allergy; risk of anaphylaxis | | **Vancomycin** | Reserved for serious infections (endocarditis, meningitis); overkill for pharyngitis; IV-only; expensive | | **Cephalexin** | 1–3% cross-reactivity with penicillin; acceptable only if allergy is non-anaphylactic rash | **Mnemonic:** **MACROLIDE FIRST** in penicillin-allergic GAS = **M**acrolides **A**void **C**ross-reactivity, **R**eliable **O**ral **L**ow-cost **I**ncisive **D**osing, **E**xcellent **F**or **I**mmunity **R**ecovery, **S**afe **T**herapy [cite:KD Tripathi 8e Ch 46; Harrison 21e Ch 329]
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