What are the first-line antibiotics for an adult patient with acute pharyngitis, considering penicillin (PCN) allergy status?

First-Line Antibiotics for Acute Pharyngitis in Adults

Penicillin or amoxicillin is the first-line antibiotic for acute group A streptococcal pharyngitis in adults without penicillin allergy, given for 10 days. 1

Treatment Algorithm Based on Penicillin Allergy Status

For Non-Allergic Patients (First-Line)

• Penicillin V or amoxicillin for 10 days is the drug of choice based on narrow spectrum, proven efficacy, zero documented resistance worldwide, safety profile, and low cost 1, 2
• Group A streptococcus has never developed resistance to penicillin in over five decades of use 1, 3
• Penicillin is the only antibiotic proven in controlled trials to prevent acute rheumatic fever, which is the primary goal of treatment 2

For Penicillin-Allergic Patients (Non-Anaphylactic)

• First-generation cephalosporins (cephalexin 500 mg twice daily or cefadroxil 1 gram daily) for 10 days are the preferred first-line alternatives 1, 4
• These have strong, high-quality evidence for efficacy with only 0.1% cross-reactivity risk in patients with non-immediate penicillin reactions 5, 4
• Cross-reactivity with cephalosporins is approximately 10% only in patients with immediate/anaphylactic penicillin hypersensitivity 1, 5

For Immediate/Anaphylactic Penicillin Allergy

• Clindamycin 300 mg three times daily for 10 days is the preferred choice 1, 5
• Clindamycin has strong, moderate-quality evidence with approximately 1% resistance rate among Group A streptococcus in the United States 5, 4
• Clindamycin demonstrates high efficacy even in chronic carriers who have failed penicillin treatment 5

Alternative macrolides for immediate allergy:

• Azithromycin 500 mg once daily for 5 days (only antibiotic requiring less than 10 days due to prolonged tissue half-life) 1, 5
• Clarithromycin 250 mg twice daily for 10 days 1

Critical Treatment Duration Requirements

• All antibiotics except azithromycin require a full 10-day course to achieve maximal pharyngeal eradication and prevent acute rheumatic fever 1, 5
• Shortening courses below 10 days dramatically increases treatment failure rates and rheumatic fever risk 5, 2
• Therapy can be safely postponed up to 9 days after symptom onset and still prevent acute rheumatic fever 5

Important Resistance Considerations

• Macrolide resistance among Group A streptococcus is 5-8% in the United States and varies geographically 5, 2, 6
• Some regions experience significantly higher macrolide resistance rates, making clindamycin or cephalosporins more reliable alternatives 5
• Clindamycin resistance remains very low at approximately 1% in the United States 5, 7

Common Pitfalls to Avoid

• Do not prescribe azithromycin as first-line therapy when penicillin can be used—this unnecessarily broadens spectrum and increases resistance selection pressure 2
• Do not use cephalosporins in patients with immediate/anaphylactic penicillin reactions (anaphylaxis, angioedema, respiratory distress, or urticaria within 1 hour) due to 10% cross-reactivity risk 1, 5
• Do not use trimethoprim-sulfamethoxazole (Bactrim) for strep throat—it has high resistance rates and is not effective against Group A streptococcus 5
• Do not shorten antibiotic courses based on clinical improvement—complete the full 10 days (except azithromycin's 5-day regimen) 5, 2

When to Test Before Treating

• Use the Centor criteria (fever, tonsillar exudates, tender anterior cervical lymphadenopathy, absence of cough) to guide testing 1, 8
• Patients with 0-1 criteria should not be tested or treated 1, 8
• Patients with 2 or more criteria should undergo rapid antigen testing before prescribing antibiotics 1, 8, 6
• Throat culture is the gold standard but rapid antigen tests with >80% sensitivity are acceptable 8, 9

Adjunctive Symptomatic Treatment

• Acetaminophen or NSAIDs (such as ibuprofen) should be considered for moderate to severe symptoms or high fever 1, 5
• NSAIDs relieve pharyngitis pain better than acetaminophen in multiple studies 3
• Aspirin must be avoided in children due to Reye syndrome risk 1, 5
• Corticosteroids are not recommended as adjunctive therapy 1, 5