What are the first-line antibiotics for bacterial tonsillitis?

First-Line Antibiotics for Bacterial Tonsillitis

Amoxicillin or penicillin V are the first-line antibiotics for bacterial tonsillitis, with cephalexin as the preferred second-line option for treatment failures or when beta-lactamase-producing bacteria are suspected. 1

Primary Treatment Options

Penicillin V (Phenoxymethylpenicillin) - Gold Standard

• Penicillin V remains the gold standard with proven efficacy over five decades and no documented resistance development by Group A streptococci. 1
• Pediatric dosing: 250 mg two or three times daily for 10 days 1
• Adult dosing: 250 mg four times daily OR 500 mg twice daily for 10 days 1
• The FDA and multiple guideline societies confirm penicillin as the usual drug of choice for Streptococcus pyogenes infection and rheumatic fever prophylaxis 2

Amoxicillin - Preferred in Young Children

• Amoxicillin is preferred in younger children due to better taste and suspension availability. 1
• Pediatric dosing: 50 mg/kg once daily (maximum 1,000 mg) for 10 days 1
• Adult dosing: 250 mg four times daily OR 500 mg twice daily for 10 days 1
• Some evidence suggests amoxicillin may achieve superior bacteriologic cure rates (76% vs 64%) and clinical cure rates (84% vs 73%) compared to penicillin V 3

Intramuscular Option

• Penicillin G benzathine (single IM dose): 600,000 units for patients <27 kg; 1,200,000 units for patients ≥27 kg 1

When to Consider Watchful Waiting

• Consider watchful waiting with symptom relief as the initial approach in less severe presentations, as antibiotics provide modest benefit but carry risks of side effects, antimicrobial resistance, and costs. 1
• Delayed prescribing (>48 hours after consultation) shows no significant differences in complication rates compared to immediate treatment 1

Second-Line Treatment Options

Cephalexin - Preferred Second Choice

• Cephalexin is the preferred second-line antibiotic based on lower relapse rates, good tolerability, and narrow spectrum. 1
• Dosing: 20 mg/kg per dose twice daily (maximum 500 mg per dose) for 10 days 1
• Consider when penicillin fails, as beta-lactamase-producing bacteria may "shield" Group A streptococci by inactivating penicillin 4

Augmentin (Amoxicillin-Clavulanate) - For Treatment Failures

• The American College of Physicians and IDSA recommend considering Augmentin for penicillin treatment failures, as it achieves higher eradication rates 5
• Use when beta-lactamase-producing bacteria are suspected (recovered from >75% of tonsils in recurrent infection cases) 4
• Adult dosing: 500 mg amoxicillin/125 mg clavulanate three times daily for 10 days 5
• Pediatric dosing: 45 mg/kg/day of amoxicillin component divided into 2-3 doses 5

Penicillin Allergy Options

Clarithromycin - For Severe Penicillin Allergy

• Use clarithromycin only when severe penicillin allergy exists, as its effectiveness is significantly compromised in areas with high macrolide resistance. 1
• Pediatric dosing: 7.5 mg/kg per dose twice daily (maximum 250 mg per dose) for 10 days 1
• Macrolide resistance is geographically variable and temporally changing—check local resistance patterns before use 1

Clindamycin - Alternative for Severe Allergy

• Dosing: 7 mg/kg per dose three times daily (maximum 300 mg per dose) for 10 days 1

Azithromycin - Limited Role

• Azithromycin is FDA-approved as an alternative to first-line therapy only in individuals who cannot use first-line therapy, but approximately 1% of susceptible strains become resistant following therapy. 2
• The FDA label explicitly states penicillin is the usual drug of choice, and susceptibility testing should be performed when azithromycin is used 2
• Azithromycin showed clinical superiority to penicillin V in FDA trials (98% vs 84% success at Day 14), but resistance concerns limit its use 2

Critical Treatment Principles

Duration of Therapy

• 10-day treatment courses are essential for penicillin, amoxicillin, and clarithromycin to prevent rheumatic fever and ensure bacterial eradication. 1
• This is non-negotiable for rheumatic fever prevention 1, 5

Reassessment Protocol

• Reassess patients showing no improvement within 48-72 hours and consider switching to a broader-spectrum antibiotic such as amoxicillin-clavulanate. 5
• Fever should resolve within 24 hours for pneumococcal infections and 2-4 days for other bacterial etiologies 6

Clinical Benefits of Antibiotic Treatment

• Antibiotics reduce risk of rheumatic fever (RR 0.27) 1
• Reduce suppurative complications including peritonsillar abscess (RR 0.15) and acute otitis media (RR 0.30) 1

Key Pitfalls to Avoid

• Group A streptococci have shown no resistance to penicillins over five decades—do not avoid penicillin due to unfounded resistance concerns. 1
• Routine skin testing for penicillin allergy before first exposure is not necessary 1
• Up to 20% bacteriologic failure with penicillin may occur due to beta-lactamase-producing bacteria, noncompliance, or carrier state—not true resistance 4
• Data establishing efficacy of azithromycin in subsequent prevention of rheumatic fever are not available, making it a less reliable choice. 2