First-Line Antibiotic Treatment for Tonsillitis
Penicillin V (phenoxymethylpenicillin) or amoxicillin are the first-line antibiotics for bacterial tonsillitis, with penicillin V dosed at 500 mg twice daily or 250 mg four times daily for 10 days in adults, and amoxicillin dosed at 500 mg twice daily or 250 mg four times daily for 10 days. 1
Primary Treatment Recommendations
Penicillin remains the gold standard after five decades of use with no documented resistance in Group A beta-hemolytic streptococci (GABHS), making it the preferred narrow-spectrum, cost-effective choice 2, 1. The American Academy of Pediatrics and guideline societies consistently recommend penicillin V or amoxicillin as first-line agents 1.
Specific Dosing Regimens:
Adults:
- Penicillin V: 500 mg twice daily OR 250 mg four times daily for 10 days 1
- Amoxicillin: 500 mg twice daily OR 250 mg four times daily for 10 days 1
Pediatric patients:
- Amoxicillin: 50 mg/kg once daily (maximum 1,000 mg) for 10 days 1
- Penicillin V: 250 mg two or three times daily for 10 days 1
Alternative single-dose option:
- Penicillin G benzathine (intramuscular): 600,000 units for patients <27 kg; 1,200,000 units for patients ≥27 kg 1
When to Consider Antibiotics vs. Watchful Waiting
Not all tonsillitis requires immediate antibiotics. Use the McIsaac or Centor scoring system to determine likelihood of GABHS infection 2, 3:
Score interpretation:
- Score of 1: Neither antibiotics nor culture required 2
- Score of 2-3: Obtain throat culture or rapid strep test; base antibiotic decision on result 2, 3
- Score of 4: Initiate antibiotics immediately or obtain culture 2
Delayed prescribing (waiting >48 hours after initial consultation) is a valid strategy with no significant difference in complication rates compared to immediate treatment 1.
Second-Line Options
For penicillin treatment failure or when more reliable eradication is needed:
Cephalexin is the preferred second-choice antibiotic based on lower relapse rates, good tolerability, and narrow spectrum 1:
- Pediatric: 20 mg/kg per dose twice daily (maximum 500 mg per dose) for 10 days 1
- Adult: Standard cephalosporin dosing for 10 days
Alternative cephalosporins include cefadroxil or first/second-generation options, which have demonstrated superiority over penicillin in some studies for GABHS eradication 2, 4, 3.
Penicillin Allergy Management
For patients with penicillin allergy:
Clarithromycin (for severe allergy):
- Pediatric: 7.5 mg/kg per dose twice daily (maximum 250 mg per dose) for 10 days 1
- Critical caveat: Effectiveness is significantly compromised in areas with high macrolide resistance 1, 3
Clindamycin (alternative for severe allergy):
- 7 mg/kg per dose three times daily (maximum 300 mg per dose) for 10 days 1
Erythromycin is effective but complicated by multiple daily doses and high gastrointestinal side effects, making newer macrolides preferable 5, 3.
Critical Treatment Pitfalls to Avoid
The 10-day treatment duration is non-negotiable for penicillin, amoxicillin, and clarithromycin to prevent rheumatic fever and ensure bacterial eradication 1, 3. Seven-day courses are used in some countries (e.g., Netherlands), but 3- and 5-day penicillin courses are insufficient 2.
Do not perform routine skin testing for penicillin allergy before first exposure 1.
Check local macrolide resistance patterns before prescribing clarithromycin or erythromycin, as resistance is geographically variable and temporally changing 1.
Antibiotics provide meaningful clinical benefits beyond symptom relief: they reduce rheumatic fever risk (RR 0.27) and suppurative complications including peritonsillar abscess (RR 0.15) and acute otitis media (RR 0.30) 1.
Why Penicillin Failure Occurs
Despite no documented in vitro resistance, clinical and bacteriologic failure with penicillin has increased from 2-10% historically to approximately 30% currently 4. The primary cause is poor adherence to the 10-day regimen 4. Other contributing factors include re-infection from family members, co-pathogenicity with beta-lactamase producing bacteria, eradication of protective pharyngeal flora, and streptococcal penicillin tolerance 2, 4.