What is the first-line antibiotic treatment for an adult patient with acute tonsillitis, without known allergies or complicating factors?

Antibiotic of Choice for Acute Tonsillitis

Penicillin V (oral) or amoxicillin is the first-line antibiotic for acute bacterial tonsillitis in adults, with treatment duration of 10 days to ensure eradication of Group A β-hemolytic streptococci and prevent complications. 1

When to Prescribe Antibiotics

• Only treat with antibiotics if Group A streptococcal infection is confirmed by rapid antigen detection test (RADT) or throat culture 2
• Use the modified Centor/McIsaac score ≥3 (considering age and absence of respiratory symptoms) as an indication to test for streptococcal infection 3
• Key clinical features suggesting bacterial tonsillitis include: persistent fever, anterior cervical adenitis (tender lymph nodes), tonsillopharyngeal exudates, and absence of cough 2
• Do not prescribe antibiotics for viral pharyngitis, which accounts for the majority of sore throat cases 2

First-Line Treatment Algorithm

For Patients Without Penicillin Allergy:

• Penicillin V (oral): First choice due to proven efficacy against Group A β-hemolytic streptococci, narrow spectrum, safety profile, and low cost 1
• Amoxicillin: Equally effective alternative, often preferred due to better taste and easier dosing schedule (can be given twice daily vs. three times daily for penicillin V) 1
• Treatment duration: 10 days to achieve adequate bacterial eradication and reduce risk of recurrence 2, 1, 3

The evidence strongly supports 10-day courses over shorter durations. A 2023 meta-analysis found that 5-day courses of standard-dose penicillin are less effective for Group A streptococcal pharyngitis (OR 0.43; 95% CI 0.23-0.82) 2. While high-dose penicillin given four times daily for 5 days showed non-inferior clinical cure rates (89.6% vs 93.3%), bacterial eradication was lower in the short-course group 2.

For Patients With Penicillin Allergy:

Non-Type I (non-anaphylactic) allergy:

• First-generation cephalosporins (e.g., cephalexin) are safe and effective alternatives 1
• These have distinct chemical structures with minimal cross-reactivity risk 2

Type I hypersensitivity (anaphylaxis history):

• Clindamycin: Preferred alternative with excellent gram-positive coverage against Streptococcus pyogenes 1
• Dosing: 20-30 mg/kg/day in 3 divided doses (maximum 300 mg/dose) 1

Macrolides (azithromycin, clarithromycin, erythromycin):

• Should be used cautiously due to lower efficacy rates (77-78%) compared to first-line options 1
• Not recommended as first-line therapy due to increasing resistance in Group A streptococci 2, 3
• A 2004 study found clarithromycin failed to eradicate clarithromycin-resistant S. pyogenes isolates (only 14-19% eradication vs 83% for amoxicillin/clavulanate) 4
• Approximately 1% of azithromycin-susceptible S. pyogenes isolates became resistant following azithromycin therapy 5

Treatment Failure Management

• Reassess at 72 hours if no improvement or worsening symptoms 1
• Consider switching to clindamycin if initial penicillin therapy fails 1
• Treatment failure may be due to beta-lactamase-producing bacteria (recovered from >75% of tonsils in recurrent infection cases) that "shield" Group A streptococci by inactivating penicillin 6
• Amoxicillin-clavulanate can be considered for treatment failures, as it provides coverage against beta-lactamase-producing organisms 7, 6
• Obtain throat culture if symptoms persist despite appropriate second-line therapy 1

Critical Pitfalls to Avoid

• Do not use broad-spectrum antibiotics unnecessarily when narrow-spectrum penicillin would be effective 1
• Avoid amoxicillin in suspected Epstein-Barr virus (infectious mononucleosis) due to risk of severe rash 1
• Do not confuse chronic streptococcal carriers with active infection - carriers do not require antibiotic treatment 2, 1
• Do not prescribe antibiotics for low-risk patients (Centor score <3 without positive testing) as this does not prevent rheumatic fever or acute glomerulonephritis in these populations 3
• Macrolides should not be first-line therapy given resistance patterns and lower efficacy 2, 1, 3

Symptomatic Management

• Provide analgesic therapy regardless of antibiotic decision: acetaminophen, ibuprofen, aspirin (in adults), or throat lozenges 2
• Pain management should be addressed immediately, especially during the first 24 hours 2
• Topical agents (benzalkonium chloride + tyrothricin + benzocaine) may provide additional symptomatic relief and potentially shorten disease duration 3

Special Considerations

• Group A β-hemolytic streptococci have not developed resistance to penicillins over five decades, making penicillin remain highly effective 1
• Antibiotics shorten symptom duration by only 1-2 days, with number needed to treat of 6 at 3 days and 21 at 1 week 2
• The primary benefits of antibiotic therapy are prevention of suppurative complications (peritonsillar abscess) and spread of infection, not symptom relief 2
• "Delayed antibiotic prescription" strategy (monitoring for 2-3 days before starting antibiotics) is appropriate in doubtful cases and highly effective in reducing unnecessary antibiotic use 3