What alternative antibiotics can be used for a patient with tonsillitis who develops diarrhea while taking amoxicillin-clavulanate (amox CV)?

Alternative Antibiotics for Tonsillitis When Amoxicillin-Clavulanate Causes Diarrhea

For patients with tonsillitis who develop diarrhea on amoxicillin-clavulanate, switch to oral clindamycin 300 mg twice daily for 10 days, which provides superior clinical cure rates and lower gastrointestinal side effects. 1, 2

Immediate Management of Diarrhea

• For mild, non-bloody diarrhea: Continue the antibiotic if clinically necessary while monitoring symptoms, as most cases are self-limited 1
• For moderate to severe diarrhea or any red flags (bloody stools, fever, severe abdominal pain): Immediately discontinue amoxicillin-clavulanate and test for C. difficile toxin before starting alternative therapy 1
• Do not use empiric antibiotics for the diarrhea itself while awaiting C. difficile results unless the patient shows signs of sepsis 1

First-Line Alternative: Clindamycin

Clindamycin is the preferred alternative antibiotic for tonsillitis in patients who cannot tolerate amoxicillin-clavulanate. 3, 4, 2

• Dosing: 300 mg orally twice daily for 10 days in adults and adolescents 2
• Clinical efficacy: Achieves 92.6% clinical cure rates at day 12 compared to 85.2% with amoxicillin-clavulanate (p<0.003) 2
• Bacteriologic eradication: 97.9% eradication of Group A streptococci, comparable to amoxicillin-clavulanate 2
• Gastrointestinal tolerability: Significantly lower rates of diarrhea (8.6%) compared to amoxicillin-clavulanate (29.89% in adults, up to 44-52% in high-dose regimens) 3, 5, 2
• Long-term outcomes: Prevents future episodes of recurrent pharyngotonsillitis more effectively than penicillin 6

Second-Line Alternatives

Cephalosporins

Cefaclor or cefuroxime are effective alternatives with lower gastrointestinal side effects than amoxicillin-clavulanate. 3, 5, 7

• Cefaclor: 375 mg twice daily for 10 days in adults; 20 mg/kg/day in children 5, 7
• Provides 99% clinical effectiveness with only 16.84% gastrointestinal adverse events compared to 29.89% with amoxicillin-clavulanate (p<0.03) 5
• Lower relapse rates (3.29%) compared to amoxicillin-clavulanate (8.33%); relative risk of relapse 2.6 times lower 5, 7
• Cefuroxime: Recommended as an alternative in sinusitis guidelines, applicable to pharyngitis 3

Macrolides (Use with Caution)

Macrolides should be reserved for patients with true penicillin allergy, not for gastrointestinal intolerance alone. 3

• Azithromycin should be avoided as first-line replacement due to inadequate coverage for common respiratory pathogens and risk of QT prolongation 3, 1
• Clarithromycin or erythromycin may be considered but have lower efficacy than clindamycin 3
• A systematic review found no evidence of differing efficacy between azithromycin and comparator agents, but this does not make it preferable 3

Key Clinical Pitfalls to Avoid

• Do not switch to azithromycin as it provides inadequate coverage and carries cardiac risks 3, 1
• Do not use shorter courses of penicillin (3-5 days) as alternatives, as 7-10 day courses are superior for symptom resolution 3
• Do not assume all diarrhea is benign: Test for C. difficile if diarrhea is moderate-severe, bloody, or associated with fever 1
• Do not use fluoroquinolones (ciprofloxacin, levofloxacin) for simple tonsillitis; these are reserved for more severe infections and carry resistance concerns 3

Mechanism of Amoxicillin-Clavulanate-Associated Diarrhea

The high incidence of diarrhea (44-52% in some studies) occurs through two mechanisms: 3, 1

• Dose-dependent gastrointestinal toxicity from clavulanate itself 1
• Disruption of normal intestinal flora leading to potential C. difficile overgrowth 1

Treatment Duration

• Standard duration: 10 days for all alternative antibiotics to ensure complete eradication and prevent relapse 3, 2
• Shorter courses (3-5 days) show inferior outcomes with higher relapse rates 3
• Continue treatment for 7 days after the patient is symptom-free 3