What are alternative treatments to penicillin (pen) for streptococcal infections?

Alternative Treatments to Penicillin for Streptococcal Infections

For penicillin-allergic patients with streptococcal pharyngitis, erythromycin or other macrolides (azithromycin, clarithromycin) are suitable alternatives, while first- or second-generation cephalosporins are acceptable for those without immediate hypersensitivity to β-lactam antibiotics. 1

Treatment Algorithm Based on Type of Penicillin Allergy

Non-Immediate (Non-Anaphylactic) Penicillin Allergy

• First-generation cephalosporins are the preferred alternative, specifically cephalexin 20 mg/kg per dose twice daily (maximum 500 mg per dose) or cefadroxil 30 mg/kg once daily for 10 days 2, 3
• These agents have strong, high-quality evidence for efficacy and are generally effective in eradicating streptococci from the nasopharynx 1, 3
• Cephalosporins should not be used in patients with immediate hypersensitivity to β-lactam antibiotics, as up to 10% may have cross-reactivity 1, 2

Immediate/Anaphylactic Penicillin Allergy

Macrolides or clindamycin are the recommended alternatives 1, 2:

• Azithromycin: 12 mg/kg once daily (maximum 500 mg) for 5 days 2, 4

  • This is the only antibiotic that requires just 5 days due to its prolonged tissue half-life 2, 5
  • Macrolide resistance among Group A Streptococcus is approximately 5-8% in the United States 2, 6
  • The FDA label specifically notes that susceptibility testing should be performed when treating with azithromycin, as some strains are resistant 4

• Clarithromycin: 7.5 mg/kg per dose twice daily (maximum 250 mg per dose) for 10 days 2

• Erythromycin: 20-40 mg/kg/day divided 2-3 times daily for 10 days 1, 2

  • Erythromycin estolate or ethyl succinate formulations are both acceptable 1
  • Higher rates of gastrointestinal side effects limit compliance, especially in children 5

• Clindamycin: 7 mg/kg per dose three times daily (maximum 300 mg per dose) for 10 days 2

  • Clindamycin has strong, moderate-quality evidence and demonstrates high efficacy in eradicating streptococci, even in chronic carriers 2
  • Clindamycin resistance among Group A Streptococcus isolates in the United States is approximately 1% 2

Critical Treatment Duration Considerations

• Most oral antibiotics require a full 10-day course to achieve maximal pharyngeal eradication of Group A Streptococcus 1, 2
• Azithromycin is the only exception, requiring only 5 days due to its pharmacokinetic profile 2, 6
• Shorter courses with other antibiotics can lead to treatment failure and increased risk of complications such as rheumatic fever 1, 2

Important Caveats and Common Pitfalls

Resistance Patterns

• Be aware of local macrolide resistance patterns when prescribing azithromycin, clarithromycin, or erythromycin 2, 6
• In areas with high macrolide resistance, cephalexin may be preferred for non-anaphylactic penicillin-allergic patients 2
• The FDA label for azithromycin emphasizes that it should not be relied upon to treat syphilis and that data establishing efficacy in preventing rheumatic fever are not available 4

Cross-Reactivity Concerns

• Do not assume all penicillin-allergic patients cannot receive cephalosporins - only those with immediate/anaphylactic reactions should avoid them 2
• First-generation cephalosporins carry approximately 10% cross-reactivity risk in patients with immediate penicillin hypersensitivity 1, 2

Clinical Outcomes vs. Bacteriologic Eradication

• Research shows that azithromycin at 10 mg/kg for 3 days had inferior bacteriologic eradication (65%) compared to penicillin V (82%), though clinical success rates were similar 7
• This supports the current guideline recommendation of 12 mg/kg daily for 5 days rather than lower doses or shorter durations 2, 6

Post-Treatment Monitoring

• Routine post-treatment throat cultures are not recommended for asymptomatic patients who have completed therapy 2, 6
• Follow-up testing should only be considered in special circumstances, such as patients with a history of rheumatic fever 2

Special Populations

Chronic Carriers

• For chronic streptococcal carriers, clindamycin may be particularly effective due to its ability to eradicate the organism 2
• However, chronic carriers generally do not require antimicrobial therapy as they are unlikely to spread infection and are at little risk for complications 2

Pediatric Considerations

• For Group A Streptococcus pneumonia in children, alternatives include ceftriaxone, cefotaxime, or clindamycin if susceptible 1
• Amoxicillin is often preferred over penicillin V in young children due to better taste acceptance, though efficacy is equal 1