What is the recommended treatment for a penicillin-resistant streptococcal (strep) throat infection?

Treatment of Penicillin-Resistant Streptococcal Throat Infection

Clindamycin is the recommended first-line treatment for penicillin-resistant streptococcal throat infections due to its very low resistance rate (approximately 1%) and high clinical efficacy. 1

Understanding Penicillin Resistance in Strep Throat

• No clinical isolate of Group A Streptococcus (GAS) has ever been documented to be resistant to penicillin anywhere in the world 2, 3, 1
• When patients appear to have "penicillin-resistant" strep throat, this is typically due to:
  • Treatment non-compliance with the full 10-day regimen 4
  • Reexposure to infected family members or peers 4
  • Co-pathogenicity with other bacteria 4
  • Eradication of normal protective pharyngeal flora 4
  • Penicillin tolerance due to repeated exposure to sublethal antibiotic concentrations 4

Treatment Algorithm for Apparent Penicillin Failure

First-Line Treatment:

• Clindamycin: 300-450 mg orally three times daily for 10 days in adults and children >30kg; 20 mg/kg/day divided in 3 doses for 10 days in children 1
  • Extremely low resistance rate (approximately 1%) 1
  • High clinical efficacy (90-92%) 5

Second-Line Options:

• Narrow-spectrum cephalosporins for 10 days 1:
  • Cefadroxil or cephalexin are preferred over broad-spectrum cephalosporins 3
  • These have lower risk of selecting for antibiotic-resistant flora 3

For Patients with Penicillin Allergy:

• For non-anaphylactic penicillin allergy: First-generation cephalosporins (cefadroxil, cephalexin) 3, 6
• For immediate/anaphylactic penicillin allergy: Clindamycin 3, 5
• Note: Up to 10% of penicillin-allergic persons are also allergic to cephalosporins 3

Important Considerations

Macrolide Resistance:

• Macrolide resistance (erythromycin, clarithromycin, azithromycin) among GAS isolates in the US is approximately 5-8% 1, 5
• In areas with high macrolide resistance, these antibiotics should be avoided 7
• Azithromycin is given for 5 days due to its prolonged tissue half-life 1

Duration of Therapy:

• Standard treatment duration is 10 days for most antibiotics to achieve maximal pharyngeal eradication of GAS 2, 1
• Although some studies suggest shorter courses (5 days) with certain cephalosporins may be effective, the standard 10-day course is still recommended by major guidelines 3, 6

Medications to Avoid:

• Tetracyclines should not be used due to high prevalence of resistant strains 1
• Sulfonamides and trimethoprim-sulfamethoxazole are ineffective against GAS 1

Follow-Up

• Routine post-treatment testing is not recommended unless the patient is at high risk for acute rheumatic fever or has recurrence of symptoms 1
• If symptoms worsen after 72 hours of appropriate antibiotic therapy or persist for 5 days after treatment initiation, the patient should be reevaluated 5, 6

Pitfalls to Avoid

• Do not assume true penicillin resistance in GAS, as this has never been documented 2, 3, 1
• Do not use broad-spectrum antibiotics unnecessarily, as they increase the risk of selecting for resistant flora 3
• Do not use macrolides in areas with known high resistance rates 7
• Do not forget to complete the full course of antibiotics (typically 10 days) to prevent treatment failure and complications 2, 1