Is azithromycin (Zithromax) effective against gram-positive Streptococcus infections?

Azithromycin's Effectiveness Against Gram-Positive Streptococcus

Azithromycin is effective against gram-positive Streptococcus infections, but it should be used as an alternative therapy rather than first-line treatment due to increasing resistance patterns and its inferior efficacy compared to beta-lactams for streptococcal infections. 1

Efficacy Against Streptococcal Species

Azithromycin demonstrates activity against several streptococcal species:

• Streptococcus pyogenes (Group A Strep): FDA-approved for pharyngitis/tonsillitis, but only as an alternative to first-line therapy 1
• Streptococcus pneumoniae: Active against susceptible strains 1
• Streptococcus agalactiae (Group B Strep): Included in the spectrum of activity 1

Mechanism of Action

Azithromycin belongs to the azalide class (related to macrolides) and works by:

• Binding to the 23S rRNA of the bacterial 50S ribosomal subunit
• Blocking protein synthesis by inhibiting the transpeptidation/translocation step
• Inhibiting assembly of the 50S ribosomal subunit 1

Resistance Concerns

Several important resistance issues must be considered:

• Increasing resistance among streptococcal species has been documented
• The most common resistance mechanism is modification of the 23S rRNA at positions A2058 and A2059 1
• Cross-resistance exists between azithromycin and other macrolides (erythromycin, clarithromycin) 1
• Resistance rates for macrolides among Group A Streptococcus in the US are approximately 5-8% 2

Clinical Applications for Streptococcal Infections

Streptococcal Pharyngitis/Tonsillitis

• First-line therapy: Penicillin (intramuscular or oral)
• Azithromycin role: Alternative for penicillin-allergic patients
• Dosing: 12 mg/kg once daily (maximum 500 mg) for 5 days 2, 1
• Important note: Penicillin remains the drug of choice for S. pyogenes to prevent rheumatic fever; azithromycin lacks data on rheumatic fever prevention 1

Skin and Soft Tissue Infections

• Azithromycin is effective for uncomplicated skin infections caused by susceptible strains of S. pyogenes and S. agalactiae 1
• For necrotizing infections involving streptococci, combination therapy with clindamycin and penicillin is preferred over azithromycin 3

Pharmacodynamic Considerations

Azithromycin exhibits time-dependent killing with moderate to prolonged persistent effects:

• The pharmacodynamic parameter correlating with efficacy is the AUC to MIC ratio rather than time above MIC
• Optimal AUC:MIC ratio is approximately 25 for clinical efficacy 3
• Achieves high tissue concentrations despite relatively low serum levels 3

Pitfalls and Caveats

1. Resistance development: The long half-life of azithromycin (68 hours) creates a prolonged period of subinhibitory concentrations, potentially promoting resistance development 3

2. Inferior efficacy: For streptococcal pharyngitis, studies show higher recurrence rates with azithromycin compared to penicillin 4

3. Not for severe infections: Azithromycin should not be used for severe streptococcal infections due to its bacteriostatic nature and increasing resistance patterns 3

4. Susceptibility testing: Due to variable resistance, susceptibility testing should be performed when treating streptococcal infections with azithromycin 1

In conclusion, while azithromycin does cover gram-positive streptococci, it should be reserved as an alternative agent when first-line therapies (particularly beta-lactams) cannot be used due to allergies or other contraindications.