Is Azithromycin (macrolide antibiotic) effective against Streptococcus pneumoniae?

Azithromycin Susceptibility for Streptococcus pneumoniae

Azithromycin is only partially effective against Streptococcus pneumoniae, with 20-30% of S. pneumoniae strains showing resistance to macrolides, making it a suboptimal choice for empiric monotherapy in respiratory infections where S. pneumoniae is a likely pathogen. 1

Current Susceptibility Patterns

• According to clinical guidelines, approximately 90-95% of S. pneumoniae strains were susceptible to azithromycin in earlier studies 1
• However, more recent data indicates increasing resistance rates:
  • 20-30% of S. pneumoniae isolates overall show erythromycin/macrolide resistance 1
  • Resistance rates are significantly higher (up to 70%) among penicillin-resistant S. pneumoniae strains 1
  • Resistance can develop through two primary mechanisms:
    • mef(A)-mediated (low-level resistance)
    • erm(B)-mediated (high-level resistance) 2, 3

Clinical Implications

• FDA labeling specifically states azithromycin is indicated for community-acquired pneumonia due to S. pneumoniae in patients appropriate for oral therapy 4
• However, breakthrough bacteremia with macrolide-resistant strains appears more common with macrolides than with other agents 1
• Pharmacodynamic studies demonstrate:
  • Azithromycin achieves its pharmacodynamic target against only 59.9% of S. pneumoniae isolates based on serum concentrations 5
  • Even with epithelial lining fluid concentrations, azithromycin reaches its target in only 74.6% of isolates 5
  • Against penicillin-resistant isolates, azithromycin achieves its pharmacodynamic target in only 28.3% of cases 5

Treatment Recommendations

• For empiric treatment of respiratory infections where S. pneumoniae is a concern:

  • First-line options (preferred over azithromycin):
    • Respiratory fluoroquinolones (levofloxacin, moxifloxacin) - active against >98% of S. pneumoniae strains 1
    • High-dose amoxicillin (3-4g/day) - active against 90-95% of S. pneumoniae strains 1

• When to consider azithromycin:

  • In previously healthy patients with no antibiotic exposure in the past 3 months 1
  • When atypical pathogens are strongly suspected
  • As part of combination therapy with a β-lactam for hospitalized patients 1

Important Caveats

• Clinical failures attributed to resistant strains have been reported with macrolides 1
• Increasing use of macrolides provides strong selective pressure for resistance development 1
• Studies show that azithromycin use can select for macrolide-resistant strains of pneumococci, with resistance rates increasing from 2% to 8% after treatment 6
• Interestingly, some clinical studies show good outcomes with azithromycin even against macrolide-resistant S. pneumoniae, suggesting a potential disconnect between in vitro resistance and clinical outcomes 7

Conclusion

When treating infections potentially caused by S. pneumoniae, clinicians should consider local resistance patterns and patient risk factors. For empiric therapy, fluoroquinolones or high-dose amoxicillin provide more reliable coverage against S. pneumoniae than azithromycin alone.