Clarithromycin Antimicrobial Coverage
Clarithromycin provides reliable coverage against most gram-positive cocci, atypical respiratory pathogens, and Mycobacterium avium complex, but has limited activity against gram-negative organisms (except H. influenzae when combined with its active metabolite) and no coverage against Enterobacteriaceae or Pseudomonas species. 1
Organisms Covered by Clarithromycin
Gram-Positive Bacteria
- Staphylococcus aureus (methicillin-sensitive strains only; methicillin-resistant strains are resistant to clarithromycin) 1
- Streptococcus pneumoniae (susceptible strains; macrolide resistance rates vary globally from <10% to >90%) 2, 1
- Streptococcus pyogenes (Group A Streptococcus) 1, 3
- Streptococcus agalactiae (Group B Streptococcus) 1
- Viridans group streptococci 1
- Coagulase-negative staphylococci (susceptible strains) 2
Gram-Negative Bacteria (Limited Coverage)
- Haemophilus influenzae - clarithromycin demonstrates enhanced activity when the parent drug combines with its 14-hydroxy metabolite in vivo, achieving intermediate susceptibility 1, 4, 5
- Haemophilus parainfluenzae 1
- Moraxella catarrhalis 1, 5
- Legionella pneumophila and other Legionella species 1, 4
- Pasteurella multocida 1
Atypical Pathogens (Excellent Coverage)
- Mycoplasma pneumoniae 1, 6
- Chlamydophila pneumoniae (formerly Chlamydia pneumoniae) 1, 4
- Chlamydia trachomatis 4
Mycobacteria (Critical Coverage)
- Mycobacterium avium complex (MAC) - clarithromycin is the cornerstone of MAC treatment, with documented correlation between in vitro susceptibility and clinical response 2, 1
- Mycobacterium intracellulare 1
- Mycobacterium chelonae subspecies 4
- Mycobacterium leprae 4
- Mycobacterium marinum 4
Other Organisms
Anaerobes (Selected Coverage)
- Clostridium perfringens 1
- Peptococcus niger 1
- Prevotella melaninogenica (formerly Bacteroides melaninogenicus) 1, 4
- Propionibacterium acnes 1
Organisms NOT Covered by Clarithromycin
Gram-Negative Bacteria (No Coverage)
- Enterobacteriaceae (E. coli, Klebsiella, Proteus, etc.) - intrinsically resistant due to reduced outer membrane permeability 2
- Pseudomonas aeruginosa - intrinsically resistant 2
- Acinetobacter species - intrinsically resistant 2
- All other gram-negative enteric bacilli 2
Resistant Gram-Positive Organisms
- Methicillin-resistant Staphylococcus aureus (MRSA) - most isolates are clarithromycin-resistant 1
- Oxacillin-resistant staphylococci 1
- Macrolide-resistant Streptococcus pneumoniae - resistance mediated by erm genes causing 23S rRNA modification, with cross-resistance to all macrolides 2
- Macrolide-resistant Streptococcus pyogenes 2
Organisms with Acquired Resistance
- Enterococcus species - not reliably covered 2
- Mycobacterium avium complex with clarithromycin MIC ≥32 μg/mL (treatment failures/relapses) - these strains have point mutations in the 23S rRNA gene conferring cross-resistance to all macrolides 2
Critical Clinical Considerations
Resistance Mechanisms and Cross-Resistance
- Clarithromycin resistance occurs through three main mechanisms: reduced permeability (gram-negatives), increased efflux (staphylococci), and ribosomal target modification via erm genes (streptococci, MAC) 2
- Cross-resistance exists between clarithromycin and azithromycin - strains resistant to one macrolide are resistant to all macrolides 2, 5
- Resistance may be co-inherited with resistance to lincosamides (clindamycin) when mediated by erm genes 2
Monotherapy Risks
- Never use clarithromycin as monotherapy for MAC disease - this rapidly selects for resistance with MICs rising to ≥1024 μg/mL 2
- In cystic fibrosis patients receiving azithromycin who culture NTM, discontinue the macrolide immediately to prevent resistance development 2
- For MAC treatment, always combine clarithromycin (500 mg twice daily) with ethambutol (15 mg/kg daily), with or without rifabutin 2