Azithromycin Antimicrobial Coverage
Azithromycin provides broad-spectrum coverage against Gram-positive cocci (particularly Streptococcus pneumoniae and Streptococcus pyogenes), atypical respiratory pathogens (Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila), select Gram-negative organisms (Haemophilus influenzae, Moraxella catarrhalis), and certain intracellular pathogens including Chlamydia trachomatis and Mycobacterium avium complex. 1
Gram-Positive Bacteria
Streptococcal species: Streptococcus pneumoniae, Streptococcus pyogenes (Group A strep), Streptococcus agalactiae (Group B strep), and beta-hemolytic streptococci (Groups C, F, G) are covered, though rising macrolide resistance rates (ranging from <10% to >90% globally for S. pneumoniae) significantly impact clinical efficacy. 2, 1
Staphylococcus aureus: Azithromycin has activity against methicillin-susceptible S. aureus and coagulase-negative staphylococci, though plasmid-mediated resistance through increased efflux is common. 2, 1
Important resistance caveat: Penicillin-resistant S. pneumoniae isolates show high co-resistance to macrolides (up to 70% in the USA), making azithromycin less reliable in these cases. 2
Gram-Negative Bacteria
Respiratory pathogens: Haemophilus influenzae (MIC90 0.5 mcg/mL) and Moraxella catarrhalis are well-covered, representing a significant advantage over erythromycin. 1, 3, 4
Sexually transmitted pathogens: Neisseria gonorrhoeae and Haemophilus ducreyi (chancroid) are susceptible. 1
Enteric pathogens: Effective against Campylobacter species (100% cure rates reported), Shigella species, enteroinvasive E. coli, Aeromonas spp., Plesiomonas spp., and Yersinia enterocolitica. 5
Azithromycin penetrates Gram-negative bacterial cells more effectively than erythromycin, explaining its superior activity against organisms like Enterobacteriaceae, though many remain intrinsically resistant due to reduced outer membrane permeability. 2
Atypical and Intracellular Pathogens
Respiratory atypicals: Excellent activity against Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila—these are primary targets in community-acquired pneumonia. 2, 1
Sexually transmitted intracellular organisms: Chlamydia trachomatis and Ureaplasma urealyticum are highly susceptible, with single-dose regimens proving effective. 1, 6
Mycobacterial coverage: Mycobacterium avium complex (MAC) and Mycobacterium leprae are covered, making azithromycin essential for MAC prophylaxis and treatment in AIDS patients. 2, 7
Additional Pathogens
Other bacteria: Bordetella pertussis, Helicobacter pylori, and anaerobes including Peptostreptococcus species and Prevotella bivia show susceptibility. 1
Emerging pathogens: Activity documented against Borrelia burgdorferi (Lyme disease) and Toxoplasma gondii. 3
Critical Resistance Patterns and Limitations
Pseudomonas and Acinetobacter: Intrinsically resistant due to reduced outer membrane permeability—azithromycin provides NO coverage for Pseudomonas aeruginosa. 2
Mechanism of resistance: Modification of 23S rRNA at positions A2058/A2059 confers cross-resistance to all macrolides, lincosamides, and streptogramin B antibiotics. 1
Long-term use risk: Macrolide resistance increases 2.7-fold in colonizing respiratory pathogens (S. pneumoniae, H. influenzae, M. catarrhalis) with chronic azithromycin therapy. 2
Geographic variation: Fluoroquinolone-resistant Campylobacter (85-90% in Southeast Asia) makes azithromycin the preferred agent for dysentery in these regions. 5
Mechanism of Action
Azithromycin binds to the 23S rRNA of the bacterial 50S ribosomal subunit, blocking protein synthesis by inhibiting transpeptidation/translocation and preventing 50S ribosomal subunit assembly. 1 The drug concentrates intracellularly (>30:1 intracellular:extracellular ratio), particularly in phagocytes, macrophages, and fibroblasts, delivering high concentrations to infection sites. 1, 4