Azithromycin Bacterial Coverage
Azithromycin is effective against a wide range of gram-positive, gram-negative, and atypical pathogens, with particularly strong activity against respiratory pathogens including Haemophilus influenzae, Moraxella catarrhalis, and atypical organisms like Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella species. 1
Gram-Positive Coverage
Azithromycin demonstrates activity against:
- Streptococcus pneumoniae (susceptible strains) 1
- Streptococcus pyogenes (Group A Strep) 1
- Streptococcus agalactiae (Group B Strep) 1
- Staphylococcus aureus (methicillin-susceptible strains) 1
- Viridans group streptococci 1
- Beta-hemolytic streptococci (Groups C, F, G) 1
Important Limitations
- Increasing resistance among S. pneumoniae is concerning, with resistance rates varying from <10% to >90% globally 2
- Macrolide resistance in Group A Streptococcus in the US is approximately 5-8% 3
- Cross-resistance exists between all macrolides - erythromycin-resistant organisms are also resistant to azithromycin 1
Gram-Negative Coverage
Azithromycin is active against:
- Haemophilus influenzae (including beta-lactamase producing strains) 1, 4
- Moraxella catarrhalis 2, 1
- Neisseria gonorrhoeae 1
- Bordetella pertussis 1
- Haemophilus ducreyi 1
Important Considerations
- Azithromycin has better gram-negative coverage than erythromycin 2
- Azithromycin is more active against H. influenzae than other macrolides 5
- Many Enterobacteriaceae, Pseudomonas, and Acinetobacter species have reduced permeability to macrolides 2
Atypical Pathogens
Azithromycin has excellent activity against:
- Mycoplasma pneumoniae 2, 1
- Chlamydophila pneumoniae 1
- Chlamydia trachomatis 1
- Legionella pneumophila 1
- Ureaplasma urealyticum 1
Anaerobic Coverage
Limited anaerobic coverage includes:
Mechanism of Action
Azithromycin binds to the 23S rRNA of the bacterial 50S ribosomal subunit, blocking protein synthesis by inhibiting the transpeptidation/translocation step and assembly of the 50S ribosomal subunit 1. It concentrates in phagocytes and fibroblasts, with intracellular to extracellular concentration ratios >30 after one hour, which may contribute to drug distribution to inflamed tissues 1.
Clinical Applications
Based on its spectrum of activity, azithromycin is indicated for:
- Respiratory tract infections - particularly community-acquired pneumonia caused by susceptible S. pneumoniae, H. influenzae, M. pneumoniae, and C. pneumoniae 2
- Skin and soft tissue infections caused by susceptible organisms 4
- Sexually transmitted infections - particularly those caused by C. trachomatis and N. gonorrhoeae 2
Resistance Considerations
- The most common resistance mechanism is modification of the 23S rRNA at positions corresponding to A2058 and A2059 1
- Resistance rates are increasing globally, particularly for S. pneumoniae 2
- Extensive macrolide use provides strong selective pressure for resistance development 2
- Azithromycin's long half-life (68 hours) creates prolonged periods of subinhibitory concentrations, potentially promoting resistance 3
Important Caveats
Not appropriate for severe infections - Azithromycin should not be used for severe streptococcal infections due to its bacteriostatic nature and increasing resistance patterns 3
Resistance concerns - For respiratory infections, particularly in areas with high pneumococcal resistance, alternative agents may be preferred 2
Non-tuberculous mycobacteria - Azithromycin monotherapy is contraindicated in patients with non-tuberculous mycobacterial infections due to the risk of developing resistance 2
QT prolongation risk - Azithromycin can prolong the QT interval in a dose-dependent manner, requiring caution in patients with cardiac risk factors 1
Azithromycin's unique pharmacokinetic properties, including high tissue concentrations despite low serum levels, contribute to its effectiveness against many pathogens, particularly in respiratory tract infections 1, 6.