Commentary
Azithromycin belongs to macrolides and exerts antibacterial activity through inhibition of microbial protein synthesis by binding to the 50S ribosomal subunit of susceptible pathogens. Azithromycin has oral immediate release or intravenous formulations as Zithromax®. Zmax® is a novel extended-release oral formulation of azithromycin, and allows for single-dose administration. Zmax® is pharmacokinetically bioequivalent to and interchangeable with the immediate-release oral Zithromax®. Zmax® achieves higher intracellular concentrations in mononuclear and polymorphonuclear leukocyte and alveolar cells, and higher tissue/fluid concentrations in lung serum, tissue and epithelial lining fluid than in serum. Additionally, azithromycin concentrations of Zmax® in these compartments are generally higher than those achieved with the immediate-release oral Zithromax®.
Zmax® is FDA approved for 1) mild to moderate acute bacterial sinusitis in adults due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae, and 2) community-acquired pneumonia due to Chlamydia pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, or Streptococcus pneumoniae in adults and pediatrics aged 6 months and over deemed appropriate for oral therapy.
Zithromax® is indicated in adults for infection of 1) lower respiratory tract (acute bacterial exacerbations of chronic obstructive pulmonary disease and community-acquired pneumonia of mild severity in patients appropriate for outpatient oral therapy); 2) upper respiratory tract (streptococcal pharyngitis/tonsillitis); 3) uncomplicated skin and skin structure infections; 4) sexually transmitted diseases (urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae; genital ulcer disease in men due to Haemophilus ducreyi); 5) prophylaxis and treatment of disseminated Mycobacterium avium complex (MAC) Disease. For pediatric patients, Zithromax® is indicated for acute otitis media and community-acquired pneumonia in patients appropriate for outpatient oral therapy.
Bacteria acquire resistance to azithromycin via efflux of the drug from the cell (mutations in the mefA gene) or alterations in the drug target site (mutations in the ermB gene). Generally, bacteria that are resistant to erythromycin are cross-resistant to azithromycin. In various US surveillance studies, S. pneumonia azithromycin resistance rates were 27.5%-31%, similar to that of erythromycin and clarithromycin. Compared with other macrolides, azithromycin does not interact with drugs metabolized by CYP3A4, and this applies to both Zmax® and Zithromax®. The most frequent adverse events are diarrhea or loose stools.
Clinical Trials
This trial enrolled 358 children and adult and 80% of them were culture confirmed cases. Both azithromycin and gatifolxacin had equivalent safety and efficacy in terms of resolution of fever and overall treatment success (90.7% vs. 91%) while the cost of azithromycin was higher in Vietnam.
This prospective, randomized and open-label multicentre clinical trial demonstrated that an intravenous-to-oral regimen of ceftriaxone/azithromycin had equivalent efficacy and safety as the comparator regimen did. The mean length of hospital stay was shorter for patients receiving ceftriaxone/azithromycin if the identified pathogens were atypical or atypical and conventional.
In this a retrospective cohort study of pregnant women with genital chlamydial infection, rates of test-of-cure was significantly higher in those treated with azithromycin than erythromycin, and no difference existed in complications for women or infants between azithromycin and other regimens.
In this large, randomized, controlled trial, patients in azithromycin arm had equivalent eradication rate and no bacterial recurrence as those in erythromycin group did, but had less nausea, vomiting, and diarrhea.
Review Articles
This article summarized the anti-inflammatory modes of actions of macrolies and reviewed experimental studies and clinical trials that evaluated the effects of macrolides on chronic inflammatory disorders of the lower respiratory tract, such as cystic fibrosis, and acute inflammatory conditions.
The article comprehensively reviewed the pharmacodynamic and pharmacokinetic profiles, clinical trials and indications, and tolerability of azithromycin extended release formulation. Its role in treatment of acute bacterial sinusitis and community-acquired pneumonia in the US was also discussed.
In this review, compared with fluoroquinolones, azithromycin significantly reduced clinical failure and duration of hospital stay in patients with uncomplicated enteric fever, including those with multiple-drug-resistant or nalidixic acid-of resistant strains of S. Typhi or S. Paratyphi. Compared with ceftriaxon, azithromycin significantly reduced relapse.
This review described recent changes in the burden of pertussis, its different clinical presentations in infants and adolescents, performance of diagnostic tools, and prophylaxis and treatment. Azithromycin and clarithromycin, instead of erythromycin, were recommended as first-line treatment due to equivalent efficacy and better tolerance with improved compliance.
This article summarized the recent changes in The Centers for Disease Control and Prevention revised guidelines for the prevention and treatment of sexually transmitted diseases. Currently, azithromycin (Zithromax) is recommended as a first-line treatment for Chlamydia trachomatis infection during pregnancy and close follow-up is required if azithromycin is used as an alternative treatment in the management of primary or secondary syphilis due to increasing resistance.
Adverse Drug Reactions and Warnings
FDA Information
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