Azithromycin

Abstract

Azithromycin is an azalide antimicrobial agent active in vitro against major pathogens responsible for infections of the respiratory tract, skin and soft tissues in children. Pathogens that are generally susceptible to azithromycin include Haemophilus influenzae (including ampicillin-resistant strains), Moraxella catarrhalis, Chlamydia pneumoniae, Chlamydia trachomatis, Mycoplasma pneumoniae, Legionella spp., Streptococcus pyogenes and Streptococcus agalactiae. Azithromycin is also generally active against erythromycin- and penicillin-susceptible Streptococcus pneumoniae and methicillin-susceptible Staphylococcus aureus. Azithromycin is administered once daily, achieves clinically relevant concentrations at sites of infection, is slowly eliminated from the body and has few drug interactions. In children, azithromycin is usually given as either a 3-day course of 10 mg/kg/day or a 5-day course with 10 mg/kg on the first day, followed by 5 mg/kg/day for a further 4 days. These standard regimens were as effective as amoxicillin/clavulanic acid, clarithromycin, cefaclor and amoxicillin in the treatment of children with otitis media. Azithromycin was also as effective as either phenoxy-methylpenicillin (penicillin V), erythromycin, clarithromycin or cefaclor against streptococcal pharyngitis or tonsillitis in children, but appears to result in more recurrence of infection than phenoxymethylpenicillin in this indication, necessitating a dosage of 12 mg/kg/day for 5 days. Community-acquired pneumonia, bronchitis and other respiratory tract infections in children responded as well to azithromycin as to amoxicillin/clavulanic acid, cefaclor, erythromycin or josamycin. Azithromycin was similar or superior to ceftibuten in mixed general practice populations of patients. However, symptoms of lower respiratory tract infections resolved more rapidly with azithromycin than with erythromycin, josamycin or cefaclor. Skin and soft tissue infections responded as well to azithromycin as to cefaclor, dicloxacillin or flucloxacillin, and oral azithromycin was as effective as ocular tetracycline in treating trachoma. Although not as well tolerated as phenoxymethylpenicillin in the treatment of streptococcal pharyngitis, azithromycin is at least as well tolerated as most other agents used to treat respiratory tract and other infections in children and was better tolerated than amoxicillin/clavulanic acid. Adverse events that do occur are mostly gastrointestinal and tend to be mild to moderate in severity. Conclusions: Azithromycin is an effective and well tolerated alternative to first-line agents in the treatment of respiratory tract, skin and soft tissue infections in children, offerring the convenience of a short, once-daily regimen. Azithromycin is active in vitro against major pathogens implicated in respiratory tract, skin and soft tissue infections. Although many bacteria resistant to erythromycin are also resistant to azithromycin, azithromycin is generally active against erythromycin-susceptible Gram-positive organisms and is more active against Gram-negative organisms than erythromycin. Minimum concentrations of azithromycin inhibiting 90% of isolates (MIC90) were within susceptibility limits for Moraxella catarrhalis, Streptococcus agalactiae (Haemophilus influenzae (≤4 mg/L). Streptococcus pneumoniae isolates were usually susceptible to azithromycin (S. pneumoniae that were resistant to erythromycin or penicillin were also resistant to azithromycin. Similarly, methicillin-resistant Staphylococcus aureus were not susceptible to azithromycin, although methicillin-susceptible isolates were frequently susceptible (≤2 mg/L). Streptococcus pyogenes isolates were generally susceptible to azithromycin (≤2 mg/L), although some MIC90 values were greater than this breakpoint. Pathogens for which susceptibility guidelines do not exist include Chlamydia pneumoniae, Chlamydia trachomatis and Mycoplasma pneumoniae; all MIC90 values against these species were ≤1 mg/L. Azithromycin MIC90 values against Legionella pneumophila were 45kg. In the US, usual dosages are 10 mg/kg on day 1 followed by 5 mg/kg on days 2 to 5. Usual maximum dosages are 500 mg/day or a 1.5g total dose. In the US, a dosage of azithromycin 12 mg/kg/day for 5 days is recommended for patients with group A streptococcal pharyngitis. The drug is not recommended for use in patients with hepatic failure and caution is recommended when azithromycin is used in patients with creatinine clearance values of <2.4 L/h (<40 ml/min). Plasma concentrations of cyclosporin, digoxin, theophylline and warfarin should be monitored during concomitant azithromycin use. Azithromycin should be given at least 1 hour before or 2 hours after concomitant antacids and should not be administered with ergot derivatives.