title: Clarithromycin. A review of its efficacy in the treatment of respiratory tract infections in immunocompetent patients.
abstract: Clarithromycin is a broad spectrum macrolide antibacterial agent active in vitro and effective in vivo against the major pathogens responsible for respiratory tract infections in immunocompetent patients. It is highly active in vitro against pathogens causing atypical pneumonia (Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella spp.) and has similar activity to other macrolides against Staphylococcus aureus. Streptococcus pyogenes, Moraxella catarrhalis and Streptococcus pneumoniae. Haemophilus influenzae is susceptible or intermediately susceptible to clarithromycin alone, but activity is enhanced when the parent drug and metabolite are combined in vitro. Absorption of clarithromycin is unaffected by food. More than half of an oral dose is systemically available as the parent drug and the active 14-hydroxy metabolite. Pharmacokinetics are nonlinear, with plasma concentrations increasing in more than proportion to the dosage. First-pass metabolism results in the rapid appearance of the active metabolite 14-hydroxy-clarithromycin in plasma. Clarithromycin and its active metabolite are found in greater concentrations in the tissues and fluids of the respiratory tract than in plasma. Dosage adjustments are required for patients with severe renal failure, but not for elderly patients or those with hepatic impairment. Drug interactions related to the cytochrome P450 system may occur with clarithromycin use. In addition to the standard immediate-release formulation for administration twice daily, a modified-release formulation of clarithromycin is now available for use once daily. In dosages of 500 to 1000 mg/day for 5 to 14 days, clarithromycin was as effective in the treatment of community-acquired upper and lower respiratory tract infections in hospital and community settings as beta-lactam agents (with or without a beta-lactamase inhibitor), cephalosporins and most other macrolides. Clarithromycin was similar in efficacy to azithromycin in comparative studies and is as effective as and better tolerated than erythromycin. Adverse events are primarily gastrointestinal in nature, but result in fewer withdrawals from therapy than are seen with erythromycin. Clarithromycin provides similar clinical and bacteriological efficacy to that seen with beta-lactam agents, cephalosporins and other macrolides. It offers a cost-saving alternative to intravenous erythromycin use in US hospitals and is available in both once-daily and twice-daily formulations. The spectrum of activity of clarithromycin against common and emerging respiratory tract pathogens may make it suitable for use in the community as empirical therapy of respiratory tract infections in both children and adults.
authors.affiliation: Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
authors.forename: H D
authors.initials: HD
authors.lastname: Langtry
authors.forename: R N
authors.initials: RN
authors.lastname: Brogden
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001419:Bacteria / Q000187:drug effects; D002648:Child; D017291:Clarithromycin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004347:Drug Interactions; D006801:Humans; D007121:Immunocompetence / Q000187:drug effects; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D017291:Clarithromycin