Comparative serum bactericidal activity of clarithromycin and azithromycin against macrolide-sensitive and resistant strains of Streptococcus pneumoniae

The serum pharmacodynamics of clarithromycin and azithromycin were studied against isolates of S. pneumoniae, including efflux resistant (M. phenotype) strains, by analyzing their serum bactericidal activity (SBA) over time. Normal healthy subjects were given a single 500 mg oral dose of these macro...

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Bibliographic Details
Published in:Diagnostic microbiology and infectious disease 2001-03, Vol.39 (3), p.181-185
Main Authors: Stein, Gary E, Schooley, Sharon
Format: Article
Language:English
Subjects:
Administration, Oral
Adult
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Atherosclerosis (general aspects, experimental research)
Azithromycin - blood
Azithromycin - pharmacology
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
Clarithromycin - blood
Clarithromycin - pharmacology
Drug Resistance, Microbial
Drug Therapy, Combination - blood
Drug Therapy, Combination - pharmacology
Humans
Male
Medical sciences
Microbial Sensitivity Tests
Middle Aged
Pharmacology. Drug treatments
Streptococcus pneumoniae - drug effects
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Summary:The serum pharmacodynamics of clarithromycin and azithromycin were studied against isolates of S. pneumoniae, including efflux resistant (M. phenotype) strains, by analyzing their serum bactericidal activity (SBA) over time. Normal healthy subjects were given a single 500 mg oral dose of these macrolides and serum samples were collected over 12 hrs. Paired isolates with MICs ranging from 0.25 ug/ml to 8.0 ug/ml were analyzed. Prolonged (at least 6 hrs) SBA was observed with clarithromycin for strains with MICs ≤ 2.0 ug/ml. No SBA was observed in strains with MICs ≥ 4.0 ug/ml. Azithromycin exhibited SBA for at least 6 hrs for strains up to a MIC = 0.5 ug/ml. No SBA was observed for isolates with MICs ≥ 1.0 ug/ml. In contrast to azithromycin, clarithromycin exhibited SBA for at least one-half of its normal dosing interval against S. pneumoniae strains well above its current susceptibility breakpoint concentration of 0.25 μg/ml. These findings may have relevance to the ongoing debate as to the appropriate susceptibility breakpoints for the newer macrolides.
ISSN:0732-8893
1879-0070
DOI:10.1016/S0732-8893(00)00239-X