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

• 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
• ISSN: 0732-8893; 1879-0070
• DOI: 10.1016/S0732-8893(00)00239-X

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.