In vitro comparative dynamics of modified-release clarithromycin and of azithromycin.
Antibacterial kinetics of modified-release clarithromycin (CLA) and azithromycin (AZI) against respiratory tract pathogens were compared in relation to their pharmacokinetic profile. The study was carried out in three strains of Streptococcus pneumoniae, group A beta-hemolytic Streptococcus pyogenes, Moraxella catarrhalis and Haemophilus influenzae, respectively, exposed to concentration gradients of CLA and AZI simulating human serum pharmacokinetics after administration of 500 mg p.o. in a single dose. Bactericidal kinetics were assessed by counting the number of survivors before each change in concentration over a period of 36 h. The minimal inhibitory concentrations (MICs) of CLA and AZI were evaluated at time 0 and after 36 h of exposure to antibiotics in the surviving organisms. The results showed that CLA and AZI, in the experimental conditions adopted, had different antibacterial kinetics. Moreover, the addition of the 14-OH metabolite of CLA at the same concentrations reached in human serum exerted a bactericidal effect against two strains of H. influenzae resistant to CLA and AZI. An increase in MICs was observed against S. pyogenes and H. influenzae, with higher values for AZI.
Scaglione
F
F
Department of Pharmacology, University of Milan, Italy.
Demartini
G
G
Dugnani
S
S
Fraschini
F
F
D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017963:Azithromycin / Q000008:administration & dosage* / Q000494:pharmacology; D017291:Clarithromycin / Q000008:administration & dosage* / Q000494:pharmacology; D003692:Delayed-Action Preparations; D006193:Haemophilus influenzae / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013297:Streptococcus pyogenes / Q000187:drug effects
D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D017963:Azithromycin; D017291:Clarithromycin