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Antimicrobial Chemotherapy

In Vitro Selection of Resistance to Clarithromycin in Streptococcus pneumoniae Clinical Isolates

Pages 161-168 | Published online: 18 Jul 2013
 

Abstract

In this study the effects of exposure to serum, lung and breakpoint concentrations on Streptococcus pneumoniae susceptibility to clarithromycin, azithromycin, amoxicillin/clavulanate, levofloxacin and moxifloxacin were evaluated. Development of resistance was determined by multi-step and single-step methodologies. In the first experimental set, minimum inhibitory concentrations (MICs) were determined after 10 passages on antibiotic-gradient plates and 10 passages on antibiotic-free plates. Acquisition of resistance was defined as an increase of ≥4-fold from the starting MIC. In single-step studies, the rate of spontaneous mutations was calculated after a passage on antibiotic-containing agar plates.

Azithromycin and levofloxacin gave the highest number of strains with MIC increased of at least 4 times the starting value, followed by moxifloxacin and by clarithromycin which only at the lowest concentration tested selected for resistance in 5 strains. Amoxicillin/clavulanate never displayed ≥4-fold MIC increase. Frequencies of mutation were lower for clarithromycin and moxifloxacin than for the comparators.

At lung concentrations clarithromycin had limited potential to select for resistance.

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