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

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...

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Bibliographic Details
Published in:Journal of chemotherapy (Florence) 2005-04, Vol.17 (2), p.161-168
Main Authors: Drago, L., De vecchi, E., Nicola, L., Legnani, D., Prenna, M., Ripa, S.
Format: Article
Language:English
Subjects:
Amoxicillin - pharmacology
amoxicillin/ clavulanate
Aza Compounds - pharmacology
azithromycin
Azithromycin - pharmacology
clarithromycin
Clarithromycin - pharmacology
Drug Resistance, Bacterial
Fluoroquinolones
Humans
Levofloxacin
Microbial Sensitivity Tests
moxifloxacin
Ofloxacin - pharmacology
Quinolines - pharmacology
resistance
Sampling Studies
Sensitivity and Specificity
Streptococcus pneumoniae
Streptococcus pneumoniae - drug effects
Streptococcus pneumoniae - isolation & purification
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Summary: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.
ISSN:1120-009X
1973-9478
DOI:10.1179/joc.2005.17.2.161