title: In vitro selection of resistance to clarithromycin in Streptococcus pneumoniae clinical isolates.
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 > or = 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 > or = 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.
authors.affiliation: Laboratory of Clinical Microbiology, Dept of Clinical Sciences, L. Sacco Teaching Hospital, University of Milan. lorenzo.drago@unimi.it
authors.forename: L
authors.initials: L
authors.lastname: Drago
authors.forename: E
authors.initials: E
authors.lastname: De Vecchi
authors.forename: L
authors.initials: L
authors.lastname: Nicola
authors.forename: D
authors.initials: D
authors.lastname: Legnani
authors.forename: M
authors.initials: M
authors.lastname: Prenna
authors.forename: S
authors.initials: S
authors.lastname: Ripa
mesh_terms: D000658:Amoxicillin / Q000494:pharmacology; D001372:Aza Compounds / Q000494:pharmacology; D017963:Azithromycin / Q000494:pharmacology; D017291:Clarithromycin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones; D006801:Humans; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D015242:Ofloxacin / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D064704:Levofloxacin; D000658:Amoxicillin; D017963:Azithromycin; D015242:Ofloxacin; D017291:Clarithromycin; D000077266:Moxifloxacin