title: Single and multi-step resistance selection study in Streptococcus pneumoniae comparing ceftriaxone with levofloxacin, gatifloxacin and moxifloxacin.
abstract: Attempts were made to select resistant pneumococcal mutants by sequential subculturing of 12 clinically isolated pneumococci, [four were penicillin sensitive (MIC) 0.03-0.06 mg/l, four penicillin intermediate (MIC 0.25-0.5 mg/l) and four penicillin resistant (MIC 2-4 mg/l)] in sub-inhibitory concentrations of ceftriaxone, levofloxacin, gatifloxacin and moxifloxacin. Subculturing in gatifloxacin, levofloxacin, moxifloxacin and ceftriaxone selected 12 mutants (12/12), 10 mutants (10/12), 10 mutants (10/12) and three mutants (3/12), respectively. DNA sequencing of the quinolone-resistant mutants showed that most strains had mutations in GyrA at E85 or S81. This in vitro mutation study demonstrates a clear distinction between the low frequency of development of resistance with ceftriaxone exposure as opposed to the high frequency with quinolone exposure.
authors.affiliation: Department of Medicine, Hershey Medical Center, 500 University Drive, PA 17033, USA.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Browne
authors.forename: Cathy
authors.initials: C
authors.lastname: Clark
authors.forename: Bülent
authors.initials: B
authors.lastname: Bozdogan
authors.forename: Bonifacio E
authors.initials: BE
authors.lastname: Dewasse
authors.forename: Michael R
authors.initials: MR
authors.lastname: Jacobs
authors.forename: Peter C
authors.initials: PC
authors.lastname: Appelbaum
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001372:Aza Compounds; D002443:Ceftriaxone / Q000494:pharmacology*; D003470:Culture Media; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D024841:Fluoroquinolones; D000077734:Gatifloxacin; D006801:Humans; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D009154:Mutation; D015242:Ofloxacin / Q000494:pharmacology; D011804:Quinolines; D012641:Selection, Genetic; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001372:Aza Compounds; D003470:Culture Media; D024841:Fluoroquinolones; D011804:Quinolines; D064704:Levofloxacin; D002443:Ceftriaxone; D015242:Ofloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase; D000077734:Gatifloxacin; D000077266:Moxifloxacin