title: Antimicrobial activity evaluations of two new quinolones, PD127391 (CI-960 and AM-1091) and PD131628.
abstract: The in vitro activities of PD127391 and the new fluorinated-4-quinolone, PD131628, were compared with each other and with five similar fluoroquinolones (ciprofloxacin, enoxacin, fleroxacin, norfloxacin, and ofloxacin). A total of 844 isolates mainly from recent clinical bacteremias and additional stock strains with well-characterized resistance mechanisms were tested. PD127391 had slightly more activity than PD131628 (90% minimum inhibitory concentration (MIC90)] 0.008-0.12) against the Enterobacteriaceae, but both were two- to fourfold more potent than ciprofloxacin. PD131628 activity was equal to or greater than PD127391 when tested against Pseudomonas aeruginosa. PD127391 showed greatest activity against Bacteroides fragilis group strains (MIC90, 2 micrograms/ml) when compared with PD131628 (MIC90 greater than 8 micrograms/ml). Both PD127391 (MIC90s, 0.015-1.0 micrograms/ml) and PD131628 (MIC90s, 0.03 - greater than 8 micrograms/ml) were more active than ciprofloxacin against Gram-positive organisms. Altering the medium pH, adding divalent cations (magnesium), and increasing the inoculum concentration to 10(6) colony-forming units per spot adversely effected the activity of both PD127391 and PD131628. Resistance selection and mutational rates to resistance were identical to previously studied drugs in their class.
authors.affiliation: Department of Pathology, University of Iowa College of Medicine, Iowa City.
authors.forename: M S
authors.initials: MS
authors.lastname: Barrett
authors.forename: R N
authors.initials: RN
authors.lastname: Jones
authors.forename: M E
authors.initials: ME
authors.lastname: Erwin
authors.forename: D M
authors.initials: DM
authors.lastname: Johnson
authors.forename: B M
authors.initials: BM
authors.lastname: Briggs
mesh_terms: D000890:Anti-Infective Agents; D016470:Bacteremia / Q000382:microbiology; D002939:Ciprofloxacin / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004352:Drug Resistance, Microbial; D015365:Enoxacin / Q000494:pharmacology; D004755:Enterobacteriaceae / Q000187:drug effects*; D016576:Fleroxacin / Q000494:pharmacology; D024841:Fluoroquinolones; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines; D009643:Norfloxacin / Q000494:pharmacology; D015242:Ofloxacin / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D015363:Quinolones / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D015363:Quinolones; C068217:PD 131628; D015365:Enoxacin; D002939:Ciprofloxacin; C057477:clinafloxacin; D015242:Ofloxacin; D009643:Norfloxacin; D016576:Fleroxacin