title: Antimicrobial activity of trovafloxacin tested against ciprofloxacin-susceptible and -resistant Neisseria gonorrhoeae. Interpretive criteria and comparisons with Etest results.
abstract: Trovafloxacin, a new fluorinated naphthyridine, has enhanced activity against Gram-positive cocci, while retaining an excellent spectrum against Gram-negative pathogens. It has been used successfully in clinical trials for therapy of gonorrhea, and this investigation proposes in vitro susceptibility testing criteria for trovafloxacin. A total of 150 Neisseria gonorrhoeae clinical isolates (50 resistant to ciprofloxacin; MICs > or = 0.12 microgram/mL) were tested by methods recommended by the National Committee for Clinical Laboratory Standards (NCCLS) and the Etest (AB BIODISK, Solna, Sweden). Trovafloxacin was very active against gonococci (MIC90, 0.008 to 0.015 microgram/mL), but was generally eightfold less potent versus ciprofloxacin-resistant strains. Etest results correlated well (r = 0.96; 98% of MICs +/- one log2 dilution) compared to the reference agar dilution test. Reference agar dilution and Etest MICs were compared to disk-diffusion test zones (10-micrograms trovafloxacin disk), and excellent categorical agreement (89.4 to 99.3%) was achieved without significant false-susceptible or -resistant error (< or = 1.3%). Tentative breakpoints were suggested initially to outline the ciprofloxacin-susceptible and trovafloxacin-susceptible as susceptible (MIC, < or = 0.015 microgram/mL; zones > or = 47 mm), and strains with various well-characterized mutations of the gyr A and par C genes as either intermediate or resistant to trovafloxacin. When the results of clinical studies treating ciprofloxacin-resistant N. gonorrhoeae with trovafloxacin become available, the alternative breakpoints could be utilized for resistant MIC breakpoints of > or = 0.06 microgram/mL or > or = 0.5 microgram/mL. Trovafloxacin was stable in supplemented GC agar for 21 days stored at refrigerated temperatures. These in vitro results indicate that trovafloxacin should be a very acceptable agent for therapy of gonorrhea and other common sexually transmitted pathogens.
authors.affiliation: Department of Pathology, University of Iowa College of Medicine, Iowa City 52242, USA.
authors.forename: R N
authors.initials: RN
authors.lastname: Jones
authors.forename: M S
authors.initials: MS
authors.lastname: Barrett
authors.forename: T
authors.initials: T
authors.lastname: Deguchi
mesh_terms: D000362:Agar; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001431:Bacteriological Techniques; D002939:Ciprofloxacin / Q000494:pharmacology*; D003470:Culture Media; D004352:Drug Resistance, Microbial; D004355:Drug Stability; D024841:Fluoroquinolones; D006801:Humans; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000494:pharmacology*; D009344:Neisseria gonorrhoeae / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification; D012680:Sensitivity and Specificity; D013045:Species Specificity
chemical_list: D000890:Anti-Infective Agents; D003470:Culture Media; D024841:Fluoroquinolones; D009287:Naphthyridines; D002939:Ciprofloxacin; D000362:Agar; C080163:trovafloxacin