Comparative antimicrobial spectrum and activity of the desfluoroquinolone BMS284756 (T-3811) tested against non-fermentative Gram-negative bacilli.
OBJECTIVE
To compare the in vitro activity of BMS284756, a desfluoroquinolone, with four fluoroquinolones against 129 Pseudomonas aeruginosa strains, 97 Stenotrophomonas/Burkholderia group strains and 43 Acinetobacter spp. strains by three in vitro test methods.


METHODS
The activity of BMS284756 was determined using the NCCLS reference broth microdilution method and E test (AB Biodisk, Solna, Sweden). These methods were compared for test accuracy, and 5-microg disk zone diameters were compared for interpretative accuracy using the susceptible breakpoint of < or =4 mg/L recommended by the manufacturer. All strains tested were derived from the 1999-2000 SENTRY Antimicrobial Surveillance Program organism collection.


RESULTS
Comparative quinolone potency against P. aeruginosa was as follows: ciprofloxacin (MIC50, 0.25 mg/L) > gemifloxacin (MIC50, 0.5 mg/L) > levofloxacin = gatifloxacin (MIC50, 1 mg/L) > BMS284756 (MIC50, 4 mg/L). The MIC50 value for BMS284756 versus Stenotrophomonas/Burkholderia group was 2 mg/L. This potency was similar to that of other quinolones reported previously. The MIC50 results for the Acinetobacter spp. were ciprofloxacin at >2 mg/L, levofloxacin, gatifloxacin and gemifloxacin at 4 mg/L, and BMS284756 at >4 mg/L, all intermediate or resistant concentrations. The E test results compared favorably with the reference dilution test results for P. aeruginosa, Stenotrophomonas/Burkholderia group, and Acinetobacter spp., with an overall essential agreement of 97.0% +/- 2 log2 dilution steps. E test MIC results tended to be slightly lower when testing Stenotrophomonas/Burkholderia group strains. The disk diffusion method correlated well for P. aeruginosa (r = 0.94), Stenotrophomonas/Burkholderia group (r = 0.84) and Acinetobacter spp. (r = 0.99) strains.


CONCLUSIONS
BMS284756 was generally less active than other comparison quinolones when tested against non-fermentative Gram-negative bacilli. Its spectrum remains equivalent only if dosing schedules substantiate a proposed susceptible breakpoint of < or =4 mg/L.
Howard
W
W
University of Iowa College of Medicine, Iowa City, Iowa, USA.
Biedenbach
D J
DJ
Jones
R N
RN
D000890:Anti-Infective Agents / Q000494:pharmacology*; D001407:Bacillus / Q000187:drug effects; D024841:Fluoroquinolones; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006801:Humans; D007211:Indoles; D008826:Microbial Sensitivity Tests; D015363:Quinolones
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D007211:Indoles; D015363:Quinolones; C419689:garenoxacin