Synergistic activity of the novel des-fluoro(6) quinolone, garenoxacin (BMS-284756), in combination with other antimicrobial agents against Pseudomonas aeruginosa and related species.
Non-fermentative Gram-negative bacteria (Pseudomonas aeruginosa, Burkholderia cepacia, Stenotrophomonas maltophilia and Acinetobacter spp.) are intrinsically less susceptible to many antimicrobial agents. Two-drug combinations have been used to treat infections caused by less susceptible pathogens. In this study, the antibacterial activity of garenoxacin (GARX) with non-quinolones was examined. The non-quinolones evaluated were cefepime (CEPI), imipenem (IMIP), aztreonam (AZTR), piperacillin-tazobactam (PIPC/TZ), amikacin (AMK), ceftazidime (CTAZ), trimethoprim-sulphamethoxazole (TMP/SMX) and ticarcillin-clavulanate (TICC/CA). Synergism was determined by time-kill analysis using GARX (at 2 x its MIC, not to exceed 4 mg/l) and the second drug (at 1 x MIC, not to exceed its susceptible MIC breakpoint), and is defined as > or = 2 log(10) enhanced killing at 24 h with the combination. Partial synergy is defined as > or = 1.5 log(10) but < 2 log(10) enhanced killing with the drug combination. Synergy/partial synergy was observed most often with GARX plus: CEPI, AZTR, PIPC/TZ, IMIP (five strains each) or AMK (four strains) vs. eight P. aeruginosa; CTAZ, AZTR (five strains each) vs. six B. cepacia; TICC/CA (six strains), CEPI, CTAZ or AMK (five strains each) vs. eight S. maltophilia; and CEPI, AMK (three strains each) or CTAZ, TICC/CA (two strains each) vs. four Acinetobacter spp. In conclusion, synergistic killing was observed frequently with GARX plus a non-quinolone bactericidal agents against non-fermentative Gram-negative bacteria, including strains intermediately susceptible/resistant to one or both agents.
Department of Microbiology, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06457, USA. fungtomj@bms.com
J C
JC
Fung-Tomc
E
E
Gradelski
L
L
Valera
E
E
Huczko
D P
DP
Bonner
D000890:Anti-Infective Agents / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D024841:Fluoroquinolones; D006088:Gram-Negative Aerobic Bacteria / Q000187:drug effects; D007211:Indoles; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D015363:Quinolones
D000890:Anti-Infective Agents; D004338:Drug Combinations; D024841:Fluoroquinolones; D007211:Indoles; D015363:Quinolones; C419689:garenoxacin