Comparative Antianaerobic Activity of BMS 284756

Abstract

Anaerobes are becoming increasingly resistant to ␤-lactams due to ␤-lactamase production and other mechanisms. Although ␤-lactamase production, and concomitant resistance to ␤-lactams, is the norm among the Bacteroides fragilis group, other anaerobic gram-negative bacilli in the genera Prevotella, Porphyromonas, and Fusobacterium have increasingly become ␤-lactamase positive. ␤-Lactamase production also has been described for clostridia. Metronidazole resistance in organisms other than non-spore-forming gram-positive bacilli has been described, as has clindamycin resistance in anaerobic gramnegative bacilli (1-5).Quinolones such as ciprofloxacin, ofloxacin, fleroxacin, pefloxacin, enoxacin, and lomefloxacin are inactive or marginally active against anaerobes. Newer quinolones with increased antianaerobic activity include (i) those with slightly increased activity against aerobic gram-positive and some nonfermentative gram-negative bacteria (sparfloxacin, grepafloxacin, and levofloxacin) and (ii) those with significantly improved antianaerobic activity (with clinafloxacin and sitafloxacin being the most active, followed by trovafloxacin, moxifloxacin, and gatifloxacin) (6-11, 13, 16).BMS 284756 (T-3811) (15) is a novel des-F(6)-quinolone with a broad spectrum of activity. The present study tested the antianaerobic activity of BMS 284756 compared to those of ciprofloxacin, levofloxacin, moxifloxacin, trovafloxacin, amoxicillin-clavulanate, piperacillin-tazobactam, imipenem, clindamycin, and metronidazole against 357 anaerobes.All anaerobes were clinical strains, isolated during the past four years, identified by standard procedures (14) and kept frozen in 200 g of dehydrated skim milk (Difco Laboratories, Detroit, Mich.) per liter at Ϫ70°C until use. No history regarding prior in vivo exposure to quinolones or other antibiotics tested is available, and no advanced quinolone-resistant strains or very recent clinical strains (isolated within a few months prior to the study) were included. Prior to testing, strains were subcultured twice onto enriched sheep blood agar plates (14). BMS 284756 susceptibility powder was obtained from BristolMyers Squibb Laboratories, Wallingford, Conn., and other drugs were obtained from their manufacturers. ␤-Lactamase testing was by the nitrocefin disk method (Cefinase; BBL Microbiology Systems, Cockeysville, Md.). Agar dilution susceptibility testing was according to the latest method recommended by the National Committee for Clinical Laboratory Standards (NCCLS) (12), using brucella agar with 5% sterile defibrinated sheep blood for non-B. fragilis group strains. Clavulanate was added to amoxicillin at a fixed ratio of 1:2, and tazobactam was added to piperacillin at a fixed concentration of 4.0 g/ml. All quality control gram-negative and -positive strains recommended by NCCLS were included with each run; in every case, results (where available) were in the control range.Among the anaerobic gram-negative bacilli tested, 76 of 80 B. fragilis group strains (95%) 54 of 89 Prevotella and...

In Vitro Activities of a New Des-Fluoro(6) Quinolone, Garenoxacin, against Clinical Anaerobic Bacteria

“…This is in accordance with previous but less extensive investigations. Hoellman et al (17) have reported a BMS-284756 (garenoxacin) MIC 50 of 0.5 g/ml and an MIC 90 of 2 g/ml for 357 recently isolated anaerobes of human origin. In a study by (29) reported MIC 50 s and MIC 90 s that were 2 to 4 log 2 dilutions lower than ours.…”

“…It displays a high degree of in vitro activity against a broad range of gram-positive and gram-negative bacterial pathogens, including anaerobes (6,12,13,15,17,24,25,29,30).…”

In Vitro Activities of the Des-Fluoro(6) Quinolone BMS-284756 against Aerobic and Anaerobic Pathogens Isolated from Skin and Soft Tissue Animal and Human Bite Wound Infections

“…Preliminary data indicate that this drug has a broad spectrum of activity against most gram-positive and gram-negative aerobes and anaerobes, including certain strains that are resistant to other fluoroquinolones (3,8).…”

In Vitro Activities of Garenoxacin (BMS 284756) against 108 Clinical Isolates of Gardnerella vaginalis

“…Garenoxacin is a new des-F(6)quinolone that lacks the six-position fluorine characterizing the previous generation of fluoroquinolones. Preliminary data (4,8) indicate that this drug has a broad spectrum of activity against many grampositive and gram-negative aerobes and anaerobes, including certain strains that are resistant to other fluoroquinolones. Consequently, we studied the in vitro activity of garenoxacin against recent clinical isolates of G. vaginalis.…”

“…While it is necessary to perform pharmacokinetic-pharmacodynamic studies before valid clinical conclusions may be drawn, garenoxacin's excellent activity against G. vaginalis, coupled with its activity against anaerobes (4,8), suggests that it deserves evaluation in the therapy of bacterial vaginosis and infections involving G. vaginalis. …”