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. 2003 Mar;47(3):910–916. doi: 10.1128/AAC.47.3.910-916.2003

Activities of Garenoxacin (BMS-284756) and Other Agents against Anaerobic Clinical Isolates

David W Hecht 1,*, J R Osmolski 1
PMCID: PMC149287  PMID: 12604521

Abstract

A total of 590 clinical isolates consisting of 33 species of both gram-positive and gram-negative anaerobes were collected from nine centers in the Chicago area in 1998-1999. The largest number of isolates (330 isolates, 56%) belonged to the Bacteroides group. Isolates were tested by agar dilution against garenoxacin (BMS-284756, T-3811 ME), trovafloxacin, moxifloxacin, clindamycin, imipenem, piperacillin-tazobactam, and cefoxitin. All but one species (2% of Bacteroides vulgatus isolates) were fully susceptible to piperacillin-tazobactam and imipenem. A number of species were resistant to clindamycin. Among the fluoroquinolones, garenoxacin and trovafloxacin had an MIC at which 90% of the isolates tested were inhibited of <4 μg/ml for all but two species (Fusobacterium mortiferum/varium and Peptostreptococcus anaerobius).

Anaerobic bacteria cause a variety of infections, in particular, abdominal surgical wound infections and periodontal disease. They also play a role in diabetic foot infections and gynecologic and obstetric infections caused by mixed aerobic and anaerobic bacteria (1). Therapeutic regimens include cephalosporins, aminoglycosides, quinolones, metronidazole, or clindamycin, depending on the source of the infection (13). However, several species are becoming increasingly resistant to cephalosporins due to the acquisition of beta-lactamases. A number of Prevotella species associated with periodontal disease have been found to be beta-lactamase positive (10). In a study of fecal anaerobic strains, resistance to ampicillin, cefoxitin, or cefuroxime was found in 70% of strains, with 19% showing multiple resistance to both ampicillin and cefuroxime (25). Resistance to clindamycin is also increasing (6), and as many as 20 to 40% of Bacteroides fragilis strains are clindamycin resistant (2, 14). Although metronidazole is effective against gram-negative anaerobes, 31% of gram-positive anaerobes have been reported to be resistant (24).

Newer respiratory quinolones such as gatifloxacin, moxifloxacin, trovafloxacin, clinafloxacin, and sitafloxacin show better antianaerobic activity than older quinolone compounds such as ciprofloxacin (3, 7, 27). Garenoxacin (BMS-284756, T-3811 ME) is a novel des-F(6)-quinolone that lacks the 6-position fluorine but retains broad-spectrum activity against gram-positive and gram-negative pathogens as well as anaerobes (12, 21). It has equivalent activity to trovafloxacin against gram-negative anaerobes and often superior activity against gram-positive anaerobes (21). It also has activity against anaerobes overall that is superior to those of levofloxacin and moxifloxacin (15).

In this study, we determined the in vitro activity of garenoxacin and compared it with those of trovafloxacin, moxifloxacin, imipenem, clindamycin, piperacillin-tazobactam, and cefoxitin against 33 species of gram-positive and gram-negative anaerobic bacteria comprising 590 recent clinical isolates obtained from the Chicago, Ill., area.

MATERIALS AND METHODS

Bacterial strains.

Clinical isolates (590) collected from 1998 to 1999 from nine medical centers in the Chicago area were selected for testing and frozen in double skim milk. Selection was from among more than 1,300 isolates collected during that time period and based upon species distribution for the purposes of this study. Sites of infection for isolates tested (when known) included intra-abdominal, pelvic, wound, blood, respiratory, and oral sites. Identifications were performed by using ANA IDENT II with additional biochemical testing as needed.

Agar dilution susceptibility testing.

The NCCLS-recommended reference agar dilution method for anaerobes (M11-A4) was used for susceptibility testing (19). Brucella agar supplemented with blood, hemin, and vitamin K1 was the test medium. Each inoculum was prepared and standardized by using a Vitek colorimeter to deliver approximately 105 CFU/spot. All antibiotic-containing plates were prepared and tested on the same day. The antimicrobials tested included trovafloxacin (0.015 to 64 μg/ml), moxifloxacin (0.015 to 64 μg/ml), garenoxacin (0.015 to 64 μg/ml), imipenem (0.015 to 64 μg/ml), clindamycin (0.015 to 64 μg/ml), piperacillin-tazobactam (0.03 to 128 μg/ml), and cefoxitin (0.03 to 128 μg/ml). Antibiotics were obtained from their respective manufacturers as follows: garenoxacin from Bristol Myers Squibb (New York, N.Y.), trovafloxacin from Pfizer Pharmaceuticals (New York, N.Y.), moxifloxacin from Bayer (West Haven, Conn.), imipenem and cefoxitin from Merck (West Point, Pa.), piperacillin-tazobactam from Wyeth Ayerst (St. Davids, Pa.), and clindamycin from Pharmacia-Upjohn (Kalamazoo, Mich.). The interpretation of endpoints was done according to NCCLS guideline M11-A4 (19).

RESULTS

The 590 selected isolates tested in this study belonged to 33 species; 56 (9%) were gram-positive anaerobes and the remainder were gram-negative, with Bacteroides spp. comprising 56% of the latter. Among the 303 isolates selected from the Bacteroides group, 103 (34%) were B. fragilis and 200 (66%) were from other members of the B. fragilis group. Of the compounds tested, piperacillin-tazobactam, imipenem, garenoxacin, and trovafloxacin demonstrated good activity against almost all species (Table 1). Only 2% of isolates, all belonging to Bacteroides vulgatus species, were highly resistant to piperacillin-tazobactam and imipenem. Garenoxacin demonstrated excellent in vitro activity against all isolates, based upon the MICs at which 50% of the isolates tested were inhibited (MIC50s) and MIC90s. The MIC90s for only two species, Fusobacterium mortiferum/varium and Peptostreptococcusanaerobius, were >4 μg/ml. Garenoxacin activity was most similar to that of trovafloxacin, and it was somewhat more active (according to MIC90s) than moxifloxacin. Based on the recommended NCCLS susceptibility breakpoint for trovafloxacin (≤2 μg/ml), garenoxacin demonstrated somewhat greater activity for four members of the B. fragilis group (B. fragilis, Bacteroidesthetaiotaomicron, B. vulgatus, and Bacteroidesuniformis) than did trovafloxacin and for all members of the B. fragilis group than did moxifloxacin. For non-B. fragilis group anaerobes, the activities of all three quinolones were excellent and very similar. Clindamycin demonstrated reduced activity against a number of species, notably those belonging to the Bacteroides fragilis group (Table 1). Resistances of B. fragilis isolates and non-B. fragilis members of the B. fragilis group to clindamycin were 23 and 33%, respectively. Seventy-seven and 64% of B. fragilis and non-B. fragilis members of the B. fragilis group, respectively, were fully susceptible to clindamycin. Cefoxitin resistances among B. fragilis and non-B. fragilis members of the B. fragilis group were only 1 and 7%, respectively. However, while 95% of B. fragilis isolates were fully susceptible to cefoxitin, only 64% of the non-B. fragilis members of the B. fragilis group were fully susceptible at the breakpoint of ≤16 μg/ml.

TABLE 1.

Ranges, MIC50s, and MIC90s for garenoxacin and other agents against 590 anaerobic isolates

Organism (n) and antibiotic Concn range (μg/ml) MIC50 (μg/ml) MIC90 (μg/ml)
B. fragilis (103)
    Garenoxacin 0.06-4 0.25 1
    Trovafloxacin 0.25-4 0.25 4
    Moxifloxacin 0.125-16 0.5 4
    Clindamycin ≤0.015->64 1 >64
    Imipenem 0.03-8 0.125 0.125
    Piperacillin-tazobactam ≤0.03-16 0.06 2
    Cefoxitin 2-64 8 16
Bacteroides distasonis (35)
    Garenoxacin 0.125-2 0.5 1
    Trovafloxacin 0.125-4 0.5 1
    Moxifloxacin 0.125-16 0.5 1
    Clindamycin 0.125->64 4 >64
    Imipenem 0.25-2 0.5 0.5
    Piperacillin-tazobactam 2-32 8 16
    Cefoxitin 1-64 32 64
B. thetaaiotaomicron (35)
    Garenoxacin 0.125-32 0.5 4
    Trovafloxacin 0.25-8 0.5 4
    Moxifloxacin 0.5-64 1 16
    Clindamycin 0.25->64 2 >64
    Imipenem 0.06-8 0.25 0.25
    Piperacillin-tazobactam 0.5-128 4 8
    Cefoxitin 2-64 16 32
B. vulagatus (35)
    Garenoxacin 0.125-4 0.25 2
    Trovafloxacin 0.125-4 0.25 4
    Moxifloxacin 0.25-16 0.5 16
    Clindamycin ≤0.015->64 0.125 >64
    Imipenem 0.03->64 0.25 0.25
    Piperacillin-tazobactam 0.125-128 2 16
    Cefoxitin 0.5-64 8 32
Bacteroides ovatus (27)
    Garenoxacin 0.5-4 0.5 2
    Trovafloxacin 0.25-4 0.5 1
    Moxifloxacin 0.5-32 1 4
    Clindamycin 0.03->64 4 >64
    Imipenem 0.03->64 0.25 0.25
    Piperacillin-tazobactam 0.125-128 4 8
    Cefoxitin 0.5-64 16 32
B. uniformis (28)
    Garenoxacin 0.125-8 1 4
    Trovafloxacin 0.25-4 1 4
    Moxifloxacin 0.25-64 2 32
    Clindamycin 0.03->64 2 >64
    Imipenem 0.125-1 0.125 0.125
    Piperacillin-tazobactam 0.5-16 2 8
    Cefoxitin 2-32 16 32
Bacteroides eggerthii/sterocoris (20)
    Garenoxacin 0.125-2 0.5 1
    Trovafloxacin 0.125-2 0.5 1
    Moxifloxacin 0.25-16 2 4
    Clindamycin <0.015->64 2 >64
    Imipenem 0.03-1 0.125 0.125
    Piperacillin-tazobactam ≤0.03-16 2 4
    Cefoxitin 0.5-64 16 32
Bacteroides caccae (20)
    Garenoxacin 0.125-1 0.25 1
    Trovafloxacin 0.125-2 0.25 1
    Moxifloxacin 0.25-8 0.5 1
    Clindamycin 0.03->64 1 >64
    Imipenem 0.03-2 0.125 0.125
    Piperacillin-tazobactam ≤0.03-32 0.5 8
    Cefoxitin 1-64 4 16/PICK>
Clostridium spp. (40)a
    Garenoxacin 0.06-2 0.5 1
    Trovafloxacin 0.06-8 0.5 1
    Moxifloxacin 0.125-8 1 2
    Clindamycin ≤0.015->64 0.5 >64
    Imipenem ≤0.015-4 0.5 0.5
    Piperacillin-tazobactam ≤0.03-8 1 4
    Cefoxitin 0.125->128 16 128
C. perfringens (40)
    Garenoxacin 0.03-0.5 0.25 0.25
    Trovafloxacin 0.06-0.5 0.125 0.125
    Moxifloxacin 0.125-2 0.25 0.5
    Clindamycin 0.03-2 0.5 2
    Imipenem 0.03-25 0.06 0.06
    Piperacillin-tazobactam ≤0.03-0.5 0.06 0.125
    Cefoxitin 0.5-4 1 1
Fusobacterium nucrophorum (11)
    Garenoxacin ≤0.015-1 0.25 0.5
    Trovafloxacin 0.03-4 0.25 4
    Moxifloxacin 0.03-4 0.25 1
    Clindamycin ≤0.015-0.125 ≤0.015 0.06
    Imipenem ≤0.015-0.5 ≤0.015 ≤0.015
    Piperacillin-tazobactam ≤0.03-8 ≤0.03 0.06
    Cefoxitin 0.03-8 0.125 1
Fusobacterium nucleatum (10)
    Garenoxacin 0.06-0.5 0.25 0.25
    Trovafloxacin 0.125-0.5 0.25 0.5
    Moxifloxacin 0.06-1 0.125 0.5
    Clindamycin ≤0.015-2 0.03 0.125
    Imipenem ≤0.015-0.25 ≤0.015 ≤0.015
    Piperacillin-tazobactam ≤0.03-2 ≤0.03 0.125
    Cefoxitin ≤0.03-8 0.125 4
F. mortiforum/varium (10)
    Garenoxacin 0.06->64 0.25 >64
    Trovafloxacin 0.06-64 0.5 8
    Moxifloxacin 0.03-64 0.25 32
    Clindamycin ≤0.015-16 0.06 16
    Imipenem ≤0.015-0.5 0.25 0.25
    Piperacillin-tazobactam ≤0.03-8 0.5 4
    Cefoxitin 0.06-32 4 8
Prevotella bivia (26)
    Garenoxacin 0.125-2 1 1
    Trovafloxacin 0.5-2 1 2
    Moxifloxacin 0.06-2 1 2
    Clindamycin ≤0.015->64 ≤0.015 >64
    Imipenem ≤0.015-0.125 0.03 0.03
    Piperacillin-tazobactam ≤0.03 ≤0.03 ≤0.03
    Cefoxitin 0.125-16 1 8
Prevotella buccae (12)
    Garenoxacin 0.06-0.25 0.125 0.25
    Trovafloxacin 0.5-1 0.5 1
    Moxifloxacin 0.25-0.5 0.25 0.5
    Clindamycin ≤0.015 ≤0.015 ≤0.015
    Imipenem ≤0.015-0.125 0.03 0.03
    Piperacillin-tazobactam ≤0.03-0.125 ≤0.03 ≤0.03
    Cefoxitin 0.5-8 1 8
Prevotella intermedia (9)
    Garenoxacin 0.03-8 0.125
    Trovafloxacin 0.25-4 0.5
    Moxifloxacin 0.25-16 0.25
    Clindamycin ≤0.015->64 0.03
    Imipenem 0.015-0.125 0.03
    Piperacillin-tazobactam ≤0.03-0.5 ≤0.03
    Cefoxitin ≤0.03-8 1
Prevotella loeschii (10)
    Garenoxacin 0.06-4 0.5 2
    Trovafloxacin 0.125-2 0.5 2
    Moxifloxacin 0.125-4 0.5 4
    Clindamycin ≤0.015->64 2 >64
    Imipenem ≤0.015-0.25 0.125 0.125
    Piperacillin-tazobactam ≤0.03-8 0.5 4
    Cefoxitin 0.25-16 8 16
Prevotella melanogenica (11)
    Garenoxacin 0.06-1 0.125 0.5
    Trovafloxacin 0.25-2 1 2
    Moxifloxacin 0.25-4 0.5 1
    Clindamycin ≤0.015->64 ≤0.015 0.25
    Imipenem 0.015-0.5 0.03 0.03
    Piperacillin-tazobactam ≤0.03-1 ≤0.03 0.06
    Cefoxitin 0.06-8 1 4
Prevotella spp. (10)b
    Garenoxacin 0.125-1 0.25 1
    Trovafloxacin 0.5-4 1 1
    Moxifloxacin 0.25-1 0.5 1
    Clindamycin ≤0.015-1 ≤0.015 >64
    Imipenem ≤0.015-0.25 0.03 0.03
    Piperacillin-tazobactam ≤0.03-4 ≤0.03 1
    Cefoxitin 0.25-8 2 4
Porphyromonas spp. (11)c
    Garenoxacin ≤0.015-0.025 ≤0.015 0.25
    Trovafloxacin 0.03-1 0.5 0.5
    Moxifloxacin ≤0.015-0.5 0.25 0.25
    Clindamycin ≤0.015-0.06 ≤0.015 0.03
    Imipenem ≤0.015 ≤0.015 ≤0.015
    Piperacillin-tazobactam ≤0.03 ≤0.03 ≤0.03
    Cefoxitin 0.06-0.125 0.06 0.125
Peptostreptococcus micros (12)
    Garenoxacin 0.03-1 0.06 0.5
    Trovafloxacin 0.06-1 0.125 1
    Moxifloxacin 0.125-4 0.25 2
    Clindamycin 0.125-0.25 0.125 0.25
    Imipenem ≤0.015-0.06 0.06 0.06
    Piperacillin-tazobactam ≤0.03-0.125 0.03 0.06
    Cefoxitin 0.25-2 0.5 2
Peptostreptococcus magnus (10)
    Garenoxacin 0.03-0.25 0.06 0.25
    Trovafloxacin 0.06-0.25 0.125 0.25
    Moxifloxacin 0.06-0.5 0.125 0.25
    Clindamycin ≤0.015->64 0.125 1
    Imipenem ≤0.015-0.25 0.06 0.06
    Piperacillin-tazobactam ≤0.03-0.5 ≤0.03 0.125
    Cefoxitin 0.25-2 0.25 1
Peptostreptococcus assacharolyticus (15)
    Garenoxacin 0.03-0.125 0.125 0.125
    Trovafloxacin 0.25-1 0.5 0.5
    Moxifloxacin ≤0.015-1 0.25 0.25
    Clindamycin ≤0.015-0.25 0.125 >64
    Imipenem ≤0.015-0.03 ≤0.015 ≤0.015
    Piperacillin-tazobactam ≤0.03-0.125 ≤0.03 0.06
    Cefoxitin ≤0.03-8 0.125 1
P. anaerobius (10)
    Garenoxacin 0.03-8 0.06 8
    Trovafloxacin 0.06-8 0.125 8
    Moxifloxacin 0.125-16 0.125 8
    Clindamycin ≤0.015-0.25 0.125 0.25
    Imipenem 0.03-1 0.06 0.06
    Piperacillin-tazobactam ≤0.03-32 0.25 16
    Cefoxitin 0.25-16 0.5 16
Peptostreptococcus prevotii (9)
    Garenoxacin 0.06-0.5 0.125
    Trovafloxacin 0.125-1 0.5
    Moxifloxacin 0.125-1 0.25
    Clindamycin ≤0.015-64 0.25
    Imipenem ≤0.015-0.125 ≤0.015
    Piperacillin-tazobactam ≤0.03-16 ≤0.03
    Cefoxitin 0.06-16 0.5
Actinomyces spp. (8)d
    Garenoxacin 0.06-1 1
    Trovafloxacin 0.06-4 1
    Moxifloxacin 0.125-2 0.5
    Clindamycin 0.03->64 0.25
    Imipenem ≤0.015-0.125 ≤0.015
    Piperacillin-tazobactam ≤0.03-1 ≤0.03
    Cefoxitin ≤0.03-1 0.125
Eubacterium lentum (8)
    Garenoxacin 0.06-1 0.5
    Trovafloxacin 0.125-8 0.25
    Moxifloxacin 0.125-4 0.25
    Clindamycin ≤0.015-16 0.25
    Imipenem 0.03-0.5 0.25
    Piperacillin-tazobactam 0.125-32 16
    Cefoxitin 1-64 4
Propionibacterium acnes (15)
    Garenoxacin 0.06-0.5 0.25 0.5
    Trovafloxacin 0.5-1 0.5 1
    Moxifloxacin 0.125-0.25 0.125 0.25
    Clindamycin ≤0.015-0.125 0.03 0.125
    Imipenem ≤0.015-0.03 ≤0.015 ≤0.015
    Piperacillin-tazobactam ≤0.03-0.5 ≤0.03 0.25
    Cefoxitin 0.06-0.5 0.125 0.25
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a

Clostridium tertium (3), Clostridium limosum (1), Clostridium tetani (2), Clostridium innocuum (9), Clostridium subterminale (9), Clostridium butryicuum (4), Clostridium ramosum (6), Clostridium sordellii (4).

b

Prevotella oralis (3), Prevotella corporis (2), Prevotella disiens (5).

c

Porphyromonas asaccharolytica (5), Porphyromonas endodontalis (3), Porphyromonas gingivalis (3).

d

Actinomyces israelii (1), Actinomyces meyeri (6), Actinomyces naeslundii (1).

The species with the largest number of isolates (n = 103) tested was B. fragilis. Piperacillin-tazobactam had the best activity against B. fragilis, with all isolates showing susceptibility to this compound (Table 2). Imipenem with an MIC90 of 0.25 μg/ml also showed good activity. Among the quinolones, garenoxacin had a fourfold-lower MIC90 than either trovafloxacin or moxifloxacin. A single isolate showed nonsusceptibility to garenoxacin, whereas with trovafloxacin and moxifloxacin, 18 and 21 isolates, respectively, were nonsusceptible (Table 2).

TABLE 2.

MIC distribution of antimicrobials tested against B. fragilis (n = 103)

Antimicrobial No. (cumulative %) of strains for which the MIC (μg/ml) was:
0.015 0.03 0.06 0.125 0.25 0.5 1 2 4 8 16 32 64 128 256 512
Garenoxacin 0 0 1 (1) 31 (31) 29 (52) 15 (74) 19 (92) 7 (99) 1 (100) 0 0 0 0 0 0 0
Trovafloxacin 0 0 0 12 (12) 47 (57) 16 (73) 3 (76) 7 (83) 18 (100) 0 0 0 0 0 0 0
Moxifloxacin 0 0 0 1 (1) 37 (37) 30 (66) 9 (75) 5 (80) 15 (94) 5 (99) 1 (100) 0 0 0 0 0
Clindamycin 1 (1) 1 (2) 0 5 (7) 14 (20) 24 (44) 25 (68) 9 (77) 0 (77) 0 (77) 1 (78) 0 (78) 0 (78) 23 (100) 0 0
Piperacillin-tazobactam 0 1 (1) 52 (51) 27 (78) 6 (84) 4 (87) 1 (88) 7 (95) 3 (98) 1 (99) 1 (100) 0 0 0 0 0
Imipenem 0 8 (8) 34 (41) 42 (82) 10 (91) 6 (97) 2 (99) 0 (99) 0 (99) 1 (100) 0 0 0 0 0 0
Cefoxitin 0 0 0 0 0 0 0 1 (1) 39 (39) 42 (80) 15 (95) 4 (99) 1 (100) 0 0 0
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The second-largest group of isolates belonging to a single species were Clostridium perfringens strains (n = 40). Most compounds showed good activity against these isolates, and no resistant strains were identified. Garenoxacin showed twofold-better activity than moxifloxacin for the majority of strains tested and was slightly less active than trovafloxacin.

DISCUSSION

Appropriate antimicrobial therapy, particularly in the treatment of surgical wound infections, has been found to have a major impact on the outcome. The mortality rate is more than doubled in cases of inappropriate therapy (18). In patients with bacteremia caused by Bacteroides spp., patients receiving inactive therapy had a mortality rate of 45% compared with 16% in those receiving active therapy and clinical failure was 82 and 22% in the two groups, respectively (20). Consequently, the choice of an effective agent for treatment of both single-anaerobe infections as well as polymicrobial infections is critical.

In this study, clindamycin showed reduced activity against a number of species compared with other agents. Of 303 Bacteroides spp. isolates tested, 220 (28%) showed high-level resistance to clindamycin. Increased resistance of B. fragilis to clindamycin has been noted in other studies, with rates of 23 and 19%, respectively, previously reported in the United States and Canada (2, 16, 22). In a study of Spanish isolates, 34% were clindamycin resistant (5), and a similar rate of resistance (32%) was found in South Africa (17). Resistance to cefoxitin was also noted in some of these studies, although it was low among the Bacteroides spp. tested in this study. However, the number of isolates with reduced susceptibility to cefoxitin among non-B. fragilis members of the B. fragilis group reflects a large number of isolates near the breakpoint.

Piperacillin-tazobactam, imipenem, and the quinolones showed good activity against most species, as has been noted in other studies (6, 12, 15, 21, 25). Reduced activity to all of these agents was only found among isolates of B. vulgatus and B. thetaiotaomicron species. Of interest, one B. thetaiotaomicron isolate was resistant to piperacillin-tazobactam (MIC = 128 μg/ml), intermediate to imipenem (MIC = 8 μg/ml), but sensitive to cefoxitin (MIC = 16 μg/ml). Similarly, one B. vulgatus isolate was resistant to both imipenem (MIC > 64 μg/ml) and piperacillin-tazobactam (MIC = 128 μg/ml) but only intermediate to cefoxitin (MIC = 32 μg/ml). These results were confirmed upon repeat testing. Imipenem-resistant isolates that express metalloenzymes are typically resistant to all beta-lactam antibiotics. The mechanism of resistance in these two organisms has not been characterized but may be different from reported metalloenzyme beta-lactamases.

Among the quinolones, garenoxacin showed comparable activity to trovafloxacin and activity superior to that of moxifloxacin against these species, and this trend was evident for most of the species tested. Interestingly, garenoxacin had superior activity to these two agents against B. fragilis strains, which are often beta-lactamase positive (8, 23) and clindamycin resistant (2).

Garenoxacin has been shown to have good activity not only against anaerobes but also against gram-positive and gram-negative aerobes of clinical importance (4, 9, 12, 26). It is effective in vitro against Staphylococcus aureus, Legionella sp., Campylobacter jejuni, and Helicobacter pylori (11, 21). Among the quinolones, it has comparable activity to trovafloxacin and activity superior to those of other quinolones against anaerobes as demonstrated in this and other studies (15, 21). Consequently, it could prove to be a useful agent for the treatment of anaerobic and polymicrobial infections, particularly in the nosocomial setting.

Acknowledgments

This work was supported by the Bristol Myers Squibb Company.

We thank Gayatri Vedantam for assistance in data analysis. We also thank Joyce de Azavedo for help in preparing the manuscript.

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