In Vitro Activity of Moxifloxacin against 923 Anaerobes Isolated from Human Intra-Abdominal Infections

Abstract

The in vitro activity of moxifloxacin against 923 recent anaerobic isolates obtained from pretreatment cultures in patients with complicated intra-abdominal infections was studied using the CLSI M11-A-6 agar dilution method. Moxifloxacin was active against 87% (96 of 110) Bacteroides fragilis strains at <1 g/ml and 87% (79 of 90) B. thetaiotaomicron strains at <2 g/ml. Species variation was seen, with B. uniformis, B. vulgatus, Clostridium clostridioforme, and C. symbiosum being least susceptible and accounting for most of the resistant isolates; excluding the aforementioned four resistant species, 86% (303 of 363) of Bacteroides species isolates and 94% (417 of 450) of all other genera and species were susceptible to <2 g/ml of moxifloxacin. Overall, moxifloxacin was active against 763 of 923 (83%) of strains at <2 g/ml, supporting its use as a monotherapy for some community-acquired intra-abdominal infections.Intra-abdominal infections are known to be composed of mixed aerobic and anaerobic bacteria (9). Current guidelines (22) recommend combining a fluoroquinolone with metronidazole for therapy of community-acquired intra-abdominal infections. Moxifloxacin, an 8-methoxyquinolone, has been reported to have activity against a broad spectrum of both aerobic and anaerobic bacteria (1, 4-6, 10, 14, 15, 25) such as encountered in intra-abdominal infections. However, many older in vitro studies employed a variety of media and methods and utilized isolates collected from a wide range of clinical sources. Moreover, older isolates may not reflect potential resistance that has since developed from use of the fluoroquinolones. Moxifloxacin has been reported to penetrate and accumulate in the human gastrointestinal mucosa (24) and a comparative mouse model study (19) has supported its use as a single agent in intra-abdominal infections. Clinical studies performed to evaluate the efficacy of moxifloxacin in mixed aerobic/anaerobic intra-abdominal infections have been reported in abstract form (M. Malangoni, J. Song, S. Choudri, P. Potgieter, and P. Cyrus, 44th Intersci. Conf. Antimicrob. Agents Chemother., abstr. L-990, 2004). In order to further evaluate its potential for this indication, we studied the comparative activity of moxifloxacin against 923 sequential anaerobic strains isolated from pretherapy cultures of patients with complicated intra-abdominal infections. MATERIALS AND METHODSIsolates were collected between 2001 and April 2004 from pretherapy clinical specimens from patients with complicated community-acquired intra-abdominal infections, some as part of a 56-site United States clinical trial for which we were a reference laboratory. The primary specimens were sent by overnight courier and cultured in our laboratory. All isolates were identified by standard criteria (13, 16) and some, when required, were identified by sequencing of the 16S RNA gene.Standard laboratory powders of the following antimcirobial agents were obtained as follows: moxifloxacin, Bayer Inc., West Haven, CT; levofloxacin, R.W. Johnson P...

Antianaerobic Antimicrobials: Spectrum and Susceptibility Testing

“…The most recent national survey (27) reported that 27% of B. fragilis, 26% of B. thetaiotaomicron, 38% of B. ovatus, and 55% of B. vulgatus isolates were resistant to moxifloxacin. A study of strains isolated from intra-abdominal infections (2001 to 2004) found 87% of B. fragilis and 87% of B. thetaiotaomicron isolates to be susceptible to moxifloxacin (143). The overall results showed that 86% (303/363) of all B. fragilis group isolates and 417/450 isolates of all other anaerobic genera and species, including Fusobacterium, Prevotella, Porphyromonas, C. perfringens, Eubacterium, and Peptostreptococcus spp., were susceptible to Յ2 g/ml of moxifloxacin.…”

“…Moxifloxacin has been studied and approved by the FDA as monotherapy in intra-abdominal infections in adults (76,90) and has shown activity against intra-abdominal anaerobic isolates (143,144). However, concern over increasing fluoroquinolone resistance in both E. coli and B. fragilis group species has made clinicians cautious in its use in intra-abdominal infections (76).…”

Clostridium aldenense sp. nov. and Clostridium citroniae sp. nov. Isolated from Human Clinical Infections

“…Many clinical laboratories do not identify anaerobes, especially to the species level (12). However, identifying some of the clinically common clostridial isolates is necessary because susceptibility is often species specific, and the importance of performing susceptibility testing on clostridial isolates other than C. perfringens has been shown in several studies (10,11,36). Our susceptibility results were different from those of the study by Finegold et al (9) in that most strains in all five species appeared resistant to moxifloxacin by use of FDAdefined breakpoints.…”

In Vitro Antianaerobic Activity of DX-619, a New Des-Fluoro(6)Quinolone

“…Its potent antianaerobic activity seems to be close to that of sitafloxacin and comparable to that of trovafloxacin (1,3,8,11,15,20,21,25,26). Fujikawa et al comprehensively studied the antibacterial activities of DX-619 and reference agents, including IPM and LVX (5).…”

“…Newer quinolones, such as sparfloxacin and levofloxacin (LVX), have improved in vitro activities against anaerobic bacteria but still have limited activities against certain gram-positive and gram-negative anaerobic bacilli (3,7,8,11,12,15,23,25). Some of the newer fluoroquinolones are much more active to both gram-positive and gram-negative anaerobic bacteria (3,8,11,12,15,20,26). DX-619 is a new derivative of quinolone, defined as a des-F (6) quinolone that lacks the six-position fluorine characteristic of the previous generation of fluoroquinolones.…”