Bacteremia Due to
            <i>Bacteroides fragilis</i>
            Group: Distribution of Species, β-Lactamase Production, and Antimicrobial Susceptibility Patterns

The in vitro activities of moxifloxacin, ciprofloxacin, levofloxacin, gatifloxacin, imipenem, piperacillintazobactam, clindamycin, and metronidazole against 900 surgical isolates were determined using NCCLS testing methods. Moxifloxacin exhibited good to excellent antimicrobial activity against most aerobic (90.8%) and anaerobic (97.1%) microorganisms, suggesting that it may be effective for the treatment of polymicrobial surgical infections.Infections of the abdominal-pelvic vaults and diabetic limbs involve a mixed microbial flora, often characterized by a high level of antimicrobial resistance (5-7). In addition to appropriate antimicrobial spectrum, the ideal antimicrobial agent must also have extensive tissue distribution, as many surgical infections occur in sites where there is significant disruption of tissue plains and vascular supply (7,17,22). Since the introduction of ciprofloxacin in the late 1980s, the fluoroquinolones have been viewed as potent antimicrobials for the treatment of serious gram-negative infections. Newer quinolones have improved in vitro activity against anaerobes, with trovafloxacin, moxifloxacin, and gatifloxacin having more potent activities than levofloxacin and ciprofloxacin (1, 3). Unfortunately, safety and toxicity concerns have limited the potential therapeutic usefulness of many of these agents (11,14,15,21). The present study was undertaken to investigate the in vitro activity of moxifloxacin against aerobic and anaerobic clinical isolates recently obtained from surgical patients with diabetic foot and intra-abdominal infections.Nine hundred sequential, nonduplicated clinical isolates (350 aerobic and 550 anaerobic strains) were collected over a 3-year period (1999 to 2002) from patients with intra-abdominal and diabetic foot infections in a tertiary care medical center in Milwaukee, Wis. (three surgical services: vascular surgery, trauma and critical care, and pancreatobiliary surgery). NCCLS-recommended reference broth and agar dilution methods were used for aerobic and anaerobic susceptibility testing, respectively (18,19). Microbroth and agar dilution plates were prepared on the day of testing and incubated at 35°C for 24 h (aerobes) and 48 h (anaerobes), respectively. Gram-positive and gram-negative aerobic-facultative isolates were tested in Mueller-Hinton broth. Anaerobic strains were tested within an anaerobic chamber on brucella blood agar plates supplemented with 5 g of hemin, 1 g of vitamin K 1 per ml, and 5% lysed sheep blood. The agar dilution plates were inoculated (10 5 CFU/spot) using a 32- The susceptibilities of the aerobic isolates, listed by species, are shown in Table 1. The results are expressed as the MICs at which 50 and 90% of strains were inhibited (MIC 50 and MIC 90 , respectively) and the ranges for all strains. While moxifloxacin, gatifloxacin, and imipenem demonstrated good activity against methicillin-susceptible S. aureus, E. faecalis, and Streptococcus spp., all agents tested failed to provide reliable in vitro activity (based on MIC 90 s) ...

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confidence: 78%

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confidence: 99%

In Vitro Activities of Moxifloxacin against 900 Aerobic and Anaerobic Surgical Isolates from Patients with Intra-Abdominal and Diabetic Foot Infections

Edmiston¹,

Krepel²,

Seabrook³

et al. 2004

“…The studies of the in vitro activity of moxifloxacin against anaerobic bacteria have been based on strains from diverse sites of isolation and have shown disparate results (2,3,6,7,12,14,15,21,23). Snydman et al (20) noted that different media resulted in higher geometric mean MICs for ciprofloxacin and trovafloxacin when tested on Wilkins-Chalgren agar compared to brucella blood agar.…”

Section: Discussionmentioning

confidence: 99%

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

Goldstein

Citron²,

Warren³

et al. 2006

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...

“…Although it accounts for only 0.5% of the enteric flora, it is the Bacteroides species most frequently isolated from patients with intra-abdominal infections and/or bacteremia (in which mortality reached 45% if inactive therapy was given). It often presents a serious problem for therapy, since it is resistant to many antibiotics, including most of the penicillins, cephalosporins, and the quinolones (1,3,19,20,25).Gram-negative bacteria including B. fragilis are usually more resistant to a large number of antibiotics and other noxious agents than are gram-positive bacteria. Clinically significant levels of antibiotic resistance are caused by interplay between the efficient outer membrane (OM) permeability barrier, ubiquitous periplasmic ␤-lactamases, and recently recognized multidrug resistance (MDR) efflux pumps (17).…”

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confidence: 99%

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confidence: 99%

Sixteen Homologs of the Mex-Type Multidrug Resistance Efflux Pump in Bacteroides fragilis

Ueda

Wexler

Hirai

et al. 2005

Sixteen homologs of multidrug resistance efflux pump operons of the resistance-nodulation-cell division (RND) family were found in the Bacteroides fragilis genome sequence by homology searches. Disruption mutants were made to the mexB homologs of the four genes most similar to Pseudomonas aeruginosa mexB. Reverse transcription-PCR was conducted and indicated that the genes were transcribed in a polycistronic fashion and that the promoter was upstream of bmeA (the mexA homolog). One of these disruption mutants (in bmeB, the mexB homolog) was more susceptible than the parental strain to certain cephems, polypeptide antibiotics, fusidic acid, novobiocin, and puromycin. The gene for this homolog and the adjacent upstream gene, bmeA, were cloned in a hypersensitive Escherichia coli host. The resultant transformants carrying B. fragilis bmeAB were more resistant to certain agents; these agents also had lower MICs for the B. fragilis bmeB disruption mutants than for the parental strain. The putative efflux pump operon is composed of bmeA, bmeB, and bmeC (a putative outer membrane channel protein homologous with OprM). Addition of the efflux pump inhibitors, carbonyl cyanide m-chlorophenylhydrazone (a proton conductor that eliminates the energy source) and Phe-Arg ␤-naphthylamide (MC-207,110) (the first specific inhibitor described for RND pumps in P. aeruginosa), resulted in lowered MICs in the parental strain but not in the bmeB disruption mutant, indicating that the bmeB pump is affected by these inhibitors. This is the first description of RND type pumps in the genus Bacteroides.Bacteroides fragilis, an anaerobic gram-negative rod, is an opportunistic pathogen that can cause significant mortality in infections resulting from abdominal trauma or surgery (7,19). Although it accounts for only 0.5% of the enteric flora, it is the Bacteroides species most frequently isolated from patients with intra-abdominal infections and/or bacteremia (in which mortality reached 45% if inactive therapy was given). It often presents a serious problem for therapy, since it is resistant to many antibiotics, including most of the penicillins, cephalosporins, and the quinolones (1,3,19,20,25).Gram-negative bacteria including B. fragilis are usually more resistant to a large number of antibiotics and other noxious agents than are gram-positive bacteria. Clinically significant levels of antibiotic resistance are caused by interplay between the efficient outer membrane (OM) permeability barrier, ubiquitous periplasmic ␤-lactamases, and recently recognized multidrug resistance (MDR) efflux pumps (17). These pumps have broad substrate specificity and may act synergistically with the permeability barrier to result in significant intrinsic resistance to many antimicrobials. These pumps expel the antimicrobial from the cell into the surrounding space, and the antimicrobials then have to pass through the OM permeability barrier to regain entry to the cell (18). Thus, the MDR pumps can effect significant resistance even when their transporter activi...