Department of Clinical Microbiology, Hospital Clínico San Carlos, 28040 Madrid, Spain
Received 3 March 2005; returned 4 May 2005; revised 19 May 2005; accepted 20 May 2005
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Abstract |
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Methods: A total of 400 non-duplicate clinical isolates of the B. fragilis group collected from 2000 to 2002 were studied. Susceptibility testing was performed according to the reference agar dilution method described by the NCCLS. The following antimicrobials were tested: tigecycline, clindamycin, metronidazole, chloramphenicol, cefoxitin, imipenem, amoxicillinclavulanate and piperacillintazobactam.
Results: All strains were susceptible to metronidazole and chloramphenicol. For clindamycin and cefoxitin, the overall susceptibility rates were 59.5% and 83%, respectively. Imipenem and piperacillintazobactam were the most active ß-lactam agents tested. Tigecycline inhibited 89.8% of the strains at a concentration of 8 mg/L with an MIC range of 0.01 to >16 mg/L. By comparing the MIC50 and MIC90 values of tigecycline among the various species of the group, B. fragilis, Bacteroides thetaiotaomicron and Bacteroides vulgatus were the most susceptible (MIC50/MIC90s of 0.51/8 mg/L).
Conclusions: Tigecycline exhibited activity against most isolates of the B. fragilis group tested. These results indicate that tigecycline may be useful in the treatment and prophylaxis of infections involving these organisms.
Keywords: susceptibility , glycylcyclines , Bacteroides fragilis group
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Introduction |
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The increasing antimicrobial resistance among the B. fragilis group has important implications in the selection of antimicrobial agents for empirical therapy. It has been demonstrated that treatment with inappropriate antibiotics influences the clinical outcome of patients with Bacteroides bacteraemia.11 Therefore, there is a need for periodic susceptibility studies and for the evaluation of new agents to provide data to guide the appropriate empirical antimicrobial therapy. Tigecycline is the 9-t-butylglycylamino derivative of minocycline and has a broad spectrum of activity against aerobic and anaerobic bacteria.1217 The aim of this study was to ascertain the current susceptibility patterns of members of the B. fragilis group in our hospital and to assess the in vitro activity of tigecycline against these organisms.
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Materials and methods |
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Antimicrobial susceptibility tests were performed according to the reference agar dilution method described by the NCCLS18 with brucella agar supplemented with haemin, vitamin K1 and 5% laked sheep blood. Approximately 105 cfu/spot was inoculated using a Steers multipoint replicator. The agar dilution test plates were incubated at 35°C for 48 h in an anaerobic chamber. MICs were defined as the lowest concentration of an antimicrobial agent where a marked reduction occurred in the appearance of growth on the test plate compared with that of growth on the anaerobic control plate. Reference strains B. fragilis ATCC 25285 and B. thetaiotaomicron ATCC 29741 were used as controls.
Standard laboratory powders were supplied as follows: tigecycline and piperacillintazobactam (Wyeth, Philadelphia, PA, USA), clindamycin (Pfizer Inc., Groton, CT, USA), metronidazole (Aventis Pharma, S.A., Madrid, Spain), chloramphenicol (SigmaAldrich Química, S.A., Madrid, Spain), cefoxitin and imipenem (Merck Sharp & Dohme de España, S.A., Madrid, Spain) and amoxicillinclavulanate (GlaxoSmithKline S.A., Madrid, Spain). MICs were determined for both the group as a whole and for the individual species.
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Results and discussion |
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Previous reports12,13,17 showed that tigecycline exhibited activity against most isolates of the B. fragilis group tested. This new antibiotic inhibited 89.8% of the strains at a concentration of 8 mg/L with an MIC range of 0.01 to >16 mg/L. A comparison of the MIC50 and MIC90 values of tigecycline among the various species of the group, revealed that B. fragilis, B. thetaiotaomicron and B. vulgatus were the most susceptible (MIC50/MIC90s of 0.51/8 mg/L). Higher tigecycline MICs were observed among the other members of the group. The three isolates resistant to imipenem were inhibited by 0.5, 4 and 8 mg/L of tigecycline, respectively. For the entire group, the MIC50 and MIC90 values of tigecycline are similar to those recently described by Jacobus et al.17 These results, together with its activity against most members of the family of Enterobacteriaceae and enterococci,1416 suggest that tigecycline may be useful in the treatment and prophylaxis of mixed intra-abdominal infections involving these organisms.
Tigecycline has also demonstrated in vivo efficacy in several infection models in animals.2022 A Phase 2 clinical trial demonstrated the efficacy and safety of tigecycline in the treatment of complicated intra-abdominal infections in hospitalized patients.23 Phase 3 clinical trials to evaluate the role of tigecycline in such infections are currently being performed.
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Acknowledgements |
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References |
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