Bacteroides fragilis fragilis P1208 IHMA, Inc. 2122 Palmer Dr. Schaumburg, IL 60173 Schaumburg, IL 60173 USA Tel: +1.847.303.5003 Fax: +1.847.303.5601 M. Hackel 1 , S. Bouchillon 1 , R. Badal 1 , S. Hawser 2 , D. Hoban 1 , M. Dowzicky 3 1 International Health Management Associates, Inc., Schaumburg, IL, USA 2 IHMA Europe Sàrl, Epalinges, Switzerland 2 IHMA Europe Sàrl, Epalinges, Switzerland 3 Pfizer Inc., Collegeville, PA, USA Results Revised Abstract Results Background: Bacteroides fragilis group organisms are important anaerobic co-pathogens in many polymicrobial infections. Reduced Revised Abstract anaerobic co-pathogens in many polymicrobial infections. Reduced susceptibility to carbapenems in B. fragilis group is due primarily to the metallo-beta-lactamase CfiA gene (meropenem MICs 1-4) with high-level resistance secondary to acquired upstream insertion sequences (IS) Figure 1. Distribution of all isolates (n = 1,842) by location. Figure 5. Percent of all isolates (n = 1,842) and isolates with meropenem MICs ≥1 mg/L (n = 154) by infection source. resistance secondary to acquired upstream insertion sequences (IS) causing expression of CfiA (MICs >16). Methods: The Tigecycline European Surveillance Trial (TEST) evaluated 154/1842 (8.4%) B. fragilis group organisms with reduced susceptibility to carbapenems 154) by infection source. group organisms with reduced susceptibility to carbapenems (meropenem MIC ≥1 mg/L) from a collection of anaerobes spanning four years, 2007 - 2010. The isolates were identified to the species level at the participating sites and confirmed by a central laboratory . MICs were determined by the central laboratory using agar dilution according to CLSI guidelines. Results: MIC 90 (mg/L)/% susceptible* of B. fragilis group with meropenem MICs of ≥1 mg/L by year (n/n total B. fragilis group isolates): group isolates): 2007(40/506) 2008(33/430) 2009(43/508) 2010(38/398) Tigecycline 2/100 4/97 2/98 4/92 Figure 6. Percent susceptibility of all isolates (n = 1,842) to tigecycline and comparators from Tigecycline 2/100 4/97 2/98 4/92 Metronidazole 2/100 2/100 1/100 1/100 Pip-Tazo 16/80 32/85 64/79 32/84 Meropenem 8/70 8/55 >8/44 >8/42 *EUCAST breakpoints used where available; CLSI breakpoint used for cefoxitin; FDA breakpoint used for = 1,842) to tigecycline and comparators from 2007 – 2010. Meropenem 8/70 8/55 >8/44 >8/42 Clindamycin >8/65 >8/61 >8/65 >8/55 Cefoxitin >32/53 >32/58 >32/56 >32/53 *EUCAST breakpoints used where available; CLSI breakpoint used for cefoxitin; FDA breakpoint used for tigecycline (Tygacil ® , 2009). Conclusions: B. fragilis group isolates with reduced susceptibility to meropenem increased significantly between 2007-2010 (p<0.05, Fisher’s exact test). Greater than 92% of these isolates were susceptible to tigecycline and metronidazole, with no significant reduction in susceptibility for any of the compounds tested over the four years of Figure 2. Distribution of isolates with meropenem MICs ≥1 mg/L (n = 154) by susceptibility for any of the compounds tested over the four years of analysis. meropenem MICs ≥1 mg/L (n = 154) by location. Introduction Susceptibility patterns of anaerobes have become less predictable owing to increasing antibacterial resistance. Emergence of highly virulent or multidrug-resistant strains is further challenging current therapies. To counteract these trends, regular resistance surveillance in anaerobes, rational antibiotic use and evaluation of new treatment alternatives are important. Figure 7. Percent susceptibility of isolates with use and evaluation of new treatment alternatives are important. Management of anaerobic infections encompasses surgical procedures, antibacterial therapy and adjuncts. At present, metronidazole, penems, beta-lactam/beta-lactamase inhibitor Figure 7. Percent susceptibility of isolates with meropenem MICs ≥1 mg/L (n = 154) to tigecycline and comparators from 2007 – 2010. metronidazole, penems, beta-lactam/beta-lactamase inhibitor combinations exhibit the most promising activity though reports of increasing resistance to these agents are emerging (1). Recent data from the the Tigecycline Evaluation and Surveillance Trial tigecycline and comparators from 2007 – 2010. data from the the Tigecycline Evaluation and Surveillance Trial (TEST) has shown that in addition to the above agents, tigecycline also exhibits promising activity and high susceptibilities against a wide range of anaerobes (2). The susceptibilities against a wide range of anaerobes (2). The current study describes data from T.E.S.T, from 2007 to 2010, based on the activity of tigecycline and comparators against 1,842 isolates of Bacteroides spp. clinical isolates from various 1,842 isolates of Bacteroides spp. clinical isolates from various infection sources. Figure 3. Percent of all isolates (n = 1,842) and isolates with meropenem MICs ≥1 mg/L isolates with meropenem MICs ≥1 mg/L (n = 154) by location. Materials & Methods Conclusions Clinical isolates: A total of 1,842 clinical isolates of Bacteroides spp. were collected during 2007 - 2010. Isolates were identified to the species level and tested at each participating laboratory . All o Of the total of 1,842 clinical isolates Conclusions to the species level and tested at each participating laboratory . All organisms were deemed clinically significant by local participant criteria. Isolate inclusion was independent of medical history, antimicrobial use, age or gender . All sites identified each study collected from 2007 – 2010, 154 (8.4%) had meropenem MICs ≥1 mg/L. the antimicrobial use, age or gender . All sites identified each study isolate utilizing local laboratory criteria. All isolates were from the period 2007 - 2010 and originated from various infection sources and loc ations. majority of all isolates and isolates with meropenem MICs ≥ mg/L were from and loc ations. Susceptibility testing: All isolates were sent to a single reference laboratory for evaluation. Minimum inhibitory inpatient hospital locations o The 1,842 isolates were most commonly reference laboratory for evaluation. Minimum inhibitory concentrations (MICs) were determined by agar dilution as specified by the Clinical and Laboratory Standards Institute (CLSI) (3) Susceptibility was determined using clinical isolated from skin and skin structure infections (51%) followed by gastrointestinal infection (25%). Isolates Figure 4. Distribution of all isolates (n = 1,842) (CLSI) (3) Susceptibility was determined using clinical breakpoints published by EUCAST (4). References gastrointestinal infection (25%). Isolates with meropenem MICs ≥1 mg/L were almost most commonly isolated from these and isolates with meropenem MICs ≥1 mg/L (n = 154) by infection source. 1. Boyanova, L., R. Kolarov, and I. Mitov. 2007. Antimicrobial resistance and the management of anaerobic infections. Exp. Rev. Anti. Infect. Ther. 5: 685-701. 2. Nagy, E., and M.J. Dowzicky . 2010. In vitro activity of tigecycline and almost most commonly isolated from these sources (47% and 21%, respectively). o Analysis of susceptibility to all isolates for 2. Nagy, E., and M.J. Dowzicky . 2010. In vitro activity of tigecycline and comparators against a European compilation of anaerobes collected as part of the Tigecycline Evaluation and Surveillance Trial (TEST). Scand. J. Infect. Dis. 42: 33-38. o Analysis of susceptibility to all isolates for all years of the study showed that percent susceptibility to tigecycline, metronidazole, J. Infect. Dis. 42: 33-38. 3. Clinical and Laboratory Standards Institute. Methods for Antimicrobial Susceptibility Tests of Anaerobic Bacteria. Seventh Edition: Approved Standard M11-A7: CLSI, 940 West Valley Road, Suite 1400, Wayne, susceptibility to tigecycline, metronidazole, piperacillin-tazobactam and meropenem remained ≥90% however decreases during Pennsylvania 19087-1898 USA, 2007. 4. The European Committee on Antimicrobial Susceptibility Testing – EUCAST Clinical Breakpoints; http://www.eucast.org/clinical_breakpoints remained ≥90% however decreases during the study period were noted for meropenem (98% in 2007 to 94% in 2010). Acknowledgements (98% in 2007 to 94% in 2010). o Against isolates with meropenem MICs ≥1 mg/L, only tigecycline and metronidazole We gratefully acknowledge the contributions of the investigators, laboratory personnel, and all members of the Tigecycline European Study Trial program group. This study Acknowledgements mg/L, only tigecycline and metronidazole exhibited percent susceptibility of ≥90% for the whole study period. and all members of the Tigecycline European Study Trial program group. This study was sponsored by Pfizer, Inc. the whole study period.