IHMA, Inc. 2122 Palmer Drive Antibiotic Susceptibility Profiles of Recent European Gram-negative Anaerobes Schaumburg, IL 60173 USA P0679 M. Hackel1, M. Bailey-Person1, D. Sahm1, H. Leister-Tebbe2 1 Phone: +1.847.303.5003 International Health Management Associates, Inc., Schaumburg, IL, USA Fax: +1.847.303.5601 2 Pfizer Inc., Collegeville, PA, USA www.ihmainc.com Revised Abstract Results Conclusions Background: Anaerobic infections tend to be polymicrobial, and are often treated empirically with broad-spectrum therapies. Continual monitoring is required to provide clinicians with accurate and up-to-date data on which to base Figure 1. Distribution of Gram-negative Anaerobes by Country, TEST 2013-2015. Table 1. Bacteroides and Prevotella species Included in Study. • Tigecycline, meropenem and empiric treatment. The Tigecycline European Surveillance Trial (TEST) has monitored susceptibility patterns of metronidazole showed excellent in vitro Organism N Organism N anaerobic bacteria since 2004. In this study we evaluated tigecycline and five comparator compounds against recent Czech Republic activity against B. fragilis group European anaerobic isolates. Material/methods: 1,950 gram-negative anaerobic pathogens (1,276 Bacteroides fragilis Bacteroides fragilis group 1,276 Prevotella nigrescens 42 Sweden Italy organisms isolated from European group and 674 Prevotella spp.) were collected from 2013-2015 from 18 sites in 8 countries in Europe (Belgium, Czech 9% Bacteroides fragilis 647 Prevotella intermedia 31 Republic, France, Germany, Hungary, Italy, Spain, and Sweden). Organism identification was confirmed at a central 4% 0.1% hospitals, with >93% susceptible. laboratory (IHMA, Inc., Schaumburg, IL, US), and MIC values were determined using agar dilution following CLSI Hungary Bacteroides thetaiotaomicron 196 Prevotella oris 29 Clindamycin, piperacillin-tazobactam and guidelines. Percent susceptible was calculated using EUCAST (clindamycin, meropenem, metronidazole, and Bacteroides ovatus 141 Prevotella nanceinsis 18 cefoxitin exhibited lower activity, with only piperacillin-tazobactam), CLSI (cefoxitin) and FDA (tigecycline) breakpoints. Results: In vitro activity (MIC90 and 10% percent susceptible [%S]) is shown in the table. Belgium Bacteroides vulgatus 127 Prevotella, non-speciated 15 65% of B. fragilis group isolates 13% Parabacteroides distasonis 62 Prevotella oralis 14 susceptible to clindamycin. Antimicrobial B. fragilis group (1,276) Prevotella spp. (674) Germany Bacteroides uniformis 58 Prevotella bergensis 9 MIC90 % S MIC90 % S • Tigecycline, cefoxitin, meropenem, Tigecycline 4 93.3 0.5 99.4 Bacteroides caccae 29 Prevotella buccalis 9 30% metronidazole and piperacillin- Cefoxitin 32 80.2 4 99.0 Spain Bacteroides stercoris 14 Prevotella salivae 9 Clindamycin > 8 64.7 > 8 72.6 tazobactam each inhibited >99% of Meropenem 1 94.8 0.12 100 15% Bacteroides eggerthii 1 Prevotella baroniae 8 Prevotella spp. at their susceptible Metronidazole 1 99.9 2 100 Bacteroides fragilis Group 2 1 Prevotella corporis 7 Piperacillin Tazobactam 16 85.9 0.12 99.3 breakpoints, whereas clindamycin had France Prevotella species 674 Prevotella pallens 7 lower activity, with only 73% susceptible. Conclusions: Tigecycline, meropenem and metronidazole showed excellent in vitro activity against B. fragilis group 19% Prevotella bivia 190 Prevotella histicola 6 organisms isolated from European hospitals, with >93% susceptible. Clindamycin, piperacillin-tazobactam and • Differences in susceptibilities between cefoxitin exhibited lower activity, with only 65% of B. fragilis group isolates susceptible to clindamycin. Tigecycline, Prevotella buccae 94 Prevotella maculosa 2 genera highlight the need for continued cefoxitin, meropenem, metronidazole and piperacillin-tazobactam each inhibited >99% of Prevotella spp. at their Prevotella melaninogenica 80 Prevotella heparinolytica 1 EUCAST susceptible breakpoints, whereas clindamycin had lower activity, with only 73% susceptible. Differences in evaluation of antimicrobial susceptibilities susceptibilities between genera highlight the need for continued evaluation of antimicrobial susceptibilities of gram- Prevotella denticola 59 Prevotella loescheii 1 of gram-negative anaerobic organisms to negative anaerobic organisms to aid in the selection of empiric therapy and monitor resistance trends. Prevotella disiens 42 Prevotella oulorum 1 aid in the selection of empiric therapy and Introduction monitor resistance trends. Anaerobic infections tend to be polymicrobial, and are often treated empirically with broad-spectrum therapies. Susceptibility to the most commonly used antimicrobials varies Figure 2. Distribution of Gram-negative Anaerobes by Specimen Source, TEST Table 2. In Vitro Activity of Tigecycline and Conparators Against Gram- among genera and even the species within a genus. Although there are many 2013-2015. negative Anaerobes from Europe. References and Acknowledgments: antimicrobial agents with activity against anaerobic bacteria, antimicrobial resistance 1. Nagy, E. (2010). Anaerobic infections. Drugs, 70(7), continues to rise [1]. Difficulty in isolating primary anaerobic pathogens and limited Organism (N) Antimicrobial MIC50 MIC90 %S %I %R Range 841-858. susceptibility testing by microbiology laboratories often results in the use of empirical Blood Other Genitourinary Respiratory B. fragilis group (1,276) Tigecycline 0.5 4 93.3 4.3 2.4 ≤ 0.06 - 32 2. Clinical and Laboratory Standards Institute. Methods treatment. For this reason, it is important to provide surveillance data to guide providers in 6% 2% the most effective choices for anti-anaerobic therapy. The Tigecycline European Gastro-intestinal 6% 6% Cefoxitin 8 32 80.2 14.8 5.0 ≤ 2 - > 32 for antimicrobial susceptibility testing of anaerobic Surveillance Trial (TEST), a longitudinal surveillance study, has been monitoring the bacteria; approved standard. 9th ed. M11–A9. Wayne, 6% PA: CLSI; 2012. activity of a number of antimicrobial agents against both gram-negative and gram-positive Bone Clindamycin 2 > 8 64.7 0 35.3 ≤ 0.25 - > 8 anaerobic organisms in Europe since 2007. This study reports the susceptibility data for 1% Meropenem 0.12 1 94.8 4.6 0.7 ≤ 0.06 - > 8 3. European Committee on Antimicrobial Susceptibility select gram-negative anaerobic bacteria from European hospitals from 2013 through Testing (EUCAST). 2016. Breakpoint tables for 2015. Metronidazole 0.5 1 99.9 0 0.1 ≤ 0.12 - 8 interpretation of MICs and zone diameters, version 3.0. http://www.eucast.org. Piperacillin Tazobactam 1 16 85.9 8.1 6.0 ≤ 0.06 - > 64 Materials & Methods 4. Clinical and Laboratory Standards Institute. Prevotella spp. (674) Tigecycline 0.12 0.5 99.4 0.6 0 ≤ 0.06 - 8 Performance Standards for Antimicrobial Susceptibility 1,950 gram-negative anaerobic pathogens (1,276 Bacteroides fragilis group and 674 Wound Testing; approved standard. 26th ed. M1100S–A26. Prevotella spp.) were collected over the years 2013-2015 from 18 sites in eight countries 23% Cefoxitin ≤ 2 4 99.0 0.9 0.2 ≤ 2 - > 32 Wayne, PA: CLSI; 2016. in Europe (Belgium, Czech Republic, France, Germany, Hungary, Italy, Spain, and Clindamycin ≤ 0.25 > 8 72.6 0 27.5 ≤ 0.25 - > 8 5. Tygacil®, 2010. Federal Drug Administration, Product Sweden). Only one isolate per patient was accepted. Sites were requested to send in a Information. Pfizer Inc., Collegeville, PA, USA. specific number of a select group of species. Isolates were identified to genus and Meropenem ≤ 0.06 0.12 100 0 0 ≤ 0.06 - 1 species by the local laboratory, and sent to the central laboratory (IHMA, Inc., Metronidazole 1 2 100 0 0 ≤ 0.12 - 4 We gratefully acknowledge the contributions of the Schaumburg, IL, US) for confirmation of identification and MIC testing. MIC values for investigators, laboratory personnel, and all members tigecycline and five comparators were determined by agar dilution following CLSI Piperacillin Tazobactam ≤ 0.06 0.12 99.3 0.6 0.2 ≤ 0.06 - 64 of the Tigecycline European and Surveillance Trial guidelines [2]. Percent susceptible (%S) was calculated using EUCAST (clindamycin, Body fluid group. This study was sponsored by Pfizer Inc. IHMA meropenem, metronidazole, and piperacillin-tazobactam) [3], CLSI (cefoxitin) [4] or FDA is a clinical research organization that has been 50% contracted by Pfizer Inc, to manage the TEST (tigecycline) [5] breakpoints. program.