Bacteroidesfragilisfragilis

P1208 IHMA, Inc.2122 Palmer Dr.

Schaumburg, IL 60173Schaumburg, IL 60173USA

Tel: +1.847.303.5003Fax: +1.847.303.5601

M. Hackel1, S. Bouchillon1, R. Badal1, S. Hawser2, D. Hoban1, M. Dowzicky3

1International Health Management Associates, Inc., Schaumburg, IL, USA2IHMA Europe Sàrl, Epalinges, Switzerland

Fax: +1.847.303.56012IHMA Europe Sàrl, Epalinges, Switzerland

3Pfizer Inc., Collegeville, PA, USA

ResultsRevised Abstract Results

Background: Bacteroides fragilis group organisms are importantanaerobic co-pathogens in many polymicrobial infections. Reduced

Revised Abstract

anaerobic co-pathogens in many polymicrobial infections. Reducedsusceptibility to carbapenems in B. fragilis group is due primarily to themetallo-beta-lactamase CfiA gene (meropenem MICs 1-4) with high-levelresistance 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) andisolates 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 TigecyclineEuropean Surveillance Trial (TEST) evaluated 154/1842 (8.4%) B. fragilisgroup 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 fouryears, 2007 - 2010. The isolates were identified to the species level atthe participating sites and confirmed by a central laboratory. MICs werethe participating sites and confirmed by a central laboratory. MICs weredetermined by the central laboratory using agar dilution according toCLSI guidelines. Results: MIC90 (mg/L)/% susceptible* of B. fragilisgroup with meropenem MICs of ≥1 mg/L by year (n/n total B. fragilisgroup 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 from2007 – 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 fortigecycline (Tygacil®, 2009).

Conclusions: B. fragilis group isolates with reduced susceptibility tomeropenem increased significantly between 2007-2010 (p<0.05, Fisher’smeropenem increased significantly between 2007-2010 (p<0.05, Fisher’sexact test). Greater than 92% of these isolates were susceptible totigecycline and metronidazole, with no significant reduction insusceptibility for any of the compounds tested over the four years of

Figure 2. Distribution of isolates withmeropenem MICs ≥1 mg/L (n = 154) bysusceptibility for any of the compounds tested over the four years of

analysis.meropenem MICs ≥1 mg/L (n = 154) bylocation.

Introduction

Susceptibility patterns of anaerobes have become lesspredictable owing to increasing antibacterial resistance.Emergence of highly virulent or multidrug-resistant strains isEmergence of highly virulent or multidrug-resistant strains isfurther challenging current therapies. To counteract these trends,regular resistance surveillance in anaerobes, rational antibioticuse and evaluation of new treatment alternatives are important.

Figure 7. Percent susceptibility of isolates withuse and evaluation of new treatment alternatives are important.Management of anaerobic infections encompasses surgicalprocedures, antibacterial therapy and adjuncts. At present,metronidazole, penems, beta-lactam/beta-lactamase inhibitor

Figure 7. Percent susceptibility of isolates withmeropenem MICs ≥1 mg/L (n = 154) totigecycline and comparators from 2007 – 2010.metronidazole, penems, beta-lactam/beta-lactamase inhibitor

combinations exhibit the most promising activity though reports ofincreasing resistance to these agents are emerging (1). Recentdata 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 highsusceptibilities against a wide range of anaerobes (2). Thesusceptibilities against a wide range of anaerobes (2). Thecurrent study describes data from T.E.S.T, from 2007 to 2010,based on the activity of tigecycline and comparators against1,842 isolates of Bacteroides spp. clinical isolates from various1,842 isolates of Bacteroides spp. clinical isolates from variousinfection sources. Figure 3. Percent of all isolates (n = 1,842) and

isolates with meropenem MICs ≥1 mg/Lisolates with meropenem MICs ≥1 mg/L(n = 154) by location.Materials & Methods

Conclusions

Clinical isolates: A total of 1,842 clinical isolates of Bacteroidesspp. were collected during 2007 - 2010. Isolates were identifiedto the species level and tested at each participating laboratory. All

o Of the total of 1,842 clinical isolates

Conclusionsto the species level and tested at each participating laboratory. Allorganisms were deemed clinically significant by local participantcriteria. Isolate inclusion was independent of medical history,antimicrobial use, age or gender. All sites identified each study o Of the total of 1,842 clinical isolates

collected from 2007 – 2010, 154 (8.4%)had meropenem MICs ≥1 mg/L. the

antimicrobial use, age or gender. All sites identified each studyisolate utilizing local laboratory criteria. All isolates were from theperiod 2007 - 2010 and originated from various infection sourcesand loc ations.

had meropenem MICs ≥1 mg/L. themajority of all isolates and isolates withmeropenem MICs ≥ mg/L were from

and loc ations.

Susceptibility testing: All isolates were sent to a singlereference laboratory for evaluation. Minimum inhibitory

inpatient hospital locationso The 1,842 isolates were most commonly

reference laboratory for evaluation. Minimum inhibitoryconcentrations (MICs) were determined by agar dilution asspecified by the Clinical and Laboratory Standards Institute(CLSI) (3) Susceptibility was determined using clinical isolated from skin and skin structure

infections (51%) followed bygastrointestinal infection (25%). Isolates

Figure 4. Distribution of all isolates (n = 1,842)

(CLSI) (3) Susceptibility was determined using clinicalbreakpoints published by EUCAST (4).

Referencesgastrointestinal infection (25%). Isolateswith meropenem MICs ≥1 mg/L werealmost most commonly isolated from these

Figure 4. Distribution of all isolates (n = 1,842)and isolates with meropenem MICs ≥1 mg/L(n = 154) by infection source.

1. Boyanova, L., R. Kolarov, and I. Mitov. 2007. Antimicrobial resistanceand 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 thesesources (47% and 21%, respectively).

o Analysis of susceptibility to all isolates for2. Nagy, E., and M.J. Dowzicky. 2010. In vitro activity of tigecycline andcomparators against a European compilation of anaerobes collected aspart of the Tigecycline Evaluation and Surveillance Trial (TEST). Scand.J. Infect. Dis. 42: 33-38.

o Analysis of susceptibility to all isolates forall years of the study showed that percentsusceptibility to tigecycline, metronidazole,J. Infect. Dis. 42: 33-38.

3. Clinical and Laboratory Standards Institute. Methods for AntimicrobialSusceptibility Tests of Anaerobic Bacteria. Seventh Edition: ApprovedStandard M11-A7: CLSI, 940 West Valley Road, Suite 1400, Wayne,

susceptibility to tigecycline, metronidazole,piperacillin-tazobactam and meropenemremained ≥90% however decreases during

Standard M11-A7: CLSI, 940 West Valley Road, Suite 1400, Wayne,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 duringthe 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 metronidazoleexhibited percent susceptibility of ≥90% forthe 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.