Trends in Activity of Tigecycline against Clostridium spp. From Cardiovascular Sources

C-22 IHMA, Inc.

Trends in Activity of Tigecycline against Clostridium spp. From Cardiovascular Sources(TEST 2008 – 2011)

S.HAWSER1, C. ZAMPALONI1, F. MONTI1, S. BOUCHILLON2, H. LEISTER-TEBBE3

C-222122 Palmer Dr.Schaumburg, IL

60173Tel: 847.303.5003www.ihmainc.com

1IHMA Europe Sàrl, Epalinges, Switzerland2International Health Management Associates, Inc., Schaumburg, IL, USA

3Pfizer Inc., Collegeville, PA, USA

ISAAR Kuala Lumpur 2013 www.ihmainc.com

Results

ISAAR Kuala Lumpur 2013

Revised Abstract Results

Figure 1. Distribution of Clostridium spp.isolates (n = 128) from 2008 – 2011 by country.

Background: Clostridium spp., especially C. difficile, comprise the major causative pathogens ofnosocomial gastrointestinal disorders and in the case of C. difficile have been associated with causinglarge outbreaks of infection including the emergence of “hyper-virulent” strains. More rarely, Clostridium

Revised Abstract

Figure 2. Distribution of Clostridium spp.isolates (n = 128) by infection location.isolates (n = 128) from 2008 – 2011 by country.large outbreaks of infection including the emergence of “hyper-virulent” strains. More rarely, Clostridium

spp. can cause blood infections and more cardiac specific infections. The current study describes trendsin susceptibilities of Clostridium spp. from vascular sources as part of the Tigecycline EvaluationSurveillance Trial (TEST). Methods: A total of 128 isolates of Clostridium spp. were collected fromcardiovascular sources including blood, heart tissue, blood vessels from 2008 to 2011. The majority of theisolates were not speciated and those with species identified had <6 isolates other than C. perfringens. All

isolates (n = 128) by infection location.

isolates were not speciated and those with species identified had <6 isolates other than C. perfringens. Allisolates were from Europe. MICs were performed as specified by CLSI by agar dilution and interpretedper CLSI guidelines. FDA guidelines were used for tigecycline (4). Results:

Figure 3. Susceptibility trends of Clostridium spp. isolates (n = 128) to tigecycline and comparators.Figure 3. Susceptibility trends of Clostridium spp. isolates (n = 128) to tigecycline and comparators.

Conclusions: During 2008 to 2011, susceptibilities of Clostridium spp. from cardiovascular sources totigecycline, meropenem, metronidazole and piperacillin/tazobactam all remained high. Susceptibilities to

Introduction

tigecycline, meropenem, metronidazole and piperacillin/tazobactam all remained high. Susceptibilities toboth penicillin and clindamycin were generally lower and more variable.

Susceptibility patterns of anaerobes have become less predictable owing to increasing antibacterial resistance.Emergence of highly virulent or multidrug-resistant strains is challenging the current therapy. To counteractthese trends, regular resistance surveillance in anaerobes, rational antibiotic use, and evaluation of newtreatment alternatives are important. Management of anaerobic infections encompasses surgical procedures,treatment alternatives are important. Management of anaerobic infections encompasses surgical procedures,antibacterial therapy and adjuncts. At present, metronidazole, carbapenems, and beta-lactam/beta-lactamaseinhibitor combinations exhibit the most promising activity, though reports of increasing resistance to theseagents are emerging (1). Recent data from the Tigecycline European Surveillance Trial (TEST) has shown thatin addition to the above agents, tigecycline also exhibits promising activity and high susceptibilities against awide range of anaerobes (2). Clostridium spp., comprise the major causative pathogens of nosocomialwide range of anaerobes (2). Clostridium spp., comprise the major causative pathogens of nosocomialgastrointestinal disorders. However, these species can be associated with much rarer events includinginfections associated with the cardiovascular system. The current study describes data from TEST, from 2008to 2011, on the activity of tigecycline and comparators against 128 Clostridium spp. isolates fromcardiovascular sources.cardiovascular sources.

Clinical isolates:

Materials & Methods

Clinical isolates: A total of 128 clinical isolates of Clostridium spp. were collected during 2008 – 2011 fromcardiovascular sources. Isolates were identified to the species level. All organisms were deemed clinicallysignificant by local participant criteria. Isolate inclusion was independent of medical history, antimicrobialuse, age or gender. All sites identified each study isolate utilizing local laboratory criteria. All isolates werefrom the period 2008 – 2011 and originated from various countries in Europe and from multiple clinicalfrom the period 2008 – 2011 and originated from various countries in Europe and from multiple clinicalsources and locations (Figure 1). Only susceptibility data for Clostridium spp. isolates from cardiovascularsources are reported (Figure 2 and 3).

Susceptibility testing: All isolates were sent to a single reference laboratory for evaluation. Minimuminhibitory concentrations (MICs) were determined by agar dilution as specified by the Clinical and

References

inhibitory concentrations (MICs) were determined by agar dilution as specified by the Clinical andLaboratory Standards Institute (CLSI) (3). Susceptibility results were interpreted using clinical breakpointspublished by the CLSI or FDA (3, 4).

Conclusions

1. Boyanova, L., R. Kolarov, and I. Mitov. 2007. Antimicrobial resistance and the management of anaerobicinfections. Exp. Rev. Anti. Infect. Ther. 5: 685-701.

2. Nagy, E., and M.J. Dowzicky. 2010. In vitro activity of tigecycline and comparators against a European

References

Susceptibility percentages were highest for meropenem, piperacillin/tazobactam andtigecycline, with percent susceptibilities of 100 for each drug for each year of the current

Conclusions

2. Nagy, E., and M.J. Dowzicky. 2010. In vitro activity of tigecycline and comparators against a Europeancompilation of anaerobes collected as part of the Tigecycline Evaluation and Surveillance Trial (TEST).Scand. J. Infect. Dis. 42: 33-38.

3. Clinical and Laboratory Standards Institute. Methods for Antimicrobial Susceptibility Tests of AnaerobicBacteria. Seventh Edition: Approved Standard M11-A7: CLSI, 940 West Valley Road, Suite 1400, Wayne,

tigecycline, with percent susceptibilities of 100 for each drug for each year of the currentreport.

The majority of isolates (>90%) were susceptible to metronidazole with lowestsusceptibility of 94% in 2009 to 100% in 2010 and 2011.

Pennsylvania 19087-1898 USA, 2007.4. Tygacil®, 2010. Federal Drug Administration (FDA) product information. Pfizer, Inc., Collegeville, PA, USA.

Acknowledgements

susceptibility of 94% in 2009 to 100% in 2010 and 2011. Susceptibility to clindamycin was highly variable with only 50% of isolates clindamycin-

susceptible in 2010 and 88% of isolates in 2009 and 2011. In a similar fashion,susceptibilities to penicillin were also variable ranging from 75% in 2011 to 88% in 2010.

We gratefully acknowledge the contributions of the investigators, laboratory personnel, and all members of theTigecycline Evaluation and Surveillance Trial group. This study was sponsored by Pfizer Inc.

Acknowledgements susceptibilities to penicillin were also variable ranging from 75% in 2011 to 88% in 2010. Despite variations in susceptibility to clindamycin and penicillin, all other agents,

including tigecycline, had consistently high susceptibilities.