Antimicrobial Susceptibility Studies
Tigecycline activity tested against antimicrobial resistant surveillance subsets of clinical bacteria collected worldwide (2011)

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Abstract

Tigecycline was approved by the United States Food and Drug Administration in 2005 and has generally retained activity against resistant Gram-positive and Gram-negative organisms. We monitored the in vitro activity of this glycylcycline in 2011 for continued potency worldwide. A total of 22,005 unique clinical isolates were consecutively collected in North America (NA; 9232 isolates), Europe (EU; 6776), Latin America (LA; 2016), and Asia-Pacific region (APAC, 3981) and tested for susceptibility according to the reference broth microdilution method recommendations against tigecycline and numerous comparators. Oxacillin (methicillin) resistance rates in methicillin-resistant Staphylococcus aureus (MRSA) were 49.3%, 30.2%, 42.9%, and 37.8%, and vancomycin resistance rates in enterococci (VRE) were 27.0%, 11.3%, 6.3%, and 4.0% in NA, EU, LA, and APAC, respectively. All MRSA (2839) and >99% of VRE were susceptible to tigecycline. Among Escherichia coli, extended-spectrum β-lactamase (ESBL) rates varied from 12.6% in the NA to 57.4% in APAC, and only one strain was nonsusceptible to tigecycline. Tigecycline was active against ESBL phenotype (96.5–98.4% susceptible) and meropenem-nonsusceptible Klebsiella spp. (94.3–100.0% susceptible). Only 4 of 213 (1.9%) meropenem-nonsusceptible Klebsiella spp. were tigecycline-nonsusceptible, all with tigecycline minimum inhibitory concentration (MIC) of 4 μg/mL (intermediate). Among ceftazidime-nonsusceptible Enterobacter spp., 94.7–98.2% were susceptible to tigecycline. Meropenem-nonsusceptible Acinetobacter spp. varied from 51.2% in NA to 80.9% in APAC; and 83.8% (LA) to 93.9% (APAC) of strains were inhibited at a tigecycline MIC of ≤2 μg/mL. Tigecycline showed potent activity against Stenotrophomonas maltophilia (89.3–98.3% inhibited at ≤2 μg/mL). In summary, tigecycline has sustained potent activity and a broad-spectrum against clinically important bacteria causing infections worldwide, including multidrug-resistant organism subsets.

Introduction

Tigecycline was approved by the United States Food and Drug Administration (USA-FDA; 2005) for acute bacterial skin and skin structure infections and complicated intra-abdominal infections, and in 2009 for treatment of community-acquired bacterial pneumonia (Noskin, 2005, Tygacil Package Insert, 2011). Sentinel monitoring through surveillance programs, including the global SENTRY Antimicrobial Surveillance Program, has provided information on the continuing activity of tigecycline against antimicrobial-resistant Gram-positive and Gram-negative bacteria over time (Castanheira et al., 2010, Farrell et al., 2010, Mendes et al., 2008, Sader et al., 2011b).

The occurrence of multidrug-resistant (MDR) Gram-positive and Gram-negative bacteria continues to increase. This problem has fostered recommendations from professional societies such as the Infectious Disease Society for America (IDSA) and governmental agencies to encourage the development of new antimicrobial agents (Boucher et al., 2009, IDSA, 2010). However, therapeutic options for the treatment of MDR pathogens remain limited as diverse regional and local resistance patterns evolve. In this study, the activity of tigecycline tested against resistant subsets of bacteria from the SENTRY Program was evaluated.

Section snippets

Materials and methods

A total of 22,005 unique clinical isolates were consecutively collected (2011) in North America (NA; 9232 isolates [42.0% of total]), Europe and Mediterranean region (EU; 6776 [30.8%]), Latin America (LA; 2016 [9.2%]) and Asia-Pacific region (APAC, 3981 [18.1%]). Countries sampled were USA and Canada in NA; Belgium, Czech Republic, France, Germany, Greece, Ireland, Israel, Italy, Poland, Portugal, Romania, Russia, Slovakia, Slovenia, Spain, Sweden, Turkey, United Kingdom, and Ukraine in EU;

Results

The activity of tigecycline (MIC distributions) tested against resistant surveillance subsets of clinical bacteria collected worldwide and the corresponding susceptible subsets are summarized in Table 1. Tigecycline was highly active against Gram-positive organisms (MIC50, ≤0.03–0.06 μg/mL and MIC90, 0.06–0.12 μg/mL) and tigecycline MIC distributions for MRSA, VRE and penicillin-resistant S. pneumoniae were very similar to those of their susceptible counterparts. Among the Enterobacteriaceae

Discussion

The prevalence of resistance to key therapeutic antimicrobial agents continues to increase among the bacterial species most frequently isolated in the clinical settings; and infections caused by resistant organisms remain difficult to treat. Monitoring antimicrobial resistance through international, multicenter surveillance programs remains important to detect regional variations in resistance patterns and to guide empirical antimicrobial therapy. The SENTRY Program annually evaluates the

Acknowledgments

The authors would like to thank all participating centers worldwide for contributing isolates to this surveillance protocol. All co-authors are employees of JMI Laboratories who were paid consultants to Pfizer in connection with the development of this manuscript. Laboratory testing of clinical isolates was performed by JMI Laboratories via the SENTRY Antimicrobial Surveillance platform and funded by Pfizer Inc.

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