Symposium section (Tigecycline)In vitro activity of tigecycline against 3989 Gram-negative and Gram-positive clinical isolates from the United States Tigecycline Evaluation and Surveillance Trial (TEST Program; 2004)
Introduction
There continues to be a dramatic rise in resistance to commonly used antimicrobial agents for the treatment of both community-acquired and nosocomially acquired infections (Schito et al., 2000, Henwood et al., 2002). Many of these strains have developed resistance to 2 or more antimicrobial agents curtailing the use of entire classes of antimicrobials. Tigecycline is a novel antimicrobial with an expanded broad spectrum of activity from a new class of compounds, glycylcyclines. Tigecycline inhibits protein synthesis by binding to the 30S ribosomal subunit. Although it is considered to be bacteriostatic, its antibacterial activity is significant and has shown some bactericidal activity against many targeted pathogens (Schito et al., 2000, Abbanat et al., 2003). Tigecycline provides good activity against tetracycline and multidrug-resistant (MDR) Gram-positive pathogens. It has also demonstrated significant broad-spectrum activity against aerobic and anaerobic Gram-positive and Gram-negative microorganisms (Betriu et al., 2002a).
Tigecycline resistance is very infrequent and difficult to induce in the laboratory with a selection frequency observed at less than 10−9 (Betriu et al., 2002b, Dean et al., 2003). Most tetracycline-resistant bacteria with either tetracycline efflux pumps or ribosomal protective features are sensitive to tigecycline (Visalli et al., 2003). In addition, the absence of coresistance for tigecycline with other phenotypes such as vancomycin-resistant enterococci, methicillin-resistant staphylococci (MRSA), penicillin-resistant pneumococci, and Enterobacteriaceae producing extended-spectrum β-lactamases (ESBLs) or AmpC type β-lactamases have previously been reported (Biedenbach et al., 2001).
This study compared the in vitro activity of tigecycline with comparative agents against 3989 of the most commonly encountered nosocomial pathogens and community-acquired respiratory pathogens collected from geographically diverse institutions in the United States. This analysis is a component of the larger Tigecycline Evaluation and Surveillance Trial, a prospective global surveillance program.
Section snippets
Bacterial isolates
All isolates were derived from blood, respiratory tract, urine, skin, wound, body fluids, and other defined sources. Only 1 isolate per patient was accepted into the study. Clinical isolates were collected and tested between January and December 2004 from 23 study centers across the United States. Isolates were identified to the species level and tested at each site by the participating laboratory.
Organism collection, transport, confirmation of organism identification, as well as development
Results
A total of 3989 isolates of Gram-positive aerobes, Enterobacteriaceae, and Gram-negative aerobes were included in this study from 23 collection sites in the United States. Susceptibilities were determined for tigecycline, ampicillin, amoxicillin/clavulanic acid, imipenem, ceftriaxone, levofloxacin, minocycline, and piperacillin/tazobactam against Gram-negative and Gram-positive pathogens. MICs were determined for linezolid, penicillin, and vancomycin against Gram-positive pathogens. MIC results
Discussion
The results of this study demonstrate the high potency of tigecycline against a broad range of pathogens and are generally in agreement with other recent studies (Betriu et al., 2002a, Cercenado et al., 2003, Dean et al., 2003, Fritsche & Jones, 2004, Karlowsky et al., 2002a, Karlowsky et al., 2002b, Kitzis et al., 2004, Mercier et al., 2002, Milatovic et al., 2003, Nannini et al., 2003, Pachon-Ibanez et al., 2004, Postier et al., 2004, Rhomberg et al., 2004, Wallace et al., 2002, Zhang et al.,
Acknowledgments
This study was supported by a grant from Wyeth Pharmaceuticals. IHMA gratefully acknowledges the participation the members of the Tigecycline Evaluation and Surveillance Trial Group, their institutions, and staff.
Since acceptance of this publication, the US Food and Drug Administration (FDA) has granted approval of tigecycline (June 15, 2005) for treatment of complicated skin and skin-structure infections and for complicated intra-abdominal infections produced by designated organisms.
References (27)
- et al.
In vitro antimicrobial activity of GAR-936 tested against antibiotic-resistant gram-positive blood stream infection isolates and strains producing extended-spectrum beta-lactamases
Diagn. Microbiol. Infect. Dis.
(2001) - et al.
Antimicrobial activity of tigecycline (GAR-936) tested against 3498 recent isolates of Staphylococcus aureus recovered from nosocomial and community-acquired infections
Int. J. Antimicrob. Agents
(2004) - et al.
Antimicrobial activity and spectrum of the new glycylcycline, GAR-936 tested against 1,203 recent clinical bacterial isolates
Diagn. Microbiol. Infect. Dis.
(2000) - et al.
Antimicrobial susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated in two successive respiratory seasons in the US
Int. J. Antimicrob. Agents
(2002) - et al.
Results of a multicenter, randomized, open-label efficacy and safety study of two doses of tigecycline for complicated skin and skin-structure infections in hospitalized patients
Clin. Ther.
(2004) - et al.
Results from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme: report of the 2001 data from 15 United States medical centres
Int. J. Antimicrob. Agents
(2004) - et al.
In vitro activities of tigecycline against clinical isolates from Shanghai, China
Diagn. Microbiol. Infect. Dis.
(2004) - et al.
Novel antibacterial agents for the treatment of serious Gram-positive infections
Expert. Opin. Investig. Drugs
(2003) - et al.
In vitro activities of tigecycline (GAR-936) against recently isolated clinical bacteria in Spain
Antimicrob. Agents Chemother.
(2002) - et al.
Comparative in vitro activities of tigecycline (GAR-936) and other antimicrobial agents against Stenotrophomonas maltophilia
J. Antimicrob. Chemother.
(2002)
In vitro activity of tigecycline (GAR-936), a novel glycylcycline, against vancomycin-resistant enterococci and staphylococci with diminished susceptibility to glycopeptides
J. Antimicrob. Chemother.
Performance standard for antimicrobial susceptibility testing
Efflux-mediated resistance to tigecycline (GAR-936) in Pseudomonas aeruginosa PAO1
Antimicrob. Agents Chemother.
Cited by (97)
Staphylococcus aureus
2018, Principles and Practice of Pediatric Infectious DiseasesPenicillins and β-Lactamase Inhibitors
2014, Mandell, Douglas, and Bennett's Principles and Practice of Infectious DiseasesTetracyclines, Glycylcyclines, and Chloramphenicol
2014, Mandell, Douglas, and Bennett's Principles and Practice of Infectious DiseasesPreserving the efficacy of front-line fluoroquinolones through selective use to optimise clinical outcomes
2014, International Journal of Antimicrobial AgentsDetection of vancomycin-resistant enterococci (VRE) at four U.S. wastewater treatment plants that provide effluent for reuse
2014, Science of the Total EnvironmentContemporary potencies of minocycline and tetracycline HCL tested against Gram-positive pathogens: SENTRY Program results using CLSI and EUCAST breakpoint criteria
2013, Diagnostic Microbiology and Infectious Disease