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Antimicrob. Agents Chemother. doi:10.1128/AAC.00625-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Occurrence of Tetracycline Resistance Genes Among Escherichia coli Isolates from the Phase 3 Clinical Trials for Tigecycline

Margareta Tuckman, Peter J. Petersen, Anita Howe, Mark Orlowski, Stan Mullen, Karen Chan, Patricia A. Bradford, and C. Hal Jones*

Infectious Diseases Discovery Research and Vaccines Discovery Research, Wyeth Research, Pearl River, NY

* To whom correspondence should be addressed. Email: jonesh3{at}wyeth.com.


   Abstract

Tigecycline, a member of the glycylcycline class of antibiotics, was designed to maintain the antibacterial spectrum of the tetracyclines while overcoming the classic mechanisms of tetracycline resistance. The current study was designed to monitor the prevalence of the tet(A), tet(B), tet(C) tet(D), tet(E) and tet(M) resistance determinants in E. coli isolates collected during the worldwide tigecycline phase 3 clinical trials. A subset of strains were also screened for the tet(G), tet(K), tet(L), and tet(Y) genes. Of the 1680 E. coli clinical isolates screened for resistance to classical tetracyclines, 405 (24 %) were minocycline-resistant (MIC ≥8 µg/mL) and 248 (15 %) were tetracycline-resistant (MIC ≥8 µg/mL) but susceptible to minocycline (MIC ≤4 µg/mL). 452 tetracycline resistant, non-duplicate isolates were positive by PCR for at least one of the six tetracycline resistance-determinants examined. Over half of the isolates encoding a single determinant were positive for tet(A) (26%) or tet(B) (32%) with tetC), tet(D), tet(E), and tet(M) collectively found in 4% of isolates. Approximately 33% of the isolates were positive for more than one resistance determinant with the tetB) plus tet(E) combination the most highly represented, found in 11% of isolates. The susceptibilities of the tetracycline resistant strains to tigecycline (MIC90 0.5 µg/mL), regardless of the encoded tet determinant(s), were comparable to the tigecycline susceptibility of tetracycline susceptible strains (MIC90 0.5 µg/mL). The results provide a current (2002-2006), picture of the distribution of common tetracycline resistance determinants encoded in a globally sourced collection of clinical E. coli strains.




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