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

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 Escherichia 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 1,680 E. coli clinical isolates screened for resistance to classical tetracyclines, 405 (24%) were minocycline resistant (MIC > or = 8 microg/ml) and 248 (15%) were tetracycline resistant (MIC > or = 8 microg/ml) but susceptible to minocycline (MIC < or = 4 microg/ml). A total of 452 tetracycline-resistant, nonduplicate 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 tet(C), 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 tet(B) plus tet(E) combination the most highly represented, found in 11% of isolates. The susceptibilities of the tetracycline-resistant strains to tigecycline (MIC(90), 0.5 microg/ml), regardless of the encoded tet determinant(s), were comparable to the tigecycline susceptibility of tetracycline-susceptible strains (MIC(90), 0.5 microg/ml). The results provide a current (2002 to 2006) picture of the distribution of common tetracycline resistance determinants encoded in a globally sourced collection of clinical E. coli strains.

Antimicrobial Susceptibility of <i>Escherichia coli</i> Isolated from Feces of Wild Cranes Migrating to Kagoshima, Japan

“…The frequencies in other wild bird reports [5,9,15,20] tended to be a little lower than that of our present results. Tsubokura et al [19] reported that whistling swans harbored multi-antimicrobial-resistant E. coli at a higher rate (80%) than pintail (22%) and black-tailed gulls (46%) among migratory waterfowl in Japan.…”

“…The MINO-resistant strains with MIC value of 32 or 64 μg/ml isolated in the present study harbored the tet(B) gene as well as the previous study [20]. The bla TEM gene was detected in all four ABPC-resistant isolates.…”

“…The aphA1 gene, which is one of the representative genes conferring resistance to KM [18], was detected in our KM-resistant E. coli isolate. These resistance genes have been widely found in the resistant isolates from humans, food and wild animals [2,5,7,18,20].…”

Patterns of Efflux Pump Genes Among Tetracycline Resistance Uropathogenic Escherichia coli Isolates Obtained From Human Urinary Infections

“…However, the most common tet resistance mechanism in E. coli is tetracycline efflux pumps, which exports the drug out of the cell (17). These proteins belong to 6 groups: tetA, tetB, tetC, tetD, tetG, tetH, tetZ , tetE, tetI, and tet30 that are placed in Group 1.…”

“…Chlortetracycline was the first tetracycline identified in the late 1940s (16). However, heavy clinical use of tetracyclines has a major role in the emergence and dissemination of tetracycline resistance among infectious bacteria (17).…”