Diagnostic PCR analysis of the occurrence of methicillin and tetracycline resistance genes among Staphylococcus aureus isolates from phase 3 clinical trials of tigecycline for complicated skin and skin structure infections.
Diagnostic PCR assays were developed to track common genetic determinants of oxacillin resistance as well as resistance to classical tetracyclines in Staphylococcus aureus isolates from the recently completed worldwide phase 3 clinical trials of tigecycline. A total of 503 unique S. aureus strains isolated from complicated skin and skin structure infections were analyzed. The mecA gene was amplified from 120 strains (23.9%) determined to be resistant to oxacillin (MICs > or = 4 microg/ml). The prevalence of the mecA gene was found to vary regionally from 6.5% to 50.9% among isolates originating in Eastern Europe and North America, respectively. The presence of a tetracycline resistance determinant, tet(M) or tet(K), among methicillin-resistant S. aureus (MRSA) isolates also varied regionally, with a range of 11.9% to 46.2% among isolates tested from North America and Eastern Europe, respectively. The occurrence of a tetracycline resistance marker in methicillin-susceptible S. aureus (MSSA) strains varied from 2.5 to 16.1% among the isolates tested across the regions of study. The presence of tet(M) or tet(K) had no discernible effect on the tigecycline MICs for either MRSA or MSSA strains, which is consistent with the ability of the glycylcyclines to retain activity in the presence of both the ribosomal protection and efflux mechanisms of resistance to the tetracyclines.
Jones
C Hal
CH
Infectious Diseases Discovery Research, Wyeth Research, 401 N. Middletown Rd., Bldg. 200, Rm. 3219, Pearl River, NY 10965, USA. jonesh3@wyeth.com
Tuckman
Margareta
M
Howe
Anita Y M
AY
Orlowski
Mark
M
Mullen
Stanley
S
Chan
Karen
K
Bradford
Patricia A
PA
D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D016106:Methicillin Resistance / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction / Q000379:methods*; D013207:Staphylococcal Skin Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics*; D013753:Tetracycline Resistance / Q000235:genetics*; D000078304:Tigecycline
D000078304:Tigecycline; D008911:Minocycline