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Antimicrobial Agents and Chemotherapy, November 2005, p. 4521-4529, Vol. 49, No. 11
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.11.4521-4529.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Use of Ribotyping To Retrospectively Identify Methicillin-Resistant Staphylococcus aureus Isolates from Phase 3 Clinical Trials for Tigecycline That Are Genotypically Related to Community-Associated Isolates

Fionnuala McAleese,1 Ellen Murphy,1 Timothy Babinchak,3 Guy Singh,1 Battouli Said-Salim,4 Barry Kreiswirth,4 Paul Dunman,1,{dagger} John O'Connell,1 Steven J. Projan,2 and Patricia A. Bradford1*

Wyeth Research, Pearl River, New York,1 Wyeth Research, Cambridge, Massachusetts,2 Wyeth Research, Collegeville, Pennsylvania,3 Public Health Research Institute, Newark, New Jersey4

Received 15 June 2005/ Returned for modification 24 July 2005/ Accepted 18 August 2005

A retrospective study was performed to identify methicillin-resistant Staphylococcus aureus (MRSA) isolates obtained from patients enrolled in phase 3 clinical trials for tigecycline that were genotypically similar to known community-associated MRSA (CA-MRSA) strains. The clinical trials were double-blind comparator studies for complicated skin and skin structure infections or complicated intra-abdominal infections. We obtained 85% of the MRSA isolates from patients with complicated skin and skin structure infections. Using ribotyping, MRSA isolates were compared with well-characterized North American CA-MRSA strains and negative-control hospital-associated (HA) MRSA strains by cluster analysis; 91 of the 173 isolates clustered with two groups of known CA-MRSA strains, 60% of which shared an indistinguishable ribotype. These isolates were subsequently tested for the presence of SCCmec type IV and the Panton-Valentine leukocidin (PVL)-encoding genes as well as susceptibility to clindamycin, characteristics that are typically associated with CA-MRSA; 89 of the 91 isolates carried the type IV SCCmec element and 76 were also positive for the PVL-encoding genes; 73 of these isolates were susceptible to clindamycin. A similar analysis performed on 26 nonclustering isolates identified only four with these characteristics; 89 of the 91 clustering isolates were inhibited by tigecycline at MICs of ≤0.5 µg/ml. On the basis of clustering information and preliminary genetic characterization, it appears that ribotyping is a useful tool in identifying potential CA-MRSA isolates and 76 MRSA isolates from patients enrolled in the tigecycline phase 3 trials have genetic markers typically associated with CA-MRSA.


* Corresponding author. Mailing address: Wyeth Research, Room 3301, Bldg. 200, 401 N. Middletown Rd., Pearl River, NY 10965. Phone: (845) 602 4396. Fax: (845) 602 5671. E-mail: bradfop{at}wyeth.com.

{dagger} Present address: Department of Microbiology and Pathology, University of Nebraska Medical Center, Omaha, NE 68198.


Antimicrobial Agents and Chemotherapy, November 2005, p. 4521-4529, Vol. 49, No. 11
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.11.4521-4529.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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