title: 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.
abstract: 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 < or = 0.5 microg/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.
authors.affiliation: Wyeth Research, Room 3301, Bldg. 200, 401 N. Middletown Rd., Pearl River, New York 10965, USA.
authors.forename: Fionnuala
authors.initials: F
authors.lastname: McAleese
authors.forename: Ellen
authors.initials: E
authors.lastname: Murphy
authors.forename: Timothy
authors.initials: T
authors.lastname: Babinchak
authors.forename: Guy
authors.initials: G
authors.lastname: Singh
authors.forename: Battouli
authors.initials: B
authors.lastname: Said-Salim
authors.forename: Barry
authors.initials: B
authors.lastname: Kreiswirth
authors.forename: Paul
authors.initials: P
authors.lastname: Dunman
authors.forename: John
authors.initials: J
authors.lastname: O'Connell
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Projan
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Bradford
mesh_terms: D016000:Cluster Analysis; D017714:Community-Acquired Infections / Q000188:drug therapy / Q000382:microbiology*; D006801:Humans; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D012189:Retrospective Studies; D021521:Ribotyping; D013211:Staphylococcus aureus / Q000145:classification* / Q000187:drug effects*; D000078304:Tigecycline
chemical_list: D000078304:Tigecycline; D008911:Minocycline