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Genetic relatedness among European meticillin-susceptible and -resistant Staphylococcus aureus isolates from ceftobiprole clinical trials

Abstract number: P1428

Davies T., Shang W., Amsler K., Flamm R., Bush K.

Objectives: Ceftobiprole (BPR) is an investigational parenteral cephalosporin that is unique from currently marketed cephalosporins in that it has broad-spectrum activity, including both meticillin-resistant Staphylococcus aureus (MRSA) and meticillin-susceptible S. aureus (MSSA). It is currently under clinical development for treatment of complicated skin and soft tissue infections (cSSSI) and pneumonia. The genetic relatedness among European MSSA and MRSA isolates collected from ceftobiprole cSSSI clinical trials was compared using spa typing and pulsed-field gel electrophoresis (PFGE).

Methods: Baseline isolates of MSSA [N=169; 73 were Panton-Valentine leukocidin (PVL) positive] and MRSA (N=74; 5 were PVL positive) from Eastern Europe (Bulgaria, Hungary, Latvia, Lithuania, Romania, Russia, Serbia & Montenegro, and Ukraine) were analysed. Spa typing and SCCmec typing (MRSA isolates) was done by PCR and/or DNA sequencing. PFGE was done on chromosomal DNA digested with SmaI. BPR MICs were determined according to CLSI methods.

Results: There were 106 different spa types among all isolates analysed: MSSA PVL- (N=63), MSSA PVL+ (N=33), MRSA PVL- (N=17), MRSA PVL+ (N=3). Only nine spa types were found among two or more of the isolate groups. The nine most common spa types (Table) accounted for 44% (N=108) of isolates. The most prevalent MRSA clone had spa type 1 but PFGE patterns were not all the same; 57% had SCCmec type IV. Two MSSA isolates also had spa type I. Spa types 3 and ``unique'' were similar, differing by one motif. MRSA isolates with these spa types had SCCmec type III, similar PFGE patterns, higher BPR MICs (MIC50/90 of 2 mg/L) and were predominantly (78%) from Latvia. The most prevalent MSSA clone had spa type 287, similar PFGE patterns, and low BPR MICs (MIC50/90 of 0.25 mg/L); all were also PVL+.

Conclusion: There was little genetic similarity between MSSA PVL+, MSSA PVL-, MRSA PVL+, and MRSA PVL- isolates. From spa typing, MSSA PVL- isolates seemed the most heterogeneous and MRSA PVL- isolates the least heterogeneous. Ceftobiprole had excellent activity (BPR MIC90 of 2 mg/L) against all MSSA and MRSA isolates including those with the most common spa types.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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