In Vitro Activity of Ceftaroline against Staphylococcus aureus Isolated in 2012 from Asia-Pacific Countries as Part of the AWARE Surveillance Program

• Published in: Antimicrobial agents and chemotherapy 2016-01, Vol.60 (1), p.343-347
• Main Authors: Biedenbach, Douglas J, Alm, Richard A, Lahiri, Sushmita D, Reiszner, Edina, Hoban, Daryl J, Sahm, Daniel F, Bouchillon, Samuel K, Ambler, Jane E
• Format: Article
• Language: English
• Subjects: Amino Acid Substitution; Anti-Bacterial Agents; Anti-Bacterial Agents - pharmacology; Asia, Southeastern - epidemiology; Bacterial Proteins; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; beta-Lactam Resistance; beta-Lactam Resistance - genetics; Ceftaroline; Cephalosporins; Cephalosporins - pharmacology; Epidemiological Monitoring; Gene Expression; Humans; Methicillin-Resistant Staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - genetics; Methicillin-Resistant Staphylococcus aureus - isolation & purification; Methicillin-Resistant Staphylococcus aureus - metabolism; Microbial Sensitivity Tests; Molecular Epidemiology; Multilocus Sequence Typing; Penicillin-Binding Proteins; Penicillin-Binding Proteins - genetics; Penicillin-Binding Proteins - metabolism; Staphylococcal Infections - epidemiology; Staphylococcal Infections - microbiology; Staphylococcus aureus; Susceptibility
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.01867-15

Ceftaroline, the active metabolite of the prodrug ceftaroline-fosamil, is an advanced-generation cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA). This investigation provides in vitro susceptibility data for ceftaroline against 1,971 S. aureus isolates collected in 2012 from seven countries (26 centers) in the Asia-Pacific region as part of the Assessing Worldwide Antimicrobial Resistance and Evaluation (AWARE) program. Broth microdilution as recommended by the CLSI was used to determine susceptibility. In all, 62% of the isolates studied were MRSA, and the ceftaroline MIC90 for all S. aureus isolates was 2 μg/ml (interpretive criteria: susceptible, ≤1 μg/ml). The overall ceftaroline susceptibility rate for S. aureus was 86.9%, with 100% of methicillin-sensitive S. aureus isolates and 78.8% of MRSA isolates susceptible to this agent. The highest percentages of ceftaroline-nonsusceptible MRSA isolates came from China (47.6%), all of which showed intermediate susceptibility, and Thailand (37.1%), where over half (52.8%) of isolates were resistant to ceftaroline (MIC, 4 μg/ml). Thirty-eight ceftaroline-nonsusceptible isolates (MIC values of 2 to 4 μg/ml) were selected for molecular characterization. Among the isolates analyzed, sequence type 5 (ST-5) was the most common sequence type encountered; however, all isolates analyzed from Thailand were ST-228. Penicillin-binding protein 2a (PBP2a) substitution patterns varied by country, but all isolates from Thailand had the Glu239Lys substitution, and 12 of these also carried an additional Glu447Lys substitution. Ceftaroline-fosamil is a useful addition to the antimicrobial agents that can be used to treat S. aureus infections. However, with the capability of this species to develop resistance to new agents, it is important to recognize and monitor regional differences in trends as they emerge.