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Antimicrob Agents Chemother. 2018 Aug 27;62(9). pii: e00485-18. doi: 10.1128/AAC.00485-18. Print 2018 Sep.

Ceftaroline Resistance by Clone-Specific Polymorphism in Penicillin-Binding Protein 2a of Methicillin-Resistant Staphylococcus aureus.

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Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea.
Division of Antimicrobial Resistance, National Institute of Health, Centers for Disease Control and Prevention, Cheongju, South Korea.
Department of Laboratory Medicine, Hallym University College of Medicine, Hwaseong, South Korea.
Department of Laboratory Medicine, School of Medicine, Jeju National University, Jeju, South Korea.
Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju, South Korea.
Department of Laboratory Medicine and Paik Institute for Clinical Research, Inje University College of Medicine, Busan, South Korea.
Department of Laboratory Medicine, College of Medicine, Chungbuk National University, Cheongju, South Korea.
Department of Laboratory Medicine, National Health Insurance Service Ilsan Hospital, Goyang, South Korea.
Department of Laboratory Medicine, Yonsei University Wonju College of Medicine, Wonju, South Korea.
Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea
Contributed equally


A total of 281 nonduplicated Staphylococcus aureus blood isolates were collected from January to May 2017 from eight hospitals in South Korea to investigate the epidemiological traits of ceftaroline resistance in methicillin-resistant S. aureus (MRSA). Cefoxitin-disk diffusion tests and the mecA gene PCR revealed that 56.6% (159/281) of the S. aureus isolates were MRSA, and most belonged to ST5 (50.3%, 80/281) and ST72 (41.5%, 66/281). Of the MRSA isolates, 44.0% (70/159) were nonsusceptible to ceftaroline (MIC ≥ 2 mg/liter), whereas all of the methicillin-susceptible S. aureus isolates were susceptible to the drug. Eight amino acid substitutions in penicillin-binding protein 2a (PBP2a), including four (L357I, E447K, I563T, and S649A) in the penicillin-binding domain (PBD) and four (N104K, V117I, N146K, and A228V) in the non-PBD (nPBD) of PBP2a, were associated with ceftaroline resistance. The accumulation of substitutions in PBP2a resulted in the elevation of ceftaroline MICs: one substitution at 1 to 2 mg/liter, two or three substitutions at 2 to 4 mg/liter, and five substitutions at 4 or 16 mg/liter. Ceftaroline resistance in MRSA might be the result of clone-specific PBP2a polymorphism, along with substitutions both in PBD and nPBD, and the elevated ceftaroline MICs were associated with the substitution sites and accumulation of substitutions.


ceftaroline; methicillin-resistant Staphylococcus aureus; non-penicillin-binding domain; penicillin-binding domain; penicillin-binding protein 2a

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