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Ceftaroline Resistance by Clone-Specific Polymorphism in Penicillin-Binding Protein 2a of Methicillin-Resistant Staphylococcus aureus.
Antimicrob Agents Chemother. 2018 09; 62(9)AA

Abstract

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.

Authors+Show Affiliations

Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea.Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea.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.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 kscpjsh@yuhs.ac.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29941637

Citation

Lee, Hyukmin, et al. "Ceftaroline Resistance By Clone-Specific Polymorphism in Penicillin-Binding Protein 2a of Methicillin-Resistant Staphylococcus Aureus." Antimicrobial Agents and Chemotherapy, vol. 62, no. 9, 2018.
Lee H, Yoon EJ, Kim D, et al. Ceftaroline Resistance by Clone-Specific Polymorphism in Penicillin-Binding Protein 2a of Methicillin-Resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2018;62(9).
Lee, H., Yoon, E. J., Kim, D., Kim, J. W., Lee, K. J., Kim, H. S., Kim, Y. R., Shin, J. H., Shin, J. H., Shin, K. S., Kim, Y. A., Uh, Y., & Jeong, S. H. (2018). Ceftaroline Resistance by Clone-Specific Polymorphism in Penicillin-Binding Protein 2a of Methicillin-Resistant Staphylococcus aureus. Antimicrobial Agents and Chemotherapy, 62(9). https://doi.org/10.1128/AAC.00485-18
Lee H, et al. Ceftaroline Resistance By Clone-Specific Polymorphism in Penicillin-Binding Protein 2a of Methicillin-Resistant Staphylococcus Aureus. Antimicrob Agents Chemother. 2018;62(9) PubMed PMID: 29941637.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ceftaroline Resistance by Clone-Specific Polymorphism in Penicillin-Binding Protein 2a of Methicillin-Resistant Staphylococcus aureus. AU - Lee,Hyukmin, AU - Yoon,Eun-Jeong, AU - Kim,Dokyun, AU - Kim,Jung Wook, AU - Lee,Kwang-Jun, AU - Kim,Hyun Soo, AU - Kim,Young Ree, AU - Shin,Jong Hee, AU - Shin,Jeong Hwan, AU - Shin,Kyeong Seob, AU - Kim,Young Ah, AU - Uh,Young, AU - Jeong,Seok Hoon, Y1 - 2018/08/27/ PY - 2018/03/12/received PY - 2018/06/20/accepted PY - 2018/6/27/pubmed PY - 2019/9/27/medline PY - 2018/6/27/entrez KW - ceftaroline KW - methicillin-resistant Staphylococcus aureus KW - non-penicillin-binding domain KW - penicillin-binding domain KW - penicillin-binding protein 2a JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 62 IS - 9 N2 - 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. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/29941637/Ceftaroline_Resistance_by_Clone_Specific_Polymorphism_in_Penicillin_Binding_Protein_2a_of_Methicillin_Resistant_Staphylococcus_aureus_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=29941637 DB - PRIME DP - Unbound Medicine ER -