Abdizadeh Negin, Haeili Mehri, Kafil Hossein Samadi, Ahmadi Amin, Feizabadi Mohammad Mehdi
Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Iran J Microbiol. 2021 Aug;13(4):442-448. doi: 10.18502/ijm.v13i4.6967.
Ceftaroline (CPT) is a novel cephalosporin with potent activity against methicillin-resistant (MRSA). Despite its recent introduction, CPT resistance in MRSA has been described worldwide. We aimed in the current study to evaluate the activity of CPT against 91 clinical MRSA and 3 MSSA isolates.
Susceptibility of isolates to CPT was tested using E-test and disk diffusion (DD) method. The nucleotide sequence of the gene and molecular types of isolates with reduced susceptibility to CPT were further studied to identify resistance conferring mutations in PBP2a and the genetic relatedness of the isolates respectively.
Overall, 92.5% of isolates were found to be CPT susceptible (MICs≤1mg/l) and 7 MRSA isolates were characterized with MIC=2mg/l and categorized as susceptible dose dependent. Compared to E-test, DD revealed a categorical agreement rate of 93.6% and the obtained rates for minor, major /very major error were found to be 6.3% and 0% respectively. The MRSA isolates with increased CPT MICs (n=7), belonged to types t030 (n=6) and t13927 (n=1) and all carried N146K substitution in PBP2a allosteric domain, except for one isolate which harbored a wild-type PBP2a.
While resistance to CPT was not detected we found increased CPT MICs in 7.69% of MRSA isolates. Reduced susceptibility to CPT in the absence of mutations is indicative of contribution of secondary chromosomal mutations in resistance development.
头孢洛林（CPT）是一种新型头孢菌素，对耐甲氧西林金黄色葡萄球菌（MRSA）具有强大活性。尽管其近期才被应用，但全球已报道了MRSA对CPT的耐药情况。我们在本研究中旨在评估CPT对91株临床MRSA和3株甲氧西林敏感金黄色葡萄球菌（MSSA）分离株的活性。
采用E-test和纸片扩散法（DD）检测分离株对CPT的敏感性。进一步研究对CPT敏感性降低的分离株的基因核苷酸序列和分子类型，以分别鉴定PBP2a中赋予耐药性的突变以及分离株的遗传相关性。
总体而言，发现92.5%的分离株对CPT敏感（最低抑菌浓度≤1mg/l），7株MRSA分离株的最低抑菌浓度为2mg/l，归类为剂量依赖性敏感。与E-test相比，DD显示的分类一致率为93.6%，小误差、大/非常大误差的发生率分别为6.3%和0%。CPT最低抑菌浓度升高的MRSA分离株（n = 7）属于t030型（n = 6）和t13927型（n = 1），除一株携带野生型PBP2a的分离株外，所有分离株的PBP2a变构域均存在N146K替换。
虽然未检测到对CPT的耐药性，但我们发现7.69%的MRSA分离株的CPT最低抑菌浓度升高。在无突变情况下对CPT的敏感性降低表明二级染色体突变在耐药性发展中起作用。
