antibioticsАнтибиотики и ХимиотерапияAntibiot Khimioter = Antibiotics and Chemotherapy0235-2990ООО «Издательство ОКИ»antibiotics-682Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL PAPERSМолекулярные механизмы снижения чувствительности к цефтаролину метициллинорезистентных Staphylococcus aureusMolecular Mechanisms of Ceftaroline Susceptibility Reduction in Methicillin-Resistant Staphylococcus aureusГостевВ. В.GostevV. V.noemail@neicon.ruКалиногорскаяО. С.KalinogorskayaO. S.noemail@neicon.ruДмитренкоО. А.DmitrenkoO. A.noemail@neicon.ruЦветковаИ. А.TsvetkovaI. A.noemail@neicon.ruСидоренкоС. В.SidorenkoS. V.noemail@neicon.ruФГБУ «НИИ детских инфекций ФМБА России»РоссияScientific Research Institute of Children's InfectionsRussian FederationФедеральный научно-исследовательский центр эпидемиологии и микробиологии имени почетного академика Н. Ф. ГамалеиРоссияResearch Centre of Epidemiology and Microbiology named After Honoured Academician N. F. GamaleiRussian FederationФГБУ «НИИ детских инфекций ФМБА России»; Северо-Западный государственный медицинский университет им. И. И. МечниковаРоссияScientific Research Institute of Children's Infections; North-Western State Medical University named after I. I. MechnikovRussian Federation201613052020619-101721Copyright © ООО «Издательство ОКИ», 20202020ООО «Издательство ОКИ»ООО «Издательство ОКИ»https://www.antibiotics-chemotherapy.ru/jour/about/submissions#copyrightNoticehttps://www.antibiotics-chemotherapy.ru/jour/article/view/682

Цефтаролин - уникальным цефалоспорин с активностью в отношении метициллинорезистентных Staphylococcus aureus (MRSA) одобрен для клинического использования в США, Европе и России в 2010 году для терапии инфекций кожи и мягких тканей, а также внебольничных пневмоний. В настоящем исследовании было проведено молекулярное типирование 24 изолятов MRSA со сниженной чувствительностью к цефтаролину. Для 8 изолятов разных генетических линий (ST8, ST239, ST228) и разным уровнем МПК были определены уровни концентраций антибиотика, предотвращающих образование устойчивых мутантов (mutant prevention concentration, MPC) и диапазоны окна селекции (mutant selection window, MSW). Установлено, что подавляющее большинство изолятов со сниженной чувствительностью к цефтаролину (МПК = 2 мкг/мл) относилось к клональной линии ST228. Полногеномное секвенирование двух изолятов ST228 показало, что они относятся к эпидемической «Южно-Германской» генетической линии, характеризуются наличием мутаций в PBP2a (N146K) и PBP2 (C197Y), обуславливающих снижение чувствительности. Наиболее высокие показатели MPC = 32 мкг/мл и MSW (2-16 мкг/мл) были выявлены среди клинических изолятов, относящихся к генетической линии ST8. Для изолятов ST239 и ST228 окно селекции было в диапазоне 2-4 мкг/мл. Не было обнаружено зависимости уровней МПК и MPC / MSW.

Ceftaroline is a unique cephalosporin with activity against methicillin resistant Staphylococcus aureus (MRSA). It was approved for clinical use in the USA, Europe and Russian Federation since 2010 for the treatment of the skin and soft tissue infection and community-acquired pneumoniae. In the present study there was used molecular typing of 24 isolates of MRSA with reduced susceptibility to ceftaroline. For 8 isolates belonging to different genetic lines (ST8, ST239 and ST228) and requiring MICs there were determined antibiotic concentrations preventing formation of resistant mutants (mutant prevention concentration) and the ranges of the mutant selection window (MSW). The last majority of the isolates with reduced susceptibility to ceftaroline (MIC of 2 mcg/ml) belonged to the clonal line ST228. The whole genome sequencing of two isolates of ST228 showed that they belonged to the epidemic South Germany genetic line and were characterized by the presence of mutations in PBP2a (N146K) and PBP2 (C197Y) responsible for reduced susceptibility. The highest rates of MPC (32 mcg/ml) and MSW (2-16 mcg/ml) were observed in the clinical isolates belonging to the genetic line ST8. The isolates of ST239 and ST228 had the selection window within 2-4 mcg/ml. No dependence of the MIC and MPC/MSW levels was detected.

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The authors declare that there are no conflicts of interest present.