antibioticsАнтибиотики и ХимиотерапияAntibiot Khimioter = Antibiotics and Chemotherapy0235-2990ООО «Издательство ОКИ»antibiotics-616Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL PAPERSПрогнозирование развития антибиотикорезистентности бактерий методами фармакокинетико-фармакодинамического моделирования: альтернативные подходы к анализу экспериментальных данныхPK/PD Modeling as a Tool for Predicting Bacterial Resistance to Antibiotics: Alternative Analyses of Experimental DataГоликоваМ. В.GolikovaM. V.noemail@neicon.ruСтруковаЕ. Н.StrukovaE. N.noemail@neicon.ruПортнойЮ. А.PortnoyY. A.noemail@neicon.ruФирсовА. А.FirsovA. A.noemail@neicon.ruНИИ по изысканию новых антибиотиков им. Г.Ф. ГаузеРоссияGause Institute of New AntibioticsRussian Federation201513052020609-101216Copyright © 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/616

Оценка численности мутантов после многократного введения антибиотика (NM) - основной параметр, который используется в исследованиях процессов развития резистентности бактерий с помощью динамических систем in vitro, моделирующих фармакокинетику антибиотиков. С целью сравнения NM с недавно предложенным интегральным параметром AUBCM (площадь под кривой «численность мутантов - время») проведён анализ процессов селекции Staphylococcus aureus при моделировании in vitro режимов моно- (даптомицин, доксициклин) и комбинированной (даптомицин + рифампицин, рифампицин + линезолид) терапии. Различия в кинетических кривых изменения численности резистентных мутантов S.aureus удалось выразить параметром AUBCM, но не NM. Кроме того, в отличие от AUBCM параметр NM не позволял отразить очевидные различия в кинетических кривых изменения численности мутантов, резистентных к 2-, 4-, 8- и 16-кратному показателю МПК доксициклина и рифампицина. Полученные результаты свидетельствуют о преимуществах AUBCM перед NM при количественной оценке селекции резистентных мутантов.

Postexposure number of mutants (NM) is a conventional endpoint in bacterial resistance studies using in vitro dynamic models that simulate antibiotic pharmacokinetics. To compare NM with a recently introduced integral parameter AUBCM, the area under the time course of resistance mutants, the enrichment of resistant Staphylococcus aureus was studied in vitro by simulation of mono-(daptomycin, doxycycline) and combined treatments (daptomycin + rifampicin, rifampicin + linezolid). Differences in the time courses of resistant S.aureus could be reflected by AUBCM but not NM. Moreover, unlike AUBCM, NM did not reflect the pronounced differences in the time courses of S.aureus mutants resistant to 2X, 4X, 8X and 16XMIC of doxycycline and rifampicin. The findings suggested that AUBCM was a more appropriate endpoint of the amplification of resistant mutants than NM.

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