Golikova Maria V, Strukova Elena N, Portnoy Yury A, Dovzhenko Svetlana A, Kobrin Mikhail B, Zinner Stephen H, Firsov Alexander A
Department of Pharmacokinetics & Pharmacodynamics, Gause Institute of New Antibiotics , Moscow , Russia.
Department of Medicine, Mount Auburn Hospital, Harvard Medical School , Cambridge , Massachusetts , USA.
J Chemother. 2019 Sep;31(5):252-260. doi: 10.1080/1120009X.2019.1623361. Epub 2019 Jun 8.
Current knowledge of the emergence of resistance during treatment with aminopenicillins and macrolides is limited. In particular, clinical reports on isolation of azithromycin-resistant mutants do not relate their enrichment to the actual antibiotic concentrations in blood. In the present work, the selection of amoxicillin- and azithromycin-resistant mutants at therapeutic and subtherapeutic antibiotic exposures was studied in an dynamic model. There was no enrichment of mutants resistant to amoxicillin, while azithromycin-resistant mutants were enriched in all simulations. This difference was related to the different times above the mutant prevention concentration: 60-100% of the dosing interval for amoxicillin zero percentage for azithromycin. These findings are in concordance with the mutant selection window hypothesis.
目前关于在使用氨基青霉素和大环内酯类药物治疗期间耐药性产生的知识有限。特别是，关于分离出阿奇霉素耐药突变体的临床报告并未将其富集情况与血液中的实际抗生素浓度联系起来。在本研究中，在一个动态模型中研究了在治疗性和亚治疗性抗生素暴露水平下阿莫西林和阿奇霉素耐药突变体的选择情况。对阿莫西林耐药的突变体没有富集，而在所有模拟中阿奇霉素耐药突变体都有富集。这种差异与高于突变体预防浓度的不同时间有关：阿莫西林为给药间隔的60 - 100%，阿奇霉素为零百分比。这些发现与突变体选择窗假说是一致的。
