摘要

目前对氨基青霉素和大环内酯类治疗期间出现肺炎链球菌耐药性的认识有限。特别是，分离阿奇霉素耐药突变株的临床报告并未将它们的富集与血液中抗生素的实际浓度联系起来。在目前的工作中，选择阿莫西林和阿奇霉素耐药肺炎链球菌突变体在治疗和亚治疗抗生素暴露在体外动态模型中进行了研究。对阿莫西林耐药的肺炎链球菌突变体没有富集，而对阿奇霉素耐药的突变体在所有模拟中都富集。这种差异与突变预防浓度以上的不同时间有关:阿莫西林的给药间隔为60-100%，阿奇霉素为0%。这些发现与突变选择窗口假说一致。

Current knowledge of the emergence of Streptococcus pneumoniae 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 S. pneumoniae mutants at therapeutic and subtherapeutic antibiotic exposures was studied in an in vitro dynamic model. There was no enrichment of S. pneumoniae 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 versus zero percentage for azithromycin. These findings are in concordance with the mutant selection window hypothesis.

https://www.ncbi.nlm.nih.gov/pubmed/31179907