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药物诱导的耐受:抗生素预先暴露的影响。

Drug-induced tolerance: the effects of antibiotic pre-exposure in .

机构信息

Department of Pathology, Health Sciences Center, Universidade Federal do Espírito Santo (UFES), Av. Marechal Campos, 1468, 29040-090 Vitória, Espírito Santo, Brazil.

出版信息

Future Microbiol. 2020 May;15:497-508. doi: 10.2217/fmb-2019-0253. Epub 2020 Jun 1.

DOI:10.2217/fmb-2019-0253
PMID:32478618
Abstract

To investigate if the prior use of nontargeted antibiotics induces cross-tolerance in . Antibiotic induction was performed to evaluate daptomycin and vancomycin as possible tolerance-inducing drugs measured by minimum bactericidal concentration/minimum inhibitory concentration (MIC) ratio, adapted disk-diffusion tests and time-kill curves. After antibiotic exposure, three potentially tolerant strains were isolated, maintaining the same MIC value of levofloxacin, with minimum bactericidal concentration/MIC ratio slightly higher than the parental. In the adapted disk-diffusion test, one strain (D25) showed high tolerance level for levofloxacin, ceftazidime and ticarcillin-clavulanate. In time-kill activity of levofloxacin, D25 presented a subpopulation of persisters with survival rate higher (1.6-fold) than the parental. Previous exposure of to daptomycin can induce cross-tolerance to ceftazidime and ticarcillin-clavulanate and cross-persistence to levofloxacin.

摘要

为了研究非靶向抗生素的先前使用是否会在 中诱导交叉耐受。通过最小杀菌浓度/最小抑菌浓度(MIC)比值、适应性碟片扩散试验和时间杀伤曲线来评估达托霉素和万古霉素是否可能作为诱导耐药的药物进行抗生素诱导。在抗生素暴露后,分离出三株潜在耐受株,保持左氧氟沙星的相同 MIC 值,最小杀菌浓度/MIC 比值略高于亲本。在适应性碟片扩散试验中,一株(D25)对左氧氟沙星、头孢他啶和替卡西林-克拉维酸表现出高度耐药水平。在左氧氟沙星的时间杀伤活性中,D25 呈现出具有更高生存能力(1.6 倍)的持久性亚群。先前暴露于达托霉素可诱导对头孢他啶和替卡西林-克拉维酸的交叉耐受和对左氧氟沙星的交叉持久。

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