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对缺陷拟杆菌和优雅颗粒菌生物膜的体外抗菌活性。

In vitro antimicrobial activity against Abiotrophia defectiva and Granulicatella elegans biofilms.

机构信息

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Centre for Musculoskeletal Surgery, Charitéplatz 1, 10117 Berlin, Germany.

Berlin-Brandenburg Centre for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.

出版信息

J Antimicrob Chemother. 2019 Aug 1;74(8):2261-2268. doi: 10.1093/jac/dkz174.

DOI:10.1093/jac/dkz174
PMID:31049562
Abstract

OBJECTIVES

To determine the efficacy of different antibiotics (alone or in combination) against Abiotrophia defectiva and Granulicatella elegans biofilms and to investigate the anti-biofilm activity of gentamicin alone versus blood culture isolates from both species.

METHODS

The activity of benzylpenicillin, clindamycin, daptomycin, fosfomycin, gentamicin, levofloxacin and rifampicin against 24-hour-old biofilms of A. defectiva and G. elegans was investigated in vitro by conventional microbiological methods and isothermal microcalorimetry.

RESULTS

For planktonic bacteria, the MIC values of tested antibiotics ranged from 0.016 to 64 mg/L, as determined by microcalorimetry. Higher antibiotic concentrations, ranging from 1 to >1024 mg/L, were needed to produce an effect on biofilm bacteria. Gentamicin was an exception as it was active at 1 mg/L against both planktonic and biofilm G. elegans. A synergistic effect was observed when daptomycin was combined with benzylpenicillin, gentamicin or rifampicin against A. defectiva biofilms and when gentamicin was combined with rifampicin or levofloxacin against G. elegans biofilms. A. defectiva clinical isolates displayed greater variability in gentamicin susceptibility as compared with G. elegans strains.

CONCLUSIONS

Antimicrobial susceptibility profiles vary widely between Abiotrophia and Granulicatella biofilms, and synergistic effects of the tested antibiotics were heterogeneous. The clinical relevance of these in vitro observations needs to be confirmed in experimental in vivo conditions and human trials, before guidelines for the treatment of A. defectiva and G. elegans infections are established. This study suggests the benefit of further clinical exploration of antibiotic combinations with anti-biofilm effect.

摘要

目的

确定不同抗生素(单独或联合使用)对缺陷拟杆菌和优雅颗粒单胞菌生物膜的疗效,并研究单独使用庆大霉素与两种物种的血培养分离株的抗生物膜活性。

方法

通过常规微生物学方法和等温微量热法研究了苯唑西林、克林霉素、达托霉素、磷霉素、庆大霉素、左氧氟沙星和利福平对 24 小时龄缺陷拟杆菌和优雅颗粒单胞菌生物膜的活性。

结果

在浮游菌中,通过微量热法测定,所测试抗生素的 MIC 值范围为 0.016 至 64mg/L。需要更高的抗生素浓度(范围为 1 至>1024mg/L)才能对生物膜细菌产生作用。庆大霉素是一个例外,因为它对浮游菌和生物膜优雅颗粒单胞菌均在 1mg/L 时有效。当达托霉素与苯唑西林、庆大霉素或利福平联合使用时,观察到对缺陷拟杆菌生物膜的协同作用,当庆大霉素与利福平或左氧氟沙星联合使用时,观察到对优雅颗粒单胞菌生物膜的协同作用。与优雅颗粒单胞菌菌株相比,缺陷拟杆菌临床分离株对庆大霉素的敏感性差异更大。

结论

拟杆菌和颗粒单胞菌生物膜之间的抗菌药敏谱差异很大,并且测试抗生素的协同作用具有异质性。在制定缺陷拟杆菌和优雅颗粒单胞菌感染治疗指南之前,需要在实验体内条件和人体试验中确认这些体外观察的临床相关性。本研究表明,进一步探索具有抗生物膜作用的抗生素联合治疗具有临床意义。

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