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强力霉素在消除生物膜方面相对于万古霉素和青霉素的体外疗效

The In Vitro Efficacy of Doxycycline over Vancomycin and Penicillin in the Elimination of Biofilm.

作者信息

Budge Matthew D, Koch John A, Mandell Jonathan B, Cappellini Alex J, Orr Sara, Patel Samik, Ma Dongzhu, Nourie Olivia, Brothers Kimberly M, Urish Kenneth L

机构信息

NW Perrnanente, 5125 Skyline Rd. S., Salem, OR 97306-9427, USA.

Arthritis and Arthroplasty Design Group, Dept. of Orthopaedic Surgery, 100 Technology Dr., Pittsburgh, PA 15219, USA.

出版信息

Antimicrob Comb Devices (2019). 2020;STP1630:53-64. doi: 10.1520/stp163020200019. Epub 2020 Nov 23.

Abstract

(formerly ) is a significant pathogen in periprosthetic joint infections (PJIs) in total shoulder arthroplasty. Poor outcomes seen in PJIs are due to the established bacterial biofilms. The prolonged nature of infections makes them difficult to treat with antibiotics. The goal of this study was to determine the relative efficacy of vancomycin compared with penicillin and doxycycline against planktonic and mature biofilms. Clinical isolates from PJI patients as well as a laboratory strain of were tested. Planktonic minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were obtained using modified clinical laboratory standard index assays. Biofilm MICs and MBCs were also obtained. The MIC was determined for both using the PrestoBlue viability stain. The MBC was determined using differential reinforced clostridial medium agar plates for colony-forming unit analysis. Using the PrestoBlue viability reagent, the planktonic MIC values for vancomycin were significantly higher than doxycycline. Across 10 strains of , all three antibiotics had decreased efficacy when comparing planktonic and biofilm cultures. Although effective antibiotic doses ranged from 1 to 1,000 μg/mL, only doxycycline achieved inhibitory and bactericidal concentrations in all tested strains. Penicillin failed to achieve the minimum biofilm inhibitory concentration (MBIC) in 60% of tested strains, whereas vancomycin failed in 80% of tested strains. Penicillin, doxycycline, and vancomycin have similar abilities in inhibiting growth planktonically. The MBIC for doxycycline was within the clinical dosing range, suggesting biofilm offers minimal tolerance to these antibiotics. The MBIC for penicillin was within clinical dosing ranges in only 60% of trials, suggesting the relative tolerance of to penicillin. The minimum biofilm bactericidal concentration (MBBC) of doxycycline showed efficacy in 90% of trials, whereas penicillin and vancomycin achieved MBBC in 15% of samples.

摘要

(以前)是全肩关节置换术中人工关节周围感染(PJI)的一种重要病原体。PJI中出现的不良预后归因于已形成的细菌生物膜。感染的长期性使得用抗生素治疗它们变得困难。本研究的目的是确定万古霉素与青霉素和强力霉素相比对浮游菌和成熟生物膜的相对疗效。对PJI患者的临床分离株以及一种实验室菌株进行了测试。使用改良的临床实验室标准指数测定法获得浮游菌的最低抑菌浓度(MIC)和最低杀菌浓度(MBC)。还获得了生物膜的MIC和MBC。使用PrestoBlue活力染色剂测定两者的MIC。使用差异强化梭菌培养基琼脂平板进行菌落形成单位分析来确定MBC。使用PrestoBlue活力试剂时,万古霉素的浮游菌MIC值显著高于强力霉素。在10株[菌株名称未给出]中,与浮游菌培养物和生物膜培养物相比,所有三种抗生素的疗效均降低。尽管有效抗生素剂量范围为1至1000μg/mL,但只有强力霉素在所有测试菌株中达到了抑菌和杀菌浓度。青霉素在60%的测试菌株中未达到最低生物膜抑菌浓度(MBIC),而万古霉素在80%的测试菌株中未达到。青霉素、强力霉素和万古霉素在浮游状态下抑制[菌株名称未给出]生长的能力相似。强力霉素的MBIC在临床给药范围内,表明[菌株名称未给出]生物膜对这些抗生素的耐受性最小。青霉素的MBIC仅在60%的试验中处于临床给药范围内,表明[菌株名称未给出]对青霉素的相对耐受性。强力霉素的最低生物膜杀菌浓度(MBBC)在90%的试验中显示出疗效,而青霉素和万古霉素在15%的样本中达到了MBBC。

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