Comparative In Vitro Activity of New Lipoglycopeptides and Vancomycin Against Ocular Staphylococci and Their Toxicity on the Human Corneal Epithelium.
Comparative In Vitro Activity of New Lipoglycopeptides and Vancomycin Against Ocular Staphylococci and Their Toxicity on the Human Corneal Epithelium.
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DOI：
10.1097/ico.0000000000003197
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发表时间：
2023-05-01
期刊：
影响因子：
2.8
通讯作者：
Bispo, Paulo J. M.
中科院分区：
文献类型：
--
作者：
Andre, Camille;Islam, Mohammad Mirazul;Paschalis, Eleftherios;Bispo, Paulo J. M.
补充数字内容在文本中可用。本研究的目的是评估新的脂糖肽作为新型局部治疗药物的潜力，以改善对难治性眼部感染的治疗。我们评价了奥利万星、达巴万星和特拉万星与万古霉素（货车）相比对大量眼部葡萄球菌分离株的体外抗菌活性及其对人角膜上皮细胞（HCECs）的细胞毒性。采用微量肉汤稀释法对223株葡萄球菌进行药敏试验。临床分离株。测定金黄色葡萄球菌（MRSA）（n = 2）和表皮葡萄球菌（MRSE）（n = 1）的耐甲氧西林菌株的时间-杀灭动力学。用AlamarBlue和活/死染色对HCEC进行体外细胞毒性测定。所有新脂糖肽均显示出对眼部葡萄球菌（包括多重耐药MRSA菌株）的强体外效力，与特拉万星和奥利万星（MIC 90 0.12 μg/mL）相比，达巴万星显示出略高的总体效力[最小抑制浓度（MIC）90 0.06 μg/mL]，而货车的效力最低（MIC 90 2 μg/mL）。奥利万星在1小时内对MRSA和2小时内对MRSE产生快速杀菌活性。其他药物均在24 h内具有杀菌作用。在通常用于局部制剂的浓度（25 mg/mL）下，在孵育5分钟后观察到货车的细胞毒性，而对于特拉万星未观察到HCEC活力的降低，并且受奥利万星和达巴万星的影响较小。在30和60 min时观察到25 mg/mL的所有药物的细胞毒性，但在较低浓度下显著降低或未检测到。我们的研究表明，与货车相比，新的脂糖肽对眼部葡萄球菌分离株具有更好的体外抗菌活性，对HCEC具有相似或改善的毒性特征。
Supplemental Digital Content is Available in the Text. The purpose of this study was to assess the potential of new lipoglycopeptides as novel topical therapies for improved treatment of recalcitrant ocular infections. We evaluated the in vitro antimicrobial activity of oritavancin, dalbavancin, and telavancin compared with vancomycin (VAN) against a large collection of ocular staphylococcal isolates and their cytotoxicity on human corneal epithelial cells (HCECs). Antimicrobial susceptibility testing was performed by broth microdilution against 223 Staphylococcus spp. clinical isolates. Time–kill kinetics were determined for methicillin-resistant strains of Staphylococcus aureus (MRSA) (n = 2) and Staphylococcus epidermidis (MRSE) (n = 1). In vitro cytotoxicity assays were performed with AlamarBlue and live/dead staining on HCECs. All new lipoglycopeptides showed strong in vitro potency against ocular staphylococci, including multidrug-resistant MRSA strains, with dalbavancin showing a slightly higher potency overall [minimum inhibitory concentration (MIC)90 0.06 μg/mL] compared with telavancin and oritavancin (MIC90 0.12 μg/mL), whereas VAN had the lowest potency (MIC90 2 μg/mL). Oritavancin exerted rapid bactericidal activity within 1 h for MRSA and 2 h for MRSE. All other drugs were bactericidal within 24 h. At a concentration commonly used for topical preparations (25 mg/mL), cytotoxicity was observed for VAN after 5 min of incubation, whereas reduction in HCEC viability was not seen for telavancin and was less affected by oritavancin and dalbavancin. Cytotoxicity at 25 mg/mL was seen for all drugs at 30 and 60 min but was significantly reduced or undetected for lower concentrations. Our study demonstrates that new lipoglycopeptides have substantially better in vitro antimicrobial activity against ocular staphylococcal isolates compared with VAN, with a similar or improved toxicity profile on HCECs.