Telavancin demonstrates activity against methicillin-resistant Staphylococcus aureus isolates with reduced susceptibility to vancomycin, daptomycin, and linezolid in broth microdilution MIC and one-compartment pharmacokinetic/pharmacodynamic models.
Telavancin demonstrates activity against methicillin-resistant Staphylococcus aureus isolates with reduced susceptibility to vancomycin, daptomycin, and linezolid in broth microdilution MIC and one-compartment pharmacokinetic/pharmacodynamic models.
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在肉汤微量稀释 MIC 和一室药代动力学/药效学模型中，特拉万星表现出对耐甲氧西林金黄色葡萄球菌分离株的活性，并降低对万古霉素、达托霉素和利奈唑胺的敏感性。
DOI：
10.1128/aac.00773-15
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发表时间：
2015
影响因子：
4.9
通讯作者：
Rybak,MichaelJ
中科院分区：
文献类型：
--
作者：
Smith,JordanR;Barber,KatieE;Hallesy,Jessica;Raut,Animesh;Rybak,MichaelJ
耐甲氧西林金黄色葡萄球菌（MRSA）分离株对几种抗MRSA药物的敏感性降低。特拉万星（TLV），一种新的抗MRSA药物，保留对这些生物体的低MIC。我们的目的是确定TLV、达托霉素（DAP）、万古霉素（货车）和利奈唑胺（LZD）对达托霉素不敏感（DNS）S的MIC。金黄色葡萄球菌、万古霉素中间体S.金黄色葡萄球菌（VISA）、异源耐药VISA（hVISA）和利奈唑胺耐药（LZDr）S.金黄色。我们还在药代动力学/药效学（PK/PD）模型中针对每种表型评估了这些药物。从我们的文库中随机选择70株DNS、100株VISA、180株hVISA和25株LZDrMRSA分离株，并通过肉汤微量稀释和Trek平板进行检测，以确定其对TLV、DAP、货车和LZD的MIC。随机选择4株分离株用于168 h体外模型，以评价TLV 10 mg/kg体重/天、DAP 10 mg/kg/天、货车1 g每12 h（q12 h）和LZD 600 mg q12 h的治疗。TLV、DAP、货车和LZD对70个DNS S的MIC 50/90。金黄色葡萄球菌分离株的抑菌浓度分别为0.06/0.125 μg/ml、2/4 μg/ml、1/2 μg/ml和2/2 μg/ml。对100株VISA分离株的MIC 50/90分别为0.06/0.125 μg/ml、1/1 μg/ml、4/8 μg/ml和1/2 μg/ml。对170株hVISA分离株的MIC 50/90分别为0.06/0.125 μg/ml、0.5/1 μg/ml、1/2 μg/ml和1/2 μg/ml。对25种LZ分离物的MIC_（50）/_（90）分别为0.03/0.06 μg/ml、1/1 μg/ml、2/2 μg/ml和8/8 μg/ml。10/365（2.7%）株的TLV MIC>0.125 μg/ml。在PK/PD模型中，TLV在168 h时普遍具有杀菌作用，并且在统计学上上级所有抗生素对DNS S的抑制作用。金黄色葡萄球菌菌株R2334。这些数据进一步确立了TLV对耐药MRSA的效力。模型数据表明TLV对hVISA、VISA、DNS S均有体外杀菌活性。aureus和LZDrS。金黄色葡萄球菌进一步的临床研究是必要的。
Methicillin-resistant Staphylococcus aureus (MRSA) isolates have arisen with reduced susceptibility to several anti-MRSA agents. Telavancin (TLV), a novel anti-MRSA agent, retains low MICs against these organisms. Our objective was to determine the MICs for TLV, daptomycin (DAP), vancomycin (VAN), and linezolid (LZD) against daptomycin-nonsusceptible (DNS) S. aureus, vancomycin-intermediate S. aureus (VISA), heteroresistant VISA (hVISA), and linezolid-resistant (LZDr) S. aureus. We also evaluated these agents against each phenotype in pharmacokinetic/pharmacodynamic (PK/PD) models. Seventy DNS, 100 VISA, 180 hVISA, and 25 LZDrMRSA isolates were randomly selected from our library and tested to determine their MICs against TLV, DAP, VAN, and LZD via broth microdilution and a Trek panel. Four isolates were randomly selected for 168-hin vitromodels to evaluate treatment with TLV at 10 mg/kg of body weight/day, DAP at 10 mg/kg/day, VAN at 1 g every 12 h (q12h), and LZD at 600 mg q12h. The MIC50/90for TLV, DAP, VAN, and LZD against 70 DNS S. aureus isolates were 0.06/0.125 μg/ml, 2/4 μg/ml, 1/2 μg/ml, and 2/2 μg/ml, respectively. Against 100 VISA isolates, the MIC50/90were 0.06/0.125 μg/ml, 1/1 μg/ml, 4/8 μg/ml, and 1/2 μg/ml, respectively. Against 170 hVISA isolates, the MIC50/90were 0.06/0.125 μg/ml, 0.5/1 μg/ml, 1/2 μg/ml, and 1/2 μg/ml, respectively. Against 25 LZDrisolates, the MIC50/90were 0.03/0.06 μg/ml, 1/1 μg/ml, 2/2 μg/ml, and 8/8 μg/ml, respectively. The TLV MIC was >0.125 μg/ml for 10/365 (2.7%) isolates. In PK/PD models, TLV was universally bactericidal at 168 h and statistically superior to all antibiotics against DNS S. aureus strain R2334. These data further establish the potency of TLV against resistant MRSA. The model data demonstratein vitrobactericidal activity of TLV against hVISA, VISA, DNS S. aureus, and LZDrS. aureus strains. Further clinical research is warranted.