A randomized phase 2B trial of vancomycin versus daptomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteremia due to isolates with high vancomycin minimum inhibitory concentrations - results of a prematurely terminated study.
A randomized phase 2B trial of vancomycin versus daptomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteremia due to isolates with high vancomycin minimum inhibitory concentrations - results of a prematurely terminated study.
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DOI：
10.1186/s13063-018-2702-8
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发表时间：
2018-06-01
期刊：
影响因子：
2.5
通讯作者：
Low JGH
中科院分区：
文献类型：
--
作者：
Kalimuddin S;Chan YFZ;Phillips R;Ong SP;Archuleta S;Lye DC;Tan TT;Low JGH
研究表明，万古霉素最低抑菌浓度高时，万古霉素对耐甲氧西林金黄色葡萄球菌（MRSA）血流感染的有效性降低。可以考虑替代药物，如达托霉素。我们进行了一项随机对照研究，比较达托霉素与万古霉素治疗高万古霉素最低抑菌浓度MRSA血流感染的效果。患者随机接受万古霉素或达托霉素治疗至少14天。主要终点是第60天的全因死亡率。本研究共随机入组14例患者，每个治疗组7例患者，由于患者入组缓慢，研究提前终止。在第60天，万古霉素组有1例死亡，达托霉素组无死亡。两组中至微生物清除的中位时间均为4天（万古霉素组IQR为3-5天，达托霉素组为3-7天）。万古霉素组仅1例患者发生菌血症复发。两组的不良事件发生率相似。有1例肌肉骨骼毒性和1例药物相关性肾毒性-这两起事件均发生在达托霉素组。两个治疗组均无患者因感染恶化而需要停止研究治疗或添加第二种抗MRSA药物。基于本研究中评价的患者数量有限，尚不清楚替代的、更昂贵的药物如达托霉素在治疗高万古霉素最低抑菌浓度MRSA血流感染方面是否上级万古霉素。迫切需要更多的研究，但研究人员可能希望考虑采用新的替代试验方法，以确保更大的成功机会。ClinicalTrials.gov，NCT01975662。2013年11月5日注册。
Studies have suggested the reduced effectiveness of vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections with high vancomycin minimum inhibitory concentrations. Alternative agents such as daptomycin may be considered. We conducted a randomized controlled study comparing daptomycin against vancomycin in the treatment of MRSA bloodstream infections with high vancomycin minimum inhibitory concentrations. Patients were randomized to receive vancomycin or daptomycin for a minimum of 14 days. The primary end point was the rate of all-cause mortality at day 60. A total of 14 patients were randomized in this study, with 7 patients in each treatment arm. The study was terminated early due to slow patient accrual. At day 60, there was one death in the vancomycin arm and none in the daptomycin arm. The median time to microbiological clearance was 4 days in both arms (IQR 3–5 days in the vancomycin arm and 3–7 days in daptomycin arm). Only one patient in the vancomycin arm had recurrence of bacteremia. Rates of adverse events were similar in both arms. There was one case of musculoskeletal toxicity and one case of drug-related nephrotoxicity - both events occurred in the daptomycin arm. None of the patients in either treatment arm required cessation of study treatment or addition of a second anti-MRSA agent because of worsening infection. Based on the limited number of patients evaluated in this study, it remains unclear if alternative, more expensive agents such as daptomycin are superior to vancomycin in the treatment of high vancomycin minimum inhibitory concentration MRSA bloodstream infections. More studies are urgently needed but investigators may wish to consider employing novel, alternative trial methodologies to ensure a greater chance of success. ClinicalTrials.gov, NCT01975662. Registered on 5 November 2013.
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