当前位置:科学网首页 > 小柯机器人 >详情
万古霉素或达托霉素联合抗葡萄球菌β-内酰胺治疗MRSA菌血症并未改善临床结局
作者:小柯机器人 发布时间:2020/2/18 10:27:06

澳大利亚墨尔本大学Steven Y. C. Tong联合查尔斯达尔文大学Joshua S. Davis课题组近日取得一项新成果。他们研究了万古霉素或达托霉素联合或不联合抗葡萄球菌β-内酰胺治疗MRSA菌血症的疗效。这一研究成果发表在2020年2月11日出版的国际学术期刊《美国医学会杂志》上。

耐甲氧西林金黄色葡萄球菌(MRSA)菌血症与20%以上的死亡有关。标准疗法联合β-内酰胺抗生素可以降低死亡率,但尚未有足够有力的随机临床试验证据。

2015年8月至2018年7月,研究组在4个国家的27家医院开展了一项开放标签、随机、临床试验,招募了352名MRSA菌血症住院患者,将其随机分组,其中174名接受标准治疗(静脉注射万古霉素或达托霉素)联合抗葡萄球菌β-内酰胺(静脉注射氟氯西林、氯唑西林或头孢唑啉,给药7天);178名仅接受标准治疗。主要终点包括90天死亡率、菌血症持续5天、微生物复发和微生物治疗失败。

352名患者的平均年龄为62.2岁,女性占34.4%,有345名患者完成试验。联合治疗组中有59例(35%)患者达到主要终点,标准治疗组中有68例(39%),差异不显著。

两组间9个次要终点中有7个无显著差异。联合治疗组和标准治疗组的全因90天死亡率分别为21%和16%,菌血症持续5天率分别为11%和20%,急性肾损伤(AKI)发生率分别为23%和6%。

总之,对于MRSA菌血症患者,万古霉素或达托霉素的标准抗生素疗法联合抗葡萄球菌β-内酰胺并不能显著改善死亡率、持续菌血症、复发或治疗失败的综合结局。

附:英文原文

Title: Effect of Vancomycin or Daptomycin With vs Without an Antistaphylococcal β-Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA Bacteremia: A Randomized Clinical Trial

Author: Steven Y. C. Tong, David C. Lye, Dafna Yahav, Archana Sud, J. Owen Robinson, Jane Nelson, Sophia Archuleta, Matthew A. Roberts, Alan Cass, David L. Paterson, Hong Foo, Mical Paul, Stephen D. Guy, Adrian R. Tramontana, Genevieve B. Walls, Stephen McBride, Narin Bak, Niladri Ghosh, Benjamin A. Rogers, Anna P. Ralph, Jane Davies, Patricia E. Ferguson, Ravindra Dotel, Genevieve L. McKew, Timothy J. Gray, Natasha E. Holmes, Simon Smith, Morgyn S. Warner, Shirin Kalimuddin, Barnaby E. Young, Naomi Runnegar, David N. Andresen, Nicholas A. Anagnostou, Sandra A. Johnson, Mark D. Chatfield, Allen C. Cheng, Vance G. Fowler, Benjamin P. Howden, Niamh Meagher, David J. Price, Sebastiaan J. van Hal, Matthew V. N. O’Sullivan, Joshua S. Davis

Issue&Volume: 2020/02/11

Abstract:

Importance  Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with mortality of more than 20%. Combining standard therapy with a β-lactam antibiotic has been associated with reduced mortality, although adequately powered randomized clinical trials of this intervention have not been conducted.

Objective  To determine whether combining an antistaphylococcal β-lactam with standard therapy is more effective than standard therapy alone in patients with MRSA bacteremia.

Design, Setting, and Participants  Open-label, randomized clinical trial conducted at 27 hospital sites in 4 countries from August 2015 to July 2018 among 352 hospitalized adults with MRSA bacteremia. Follow-up was complete on October 23, 2018.

Interventions  Participants were randomized to standard therapy (intravenous vancomycin or daptomycin) plus an antistaphylococcal β-lactam (intravenous flucloxacillin, cloxacillin, or cefazolin) (n = 174) or standard therapy alone (n = 178). Total duration of therapy was determined by treating clinicians and the β-lactam was administered for 7 days.

Main Outcomes and Measures  The primary end point was a 90-day composite of mortality, persistent bacteremia at day 5, microbiological relapse, and microbiological treatment failure. Secondary outcomes included mortality at days 14, 42, and 90; persistent bacteremia at days 2 and 5; acute kidney injury (AKI); microbiological relapse; microbiological treatment failure; and duration of intravenous antibiotics.

Results  The data and safety monitoring board recommended early termination of the study prior to enrollment of 440 patients because of safety. Among 352 patients randomized (mean age, 62.2 [SD, 17.7] years; 121 women [34.4%]), 345 (98%) completed the trial. The primary end point was met by 59 (35%) with combination therapy and 68 (39%) with standard therapy (absolute difference, −4.2%; 95% CI, −14.3% to 6.0%). Seven of 9 prespecified secondary end points showed no significant difference. For the combination therapy vs standard therapy groups, all-cause 90-day mortality occurred in 35 (21%) vs 28 (16%) (difference, 4.5%; 95% CI, −3.7% to 12.7%); persistent bacteremia at day 5 was observed in 19 of 166 (11%) vs 35 of 172 (20%) (difference, −8.9%; 95% CI, −16.6% to −1.2%); and, excluding patients receiving dialysis at baseline, AKI occurred in 34 of 145 (23%) vs 9 of 145 (6%) (difference, 17.2%; 95% CI, 9.3%-25.2%).

Conclusions and Relevance  Among patients with MRSA bacteremia, addition of an antistaphylococcal β-lactam to standard antibiotic therapy with vancomycin or daptomycin did not result in significant improvement in the primary composite end point of mortality, persistent bacteremia, relapse, or treatment failure. Early trial termination for safety concerns and the possibility that the study was underpowered to detect clinically important differences in favor of the intervention should be considered when interpreting the findings.

DOI: 10.1001/jama.2020.0103

Source: https://jamanetwork.com/journals/jama/article-abstract/2760737

期刊信息

JAMA-Journal of The American Medical Association:《美国医学会杂志》,创刊于1883年。隶属于美国医学协会,最新IF:51.273
官方网址:https://jamanetwork.com/
投稿链接:http://manuscripts.jama.com/cgi-bin/main.plex