Effect of Vancomycin or Daptomycin With vs Without an Antistaphylococcal β-Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA Bacteremia,JAMA

当前位置： X-MOL 学术 › JAMA › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Effect of Vancomycin or Daptomycin With vs Without an Antistaphylococcal β-Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA Bacteremia
JAMA ( IF 63.1 ) Pub Date : 2020-02-11 , DOI: 10.1001/jama.2020.0103
Steven Y C Tong _{1,

2} , David C Lye _{3,

4,

5,

6} , Dafna Yahav _{7,

8} , Archana Sud _{9,

10} , J Owen Robinson _{11,

12,

13,

14} , Jane Nelson ₂ , Sophia Archuleta _{15,

16} , Matthew A Roberts _{17,

18} , Alan Cass ₂ , David L Paterson ₁₉ , Hong Foo ₂₀ , Mical Paul _{21,

22} , Stephen D Guy ₂₃ , Adrian R Tramontana ₂₃ , Genevieve B Walls ₂₄ , Stephen McBride ₂₄ , Narin Bak ₂₅ , Niladri Ghosh ₂₆ , Benjamin A Rogers _{27,

28} , Anna P Ralph _{2,

29} , Jane Davies _{2,

29} , Patricia E Ferguson ₃₀ , Ravindra Dotel _{30,

31} , Genevieve L McKew _{32,

33} , Timothy J Gray _{32,

33} , Natasha E Holmes ₃₄ , Simon Smith ₃₅ , Morgyn S Warner _{36,

37} , Shirin Kalimuddin _{38,

39} , Barnaby E Young _{3,

4} , Naomi Runnegar _{40,

41} , David N Andresen _{42,

43} , Nicholas A Anagnostou ₄₄ , Sandra A Johnson ₁ , Mark D Chatfield _{2,

19} , Allen C Cheng _{45,

46} , Vance G Fowler _{47,

48} , Benjamin P Howden _{34,

49} , Niamh Meagher ₅₀ , David J Price _{50,

51} , Sebastiaan J van Hal ₅₂ , Matthew V N O'Sullivan _{33,

53} , Joshua S Davis _{2,

54} ,

Affiliation

Victorian Infectious Disease Service, Royal Melbourne Hospital, and University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Menzies School of Health Research, Charles Darwin University, Casuarina, Northern Territory, Australia.
National Centre for Infectious Diseases, Singapore.
Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore.
Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Nepean Clinical School, University of Sydney, Sydney, New South Wales, Australia.
Nepean Hospital, Kingswood, New South Wales, Australia.
Royal Perth Hospital, Perth, Western Australia, Australia.
Fiona Stanley Hospital, Murdoch, Western Australia, Australia.
Pathwest Laboratory Medicine WA, Murdoch, Western Australia, Australia.
Antimicrobial Resistance and Infectious Diseases Research Laboratory, School of Veterinary and Life Sciences, Murdoch University, Murdoch, Western Australia, Australia.
Division of Infectious Diseases, National University Hospital, Singapore.
Department of Medicine, National University of Singapore, Singapore.
Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia.
Eastern Health Clinical School, Monash University, Box Hill, Victoria, Australia.
Centre for Clinical Research, University of Queensland, Herston, Australia.
Department of Microbiology and Infectious Diseases, NSW Health Pathology, Liverpool, New South Wales, Australia.
Rambam Health Care Campus, Haifa, Israel.
Technion-Israel Institute of Technology, Haifa, Israel.
Footscray Hospital, Western Health, Footscray, Victoria, Australia.
Department of Infectious Diseases, Middlemore Hospital, Auckland, New Zealand.
Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Wollongong Public Hospital, Wollongong, New South Wales, Australia.
School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
Monash Infectious Diseases, Monash Medical Centre, Clayton, Victoria, Australia.
Division of Medicine, Royal Darwin Hospital, Tiwi, Northern Territory, Australia.
Department of Infectious Diseases, Blacktown Hospital, Blacktown, New South Wales, Australia.
Centre for Infectious Diseases and Microbiology, Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia.
Department of Microbiology and Infectious Diseases, Concord Repatriation General Hospital, Concord, New South Wales, Australia.
Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Department of Infectious Diseases, Austin Health, Austin Centre for Infection Research, Heidelberg, Victoria, Australia.
Cairns Hospital, Cairns, Queensland, Australia.
The Queen Elizabeth Hospital, Woodville, South Australia, Australia.
University of Adelaide, Adelaide, South Australia, Australia.
Department of Infectious Diseases, Singapore General Hospital, Singapore.
Duke-NUS Medical School, Singapore.
Infection Management Services, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Southern Clinical School, Faculty of Medicine, University of Queensland, Brisbane, Australia.
St Vincent's Public Hospital Sydney, Darlinghurst, New South Wales, Australia.
School of Medicine, University of Notre Dame, Darlinghurst, New South Wales, Australia.
Flinders Medical Centre, Adelaide, South Australia, Australia.
School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
Infection Prevention and Healthcare Epidemiology Unit, Alfred Health, Melbourne, Victoria, Australia.
Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
Microbiological Diagnostic Unit Public Health Laboratory, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Victorian Infectious Diseases Reference Laboratory Epidemiology Unit, Royal Melbourne Hospital, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Victoria, Australia.
Department of Microbiology and Infectious Disease, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
New South Wales Health Pathology, Westmead Hospital, Westmead, Australia.
Department of Infectious Diseases, John Hunter Hospital, Newcastle, New South Wales, Australia.

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. Trial Registration ClinicalTrials.gov Identifier: NCT02365493.

中文翻译：

万古霉素或达托霉素联合与不联合抗葡萄球菌 β-内酰胺对 MRSA 菌血症患者死亡率、菌血症、复发或治疗失败的影响

重要性耐甲氧西林金黄色葡萄球菌 (MRSA) 菌血症与超过 20% 的死亡率相关。将标准疗法与 β-内酰胺类抗生素相结合可降低死亡率，尽管尚未进行这种干预措施的充分把握的随机临床试验。目的确定在 MRSA 菌血症患者中，抗葡萄球菌 β-内酰胺类药物联合标准疗法是否比单独标准疗法更有效。设计、设置和参与者 2015 年 8 月至 2018 年 7 月，在 4 个国家的 27 个医院地点对 352 名患有 MRSA 菌血症的住院成人进行了开放标签、随机临床试验。随访于2018年10月23日完成。干预参与者随机接受标准治疗（静脉内万古霉素或达托霉素）加抗葡萄球菌 β-内酰胺（静脉内氟氯西林、氯唑西林或头孢唑林）（n = 174）或单独标准治疗（n = 178）。治疗的总持续时间由治疗临床医生确定，β-内酰胺给药 7 天。主要结果和测量主要终点是死亡率、第 5 天持续菌血症、微生物学复发和微生物学治疗失败的 90 天复合终点。次要结果包括第 14、42 和 90 天的死亡率；第 2 天和第 5 天持续菌血症；急性肾损伤 (AKI); 微生物复发；微生物处理失败；和静脉注射抗生素的持续时间。结果出于安全考虑，数据和安全监察委员会建议在招募 440 名患者之前提前终止研究。在随机分配的 352 名患者中（平均年龄 62.2 [SD，17.7] 岁；121 名女性 [34.4%]），345 名 (98%) 完成了试验。59 名（35%）联合治疗达到主要终点，标准治疗 68 名（39%）达到主要终点（绝对差异，-4.2%；95% CI，-14.3% 至 6.0%）。9 个预设的次要终点中有 7 个没有显着差异。对于联合治疗组与标准治疗组，90 天全因死亡率分别为 35 (21%) 和 28 (16%)（差异，4.5%；95% CI，-3.7% 至 12.7%）；166 人中有 19 人（11%）与 172 人中有 35 人（20%）在第 5 天观察到持续性菌血症（差异，-8.9%；95% CI，-16.6% 至 -1.2%）；并且，不包括在基线时接受透析的患者，145 人中的 34 人 (23%) 与 145 人中的 9 人 (6%) 发生 AKI（差异，17.2%；95% CI，9.3%-25.2%）。结论和相关性在 MRSA 菌血症患者中，在万古霉素或达托霉素标准抗生素治疗中加入抗葡萄球菌 β-内酰胺类药物并未显着改善死亡率、持续性菌血症、复发或治疗失败等主要复合终点。在解释研究结果时，应考虑出于安全考虑而提前终止试验以及该研究不足以检测有利于干预的临床重要差异的可能性。试验注册 ClinicalTrials.gov 标识符：NCT02365493。在使用万古霉素或达托霉素的标准抗生素治疗中添加抗葡萄球菌 β-内酰胺类药物，并未显着改善死亡率、持续性菌血症、复发或治疗失败等主要复合终点。在解释研究结果时，应考虑出于安全考虑而提前终止试验以及该研究不足以检测有利于干预的临床重要差异的可能性。试验注册 ClinicalTrials.gov 标识符：NCT02365493。在使用万古霉素或达托霉素的标准抗生素治疗中添加抗葡萄球菌 β-内酰胺类药物，并未显着改善死亡率、持续性菌血症、复发或治疗失败等主要复合终点。在解释研究结果时，应考虑出于安全考虑而提前终止试验以及该研究不足以检测有利于干预的临床重要差异的可能性。试验注册 ClinicalTrials.gov 标识符：NCT02365493。在解释研究结果时，应考虑出于安全考虑而提前终止试验以及该研究不足以检测有利于干预的临床重要差异的可能性。试验注册 ClinicalTrials.gov 标识符：NCT02365493。在解释研究结果时，应考虑出于安全考虑而提前终止试验以及该研究不足以检测有利于干预的临床重要差异的可能性。试验注册 ClinicalTrials.gov 标识符：NCT02365493。

更新日期：2020-02-11

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文