BACKGROUND The optimal treatment duration for patients with bloodstream infection is understudied. The Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) pilot randomized clinical trial (RCT) determined that it was feasible to enroll and randomize intensive care unit (ICU) patients with bloodstream infection to 7 versus 14 days of treatment, and served as the vanguard for the ongoing BALANCE main RCT. We performed this BALANCE-Ward pilot RCT to examine the feasibility and impact of potentially extending the BALANCE main RCT to include patients hospitalized on non-ICU wards. METHODS We conducted an open pilot RCT among a subset of six sites participating in the ongoing BALANCE RCT, randomizing patients with positive non-Staphylococcus aureus blood cultures on non-ICU wards to 7 versus 14 days of antibiotic treatment. The co-primary feasibility outcomes were recruitment rate and adherence to treatment duration protocol. We compared feasibility outcomes, patient/pathogen characteristics, and overall outcomes among those enrolled in this BALANCE-Ward and prior BALANCE-ICU pilot RCTs. We estimated the sample size and non-inferiority margin impacts of expanding the BALANCE main RCT to include non-ICU patients. RESULTS A total of 134 patients were recruited over 47 site-months (mean 2.9 patients/site-month, median 1.0, range 0.1-4.4 patients/site-month). The overall recruitment rate exceeded the BALANCE-ICU pilot RCT (mean 1.10 patients/site-month, p < 0.0001). Overall protocol adherence also exceeded the adherence in the BALANCE-ICU pilot RCT (125/134, 93% vs 89/115, 77%, p = 0.0003). BALANCE-Ward patients were older, with lower Sequential Organ Failure Assessment scores, and higher proportions of infections caused by Escherichia coli and genito-urinary sources of bloodstream infection. The BALANCE-Ward pilot RCT patients had an overall 90-day mortality rate of 17/133 (12.8%), which was comparable to the 90-day mortality rate in the ICU pilot RCT (17/115, 14.8%) (p = 0.65). Simulation models indicated there would be minimal sample size and non-inferiority margin implications of expanding enrolment to increasing proportions of non-ICU versus ICU patients. CONCLUSION It is feasible to enroll non-ICU patients in a trial of 7 versus 14 days of antibiotics for bloodstream infection, and expanding the BALANCE RCT hospital-wide has the potential to improve the timeliness and generalizability of trial results. TRIAL REGISTRATION Clinicaltrials.gov, NCT02917551. Registered on September 28, 2016.

中文翻译：

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在非重症监护病房和重症监护病房进行的针对血液感染的抗生素治疗的7天和14天的随机对照试验的先期试验。

背景技术未充分研究血液感染患者的最佳治疗时间。临床有效性实际需要的细菌性抗生素长度（BALANCE）中试随机临床试验（RCT）确定，将有血液感染的重症监护病房（ICU）患者纳入和随机分配7天和14天治疗是可行的，并作为正在进行的BALANCE主RCT的先锋。我们执行了此BALANCE-Ward试点RCT，以检查将BALANCE主要RCT扩展到包括在非ICU病房住院的患者的可行性和影响。方法我们在参与正在进行的BALANCE RCT的六个部位的一部分中进行了开放性RCT试验，将非ICU病房中非金黄色葡萄球菌阳性血培养阳性的患者随机分为7天和14天进行抗生素治疗。共同主要的可行性结果是招募率和坚持治疗持续时间方案。我们比较了参加该BALANCE-Ward和以前的BALANCE-ICU试点RCT的受试者的可行性结果，患者/病原体特征以及总体结果。我们估计了将BALANCE主要RCT扩展到包括非ICU患者的样本量和非劣效性的影响。结果在47个站点月内招募了134位患者（平均2.9个患者/站点月，中位数1.0，范围0.1-4.4个患者/站点月）。总体招募率超过了BALANCE-ICU的RCT试点（平均1.10患者/站点-月，p <0.0001）。总体方案依从性也超过了BALANCE-ICU飞行员RCT中的依从性（125/134，93％对89/115，77％，p = 0.0003）。BALANCE-Ward患者年龄较大，顺序器官衰竭评估得分较低，大肠埃希菌和生殖泌尿生殖道感染引起的感染比例更高。BALANCE-Ward试点RCT患者的90天总死亡率为17/133（12.8％），与ICU试点RCT的90天死亡率相当（17/115，14.8％）（p = 0.65）。模拟模型表明，扩大招募人数以增加非ICU与ICU患者的比例将具有最小的样本量和非劣效性。结论将非ICU患者纳入7天和14天的抗生素用于血流感染的试验中是可行的，并且在整个医院范围内扩展BALANCE RCT有可能改善试验结果的及时性和可推广性。试验注册Clinicaltrials.gov，NCT02917551。