Infectious Diseases Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tikva.
Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
Clin Infect Dis. 2019 Sep 13;69(7):1091-1098. doi: 10.1093/cid/ciy1054.
Gram-negative bacteremia is a major cause of morbidity and mortality in hospitalized patients. Data to guide the duration of antibiotic therapy are limited.
This was a randomized, multicenter, open-label, noninferiority trial. Inpatients with gram-negative bacteremia, who were afebrile and hemodynamically stable for at least 48 hours, were randomized to receive 7 days (intervention) or 14 days (control) of covering antibiotic therapy. Patients with uncontrolled focus of infection were excluded. The primary outcome at 90 days was a composite of all-cause mortality; relapse, suppurative, or distant complications; and readmission or extended hospitalization (>14 days). The noninferiority margin was set at 10%.
We included 604 patients (306 intervention, 298 control) between January 2013 and August 2017 in 3 centers in Israel and Italy. The source of the infection was urinary in 411 of 604 patients (68%); causative pathogens were mainly Enterobacteriaceae (543/604 [90%]). A 7-day difference in the median duration of covering antibiotics was achieved. The primary outcome occurred in 140 of 306 patients (45.8%) in the 7-day group vs 144 of 298 (48.3%) in the 14-day group (risk difference, -2.6% [95% confidence interval, -10.5% to 5.3%]). No significant differences were observed in all other outcomes and adverse events, except for a shorter time to return to baseline functional status in the short-course therapy arm.
In patients hospitalized with gram-negative bacteremia achieving clinical stability before day 7, an antibiotic course of 7 days was noninferior to 14 days. Reducing antibiotic treatment for uncomplicated gram-negative bacteremia to 7 days is an important antibiotic stewardship intervention.
NCT01737320.
革兰氏阴性菌血症是住院患者发病率和死亡率的主要原因。指导抗生素治疗时间的数据有限。
这是一项随机、多中心、开放性、非劣效性试验。患有革兰氏阴性菌血症、至少 48 小时无发热且血流动力学稳定的住院患者被随机分配接受 7 天（干预组）或 14 天（对照组）的覆盖抗生素治疗。未控制感染灶的患者被排除在外。90 天的主要结局是全因死亡率；复发、化脓性或远处并发症；以及再入院或延长住院时间（>14 天）。非劣效性边界设定为 10%。
我们纳入了 2013 年 1 月至 2017 年 8 月在以色列和意大利的 3 个中心的 604 名患者（306 名干预组，298 名对照组）。604 名患者中有 411 名（68%）的感染源为尿源性；病原体主要为肠杆菌科（543/604 [90%]）。实现了覆盖抗生素的中位治疗时间相差 7 天。7 天组有 306 名患者中的 140 名（45.8%）和 14 天组有 298 名患者中的 144 名（48.3%）发生主要结局（风险差异，-2.6% [95%置信区间，-10.5%至 5.3%]）。除了短期治疗组患者在返回基线功能状态的时间较短外，其他所有结局和不良事件均无显著差异。
在第 7 天前达到临床稳定的革兰氏阴性菌血症住院患者中，7 天的抗生素疗程不劣于 14 天。将简单的革兰氏阴性菌血症的抗生素治疗时间减少到 7 天是一种重要的抗生素管理干预措施。
NCT01737320。
