感染性心内膜炎的疗效导向或标准疗程抗生素治疗
完整摘要 · 中文译文
背景：对于左侧心脏感染性心内膜炎患者，目前建议最长6周抗生素治疗的推荐主要基于专家共识意见。根据临床应答调整的抗生素管理策略能否在不影响安全性的前提下缩短治疗时长，尚不清楚。 方法：在这项国际、开放标签、随机试验中，我们将病情稳定、由金黄色葡萄球菌、粪肠球菌或链球菌属引起的感染性心内膜炎成人患者分配接受应答调整或标准疗程抗生素治疗。随机分组前，所有患者均已接受至少预先规定的2至4周治疗，并达到临床稳定标准。随机分组后，调整治疗组患者停用抗生素，标准治疗组患者继续接受标准治疗（总疗程4至6周）。主要疗效终点为随机分组后6个月内无感染性心内膜炎或菌血症且未使用抗生素治疗的存活天数（检验优效性）。主要安全性终点为随机分组后6个月内全因死亡、非计划心脏手术或症状性栓塞事件的复合终点（检验非劣效性；界值为7.5个百分点）。菌血症或感染性心内膜炎复发为关键次要终点。 结果：共有508例患者接受了随机分组，其中255例被分配至应答指导治疗组，253例被分配至标准疗程治疗组。无抗生素治疗的中位存活时间为：个体化治疗组183天（四分位距，181至183），标准治疗组169天（四分位距，166至171）（Hodges-Lehmann估计差异，13天；95%置信区间[CI]，12至13；优效性P<0.001）。个体化治疗组有21例患者（8.2%）、标准治疗组有27例患者（10.7%）发生主要安全性终点事件（绝对组间差异，-2.4个百分点；95% CI，-7.7至2.7；非劣效性P<0.001），表明非劣效性成立。个体化治疗组有13例患者（5.1%）、标准治疗组有4例患者（1.6%）出现复发（P = 0.04）。 结论：在左心感染性心内膜炎患者中，与标准疗程治疗相比，采用应答指导的抗生素策略可延长无抗生素治疗存活时间，且在安全性方面符合非劣效性标准，但菌血症或感染性心内膜炎的复发率更高。（由Sygeforsikringen “danmark”等资助；POET II ClinicalTrials.gov注册号，NCT03851575。）
完整摘要 · 英文原文
BACKGROUND: In patients with infective endocarditis on the left side of the heart, the current recommendation of up to 6 weeks of antibiotic therapy is based largely on expert consensus opinion. Whether a clinical response-tailored antibiotic management strategy can shorten treatment duration without compromising safety is unclear. METHODS: In this international, open-label, randomized trial, we assigned adults in stable condition with infective endocarditis caused by Staphylococcus aureus, Enterococcus faecalis, or streptococcus species to receive either response-tailored or standard-duration antibiotic therapy. Before randomization, all the patients received at least the prespecified 2 to 4 weeks of therapy and met criteria for clinical stabilization. After randomization, patients in the tailored-therapy group discontinued antibiotics and those in the standard-therapy group continued standard treatment (total duration, 4 to 6 weeks). The primary efficacy end point was days alive without antibiotic treatment for infective endocarditis or bacteremia within 6 months after randomization (tested for superiority). The primary safety end point was a composite of death from any cause, unplanned cardiac surgery, or symptomatic embolic events within 6 months after randomization (tested for noninferiority; margin, 7.5 percentage points). Relapse of bacteremia or infective endocarditis was a key secondary end point. RESULTS: A total of 508 patients underwent randomization, with 255 assigned to response-tailored therapy and 253 to standard-duration therapy. The median time alive without antibiotic treatment was 183 days (interquartile range, 181 to 183) with tailored therapy and 169 days (interquartile range, 166 to 171) with standard therapy (Hodges-Lehmann estimated difference, 13 days; 95% confidence interval [CI], 12 to 13; P<0.001 for superiority). A primary safety end-point event occurred in 21 patients (8.2%) with tailored therapy and in 27 patients (10.7%) with standard therapy (absolute between-group difference, -2.4 percentage points; 95% CI, -7.7 to 2.7; P<0.001 for noninferiority), indicating noninferiority. Relapse occurred in 13 patients (5.1%) with tailored therapy and in 4 patients (1.6%) with standard therapy (P = 0.04). CONCLUSIONS: Among patients with infective endocarditis on the left side of the heart, the use of a response-tailored antibiotic strategy resulted in a longer time alive without antibiotic therapy than standard-duration therapy and met the criterion for noninferiority with respect to safety but was associated with a higher incidence of relapse of bacteremia or infective endocarditis. (Funded by Sygeforsikringen "danmark" and others; POET II ClinicalTrials.gov number, NCT03851575.).