Surgical site infections (SSIs) are common complications after colorectal surgery. Oral non-absorbable antibiotic prophylaxis (OAP) can be administered preoperatively to reduce the risk of SSIs. Its efficacy without simultaneous mechanical cleaning is unknown. The Precaution trial was a double-blind, placebo-controlled randomized clinical trial conducted in six Dutch hospitals. Adult patients who underwent elective colorectal surgery were randomized to receive either a three-day course of preoperative OAP with tobramycin and colistin or placebo. The primary composite endpoint was the incidence of deep SSI or mortality within 30 days after surgery. Secondary endpoints included both infectious and non-infectious complications at 30 days and six months after surgery. The study was prematurely ended due to the loss of clinical equipoise. At that time, 39 patients had been randomized to active OAP and 39 to placebo, which reflected 8.1% of the initially pursued sample size. Nine (11.5%) patients developed the primary outcome, of whom four had been randomized to OAP (4/39; 10.3%) and five to placebo (5/39; 12.8%). This corresponds to a risk ratio in the intention-to-treat analysis of 0.80 (95% confidence interval (CI) 0.23–2.78). In the per-protocol analysis, the relative risk was 0.64 (95% CI 0.12–3.46). Observational data emerging during the study provided new evidence for the effectiveness of OAP that changed both the clinical and medical ethical landscape for infection prevention in colorectal surgery. We therefore consider it unethical to continue randomizing patients to placebo. We recommend the implementation of OAP in clinical practice and continuing monitoring of infection rates and antibiotic susceptibilities. The PreCaution trial is registered in the Netherlands Trial Register under NL5932 (previously: NTR6113) as well as in the EudraCT register under 2015–005736-17.

中文翻译：

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使用口服非吸收性抗菌药物预防结直肠手术后的严重感染并发症：多中心随机安慰剂对照临床试验的结果。

手术部位感染（SSI）是结直肠手术后的常见并发症。可以在术前口服非吸收性抗生素预防措施（OAP），以降低SSI的风险。不需同时进行机械清洁的功效尚不清楚。预防试验是在荷兰的六家医院进行的一项双盲，安慰剂对照的随机临床试验。接受择期结直肠手术的成年患者被随机分配接受三天疗程的术前OAP联合妥布霉素和粘菌素的治疗或安慰剂治疗。主要的复合终点是术后30天内深SSI或死亡率的发生率。次要终点包括手术后30天和6个月时的感染性和非感染性并发症。由于失去了临床平衡，该研究提前结束。那时候，39例患者被随机分配接受活性OAP，39例被随机分配给安慰剂，占最初研究样本量的8.1％。9名患者（11.5％）出现了主要结局，其中4名患者被随机分配到OAP（4/39; 10.3％），五名患者接受安慰剂（5/39; 12.8％）。这对应于意向性分析中的风险比为0.80（95％置信区间（CI）为0.23-2.78）。在方案分析中，相对风险为0.64（95％CI 0.12–3.46）。研究期间出现的观察数据为OAP的有效性提供了新证据，OAP的有效性改变了大肠手术中预防感染的临床和医学伦理前景。因此，我们认为继续将患者随机分组接受安慰剂是不道德的。我们建议在临床实践中实施OAP，并继续监测感染率和抗生素敏感性。PreCaution试用版已在NL5932（以前是NTR6113）的荷兰审判注册簿中以及在2015–005736-17的EudraCT注册簿中注册。