Patients with acute brain injury are at high risk of ventilator-associated pneumonia (VAP). The benefit of short-term antibiotic prophylaxis remains debated. We aimed to establish the effect of an early, single dose of the antibiotic ceftriaxone on the incidence of early VAP in patients with severe brain injury who required mechanical ventilation. PROPHY-VAP was a multicentre, randomised, double-blind, placebo-controlled, assessor-masked, superiority trial conducted in nine intensive care units in eight French university hospitals. We randomly assigned comatose (Glasgow Coma Scale score [GCS] ≤12) adult patients (age ≥18 years) who required mechanical ventilation for at least 48 h after acute brain injury to receive intravenous ceftriaxone 2 g or placebo once within the 12 h following tracheal intubation. Participants did not receive selective oropharyngeal and digestive tract decontamination. The primary outcome was the proportion of patients developing early VAP from the 2nd to the 7th day of mechanical ventilation, confirmed by masked assessors. The analysis was reported in the modified intention-to-treat population, which comprised all randomly assigned patients except those who withdrew or did not give consent to continue and those who did not receive the allocated treatment because they met a criterion for non-eligibility. The trial is registered with , . From Oct 14, 2015, to May 27, 2020, 345 patients were randomly assigned (1:1) to receive ceftriaxone (n=171) or placebo (n=174); 330 received the allocated intervention and 319 were included in the analysis (162 in the ceftriaxone group and 157 in the placebo group). 166 (52%) participants in the analysis were men and 153 (48%) were women. 15 patients did not receive the allocated intervention after randomisation and 11 withdrew their consent. Adjudication confirmed 93 cases of VAP, including 74 early infections. The incidence of early VAP was lower in the ceftriaxone group than in the placebo group (23 [14%] 51 [32%]; hazard ratio 0·60 [95% CI 0·38–0·95], p=0·030), with no microbiological impact and no adverse effects attributable to ceftriaxone. In patients with acute brain injury, a single ceftriaxone dose decreased the risk of early VAP. On the basis of our findings, we recommend that an early, single dose of ceftriaxone be included in all bundles for the prevention of VAP in patients with brain injury who require mechanical ventilation. French Ministry of Social Affairs and Health.

中文翻译：

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头孢曲松预防急性脑损伤患者早期呼吸机相关性肺炎：一项多中心、随机、双盲、安慰剂对照、评估者屏蔽的优越性试验

急性脑损伤患者患呼吸机相关性肺炎（VAP）的风险很高。短期抗生素预防的益处仍存在争议。我们的目的是确定早期单剂量抗生素头孢曲松对需要机械通气的严重脑损伤患者早期 VAP 发生率的影响。 PROPHY-VAP 是一项多中心、随机、双盲、安慰剂对照、评估者屏蔽的优效性试验，在法国八所大学医院的九个重症监护病房进行。我们将急性脑损伤后至少 48 小时需要机械通气的昏迷（格拉斯哥昏迷量表评分 [GCS] ≤ 12）成年患者（年龄≥18 岁）随机分组，在术后 12 小时内接受静脉注射头孢曲松 2 g 或安慰剂一次气管插管。参与者没有接受选择性口咽和消化道净化。主要结局是机械通气第 2 至第 7 天发生早期 VAP 的患者比例，由蒙面评估人员确认。该分析是在修改后的意向治疗人群中报告的，其中包括所有随机分配的患者，除了退出或不同意继续的患者以及因符合不合格标准而未接受分配治疗的患者。该试验已在 , 注册。从2015年10月14日至2020年5月27日，345名患者被随机分配（1:1）接受头孢曲松（n=171）或安慰剂（n=174）治疗； 330 人接受了分配的干预措施，319 人被纳入分析（头孢曲松组 162 人，安慰剂组 157 人）。参与分析的 166 名参与者（52%）为男性，153 名参与者（48%）为女性。 15 名患者在随机分组后没有接受分配的干预措施，11 名患者撤回同意。判决确认了 93 例 VAP 病例，其中包括 74 例早期感染病例。头孢曲松组早期 VAP 的发生率低于安慰剂组（23 [14%] 51 [32%]；风险比 0·60 [95% CI 0·38–0·95]，p=0· 030），没有微生物影响，也没有头孢曲松引起的副作用。在急性脑损伤患者中，单剂量头孢曲松可降低早期 VAP 的风险。根据我们的研究结果，我们建议所有捆绑包中均包含早期单剂量头孢曲松，以预防需要机械通气的脑损伤患者发生 VAP。法国社会事务和卫生部。