Ceftriaxone to Prevent Early-Onset Pneumonia in Comatose Patients Following Out-of-Hospital Cardiac Arrest: A Pilot Randomized Controlled Trial and Resistome Assessment (PROTECT).

However, it has an uncertain impact on mortality and noninfectious outcomes, with ongoing concerns about the subsequent development of antibiotic resistance.

然而，它对死亡率和非感染性结果的影响尚不确定，且人们持续担忧随后可能出现的抗生素耐药性问题。

research_question

Does prophylactic ceftriaxone reduce the incidenceof early-onset pneumonia without increasing the acquisition of antibiotic resistance genes after OHCA?

预防性使用头孢曲松是否能在不增加抗生素耐药基因获得的情况下降低心搏骤停后早期肺炎的发生率？

study_design_and_methods

Comatose survivors of OHCA treated with targeted temperature management without a clinical diagnosis of pneumonia at admission were randomized to receive ceftriaxone 2 g or matching placebo every 12 hours for 3 days.

对于入院时没有肺炎临床诊断的心搏骤停后昏迷幸存者，在目标温度管理治疗下，随机接受每12小时2克头孢曲松或匹配安慰剂，连续3天。

The primary outcome was early-onset pneumonia occurring ≤ 4 days following intubation confirmed by masked adjudicators.

主要结果是插管后≤4天内发生的早期肺炎，由蒙面评估者确认。

Abundance of antibiotic resistance genes recovered from rectal swabs before and after study drug administration were analyzed with metagenomic sequencing.

研究药物给药前后从直肠拭子中回收的抗生素耐药基因的丰度通过宏基因组测序进行分析。

Results

A total of 411 participants were screened; 53 (13%) were randomized to treatment, and 1 participant withdrew, leaving 26 in each group in the final analysis.

共有411名参与者接受了筛查；其中53名（13%）被随机分配接受治疗，有1名参与者退出，最终分析中每组各有26名参与者。

Early-onset pneumonia was diagnosed in 10 (38%) participants receiving ceftriaxone and 18 (69%) participants receiving placebo (risk ratio, 0.57; 95% CI, 0.21-1.001; P = .05).

在接受头孢曲松治疗的10名（38%）参与者中诊断出早发性肺炎，而在接受安慰剂的18名（69%）参与者中诊断出早发性肺炎（风险比，0.57；95%置信区间，0.21-1.001；P = .05）。

Open-label antibiotics were administered to 14 (54%) participants receiving ceftriaxone and 22 (85%) receiving placebo (risk ratio, 0.64; 95% CI, 0.43-0.94); most of the antibiotics were broad-spectrum agents (93% and 100%, respectively).

开放标签抗生素给予14名（54%）接受头孢曲松治疗的参与者和22名（85%）接受安慰剂的参与者（风险比，0.64；95%置信区间，0.43-0.94）；大多数抗生素是广谱药物（分别为93%和100%）。

After adjusting for differences in abundance of antibiotic resistance genes prior to study drug administration, participants randomized to receive ceftriaxone acquired significantly fewer antibiotic resistance genes to frequently used antibiotics in the ICU compared with those randomized to receive placebo (incidencerisk ratio, 0.30; 95% CI, 0.13-0.70).

在调整研究药物给药前抗生素耐药基因丰度的差异后，被随机分配接受头孢曲松治疗的参与者相比被随机分配接受安慰剂的参与者，显著较少获得经常用于ICU的抗生素的耐药基因（发生风险比，0.30；95%置信区间，0.13-0.70）。

Serious adverse drug effects were not reported in either treatment group.

在任一治疗组中均未报告严重的药物不良反应。

interpretation

This trial was inconclusive regarding the impact of ceftriaxone prophylaxis on reducing the incidenceof early-onset pneumonia following OHCA.

该试验关于头孢曲松预防措施对降低心脏骤停后早期肺炎发生率的影响无法得出明确结论。

However, ceftriaxone was associated with less frequent administration of open-label antibiotics and reduced acquisition of antibiotic resistance genes to frequently used antibiotics in the ICU.

然而，头孢曲松与较少的开放标签抗生素给药频率相关，并减少了在重症监护病房（ICU）中频繁使用的抗生素抗药性基因的获得。

clinical_trial_registration

ClinicalTrials.gov; No.: NCT04999592; URL: www.

ClinicalTrials.gov; 注册号：NCT04999592; 网址：www.

clinicaltrials

gov.

5年总生存率为65%（95%置信区间，58%-72%）。