Intensive Care Center and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
Medical Microbiology and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
JAMA. 2018 Nov 27;320(20):2087-2098. doi: 10.1001/jama.2018.13765.
The effects of chlorhexidine (CHX) mouthwash, selective oropharyngeal decontamination (SOD), and selective digestive tract decontamination (SDD) on patient outcomes in ICUs with moderate to high levels of antibiotic resistance are unknown.
To determine associations between CHX 2%, SOD, and SDD and the occurrence of ICU-acquired bloodstream infections with multidrug-resistant gram-negative bacteria (MDRGNB) and 28-day mortality in ICUs with moderate to high levels of antibiotic resistance.
DESIGN, SETTING, AND PARTICIPANTS: Randomized trial conducted from December 1, 2013, to May 31, 2017, in 13 European ICUs where at least 5% of bloodstream infections are caused by extended-spectrum β-lactamase-producing Enterobacteriaceae. Patients with anticipated mechanical ventilation of more than 24 hours were eligible. The final date of follow-up was September 20, 2017.
Standard care was daily CHX 2% body washings and a hand hygiene improvement program. Following a baseline period from 6 to 14 months, each ICU was assigned in random order to 3 separate 6-month intervention periods with either CHX 2% mouthwash, SOD (mouthpaste with colistin, tobramycin, and nystatin), or SDD (the same mouthpaste and gastrointestinal suspension with the same antibiotics), all applied 4 times daily.
The occurrence of ICU-acquired bloodstream infection with MDRGNB (primary outcome) and 28-day mortality (secondary outcome) during each intervention period compared with the baseline period.
A total of 8665 patients (median age, 64.1 years; 5561 men [64.2%]) were included in the study (2251, 2108, 2224, and 2082 in the baseline, CHX, SOD, and SDD periods, respectively). ICU-acquired bloodstream infection with MDRGNB occurred among 144 patients (154 episodes) in 2.1%, 1.8%, 1.5%, and 1.2% of included patients during the baseline, CHX, SOD, and SDD periods, respectively. Absolute risk reductions were 0.3% (95% CI, -0.6% to 1.1%), 0.6% (95% CI, -0.2% to 1.4%), and 0.8% (95% CI, 0.1% to 1.6%) for CHX, SOD, and SDD, respectively, compared with baseline. Adjusted hazard ratios were 1.13 (95% CI, 0.68-1.88), 0.89 (95% CI, 0.55-1.45), and 0.70 (95% CI, 0.43-1.14) during the CHX, SOD, and SDD periods, respectively, vs baseline. Crude mortality risks on day 28 were 31.9%, 32.9%, 32.4%, and 34.1% during the baseline, CHX, SOD, and SDD periods, respectively. Adjusted odds ratios for 28-day mortality were 1.07 (95% CI, 0.86-1.32), 1.05 (95% CI, 0.85-1.29), and 1.03 (95% CI, 0.80-1.32) for CHX, SOD, and SDD, respectively, vs baseline.
Among patients receiving mechanical ventilation in ICUs with moderate to high antibiotic resistance prevalence, use of CHX mouthwash, SOD, or SDD was not associated with reductions in ICU-acquired bloodstream infections caused by MDRGNB compared with standard care.
ClinicalTrials.gov Identifier: NCT02208154.
重要性：在抗生素耐药性处于中高水平的 ICU 中，氯己定（CHX）漱口水、选择性口咽去污（SOD）和选择性消化道去污（SDD）对患者结局的影响尚不清楚。
目的：确定 CHX 2%、SOD 和 SDD 与 ICU 获得性血流感染与多重耐药革兰氏阴性菌（MDRGNB）的发生以及中高水平抗生素耐药性 ICU 内 28 天死亡率之间的关联。
设计、设置和参与者：2013 年 12 月 1 日至 2017 年 5 月 31 日期间在 13 个欧洲 ICU 进行的随机试验，这些 ICU 中至少有 5%的血流感染是由产超广谱β-内酰胺酶的肠杆菌科引起的。预计需要机械通气超过 24 小时的患者有资格参加。最后随访日期为 2017 年 9 月 20 日。
干预措施：标准护理是每天使用 CHX 2%的全身沐浴和手部卫生改善计划。在为期 6 至 14 个月的基线期之后，每个 ICU 随机分配到 3 个单独的为期 6 个月的干预期，分别应用 CHX 2%漱口液、SOD（含有黏菌素、妥布霉素和制霉菌素的牙膏）或 SDD（相同的牙膏和含有相同抗生素的胃肠道混悬液），每日应用 4 次。
主要结局和测量：与基线期相比，每个干预期 ICU 获得性血流感染与 MDRGNB（主要结局）和 28 天死亡率（次要结局）的发生情况。
结果：共有 8665 名患者（中位年龄 64.1 岁；5561 名男性[64.2%]）纳入研究（基线期、CHX、SOD 和 SDD 期分别为 2251、2108、2224 和 2082 例）。在基线期、CHX、SOD 和 SDD 期，分别有 144 名（154 例）、1.8%、1.5%和 1.2%的患者发生 ICU 获得性血流感染与 MDRGNB。绝对风险降低分别为 0.3%（95%CI，-0.6%至 1.1%）、0.6%（95%CI，-0.2%至 1.4%）和 0.8%（95%CI，0.1%至 1.6%）。与基线相比，CHX、SOD 和 SDD 期的调整后的危险比分别为 1.13（95%CI，0.68-1.88）、0.89（95%CI，0.55-1.45）和 0.70（95%CI，0.43-1.14）。基线期、CHX、SOD 和 SDD 期的第 28 天死亡率分别为 31.9%、32.9%、32.4%和 34.1%。调整后的 28 天死亡率的比值比分别为 1.07（95%CI，0.86-1.32）、1.05（95%CI，0.85-1.29）和 1.03（95%CI，0.80-1.32），与基线相比，CHX、SOD 和 SDD 期。
结论和相关性：在中高度抗生素耐药性 ICU 中接受机械通气的患者中，与标准护理相比，使用 CHX 漱口水、SOD 或 SDD 并不能降低由 MDRGNB 引起的 ICU 获得性血流感染。
试验注册：ClinicalTrials.gov 标识符：NCT02208154。
