Department of Epidemiology, Julius Center for Health Sciences and Primary Care, Utrecht, Netherlands.
Department of Critical Care Medicine, Antwerp University Hospital, University of Antwerp, Edegem, Belgium.
PLoS One. 2022 May 3;17(5):e0265720. doi: 10.1371/journal.pone.0265720. eCollection 2022.
Repeated rotation of empiric antibiotic treatment strategies is hypothesized to reduce antibiotic resistance. Clinical rotation studies failed to change unit-wide prevalence of antibiotic resistant bacteria (ARB) carriage, including an international cluster-randomized crossover study. Unit-wide effects may differ from individual effects due to "ecological fallacy". This post-hoc analysis of a cluster-randomized crossover study assesses differences between cycling and mixing rotation strategies in acquisition of carriage with Gram-negative ARB in individual patients.
This was a controlled cluster-randomized crossover study in 7 ICUs in 5 European countries. Clinical cultures taken as routine care were used for endpoint assessment. Patients with a first negative culture and at least one culture collected in total were included. Community acquisitions (2 days of admission or less) were excluded. Primary outcome was ICU-acquisition of Enterobacterales species with reduced susceptibility to: third- or fourth generation cephalosporins or piperacillin-tazobactam, and Acinetobacter species and Pseudomonas aeruginosa with reduced susceptibility for piperacillin-tazobactam or carbapenems. Cycling (altering first-line empiric therapy for Gram-negative bacteria, every other 6-weeks), to mixing (changing antibiotic type every empiric antibiotic course). Rotated antibiotics were third- or fourth generation cephalosporins, piperacillin-tazobactam and carbapenems.
For this analysis 1,613 admissions were eligible (855 and 758 during cycling and mixing, respectively), with 16,437 microbiological cultures obtained. Incidences of acquisition with ARB during ICU-stay were 7.3% (n = 62) and 5.1% (n = 39) during cycling and mixing, respectively (p-value 0.13), after a mean of 17.7 (median 15) and 20.8 (median 13) days. Adjusted odds ratio for acquisition of ARB carriage during mixing was 0.62 (95% CI 0.38 to 1.00). Acquired carriage with ARB were Enterobacterales species (n = 61), Pseudomonas aeruginosa (n = 38) and Acinetobacter species (n = 20), with no statistically significant differences between interventions.
There was no statistically significant difference in individual patients' risk of acquiring carriage with Gram-negative ARB during cycling and mixing. These findings substantiate the absence of difference between cycling and mixing on the epidemiology of Gram-negative ARB in ICU.
This trial is registered with ClinicalTrials.gov, registered 10 January 2011, NCT01293071.
经验性抗生素治疗策略的反复轮换被假设可以降低抗生素耐药性。临床轮换研究未能改变单位范围内携带抗生素耐药菌（ARB）的流行率，包括一项国际群组随机交叉研究。由于“生态学谬误”，单位范围内的影响可能与个体影响不同。本项群组随机交叉研究的事后分析评估了在个体患者中，携带革兰氏阴性 ARB 的情况下，轮转和混合轮替策略在获得定植方面的差异。
这是在 5 个欧洲国家的 7 个 ICU 中进行的一项对照性群组随机交叉研究。临床培养物作为常规护理进行终点评估。纳入首次培养阴性且总共采集了至少一次培养物的患者。排除社区获得性感染（入院 2 天或更短时间内）。主要结局是 ICU 获得对第三代或第四代头孢菌素或哌拉西林他唑巴坦、以及对哌拉西林他唑巴坦或碳青霉烯类药物敏感性降低的肠杆菌科物种，以及对哌拉西林他唑巴坦或碳青霉烯类药物敏感性降低的鲍曼不动杆菌和铜绿假单胞菌。轮转（每隔 6 周改变一次针对革兰氏阴性菌的一线经验性治疗）至混合（每次经验性抗生素疗程改变抗生素类型）。轮换抗生素为第三代或第四代头孢菌素、哌拉西林他唑巴坦和碳青霉烯类药物。
本分析纳入了 1613 例符合条件的住院患者（分别为轮转和混合期的 855 例和 758 例），共获得 16437 份微生物培养物。ICU 住院期间 ARB 获得率分别为 7.3%（62 例）和 5.1%（39 例）（p 值为 0.13），平均分别为 17.7（中位数 15）和 20.8（中位数 13）天。混合期 ARB 携带获得的调整比值比为 0.62（95%CI 0.38 至 1.00）。获得的 ARB 携带物为肠杆菌科物种（61 例）、铜绿假单胞菌（38 例）和鲍曼不动杆菌（20 例），两种干预措施之间无统计学显著差异。
在轮转和混合组中，个体患者获得携带革兰氏阴性 ARB 的风险无统计学显著差异。这些发现证实了在 ICU 革兰氏阴性 ARB 的流行病学中，轮转和混合策略之间没有差异。
本试验在 ClinicalTrials.gov 注册，注册日期为 2011 年 1 月 10 日，注册号为 NCT01293071。
