Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
Crit Care Med. 2011 Nov;39(11):2458-63. doi: 10.1097/CCM.0b013e318225756d.
We quantified the association between antibiotic exposure and acquisition of antibiotic resistance in Pseudomonas aeruginosa and Enterobacter species in intensive care unit patients.
Prospective cohort study.
In 1,201 patients, respiratory tract colonization was determined through regular screening on admission, twice weekly, and on discharge. Primary outcome was the acquisition of antibiotic resistance in previous antibiotic sensitive P. aeruginosa and Enterobacter species, with acquisition attributable to cross-transmission excluded based on genotyping and epidemiologic linkage. Cox regression analysis, adjusted for covariates, was performed to calculate hazard ratios of patients exposed to antibiotics compared to patients not exposed to antibiotics.
In total, 194 and 171 patients were colonized with P. aeruginosa and Enterobacter species, respectively. Two or more cultures per episode were available for 126 and 108 patients. For P. aeruginosa, ceftazidime exposure was associated with 6.3 acquired antibiotic resistance events per 100 days of exposure, whereas incidence rates were lower for ciprofloxacin, meropenem, and piperacillin-tazobactam. In multivariate analysis, meropenem, ciprofloxacin, and ceftazidime were significantly associated with risk of resistance development in P. aeruginosa (adjusted hazard ratio, 11.1; 95% confidence interval, 2.4-51.5 for meropenem; adjusted hazard ratio, 4.1; 95% confidence interval, 1.1-16.2 for ciprofloxacin; adjusted hazard ratio, 2.5; 95% confidence interval, 1.1-5.5 for ceftazidime). For Enterobacter, ceftriaxone and ciprofloxacin exposure were associated with most antibiotic resistance acquisitions. No significant associations were found in multivariate analysis.
Meropenem exposure is associated with the highest risk of resistance development in P. aeruginosa. Increasing carbapenem use attributable to emergence of Gram-negative bacteria producing extended-spectrum β-lactamases will enhance antibiotic resistance in P. aeruginosa.
我们定量评估了重症监护病房患者中铜绿假单胞菌和肠杆菌属中抗生素暴露与抗生素耐药性获得之间的关联。
前瞻性队列研究。
在 1201 例患者中，通过入院时、每周两次和出院时的常规筛查来确定呼吸道定植情况。主要结局是先前对抗生素敏感的铜绿假单胞菌和肠杆菌属获得抗生素耐药性，基于基因分型和流行病学联系排除归因于交叉传播的耐药性获得。采用 Cox 回归分析，调整了协变量，计算了与未暴露于抗生素的患者相比暴露于抗生素的患者的风险比。
总共 194 例和 171 例患者分别定植了铜绿假单胞菌和肠杆菌属。126 例和 108 例患者每例有两个或更多培养物。对于铜绿假单胞菌，头孢他啶暴露与每 100 天暴露发生 6.3 例获得性抗生素耐药事件相关，而环丙沙星、美罗培南和哌拉西林他唑巴坦的发生率较低。在多变量分析中，美罗培南、环丙沙星和头孢他啶与铜绿假单胞菌耐药发展的风险显著相关（调整后的危险比，11.1；95%置信区间，2.4-51.5 为美罗培南；调整后的危险比，4.1；95%置信区间，1.1-16.2 为环丙沙星；调整后的危险比，2.5；95%置信区间，1.1-5.5 为头孢他啶）。对于肠杆菌属，头孢曲松和环丙沙星暴露与大多数抗生素耐药性获得相关。在多变量分析中未发现显著关联。
美罗培南暴露与铜绿假单胞菌耐药性发展的风险最高。由于革兰氏阴性菌产生超广谱β-内酰胺酶，碳青霉烯类药物的使用增加将增强铜绿假单胞菌的抗生素耐药性。
