多黏菌素B对于耐碳青霉烯类鲍曼不动杆菌感染重症患者的疗效和安全性分析

Efficacy and safety of polymyxin B in critically ill patients with carbapenem-resistant Acinetobacter baumannii infections

目的:围绕耐碳青霉烯类鲍曼不动杆菌(carbapenem-resistant Acinetobacter baumannii,CRAB)感染的重症患者,探索影响多黏菌素B(polymyxin B,PMB)疗效与安全性的相关因素。方法:收集南京大学医学院附属鼓楼医院重症监护室2020年1月至2021年12月感染CRAB患者的基本特征、感染情况、治疗方案等信息,首先以细菌清除率和感染缓解率作为主要结局指标开展单因素分析,而后以28 d全因死亡率为次要结局指标开展单因素分析及Logistic回归,并比较部分患者的治疗药物监测结果。结果:共纳入68例以PMB治疗的患者,其细菌清除率、感染缓解率分别为39.7%,44.1%,而28 d全因死亡率为41.2%。围绕主要结局指标,使用PMB疗程>7 d的患者相较于疗程3~7 d患者,有更高的细菌清除率与感染缓解率。对于次要结局指标,PMB疗程以及PMB治疗过程中采用的连续性肾脏替代治疗,是患者28 d全因死亡的主要相关因素。结合治疗药物监测结果的单因素分析结果显示,CRAB清除患者的PMB峰浓度以及平均稳态血药浓度更高,同时发生肾毒性患者具有更高的PMB谷浓度,差异均具有统计学意义(P<0.05)。结论:PMB治疗中,患者疗程应大于7 d以保证疗效,同时应重点关注采用连续性肾脏替代治疗患者的治疗结局;安全性方面PMB引起的肾毒性则可通过测定PMB谷浓度进行监测。

OBJECTIVE To investigate the factors related to the efficacy and safety of polymyxin B(PMB)in critically ill patients with carbapenem-resistant Acinetobacter baumannii(CRAB)infections.METHODS A retrospective study was conducted in the patients with CRAB infections admitted to the intensive care unit(ICU)from January 2019 to December 2020 based on their demographic,infection characteristics and treatment.Univariate analysis was firstly performed with CRAB clearance efficacy and clinical response efficacy as the primary outcomes,and both univariate analysis and Logistic regression were performed with the 28-day all-cause mortality as the secondary outcome.Meanwhile,therapeutic drug monitoring results were compared among part of the patients.RESULTS Sixty-eight patients treated with PMB were included.The overall CRAB clearance rate and the clinical response rate were 39.7%and 44.1%,respectively,with the 28-day all-cause mortality of 41.2%.As for the primary outcomes,both the CRAB clearance rate and the clinical response rate of cases with duration of PMB use longer than seven days were higher than those in the group with3-7 days of PMB duration.As for the secondary outcome,the main factors for the 28-day all-cause mortality were supported by continuous renal replacement therapy during the PMB treatment and the duration of PMB use.Univariate analysis on the monitoring results of therapeutic drugs showed that the PMB peak plasma concentration and the PMB steady-state plasma concentration of the group with CRAB clearance were significantly higher(P<0.05),while the group of nephrotoxicity had significantly higher PMB trough plasma concentration.CONCLUSION During the administration of PMB,patients should be treated for more than 7 days to ensure the curative effect.At the same time,attention should be paid to the patients with continuous renal replacement therapy.Moreover,the nephrotoxicity induced by PMB can be indicated through monitoring PMB trough plasma concentration.