多黏菌素治疗小儿重症耐碳青霉烯类革兰阴性菌感染的临床疗效观察

Clinical observation of polymyxin in the treatment of severe carbapene-resistant Gram-negative bacterial infection in children

目的观察多黏菌素在治疗小儿重症耐碳青霉烯类革兰阴性菌(carbapenem-resistant Gram-negative bacteria,CRGNB)感染中的有效性和安全性。方法回顾性分析2018年5月至2019年6月PICU收治的使用多黏菌素治疗的危重症CRGNB感染患儿15例,根据患儿最终转归分为存活组和死亡组,收集患儿基础资料、感染相关情况、多黏菌素治疗前后疗效观察指标以及肾毒性监测指标,评估多黏菌素的有效性和安全性。结果 (1)死亡5例,存活10例,12例患儿合并先天性消化道畸形,存活组的多黏菌素治疗时间较死亡组长(P<0.05)。(2)感染部位以血流感染为主(10例),其他部位包括肺部感染(5例)、胸腔感染(2例)、腹腔感染(2例)和中枢神经系统感染(1例),且其中4例为多部位联合感染。主要致病菌包括:肺炎克雷伯杆菌(11例)、鲍曼不动杆菌(2例)、阴沟肠杆菌(2例)、大肠埃希菌(1例),其中2例为肺炎克雷伯杆菌合并鲍曼不动杆菌感染,全部病例培养菌株均对碳青霉烯类耐药、对多黏菌素敏感。(3)12例患儿在原抗生素联合治疗失败后,启用多黏菌素;另有3例直接启用多黏菌素治疗。14例患儿为多黏菌素联合其他抗生素治疗,仅1例患儿单独应用多黏菌素治疗。体温、C反应蛋白、外周血白细胞计数、降钙素原在治疗前后两组间均无显著差异;死亡组降钙素原在多黏菌素治疗第3天较治疗结束时显著升高(P<0.05),且较存活组有显著差异(P<0.05),但与患儿预后无统计学相关性(χ2=0.837,P=0.360)。6例患儿治疗后病原学检测转阴,9例未转阴,且与多黏菌素使用时间长短(t=-0.692,P=0.502)和生存状况(χ2=0.313,P=0.576)无统计学相关性。病原学未转阴患儿中,死亡组3例,存活组6例;感染部位以血流感染(4例)、肺部感染(4例)为主。(4)尿量、血尿素氮、血肌酐和尿蛋白使用多黏菌素前后在两组间均无统计学差异;死亡组血尿素氮在治疗结束时较治疗第1天、第7天显著降低(P<0.05);存活组血肌酐在治疗第7天、治疗结束时均较治疗第1天显著降低(P<0.05)。结论针对儿童感染CRGNB的重症病例使用多黏菌素治疗具有一定的安全性,但目前亟需更多、更大规模的临床研究做进一步探索和评估。

Objective:To observe the efficacy and safety of polymyxin in the treatment of severe carbapene-resistant Gram-negative bacterial(CRGNB)infection in children.Methods:Fifteen cases of critically ill CRGNB infection in PICU treated with polymyxin were retrospectively analyzed from May 2018 to June 2019,and patients were divided into survival group and death group according to the final outcome,and by collecting basic data,infection with related situation,clinical observation index of the polymyxin before and after treatment as well as renal toxicity monitoring index,and the efficacy and safety of polymyxin in the treatment of pediatric intensive CRGNB infection was evaluated.Results:(1)Five cases died(death group),ten cases survived(survival group),and 12 cases were complicated with congenital digestive tract malformations.Duration of polymyxin treatment were longer in the survival group.(2)The infected sites were mainly bloodstream infection(ten cases),and other sites included pulmonary infection(five cases),thoracic infection(two cases),abdominal infection(two cases)and central nervous system infection(one case),among which four cases were multi-site co-infection.The main pathogenic bacteria included klebsiella pneumoniae(11 cases),acinetobacter baumannii(two cases),enterobacter cloacae(two cases)and escherichia coli(one case),among which two cases were klebsiella pneumoniae combined with acinetobacter baumannii infection.All the cultured strains were resistant to carbapenems but sensitive to polymyxin.(3)Twelve children were treated with polymyxin after the failure of the combination of the original antibiotics.The other three children were treated with polymyxin directly.Fourteen children were treated with polymyxin combined with other antibiotics,and only one child was treated with polymyxin alone.There were no significant differences in body temperature,C-reaction protein,white blood cell and procalcitonin before and after polymyxin treatment in both groups.On the 3rd day after polymyxin treatment,PCT levels of children in the death group were higher than those in the survival group,but there was no statistical correlation with the survival status.After treatment,six children turned negative by pathogen detection,nine did not turn negative,and there was no statistical correlation with the duration of polymyxin use and survival status.Nine children whose pathogen detection did not turn negative included three cases in the death group and six cases in the survival group,the infected sites were mainly bloodstream infection(four cases),pulmonary infection(four cases).(4)There were no significant differences in the urine volume,blood urea nitrogen,serum creatinine and urine protein before as well as after polymyxin treatment in both groups.Blood urea nitrogen at the end of the reatment in the death group was significantly lower compared with the 1st day and the 7th day.Serum creatinine of the survival group significantly decreased on the 7th day and the end of treatment compared with the 1st day after the use of polymyxin.Conclusion:Polymyxin may be a safe treatment for severe cases of CRGNB infection in children.However,more and large-scale clinical studies are urgently needed for further exploration and evaluation.