依拉环素治疗碳青霉烯耐药鲍曼不动杆菌肺部感染效果观察

Efficacy of eravacycline on pulmonary infection caused by carbapenem-resistant Acinetobacter baumannii

目的探讨依拉环素治疗碳青霉烯耐药鲍曼不动杆菌肺部感染的效果及安全性。方法2023年11月—2024年3月河南省人民医院诊治碳青霉烯耐药鲍曼不动杆菌肺部感染患者60例,根据抗感染治疗方案分为观察组和对照组各30例,观察组给予依拉环素1 mg/(kg·次),1次/12 h静脉滴注;对照组给予多黏菌素B 50万u/次,1次/12 h静脉滴注,首剂加倍;2组均联合使用头孢哌酮舒巴坦(3.0 g/次,1次/8 h静脉滴注)并根据患者病情给予机械通气、营养支持等治疗。治疗第5天观察2组治疗总有效率,比较治疗前、后临床评分[Murray肺损伤评分、序贯器官衰竭评估(SOFA)评分、急性生理学和慢性健康状况评估Ⅱ(APACHEⅡ)评分]、炎性指标(白细胞计数、C反应蛋白、降钙素原)、细胞因子[白细胞介素(IL)-4、IL-6、IL-10]水平及外周血T淋巴细胞亚群。观察2组治疗期间不良反应发生情况,记录机械通气时间、ICU住院时间及病死率。结果治疗第5天,观察组治疗总有效率(90.0%)高于对照组(66.7%)(χ^(2)=4.812,P=0.028)。治疗后观察组Murray肺损伤评分[1.50(1.00,4.25)分]、APACHEⅡ评分[5.50(3.00,14.25)分]、SOFA评分[3.50(2.00,5.00)分]、白细胞计数[4.66×10^(9)/L(4.23×10^(9)/L,8.05×10^(9)/L)]、C反应蛋白[24.50(14.62,68.14)mg/L]、降钙素原[0.24(0.13,0.61)μg/L]、IL-4[0.69(0.23,3.98)ng/L]、IL-6[24.11(18.62,78.05)ng/L]、IL-10[1.53(0.98,6.55)ng/L]水平均低于对照组[3.00(3.00,6.00)分、9.40(4.50,11.50)分、5.50(2.50,7.25)分、8.27×10^(9)/L(6.88×10^(9)/L,10.38×10^(9)/L)、45.67(23.78,87.78)mg/L、0.53(0.09,0.99)μg/L、1.29(0.44,3.25)ng/L、55.33(22.87,100.77)ng/L、4.55(1.23,10.11)ng/L](Z=-0.765~-0.245,P均<0.05),2组治疗后均低于治疗前(Z=-4.490~-1.675,P均<0.05);治疗后观察组外周血CD4^(+)T淋巴细胞[580(245,890)个/μL]、CD8^(+)T淋巴细胞[306(113,676)个/μL]、总T淋巴细胞[788(321,1455)个/μL]水平与对照组[536(156,754)、296(142,723)、821(356,1577)个/μL]比较差异均无统计学意义(Z=-2.121、-1.887、-1.786,P均>0.05),2组治疗后均高于治疗前(Z=-3.707~-2.998,P均<0.05);治疗前上述指标比较差异均无统计学意义(Z=-1.898~-0.022,P均>0.05)。观察组机械通气时间[(9.43±3.16)d]、ICU住院时间[(12.93±4.73)d]均短于对照组[(14.54±4.13)、(17.88±5.12)d](t=-6.488,P<0.001;t=-8.663,P<0.001),病死率(20.0%)低于对照组(46.7%)(χ^(2)=4.800,P=0.028),不良反应发生率(10.0%)与对照组(13.3%)比较差异无统计学意义(χ^(2)=0.162,P=0.688)。结论依拉环素或多黏菌素B联合头孢哌酮舒巴坦治疗碳青霉烯耐药鲍曼不动杆菌肺部感染均安全、有效;与多黏菌素B相比,依拉环素疗效更佳,可减轻炎性反应,缩短机械通气时间和ICU住院时间,降低病死率。

Objective To investigate the efficacy and safety of eravacycline in the treatment of carbapenem-resistant Acinetobacter baumannii(CRAB)pulmonary infection.Methods Sixty patients with CRAB pulmonary infection were diagnosed and treated in Henan Provincial People's Hospital from November 2023 to March 2024,among whom 30patients received intravenous drip of eravacycline 1 mg/kg once per 12 h(observation group),and the other 30 patients received intravenous drip of polymyxin B 500000 u once per 12 h with first dose doubled(control group).Besides the above treatment,both two groups were given intravenous drip of cefoperazone-sulbactam(3.0 g once per 8 h),and mechanical ventilation and nutritional support according to patients'conditions.After 5-d treatment,the total effective rate was observed in two groups,and the Murray Lung Injury Score,Sequential Organ Failure Assessment(SOFA)score,Acute Physiology and Chronic Health AssessmentⅡ(APACHEⅡ)score,inflammatory indexes(white blood cell count,C-reactive protein,procalcitonin),cytokines[interleukin(IL)-4,IL-6,IL-10],and peripheral blood T lymphocyte subsets were compared before and after treatment.The occurrence of adverse reactions during treatment was observed in two groups,and the mechanical ventilation time,length of ICU stay,and fatality rate were recorded.Results After 5-d treatment,the total effective rate was higher in observation group(90.0%)than that in control group(66.7%)(χ^(2)=4.812,P=0.028).The Murray Lung Injury Score,APACHEⅡscore,SOFA score,white blood cell count,C-reactive protein,procalcitonin,IL-4,IL-6 and IL-10 were lower after treatment in observation group[1.50(1.00,4.25),5.50(3.00,14.25),3.50(2.00,5.00),4.66×10^(9)/L(4.23×10^(9)/L,8.05×10^(9)/L),24.50(14.62,68.14)mg/L,0.24(0.13,0.61)μg/L,0.69(0.23,3.98)ng/L,24.11(18.62,78.05)ng/L,1.53(0.98,6.55)ng/L]than those in control group[3.00(3.00,6.00),9.40(4.50,11.50),5.50(2.50,7.25),8.27×10^(9)/L(6.88×10^(9)/L,10.38×10^(9)/L),45.67(23.78,87.78)mg/L,0.53(0.09,0.99)μg/L,1.29(0.44,3.25)ng/L,55.33(22.87,100.77)ng/L,4.55(1.23,10.11)ng/L](Z=-0.765 to-0.245,all P values<0.05),and were lower after treatment than those before treatment in two groups(Z=-4.490 to-1.675,all P values<0.05).No significant differences were found in the levels of CD4^(+)T lymphocytes,CD8^(+)T lymphocytes,and total T lymphocytes after treatment between observation group[580(245,890),306(113,676),788(321,1455)cells/μL]and control group[536(156,754),296(142,723),821(356,1577)cells/μL](Z=-2.121,-1.887,-1.786;all P values>0.05),and all the above indicators were higher after treatment than those before treatment in two groups(Z=-3.707 to-2.998,all P values<0.05),and showed no significant differences between two groups before treatment(Z=-1.898 to-0.022,all P values>0.05).The mechanical ventilation time and duration of ICU stay were shorter in observation group[(9.43±3.16),(12.93±4.73)d]than those in control group[(14.54±4.13),(17.88±5.12)d](t=-6.488,P<0.001;t=-8.663,P<0.001),the fatality rate was lower in observation group(20.0%)than that in control group(46.7%)(χ^(2)=4.800,P=0.028),and the incidence of adverse reactions showed no significant difference between observation group(10.0%)and control group(13.3%)(χ^(2)=0.162,P=0.688).Conclusions Eravacycline/polymyxin B combined with cefoperazone-sulbactam is safe and effective for CRAB pulmonary infection.Compared with polymyxin B,eravacycline has a better therapeutic effect,can reduce inflammatory reactions,shorten mechanical ventilation time and length of ICU stay,and reduce the fatality rate.