依据美罗培南MIC评估革兰阴性菌血流感染患者的转归

发布时间：2018-07-14 18:03

【摘要】：目的:近期发布的2013年中国细菌耐药性监测结果显示,细菌耐药性仍呈增长趋势,多重耐药和广泛耐药菌株在某些病区内的流行播散对临床构成严重威胁。广谱β-内酰胺类抗生素耐药严重,碳青霉烯类抗生素作为革兰阴性菌抗感染的一线用药,情况亦不同乐观。有研究发现,过去美国临床实验室标准化协会(CLSI)制定的碳青霉烯类抗生素判断标准过高,事实上碳青霉烯类抗生素对某些细菌的最低抑菌浓度(MIC)≤1mg/L时,临床疗效才更好。本研究主要目的:使用美罗培南治疗革兰阴性菌引起的血流感染的重症患者时,确定总住院病死率相关的美罗培南MIC折点。次要研究目的:美罗培南MIC与重症患者血流感染间接转归的相关性,如病死患者的存活时间和感染后存活患者的住院时间。方法:本研究采用单中心、回顾性、队列研究,收集2012年1月至2014年12月河北医科大学第二医院急诊重症监护病房(EICU)血流感染患者的临床资料,包括:①患者年龄、性别、急性生理与慢性健康评分II(APACHEII)、ICU住院时间、致病菌、感染源、美罗培南MIC;②是否留置中心静脉导管、抗生素联合治疗;③是否伴有急性肾损伤(AKI)、肝功能不全、糖尿病;④是否院内死亡。纳入标准:①年龄≥18岁;②符合血流感染诊断标准;③血培养分离得到铜绿假单胞菌、鲍曼不动杆菌或产超广谱β-内酰胺酶的革兰阴性杆菌;④应用美罗培南治疗,时间超过48小时。排除标准:①年龄18岁;②无相关病原菌对美罗培南敏感性测试结果;③接受美罗培南治疗48小时;④伴有真菌感染。抗生素给药方法:美罗培南为3g/d,根据患者肾功能进行剂量调整。采用SPSS17.0统计软件进行数据处理分析。结果:1共有73例患者符合标准纳入研究,其中51例存活,22例死亡。分离致病菌:产ESBL肠杆菌科细菌51株,铜绿假单胞菌17株、鲍曼不动杆菌5株.按照2012CLSI标准,其美罗培南耐药率分别为:33.33%、29.41%及40.0%。按美罗培南MIC值分组,各组人数及死亡人数(死亡率)分别为:MIC=1mg/L组37例,死亡6例(16.22%);MIC=2mg/L组19例,死亡4例(21.05%);MIC=4mg/L组2例,死亡1例(50.0%);MIC=8mg/L组6例,死亡4例(66.67%);MIC=16mg/L组9例,7例(77.78%)。经Logistic回归分析发现,美罗培南的MIC值每升高一个稀释度,死亡概率增加2.14倍(OR:2.14,95%CI:1.43~3.19;P0.01)。经分类回归树(CART)分析发现,致病菌对美罗培南MIC值为≤2mg/L和≥4mg/L的死亡率有差异(死亡率分别为17.86%与70.59%,P0.01)。2定义美罗培南MIC≥4mg/L为高MIC组,美罗培南MIC≤2mg/L为低MIC组。低MIC组患者56例,死亡10例;高MIC组患者17例,死亡12例。与低MIC组比较,高MIC组患者APACHEII评分高,病情更重(30.23±3.19:2 1.27±4.99,P0.01),ICU住院时间长(30.53±5.35:20.93±5.61,P0.01),感染源以呼吸道感染为主(47.06%:17.86%,P0.05),差异有统计学意义。进一步采用Kaplan-Meier法及Log Rank法对两组生存率估计及组间生存率比较发现,高MIC组生存率低(P0.01)。两组患者在年龄、性别、致病菌构成、肝功能不全、AKI、抗生素联合用药等方面无差异(P0.05)。3患者按预后分为死亡组与存活组。存活组患者51例,其中美罗培南MIC≥4mg/L10例;死亡组患者22例,其中美罗培南MIC≥4mg/L12例。与存活组比较,死亡组美罗培南MIC≥4mg/L发生率高(54.55%:19.61%,P0.01),与存活组比较,死亡组病情更重,APACHE II评分高(29.94±2.72:20.51±4.60,P0.01),ICU住院时间长(29.53±3.52:20.43±6.11,P0.01),差异有统计学意义。感染源:呼吸道感染存活组9例,死亡组9例,与存活组比较,死亡组以呼吸道感染为感染源发生率更高(40.91%:17.65%,P0.05)。两组患者在年龄、性别、致病菌构成、肝功能不全、AKI、抗生素联合用药等方面无差异(P0.05)。对生存组和死亡组患者各项特征进行logistic回归分析发现,患者死亡的危险因素主要是美罗培南MIC≥4mg/L(OR:11.04;95%CI:3.17~38.43;P0.01);APACHEII评分(OR:1.63;1.28~2.07;P0.01)。结论:美罗培南MIC≥4mg/L、APACHE II评分高是重症患者血流感染死亡的主要风险因素。与美罗培南对革兰阴性菌的MIC≤2mg/L者相比,当美罗培南的MIC≥4mg/L时,病情更重,ICU住院时间延长,死亡率高,患者预后较差。开始应用美罗培南治疗重症患者革兰阴性菌菌血症前,应该考虑其MIC值。对MIC理解需进一步研究。
[Abstract]:Objective: in 2013, the results of bacterial resistance monitoring in China, published in 2013, showed that bacterial resistance was still growing, and the spread of multidrug-resistant and widely resistant strains in certain areas was a serious threat to the clinic. First line use, the situation is also different. Research found that the past American clinical laboratory standardization association (CLSI) of carbapenem antibiotics established by the association is too high, in fact, the minimum inhibitory concentration (MIC) of carbapenem antibiotics to certain bacteria is less than 1mg/L, the clinical efficacy is better. In the treatment of severe patients with blood flow infection caused by gram-negative bacteria, the total hospitalization mortality associated with meropenem MIC points is determined. Secondary study is the correlation between MIC and the indirect outcome of blood flow infection in severe patients, such as the survival time of the patient and the time of hospitalization after the infection. Center, retrospective, cohort study, the clinical data of blood flow infection patients in the emergency intensive care unit (EICU) of the second hospital of Hebei Medical University from January 2012 to December 2014 were collected, including: (1) age, sex, acute physiology and chronic health score II (APACHEII), ICU hospitalization time, pathogenic bacteria, infection source, meropenem MIC; 2. Central venous catheter, combined with antibiotic therapy; (3) whether with acute renal injury (AKI), liver dysfunction, diabetes, and diabetes; whether or not in hospital death. Inclusion criteria: (1) age over 18 years old; (2) compliance with the diagnostic criteria for blood flow infection; (3) isolation of Pseudomonas aeruginosa from blood culture, Acinetobacter Bauman or gram negative rods producing hyper broad-spectrum beta lactamase Bacteria; (4) the use of meropenem for more than 48 hours. Exclusion criteria: (1) age 18 years old; (2) no related pathogenic bacteria to meropenem sensitivity test results; (3) for 48 hours of meropenem; (4) for 48 hours of meropenem; (4) with fungal infection. Data processing analysis. Results: 1 of 73 patients met the standard inclusion study, of which 51 were alive and 22 were dead. 51 strains of Enterobacteriaceae ESBL, 17 Pseudomonas aeruginosa and 5 Acinetobacter Bauman were isolated. The resistance rate of meropenem was 33.33%, 29.41% and 40.0%. according to 2012CLSI standard, respectively. C group, each group and death number (mortality) were 37 cases in group MIC=1mg/L, 6 cases of death (16.22%), 19 cases in group MIC=2mg/L, 4 cases (21.05%), 2 cases in group MIC=4mg/L, 1 death (50%), 6 cases in group MIC=8mg/L, 4 (66.67%) death, 9 cases and 7 cases in group MIC=16mg/L. Logistic regression analysis found that MIC value of meropenem was elevated by one increase. The mortality rate increased by 2.14 times (OR:2.14,95%CI:1.43~3.19; P0.01). The CART analysis showed that the pathogenic bacteria had a difference in the MIC value of meropenem to < 2mg/L and > 4mg/L > (mortality rate was 17.86% and 70.59%, P0.01).2 defined melopenem MIC > 4mg/L as high MIC group, and meropenem MIC < < < < < >. Group. 56 patients in the low MIC group, 10 cases of death, 17 cases in high MIC group and 12 cases of death. Compared with the low MIC group, the APACHEII score of the high MIC group was higher, the condition was heavier (30.23 + 3.19:2 1.27 + 4.99, P0.01), the time of hospitalization of ICU was long (30.53 + 5.35:20.93 + 5.61, P0.01), and the source of infection was mainly respiratory infection (47.06%: 17.86%, P0.05). The difference was statistically significant. The Kaplan-Meier and Log Rank methods were used to estimate the survival rate of the two groups and the survival rate of the group. The survival rate of the high MIC group was low (P0.01). There was no difference between the two groups in age, sex, pathogenic bacteria, liver dysfunction, AKI, and antibiotic combination (P0.05). The patients were divided into the death group and the survival group according to the prognosis. The survival group patients were divided into the survival group. 51 cases, including meropenem MIC > 4mg/L10, and 22 cases in the death group, including meropenem MIC > 4mg/L12. Compared with the survival group, the incidence of MIC > 4mg/L in the death group was higher (54.55%: 19.61%, P0.01). Compared with the survival group, the death group was more severe, APACHE II score was higher (29.94 + 2.72:20.51 + 4.60, P0.01), and the length of ICU was longer (29.53 +). 3.52:20.43 + 6.11, P0.01), the difference was statistically significant. The source of infection: the survival of the respiratory tract infection group 9 cases, the death group 9 cases, compared with the survival group, the death group with respiratory infection as the source of infection is higher (40.91%: 17.65%, P0.05). The two groups of patients in age, sex, pathogenic bacteria, liver dysfunction, AKI, antibiotic combined use of drug use and other aspects of no difference. P0.05. The logistic regression analysis of the characteristics of the survival and death group showed that the risk factors of death were mainly MIC > 4mg/L (OR:11.04; 95%CI:3.17~38.43; P0.01); APACHEII score (OR:1.63; 1.28~2.07; P0.01). The main risk factor of death. Compared with meropenem's MIC < 2mg/L for Gram-negative bacteria, when meropenem's MIC is more than 4mg/L, the condition is heavier, the time of hospitalization of ICU is prolonged, the mortality rate is high and the prognosis is poor. The MIC value should be considered before using meropenem to treat severe Gram-negative bacteria. The understanding of MIC needs to be further understood. Research.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R446.5

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