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依據(jù)美羅培南MIC評估革蘭陰性菌血流感染患者的轉(zhuǎn)歸

發(fā)布時(shí)間:2018-07-14 18:03
【摘要】:目的:近期發(fā)布的2013年中國細(xì)菌耐藥性監(jiān)測結(jié)果顯示,細(xì)菌耐藥性仍呈增長趨勢,多重耐藥和廣泛耐藥菌株在某些病區(qū)內(nèi)的流行播散對臨床構(gòu)成嚴(yán)重威脅。廣譜β-內(nèi)酰胺類抗生素耐藥嚴(yán)重,碳青霉烯類抗生素作為革蘭陰性菌抗感染的一線用藥,情況亦不同樂觀。有研究發(fā)現(xiàn),過去美國臨床實(shí)驗(yàn)室標(biāo)準(zhǔn)化協(xié)會(huì)(CLSI)制定的碳青霉烯類抗生素判斷標(biāo)準(zhǔn)過高,事實(shí)上碳青霉烯類抗生素對某些細(xì)菌的最低抑菌濃度(MIC)≤1mg/L時(shí),臨床療效才更好。本研究主要目的:使用美羅培南治療革蘭陰性菌引起的血流感染的重癥患者時(shí),確定總住院病死率相關(guān)的美羅培南MIC折點(diǎn)。次要研究目的:美羅培南MIC與重癥患者血流感染間接轉(zhuǎn)歸的相關(guān)性,如病死患者的存活時(shí)間和感染后存活患者的住院時(shí)間。方法:本研究采用單中心、回顧性、隊(duì)列研究,收集2012年1月至2014年12月河北醫(yī)科大學(xué)第二醫(yī)院急診重癥監(jiān)護(hù)病房(EICU)血流感染患者的臨床資料,包括:①患者年齡、性別、急性生理與慢性健康評分II(APACHEII)、ICU住院時(shí)間、致病菌、感染源、美羅培南MIC;②是否留置中心靜脈導(dǎo)管、抗生素聯(lián)合治療;③是否伴有急性腎損傷(AKI)、肝功能不全、糖尿病;④是否院內(nèi)死亡。納入標(biāo)準(zhǔn):①年齡≥18歲;②符合血流感染診斷標(biāo)準(zhǔn);③血培養(yǎng)分離得到銅綠假單胞菌、鮑曼不動(dòng)桿菌或產(chǎn)超廣譜β-內(nèi)酰胺酶的革蘭陰性桿菌;④應(yīng)用美羅培南治療,時(shí)間超過48小時(shí)。排除標(biāo)準(zhǔn):①年齡18歲;②無相關(guān)病原菌對美羅培南敏感性測試結(jié)果;③接受美羅培南治療48小時(shí);④伴有真菌感染?股亟o藥方法:美羅培南為3g/d,根據(jù)患者腎功能進(jìn)行劑量調(diào)整。采用SPSS17.0統(tǒng)計(jì)軟件進(jìn)行數(shù)據(jù)處理分析。結(jié)果:1共有73例患者符合標(biāo)準(zhǔn)納入研究,其中51例存活,22例死亡。分離致病菌:產(chǎn)ESBL腸桿菌科細(xì)菌51株,銅綠假單胞菌17株、鮑曼不動(dòng)桿菌5株.按照2012CLSI標(biāo)準(zhǔn),其美羅培南耐藥率分別為:33.33%、29.41%及40.0%。按美羅培南MIC值分組,各組人數(shù)及死亡人數(shù)(死亡率)分別為:MIC=1mg/L組37例,死亡6例(16.22%);MIC=2mg/L組19例,死亡4例(21.05%);MIC=4mg/L組2例,死亡1例(50.0%);MIC=8mg/L組6例,死亡4例(66.67%);MIC=16mg/L組9例,7例(77.78%)。經(jīng)Logistic回歸分析發(fā)現(xiàn),美羅培南的MIC值每升高一個(gè)稀釋度,死亡概率增加2.14倍(OR:2.14,95%CI:1.43~3.19;P0.01)。經(jīng)分類回歸樹(CART)分析發(fā)現(xiàn),致病菌對美羅培南MIC值為≤2mg/L和≥4mg/L的死亡率有差異(死亡率分別為17.86%與70.59%,P0.01)。2定義美羅培南MIC≥4mg/L為高M(jìn)IC組,美羅培南MIC≤2mg/L為低MIC組。低MIC組患者56例,死亡10例;高M(jìn)IC組患者17例,死亡12例。與低MIC組比較,高M(jìn)IC組患者APACHEII評分高,病情更重(30.23±3.19:2 1.27±4.99,P0.01),ICU住院時(shí)間長(30.53±5.35:20.93±5.61,P0.01),感染源以呼吸道感染為主(47.06%:17.86%,P0.05),差異有統(tǒng)計(jì)學(xué)意義。進(jìn)一步采用Kaplan-Meier法及Log Rank法對兩組生存率估計(jì)及組間生存率比較發(fā)現(xiàn),高M(jìn)IC組生存率低(P0.01)。兩組患者在年齡、性別、致病菌構(gòu)成、肝功能不全、AKI、抗生素聯(lián)合用藥等方面無差異(P0.05)。3患者按預(yù)后分為死亡組與存活組。存活組患者51例,其中美羅培南MIC≥4mg/L10例;死亡組患者22例,其中美羅培南MIC≥4mg/L12例。與存活組比較,死亡組美羅培南MIC≥4mg/L發(fā)生率高(54.55%:19.61%,P0.01),與存活組比較,死亡組病情更重,APACHE II評分高(29.94±2.72:20.51±4.60,P0.01),ICU住院時(shí)間長(29.53±3.52:20.43±6.11,P0.01),差異有統(tǒng)計(jì)學(xué)意義。感染源:呼吸道感染存活組9例,死亡組9例,與存活組比較,死亡組以呼吸道感染為感染源發(fā)生率更高(40.91%:17.65%,P0.05)。兩組患者在年齡、性別、致病菌構(gòu)成、肝功能不全、AKI、抗生素聯(lián)合用藥等方面無差異(P0.05)。對生存組和死亡組患者各項(xiàng)特征進(jìn)行l(wèi)ogistic回歸分析發(fā)現(xiàn),患者死亡的危險(xiǎn)因素主要是美羅培南MIC≥4mg/L(OR:11.04;95%CI:3.17~38.43;P0.01);APACHEII評分(OR:1.63;1.28~2.07;P0.01)。結(jié)論:美羅培南MIC≥4mg/L、APACHE II評分高是重癥患者血流感染死亡的主要風(fēng)險(xiǎn)因素。與美羅培南對革蘭陰性菌的MIC≤2mg/L者相比,當(dāng)美羅培南的MIC≥4mg/L時(shí),病情更重,ICU住院時(shí)間延長,死亡率高,患者預(yù)后較差。開始應(yīng)用美羅培南治療重癥患者革蘭陰性菌菌血癥前,應(yīng)該考慮其MIC值。對MIC理解需進(jìn)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.
【學(xué)位授予單位】:河北醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2015
【分類號(hào)】:R446.5

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