【摘要】：目的:近期發(fā)布的2013年中國細菌耐藥性監(jiān)測結(jié)果顯示,細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)成嚴重威脅。廣譜β-內(nèi)酰胺類抗生素耐藥嚴重,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),過去美國臨床實驗室標準化協(xié)會(CLSI)制定的碳青霉烯類抗生素判斷標準過高,事實上碳青霉烯類抗生素對某些細菌的最低抑菌濃度(MIC)≤1mg/L時,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,確定總住院病死率相關(guān)的美羅培南MIC折點。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間和感染后存活患者的住院時間。方法:本研究采用單中心、回顧性、隊列研究,收集2012年1月至2014年12月河北醫(yī)科大學第二醫(yī)院急診重癥監(jiān)護病房(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住院時間、致病菌、感染源、美羅培南MIC;②是否留置中心靜脈導管、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。納入標準:①年齡≥18歲;②符合血流感染診斷標準;③血培養(yǎng)分離得到銅綠假單胞菌、鮑曼不動桿菌或產(chǎn)超廣譜β-內(nèi)酰胺酶的革蘭陰性桿菌;④應用美羅培南治療,時間超過48小時。排除標準: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;④伴有真菌感染�？股亟o藥方法:美羅培南為3g/d,根據(jù)患者腎功能進行劑量調(diào)整。采用SPSS17.0統(tǒng)計軟件進行數(shù)據(jù)處理分析。結(jié)果:1共有73例患者符合標準納入研究,其中51例存活,22例死亡。分離致病菌:產(chǎn)ESBL腸桿菌科細菌51株,銅綠假單胞菌17株、鮑曼不動桿菌5株.按照2012CLSI標準,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MIC組,美羅培南MIC≤2mg/L為低MIC組。低MIC組患者56例,死亡10例;高MIC組患者17例,死亡12例。與低MIC組比較,高MIC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)計學意義。進一步采用Kaplan-Meier法及Log Rank法對兩組生存率估計及組間生存率比較發(fā)現(xiàn),高MIC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住院時間長(29.53±3.52:20.43±6.11,P0.01),差異有統(tǒng)計學意義。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特征進行l(wèi)ogistic回歸分析發(fā)現(xiàn),患者死亡的危險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險因素。與美羅培南對革蘭陰性菌的MIC≤2mg/L者相比,當美羅培南的MIC≥4mg/L時,病情更重,ICU住院時間延長,死亡率高,患者預后較差。開始應用美羅培南治療重癥患者革蘭陰性菌菌血癥前,應該考慮其MIC值。對MIC理解需進一步研究。
[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.
【學位授予單位】：河北醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R446.5

【參考文獻】

相關(guān)期刊論文 前10條

1 倪菊平;姜麗靜;沈國鋒;孫英杰;張璐;李響;;血清降鈣素原在導管相關(guān)性血流感染診斷及預后評估中的價值[J];中華實用診斷與治療雜志;2015年01期

2 李光輝;朱德妹;汪復;胡志東;李全;孫自鏞;陳中舉;徐英春;張小江;王傳清;王愛敏;倪語星;孫景勇;褚云卓;俞云松;林潔;徐元宏;沈繼錄;蘇丹虹;卓超;魏蓮花;吳玲;張朝霞;季萍;張泓;孔菁;胡云建;艾效曼;單斌;杜艷;;2012年中國CHINET血培養(yǎng)臨床分離菌的分布及耐藥性[J];中國感染與化療雜志;2014年06期

3 胡付品;朱德妹;汪復;蔣曉飛;孫自鏞;陳中舉;胡志東;李金;謝軼;康梅;徐英春;張小江;張朝霞;季萍;王傳清;王愛敏;倪語星;孫景勇;俞云松;林潔;儲云卓;田素飛;徐元宏;沈繼錄;單斌;杜艷;卓超;蘇丹虹;張泓;孔菁;魏蓮花;吳玲;胡云建;艾效曼;;2013年中國CHINET細菌耐藥性監(jiān)測[J];中國感染與化療雜志;2014年05期

4 劉云;闕軍;劉少華;鄭崇明;王勇;曹權(quán);;ICU患者血流感染病原菌及預后危險因素分析[J];江蘇醫(yī)藥;2014年12期

5 周華;李光輝;陳佰義;卓超;曹彬;楊毅;張菁;王輝;何禮賢;胡必杰;黃曉軍;呂曉菊;邵宗鴻;孫自敏;劉又寧;倪語星;邱海波;施毅;王明貴;謝燦茂;周建英;周志慧;劉正印;俞云松;;中國產(chǎn)超廣譜β-內(nèi)酰胺酶腸桿菌科細菌感染應對策略專家共識[J];中華醫(yī)學雜志;2014年24期

6 李耘;呂媛;薛峰;張秀珍;胡云建;于庭;胡志東;趙建宏;潘世揚;胡必杰;俞云松;鄧秋連;李艷;劉文恩;周玲;費櫻;府偉靈;徐修禮;裴鳳艷;孟靈;季萍;湯進;鄭波;劉健;楊維維;張佳;;衛(wèi)生部全國細菌耐藥監(jiān)測網(wǎng)(Mohnarin)2011-2012年革蘭陰性菌耐藥監(jiān)測報告[J];中國臨床藥理學雜志;2014年03期

7 孫伏喜;馮旰珠;高天明;張揚;趙水娣;;綜合重癥監(jiān)護病房腸桿菌科細菌致血流感染發(fā)生的危險因素[J];中華醫(yī)學雜志;2014年09期

8 汪復;朱德妹;胡付品;蔣曉飛;胡志東;李全;孫自鏞;陳中舉;徐英春;張小江;王傳清;王愛敏;倪語星;孫景勇;褚云卓;俞云松;林潔;徐元宏;沈繼錄;蘇丹虹;卓超;魏蓮花;吳玲;張朝霞;季萍;張泓;孔菁;胡云建;艾效曼;單斌;杜艷;;2012年中國CHINET細菌耐藥性監(jiān)測[J];中國感染與化療雜志;2013年05期

9 楊�；�;韓立中;劉怡菁;陳旭;應春妹;趙貝棣;祝燕萍;衛(wèi)穎玨;;亞胺培南聯(lián)合多黏菌素B對不同表型銅綠假單胞菌體外抗菌活性的研究[J];檢驗醫(yī)學;2013年01期

10 劉又寧;曹彬;王輝;陳良安;佘丹陽;趙鐵梅;梁志欣;孫鐵英;李燕明;童朝暉;王臻;賀蓓;楊薇;瞿介明;李向陽;陳榮昌;葉楓;康健;李爾然;陳萍;鄭巖;馬忠森;任錦;施毅;孫文逵;馮玉麟;范紅;姜淑娟;張嵩;熊盛道;左鵬;王占偉;;中國九城市成人醫(yī)院獲得性肺炎微生物學與臨床特點調(diào)查[J];中華結(jié)核和呼吸雜志;2012年10期

，

本文編號：2122514