【作者】 杨洋；

【导师】 高鲁渤；

【作者基本信息】 天津医科大学 ， 麻醉学， 2012， 硕士

【摘要】 目的本研究目的在于评价校正念珠菌定植指数(corrected colonization index, CCI)在消化道肿瘤术后重症患者ICI抢先治疗中的作用,评估其应用于临床的可行性、安全性及可靠性；评价其是否可以预测抢先抗念珠菌时机,并不增加耐药及治疗负担,改善感染归因病死率；并通过多元分析获得肿瘤患者重度定植的特异高危因素。方法1.收集2010年1月至2011年12月天津医科大学附属肿瘤医院消化道肿瘤切除术后入住ICU患者中急性生理学与慢性健康状况评分系统Ⅱ (APACHE Ⅱ)评分10分以上,具有发生ICI的高危宿主因素患者120例,进行单中心、前瞻、队列研究。2.将临床收集的120例病例随机分为CCI组和对照组,每组60例。CCI组：采集病人气道吸出物、咽拭子、胃液、尿和直肠拭子5个标本送微生物实验室,进行念珠菌平板计数法测定,计算CCI,并进行CCI监测。若患者CCI≥0.4：如出现脓毒症表现则立即给予抗念珠菌药物,并根据定植菌种结果选用药物；如无脓毒症表现则不使用抗生素以及抗念珠菌药物,继续临床密切观察,一旦出现脓毒症表现,即刻加用抗念珠菌药物。所有加用抗念珠菌治疗的病例若有证据确诊为ICI,则按照IDSA制定的ICI治疗指南要求继续规范治疗；若治疗5d仍未确诊为ICI,则需再次复查CCI。脓毒症持续存在且CCI≥0.4继续抗念珠菌治疗；脓毒症得到控制或虽然其持续存在但CCI<0.4均停用抗念珠菌药物,继续临床观察。若患者CCI<0.4：无脓毒症表现的患者继续观察,每5天复查CCI：如出现脓毒症表现,则临床上不首先考虑是ICI,故而不给予抗念珠菌药物,而是按照临床诊疗规范给予针对其他致病菌的抗生素等治疗。经治疗后如病情恢复稳定则继续临床观察,5d后复查CCI；如病情恶化并出现生命体征不稳定,则立即补救性抗念珠菌治疗。抗念珠菌药物选择根据其定植菌种选择相应敏感的抗念珠菌药物,若其均为阴性结果,则根据我院本病区病原学检测情况经验性用药。对照组：患者常规留取上述各部位标本进行CCI监测,但检测结果不对临床医师公布,由临床医师依据《重症患者侵袭性真菌感染诊断和治疗指南》决定是否进行抗念珠菌治疗。3.对两组病人的一般资料、APACHE Ⅱ评分、疾病治疗、脓毒血症发生率抢先治疗时机、ICU住院时间、高危因素(抗厌氧菌治疗、开展肠内营养、中心静脉导管、静脉营养、激素用药史、机械通气48h、血液净化、脓毒症、重症脓毒症、脓毒症休克)以及ICU病死率、30d病死率、抗真菌费用等进行比较,观察补救性抗真菌治疗情况,计算念珠菌定植菌种分布情况,比较重度定植情况与治疗时机,并比较重度定植患者与非重度定植患者临床治疗情况,采用多元分析评估抗念珠菌治疗、肠内营养建立情况、激素用药史等因素在消化道肿瘤术后重症患者念珠菌重度定植中的特有作用。4.统计学方法采用SPSS11.5统计软件对试验数据进行正态性检验,正态分布的计量资料以x±s表示,两组数据比较采用t或t’检验；偏态分布数据以M(IQR)表示,采用t或t’检验；分类变量资料采用χ2检验或Fisher’s精确概率法。以P≤0.05为差异有统计学意义。Logistic回归分析ICI和重度定植危险因素。结果CCI组与对照组患者性别、年龄、APACHEII评分、ICU停留时间、是否接受广谱抗生素治疗等资料进行比较,差异均无统计学意义(P>0.05)。CCI组与对照组比较,各种高危因素(抗厌氧菌治疗、开展肠内营养、中心静脉导管、静脉营养、激素用药史、机械通气48h、血液净化、脓毒血症)以及ICU病死率、30d病死率、抗真菌费用等进行比较无统计学差异。CCI组和对照组分别有33例和23例发生脓毒症,自发生脓毒症起至临床应用抗念珠菌药物所需时间分别为(0.92±0.58)d,(3.53±3.41)d(P<0.05);例)与CCI<0.4(81例)两者间ICU内停留时间分别为(13.72±12.62)d、(7.10±8.65)d,不能建立肠内营养支持率分别为82.05%、18.52%,均存在显著差异(P<0.05),而APACHE Ⅱ评分、需要机械通气和血液净化等脏器支持治疗者的比例差异均无统计学意义(P>0.05)。分析120例患者600株念珠菌多部位定植菌种分布显示,白色念珠菌仍占较大比例(55.09%),光滑念珠菌占10.18%,其他依次为热带念珠菌、西弗念珠菌、罗伦特念珠菌。长期激素用药史与肠内营养难以开展为念珠菌重度定植高危因素。结论消化道肿瘤术后重症患者ICI高危因素多,采用CCI结合临床表现进行抢先治疗可把握治疗时机,安全且不增加耐药及抗真菌费用,易于广泛开展；以CCI为ICI抢先治疗评估手段,无补救性用药情况发生,安全有效；CCI可协助临床医生早期抢抓治疗时机,改善病死率,并有利于减少非重度定植患者抗生素滥用和真菌耐药情况的发生；消化道肿瘤术后重症患者的念珠菌重度定植,可能与长期使用激素和肠内营养建立情况等因素密切相关。更多还原

【Abstract】 ObjectiveThis research aims to evaluate preemptive treatment for candida infection (ICI) with reference of corrected colonization index(CCI) in critically ill patients with high risk factors of candida infection, to collect the epidemiology data of candida infection, to evaluate its feasibility, safety and reliability, and acquire the high risk factors of severe colonization.MethodsOne hundred and twenty critically ill patients after surgical removal of digestive tumor with acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score>10were selected from intensive care unit (ICU) of Tianjin Medical University Cancer Institute and Hospital from January Ist2010to December31th2011, and they were randomly divided into two groups:CCI group and control group(60cases in each group). CC1was monitored in all patients. In control group the responsible intensivists ordered the treatment according to their own experience, and in CCI group, when the patient’s CCI>0.4and with evidence of sepsis, the patients were given anti-Candida immediately. When CCI<0.4, anti-candida treatment was not giyen. But when the patients’condition became worse or unstable, complementary anti-candida treatment was given.ResultsThere were no significant differences in general data, treatment of diseases of the patients, APACHE Ⅱ scores, length of ICU stay (LOS) between two groups(P>0.05). There were23patients and33patients developing sepsis in control group and CCI group, respectively. In CCI group, the time between the onset of sepsis to beginning of anti-candida treatment was significantly shorter than the control group (0.92±0.58) days vs.(3.53±3.41)days, P<0.05. In the group of CCI>0.4(39patients) the LOS[(13.72±12.62)days]and the incidence of failure in establishing enteral nutrition(82.05%)were significantly higher than that of the group of CCI<0.4[81patients,(7.10±8.65) days,18.52%, P<0.05].There was no significant difference in APACHE Ⅱ scores, incidence of mechanical ventilation and blood purification between two groups. Analysis of600strains of candida colonized in120patients, revealed that C. albicans ranked first(55.09%), C. glabrata ranked second(10.18%),followed by C. tropicalis, C. Seaver and Cryptococcus. Long term corticosteroid medication history and not carrying out enteral nutrition are the risk factors of severe colonization of candida.ConclusionApplication of CCI may enhance the accuracy of timely preemptive treatment for ICI, and facilitate the collection of epidemiological data of candida in critically ill patients after surgical removal of digestive tumor.更多还原