念珠菌血症患者临床特征及预后的回顾性研究
|
摘要
目的探讨念珠菌血症患者临床特征以及影响预后的危险因素。方法回顾性分析2010年1月—2016年1月四川大学华西医院经血培养确诊为念珠菌血症的临床资料,调查其临床特征(包括科室分布、基础疾病、病原菌分布、抗真菌治疗以及预后),应用STATA软件进行预后多因素生存分析。结果 6年间,共检出念珠菌血症患者162例,其中,男性132例(81%),死亡49例(30.2%)。病原菌分布包括白念珠菌(38%),热带念珠菌(24.7%),光滑念珠菌(16%),近平滑念珠菌(12.3%),克柔念珠菌(2.5%),高里念珠菌(2.5%),新隐球菌(2.5%)和酵母菌(0.6%)。多因素生存分析显示机械通气、气管切开、入住心胸外科、AECOPD、预防性给予抗真菌药的危险比(HR)分布为7.24,3.34,27.54,8.51和0.049。结论机械通气、入住心胸外科、AECOPD、气管切开是念珠菌血症患者死亡的独立危险因素,预防性抗真菌药物治疗可改善生存。监测这些因素可能对念珠菌血症患者生存率的改善具有重大临床意义。
Objective To explore clinic features and evaluate the prognosis factors for death of candidemia for early identification and prevention of the disease. Methods A retropective study based on clinic data were carried out on candidemia isolates who were collected from hospitalized patients in west china hospital of Sichuan University from January 2010 to January 2016. Underlying diseases, species distribution, antifungal therapy and prognosis were analyzed. Multivariate survival analysis was performed with the use of STATA software. Results A total of 162 cases with candidemia were identified. 132(81%) were male. 49(30.2%) were died. Of these patients, 38.3% had candidemia due to C. albicans, followed by C. tropicalis(24.7%), C. glabrata(16.0%), C. parapsilosis(12.3%), C. krusei(2.5%), C. ghauri(2.5%), C. neoformans(2.5%), Yeast(0.6%). Multivariate survival analysis showed that the hazard ratio(HR) of mechanical ventilation was 7.24, tracheotomy was 3.34, cardiothoracic surgery was 27.54, AECOPD was 8.51, and prophylaxis antifungal drugs treatment was 0.049. Conclusion Mechanical ventilation, cardiothoracic surgery, AECOPD and tracheotomy were the independent risk factors for patients' death with candidemia. Prophylaxis antifungal drugs treatment influenced the survival. Detection of these factors may have significant implications for the improvement of candidemia survival.
Objective To explore clinic features and evaluate the prognosis factors for death of candidemia for early identification and prevention of the disease. Methods A retropective study based on clinic data were carried out on candidemia isolates who were collected from hospitalized patients in west china hospital of Sichuan University from January 2010 to January 2016. Underlying diseases, species distribution, antifungal therapy and prognosis were analyzed. Multivariate survival analysis was performed with the use of STATA software. Results A total of 162 cases with candidemia were identified. 132(81%) were male. 49(30.2%) were died. Of these patients, 38.3% had candidemia due to C. albicans, followed by C. tropicalis(24.7%), C. glabrata(16.0%), C. parapsilosis(12.3%), C. krusei(2.5%), C. ghauri(2.5%), C. neoformans(2.5%), Yeast(0.6%). Multivariate survival analysis showed that the hazard ratio(HR) of mechanical ventilation was 7.24, tracheotomy was 3.34, cardiothoracic surgery was 27.54, AECOPD was 8.51, and prophylaxis antifungal drugs treatment was 0.049. Conclusion Mechanical ventilation, cardiothoracic surgery, AECOPD and tracheotomy were the independent risk factors for patients' death with candidemia. Prophylaxis antifungal drugs treatment influenced the survival. Detection of these factors may have significant implications for the improvement of candidemia survival.
引文
[1]Wisplinghoff H,Bischoff T,SM T,et al.Nosocomial bloodstream infections in US hospitals:Analysis of 24179cases from a prospective nationwide surveillance study[J].Clin Infect Dis,2004,39(3):309-317.
[2]Bassetti M,Taramasso L,Nicco E,et al.Epidemiology,species distribution,antifungal susceptibility and outcome of nosocomial candidemia in a tertiary care hospital in Italy[J].PLo S One,2011,6(9):e24198.
[3]Flevari A,Theodorakopoulou M,Velegraki A,et al.Treatment of invasive candidiasis in the elderly:A review[J].Clin Interv Aging,2013,8:1199-1208.
[4]Zhang X B,Yu S J,Yu J X,et al.Retrospective analysis of epidemiology and prognostic factors for candidemia at a hospital in China,2000—2009[J].Jpn J Infect Dis,2012,14(6):510-515.
[5]Doi A M,Pignatari A C,Edmond M B,et al.Epidemiology and microbiologic characterization of nosocomial candidemia from a Brazilian national surveillance program[J].PLo S One,2016,11(1):e0146909.
[6]Ostrosky-Zeichner L,Pappas P G.Invasive candidiasis in the intensive care unit[J].Crit Care Med,2006,34(3):857-863.
[7]Yapper N.Epidemiology and risk factors for invasive candidiasis[J].There Clin Risk Manag,2014,10:95-105.
[8]Tortorano A M,Prigitano A,Lazzarini C,et al.A 1-year prospective survey of candidemia in Italy and changing epidemiology over one decade[J].Infection,2013,41(3):655-662.
[9]Tarumoto N,Abe Y,Yamaguchi T,et al.Clinical aspects of candidemia before and after the introduction of micafungin in Saitama Medical School Hospital[J].Jpn J Chemother,2015,58(1):14-17.
[10]Clinical and Laboratory Standards Institute(CLSI).Reference method for broth dilution antifungal susceptibility testing of yeasts;fourth informational supplement.Wayne.Clinical and Laboratory Standards Institute,2012(Document M27-S4).
[11]蒙永毅.ICU念珠菌血症死亡高危因素分析[D].南宁:广西医科大学,2010.
[12]张明,周华,杨青,等.念珠菌血症的危险因素和预后分析[J].中国微生态学杂志,2014,26(11):1282-1287.
[13]Li D,Zhang W,Zheng S,et al.Surveillance study of candidemia in cancer patients in North China[J].Med Mycol,2013,51(4):378-384.
[14]Wu J Q,Zhu L P,Ou X T,et al.Epidemiology and risk factors for non-Candida albicans candidemia in nonneutropenic patients at a Chinese teaching hospital[J].Med Mycol,2011,49(5):552-555.
[15]Ma C F,Li F Q,Shi L N,et al.Surveillance study of species distribution,antifungal susceptibility and mortality of nosocomial candidemia in a tertiary care hospital in China[J].BMC Infect Dis,2013,22(13):337.
[16]张斌,王炜,刘凤奎,等.成人念珠菌血症33例临床特点分析[J].临床和实验医学杂志,2012,11(15):1190-1194.
[17]De Waele J J,Vogelaers D,Blot S,et al.Fungal infections in patients with severe acute pancreatitis and the use ofprophylactic therapy[J].Clin Infect Dis,2003,37(2):208-213.
[18]Gloor B, Müller C A, Worni M, et al. Pancreatic infection in severe pancreatitis:The role of fungus and multiresistantorganisms[J].Arch Surg,2001,136:592-596.
[19]King N K K,Siriwardana H P P,Wood B,et al.Trends in fungal colonization of pancreatic necrosis in patients undergoing necrosectomy for acute pancreatitis[J].HPB(Oxford),2005,7(2):120-123.
[20]Vege S S,Gardner T B,Chari S T,et al.Outcomes of intraabdominal fungal vs.bacterial infections in severe acute pancreatitis[J].Am J Gastroenterol,2009,104(8):2065-2070.
[21]Chowta M N,Adhikari P,Rajeev A,et al.Study of risk factors and prevalence of invasive candidiasis in a Tertiary Care Hospital[J].Indian J Crit Care Med,2007,11(2):67-73.
[22]Walsh T J,Rex J H.All catheter-related candidemia is not the same:Assessment of the balance between the risks and benefits of removal of vascular catheters[J].Clin Infect Dis,2002,34(5):600-602.
[23]Pappas P G,Kauffman C A,Andes D,et al.Clinical practice guidelines for the management of candidiasis:2009 update by the Infectious Diseases Society of America[J].Clin Infect Dis,2009,48(5):503-535.
[24]Hope W,Morton A,Eisen D P.Increase in prevalence of nosocomial non-Candida albicans candidaemia and the association of Candida krusei with fluconazole use[J].J Hosp Infect,2002,50(1):56-65.
[25]Komshian S V,Uwaydah A K,Sobel J D,et al.Fungemia caused by Candida species and Torulopsis glabrata in the hospitalized patient:Frequency,characteristics,and evaluation of factors influencing outcome[J].Rev Infect Dis,1989,11(3):379-390.
[26]Bassetti M,Ansaldi F,Nicolini L,et al.Incidence of candidaemia and relationship with fluconazole use in an intensive care unit[J].J Antimicrob Chemother,2009,64(3):625-629.
[27]Lin M Y,Carmeli Y,Zumsteg J,et al.Prior antimicrobial therapy and risk for hospital acquired Candida glabrata and Candida krusei fungemia:A case-case-control study[J].Antimicrob Agents Chemother,2005,49(11):4555-4560.
[28]Forrest G N,Weekes E,Johnson J K.Increasing incidence of Candida parapsilosis candidemia with caspofungin usage[J].J Infect,2008,56(2):126-129.
[29]Karageorgopoulos D E,Vouloumanou E K,Ntziora F,et al.Β-D-glycan assay for the diagnosis of invasive fungal infections:a meta-analysis[J].Clin Infect Dis,2011,52(6):750-770.
[30]刘英其.血清1,3-β-D-葡聚糖检测在念珠菌菌血症诊断中的价值[J].中国卫生检验杂志,2009,(9):2097-2098.
[31]王宇凡,刘树业.念珠菌对两性霉素B耐药机制及其相应治疗策略的研究进展[J].中国抗生素杂志,2014,39(9):706-711.
[32]Pfaller M A,Diekema D J,Gibbs D L,et al.Results from the ARTEMIS DISK global antifungal surveillance study,1997 to 2007:A 10.5-year analysis of susceptibilities of Candida species to fluconazole and voriconazole as determined by CLSI standardized disk diffusion[J].J Clin Microbiol,2010,48(4):1366-1377.
[33]Perea S, López-Ribot J L, Kirkpatrick W R, et al.Prevalence of molecular mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying high-level fluconazole resistance isolated from human immunodeficiency virus-infected patients[J].Antimicrob Agents Chemother,2001,45(10):2676-2684.
[34]赵文艳,严子禾.真菌耐药性及新型抗真菌药物研究进展[J].中国药业,2014,23(6):94-95.
[2]Bassetti M,Taramasso L,Nicco E,et al.Epidemiology,species distribution,antifungal susceptibility and outcome of nosocomial candidemia in a tertiary care hospital in Italy[J].PLo S One,2011,6(9):e24198.
[3]Flevari A,Theodorakopoulou M,Velegraki A,et al.Treatment of invasive candidiasis in the elderly:A review[J].Clin Interv Aging,2013,8:1199-1208.
[4]Zhang X B,Yu S J,Yu J X,et al.Retrospective analysis of epidemiology and prognostic factors for candidemia at a hospital in China,2000—2009[J].Jpn J Infect Dis,2012,14(6):510-515.
[5]Doi A M,Pignatari A C,Edmond M B,et al.Epidemiology and microbiologic characterization of nosocomial candidemia from a Brazilian national surveillance program[J].PLo S One,2016,11(1):e0146909.
[6]Ostrosky-Zeichner L,Pappas P G.Invasive candidiasis in the intensive care unit[J].Crit Care Med,2006,34(3):857-863.
[7]Yapper N.Epidemiology and risk factors for invasive candidiasis[J].There Clin Risk Manag,2014,10:95-105.
[8]Tortorano A M,Prigitano A,Lazzarini C,et al.A 1-year prospective survey of candidemia in Italy and changing epidemiology over one decade[J].Infection,2013,41(3):655-662.
[9]Tarumoto N,Abe Y,Yamaguchi T,et al.Clinical aspects of candidemia before and after the introduction of micafungin in Saitama Medical School Hospital[J].Jpn J Chemother,2015,58(1):14-17.
[10]Clinical and Laboratory Standards Institute(CLSI).Reference method for broth dilution antifungal susceptibility testing of yeasts;fourth informational supplement.Wayne.Clinical and Laboratory Standards Institute,2012(Document M27-S4).
[11]蒙永毅.ICU念珠菌血症死亡高危因素分析[D].南宁:广西医科大学,2010.
[12]张明,周华,杨青,等.念珠菌血症的危险因素和预后分析[J].中国微生态学杂志,2014,26(11):1282-1287.
[13]Li D,Zhang W,Zheng S,et al.Surveillance study of candidemia in cancer patients in North China[J].Med Mycol,2013,51(4):378-384.
[14]Wu J Q,Zhu L P,Ou X T,et al.Epidemiology and risk factors for non-Candida albicans candidemia in nonneutropenic patients at a Chinese teaching hospital[J].Med Mycol,2011,49(5):552-555.
[15]Ma C F,Li F Q,Shi L N,et al.Surveillance study of species distribution,antifungal susceptibility and mortality of nosocomial candidemia in a tertiary care hospital in China[J].BMC Infect Dis,2013,22(13):337.
[16]张斌,王炜,刘凤奎,等.成人念珠菌血症33例临床特点分析[J].临床和实验医学杂志,2012,11(15):1190-1194.
[17]De Waele J J,Vogelaers D,Blot S,et al.Fungal infections in patients with severe acute pancreatitis and the use ofprophylactic therapy[J].Clin Infect Dis,2003,37(2):208-213.
[18]Gloor B, Müller C A, Worni M, et al. Pancreatic infection in severe pancreatitis:The role of fungus and multiresistantorganisms[J].Arch Surg,2001,136:592-596.
[19]King N K K,Siriwardana H P P,Wood B,et al.Trends in fungal colonization of pancreatic necrosis in patients undergoing necrosectomy for acute pancreatitis[J].HPB(Oxford),2005,7(2):120-123.
[20]Vege S S,Gardner T B,Chari S T,et al.Outcomes of intraabdominal fungal vs.bacterial infections in severe acute pancreatitis[J].Am J Gastroenterol,2009,104(8):2065-2070.
[21]Chowta M N,Adhikari P,Rajeev A,et al.Study of risk factors and prevalence of invasive candidiasis in a Tertiary Care Hospital[J].Indian J Crit Care Med,2007,11(2):67-73.
[22]Walsh T J,Rex J H.All catheter-related candidemia is not the same:Assessment of the balance between the risks and benefits of removal of vascular catheters[J].Clin Infect Dis,2002,34(5):600-602.
[23]Pappas P G,Kauffman C A,Andes D,et al.Clinical practice guidelines for the management of candidiasis:2009 update by the Infectious Diseases Society of America[J].Clin Infect Dis,2009,48(5):503-535.
[24]Hope W,Morton A,Eisen D P.Increase in prevalence of nosocomial non-Candida albicans candidaemia and the association of Candida krusei with fluconazole use[J].J Hosp Infect,2002,50(1):56-65.
[25]Komshian S V,Uwaydah A K,Sobel J D,et al.Fungemia caused by Candida species and Torulopsis glabrata in the hospitalized patient:Frequency,characteristics,and evaluation of factors influencing outcome[J].Rev Infect Dis,1989,11(3):379-390.
[26]Bassetti M,Ansaldi F,Nicolini L,et al.Incidence of candidaemia and relationship with fluconazole use in an intensive care unit[J].J Antimicrob Chemother,2009,64(3):625-629.
[27]Lin M Y,Carmeli Y,Zumsteg J,et al.Prior antimicrobial therapy and risk for hospital acquired Candida glabrata and Candida krusei fungemia:A case-case-control study[J].Antimicrob Agents Chemother,2005,49(11):4555-4560.
[28]Forrest G N,Weekes E,Johnson J K.Increasing incidence of Candida parapsilosis candidemia with caspofungin usage[J].J Infect,2008,56(2):126-129.
[29]Karageorgopoulos D E,Vouloumanou E K,Ntziora F,et al.Β-D-glycan assay for the diagnosis of invasive fungal infections:a meta-analysis[J].Clin Infect Dis,2011,52(6):750-770.
[30]刘英其.血清1,3-β-D-葡聚糖检测在念珠菌菌血症诊断中的价值[J].中国卫生检验杂志,2009,(9):2097-2098.
[31]王宇凡,刘树业.念珠菌对两性霉素B耐药机制及其相应治疗策略的研究进展[J].中国抗生素杂志,2014,39(9):706-711.
[32]Pfaller M A,Diekema D J,Gibbs D L,et al.Results from the ARTEMIS DISK global antifungal surveillance study,1997 to 2007:A 10.5-year analysis of susceptibilities of Candida species to fluconazole and voriconazole as determined by CLSI standardized disk diffusion[J].J Clin Microbiol,2010,48(4):1366-1377.
[33]Perea S, López-Ribot J L, Kirkpatrick W R, et al.Prevalence of molecular mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying high-level fluconazole resistance isolated from human immunodeficiency virus-infected patients[J].Antimicrob Agents Chemother,2001,45(10):2676-2684.
[34]赵文艳,严子禾.真菌耐药性及新型抗真菌药物研究进展[J].中国药业,2014,23(6):94-95.