北京大学学报(医学版) ›› 2018, Vol. 50 ›› Issue (6): 1063-1069. doi: 10.19723/j.issn.1671-167X.2018.06.022

• 论著 • 上一篇    下一篇

非免疫缺陷宿主念珠菌血流感染

丁艳苓,沈宁(),周庆涛,贺蓓,郑佳佳,赵心懋   

  1. 北京大学第三医院1.呼吸内科,2.检验科,3.感染疾控科, 北京 100191
  • 收稿日期:2017-10-17 出版日期:2018-12-18 发布日期:2018-12-18
  • 通讯作者: 沈宁 E-mail:shenning1972@126.com

Clinical analysis of candidemia in immunocompetent patients

Yan-ling DING,Ning SHEN(),Qing-tao ZHOU,Bei HE,Jia-jia ZHENG,Xin-mao ZHAO   

  1. 1. Department of Respiratory Medicine, 2. Department of Laboratory Medicine, 3. Department of Nosocomial Infection,Peking University Third Hospital, Beijing 100191, China
  • Received:2017-10-17 Online:2018-12-18 Published:2018-12-18
  • Contact: Ning SHEN E-mail:shenning1972@126.com

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摘要:

目的: 探讨非免疫缺陷宿主念珠菌血流感染的病原学与临床特点。方法: 回顾性分析2010年1月至2016年6月北京大学第三医院收治的念珠菌血流感染患者的临床与微生物学资料,比较非免疫缺陷与HIV阴性免疫缺陷宿主的基础疾病、念珠菌定植、临床表现、病原分布和药敏试验结果,以及治疗结局等方面的差异。结果: 62例患者纳入分析,男36例,女26例,年龄16~100岁,平均年龄(66.02±17.65)岁。非免疫缺陷与HIV阴性免疫缺陷宿主分别为30例和32例。非免疫缺陷宿主中,19例(19/30,63.33%)患者发生血流感染时入住重症监护室(intensive care unit,ICU),21例(21/30,70.00%)合并糖尿病或高血糖未控制,22例(22/30,73.33%)接受有创机械通气,多于HIV阴性免疫缺陷者[分别为8/32(25.00%),13/32(40.63%),7/32(21.88%)];入院与发生念珠菌血流感染时急性生理学及慢性健康状况评分(acute physiology and chronic health evaluation Ⅱ, APACHEⅡ)分别为(19.98±5.81)分和(25.61±6.52)分,序贯器官衰竭评分(sequential organ failure assessment,SOFA)分别为(6.04±6.14)分和(12.75±8.42)分,高于HIV阴性免疫缺陷者[APACHEⅡ分别为(15.09±5.82)分和(22.15±5.98)分,SOFA分别为(2.87±2.73)分和(7.66±5.64)分];粗死亡率(21/30,70.00%)较HIV阴性免疫缺陷者升高(14/32,43.75%),上述结果差异均有统计学意义(P<0.05)。两组血培养念珠菌属均以白色念珠菌最常见,患者临床表现、念珠菌定植指数、病原学分布与药敏试验结果等均相似(P>0.05)。结论: 非免疫缺陷宿主念珠菌血流感染多发生于入住ICU、病情更加危重患者,其糖尿病或未控制高血糖、接受有创机械通气患者更为突出,预后更差;其临床表现、微生物学特点等与HIV阴性免疫缺陷患者均相似。

关键词: 念珠菌属, 真菌血症, 非免疫缺陷宿主, 临床表现, 预后

Abstract:

Objective: To investigate the etiological and clinical characteristics of immunocompetent patients with candidemia.Methods:The clinical and microbiological data of patients diagnosed as candidemia admitted in Peking University Third Hospital from January 2010 to June 2016 were retrospectively analyzed. Underlying diseases, Candida spp. colonization, clinical manifestations, microbiological data, treatment and the outcome were compared between the HIV-negative immunocompromised (IC) and nonimmunocompromised (NIC) patients.Results:A total of 62 cases diagnosed as candidemia were analyzed including 36 men and 26 women, with 16 to 100 years of age [(66.02±17.65) years]. There were 30 NIC and 32 HIV-negative IC patients respectively. In the NIC patients, there were 19 cases (19/30, 63.33%) with admission in intensive care unit (ICU), 21 (21/30, 70.00%) associated diabetes mellitus or uncontrolled hyperglycemia and 22(22/30,73.33%)receiving invasive mechanical ventilation,while in the HIV-negative IC patients, there were 8 (8/32, 25.00%),13 (13/32, 40.63%) and 7 (7/32, 21.88%) respectively (P<0.05). The NIC patients had higher acute physiology and chronic health evaluation (APACHEⅡ) scores and sequential organ failure assessment (SOFA) scores both at admission (19.98±5.81, 6.04±6.14) and candidemia onset (25.61±6.52, 12.75±8.42) than the HIV-negative IC patients (APACHEⅡ 15.09±5.82, 22.15±5.98) and SOFA 2.87±2.73, 7.66±5.64 respectively (P<0.05). In the NIC patients, twenty-one cases (21/30, 70.00%) died in hospital,while 14 cases (14/32, 43.75%) in HIV-negative IC.The crude mortality was significantly different between the two groups (P<0.05). By blood culture, Canidia albicans remained the the most prevalent isolates in all the patients. Clinical manifestation, Candida spp. colonization, etiology and drug susceptibility were also similar between NIC and HIV-negative IC patients (P>0.05).Conclusion:Candidemia in NIC patients tends to occur in those who are much more critically ill, more often admitted in ICU, and more frequently have diabetes mellitus or uncontrolled hyperglycemia and receive invasive mechanical ventilation than HIV-negative IC patients. NIC patients also have poorer prognosis than HIV- negative IC patients. Clinical manifestations, and microbiological characteristics are similar between HIV- negative IC and NIC patients.

Key words: Candida, Candidemia, Immunocompetent patients, Clinical manifestation, Prognosis

中图分类号: 

  • R56

表1

念珠菌血流感染的非免疫缺陷与HIV阴性免疫缺陷宿主的临床资料"

Clinical data Nonimmunocompromised patients
(n=30)
HIV-negative immunocompromised
patients (n=32)
P
Admission in ICU, n(%) 19 (63.33) 8 (25.00) 0.002
Underlying diseases
Malignant solid tumor or hematologic disease, n(%) 0 (0.00) 26 (81.25) <0.001
Diabetes mellitus or uncontrolledhyperglycemia, n(%)
Peritoneal infection, n(%)
Acute or chronic renal failure, n(%)
21 (70.00)
4 (13.33)
15 (50.00)
13 (40.63)
7 (21.88)
11 (34.38)
0.020
0.379
0.213
Hypoalbuminemia, n(%) 28 (93.33) 26 (81.25) 0.156
Neutropnia, n(%)
Multiple sites colonization with Candida spp., n(%)
0 (0.00)
22 (73.33)
7 (21.88)
20 (62.50)
0.011
0.362
Treatment measures
Presence of a central venous catheter, n(%) 28 (93.33) 27 (84.38) 0.427
Presence of a ureter, n(%) 28 (93.33) 31 (96.88) 0.607
Presence of peritoneal drainage pipes, n(%) 7 (23.33) 10 (31.25) 0.485
Prior abdominal surgery, n(%)
Prior surgery, n(%)
7 (23.33)
12 (40.00)
12 (37.50)
14 (43.75)
0.227
0.765
Parenteral nutrition, n(%) 12 (40.00) 15 (46.88) 0.585
Invasive mechanical ventilation, n(%) 22 (73.33) 7 (21.88) <0.001
Hemodialysis, n(%) 2 (6.67) 4 (12.50) 0.672
Systemic corticosteroids or cytotoxic drugs use, n(%)
Cancer chemotherapy, n(%)
0 (0.00)
0 (0.00)
12 (37.50)
15 (46.88)
<0.001
<0.001
Broad-spectrum antibiotic use, n(%) 29 (96.67) 27 (84.38) 0.197
Prior antifungal exposure, n(%)
Disease severity
APACHE Ⅱ score at admission, x-±s
APACHE Ⅱ score at candidemia, x-±s
SOFA score at admission, x-±s
SOFA score at candidemia, x-±s
Sever sepsis, n(%)
Septic shock, n(%)
Multiple organ failure, n(%)
2 (6.67)

19.98±5.81
25.61±6.52
6.04±6.14
12.75±8.42
26 (86.67)
19 (63.33)
16 (53.33)
5 (15.63)

15.09±5.82
22.15±5.98
2.87±2.73
7.66±5.64
29 (90.63)
14 (43.75)
12 (37.50)
0.427

0.048
0.037
0.011
0.007
0.623
0.122
0.211

表2

非免疫缺陷与HIV阴性免疫缺陷宿主致血流感染的念珠菌药敏试验结果"

Candida spp. Antifungal agents Nonimmunocompromised patients (n=30) HIV-negative immunocompromised patients (n=32) P
No. of strains S I R No. of strains S I R
Candida albicans Fluconazole 17 17 0 0 16 15 0 1 0.485
Itraconazole 15 1 1 12 0 4 0.249
Flucytosin 17 0 0 16 0 0 1.000
Amphotericin B 17 0 0 16 0 0 1.000
Voriconazole 17 0 0 15 1 0 0.485
Candida tropicalis Fluconazole 5 3 2 0 9 6 0 3 0.083
Itraconazole 4 0 1 5 1 3 1.000
Flucytosin 5 0 0 9 0 0 1.000
Amphotericin B 5 0 0 9 0 0 1.000
Voriconazole 3 2 0 5 1 3 0.287
Candida glabrata Fluconazole 6 6 0 0 4 4 0 0 1.000
Itraconazole 3 3 0 3 1 0 0.571
Flucytosin 6 0 0 4 0 0 1.000
Amphotericin B 6 0 0 4 0 0 1.000
Voriconazole 6 0 0 4 0 0 1.000
Candida parapsilosis Fluconazole 2 2 0 0 2 2 0 0 1.000
Itraconazole 2 0 0 1 1 0 1.000
Flucytosin 2 0 0 2 0 0 1.000
Amphotericin B 2 0 0 2 0 0 1.000
Voriconazole 2 0 0 2 0 0 1.000
Candida krusei Fluconazole 0 - - - 1 0 0 1 -
Itraconazole - - - 1 0 0 -
Flucytosin - - - 1 0 0 -
Amphotericin B - - - 1 0 0 -
Voriconazole - - - 1 0 0 -
[1] 李光辉 . 念珠菌血症的诊断与抗真菌治疗[J]. 中国感染与化疗杂志, 2011,11(2):98-100.
[2] Wisplinhoff H, Bischoff T, Tallent SM , et al. Nosocomial bloodstream infections in US hospitals: analysis of 24, 179 cases from a prospective nationwide surveillance study[J]. Clin Infect Dis, 2004,39(3):309-317.
doi: 10.1086/421946
[3] Wang H, Xiao M, Chen SC , et al. In vitro susceptibilities of yeast species to fluconazole and voriconazole as determined by the 2010 national China Hospital Invasive Fungal Surveillance Net (CHIF-NET) study[J]. J Clin Microbiol, 2012,50(12):3952-3959.
doi: 10.1128/JCM.01130-12 pmid: 23035204
[4] Guery BP, Arendrup MC, Auzinger G , et al. Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part I. Epidemiology and diagnosis[J]. Intensive Care Med, 2009,35(1):55-62.
doi: 10.1007/s00134-008-1339-6 pmid: 18972100
[5] Dimopoulos G, Karabinis A, Samonis G , et al. Candidemia in immunocompromised and immunocompetent critically ill patients: a prospective comparative study[J]. Eur J Clin Microbiol Infect Dis, 2007,26(6):377-384.
doi: 10.1007/s10096-007-0316-2 pmid: 17525857
[6] Giri S, Kindo AJ . A review of Candida species causing blood stream infection[J]. Indian J Med Microbiol, 2012,30(3):270-278.
doi: 10.4103/0255-0857.99484 pmid: 22885191
[7] Mikulska M, Bassetti M, Ratto S , et al. Invasive candidiasis in non-hematological patients[J]. Mediterr J Hematol Infect Dis, 2011,3(1):e2011007.
doi: 10.4084/MJHID.2011.007 pmid: 21625311
[8] Safdar A, Bannister TW, Safdar Z . The predictors of outcome in immunocompetent patients with hematogenous candidiasis[J]. Int J Infect Dis, 2004,89(3):180-186.
doi: 10.1016/j.ijid.2003.05.003 pmid: 15109594
[9] Vigouroux S, Morin O, Moreau P , et al. Candidemia in patients with hematologic malignancies: analysis of 7 years’ experience in a single center[J]. Haematologica, 2006,91(5):717-718.
[10] Charlson ME, Pompei P, Ales KL , et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation[J]. J Chronic Dis, 1987,40(5):373-383.
doi: 10.1016/0021-9681(87)90171-8 pmid: 3558716
[11] Marra AR, Bearman GM, Wenzel RP , et al. Comparison of severity of illness scoring systems for patients with nosocomial bloodstream infection due to Pseudomonas aeruginosa[J]. BMC Infect Dis, 2006,17(6):132.
doi: 10.1186/1471-2334-6-132 pmid: 1563469
[12] León C, Ruiz-Santana S, Saavedra P , et al. EPCAN study group. A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization[J]. Crit Care Med, 2006,34(3):730-737.
doi: 10.1097/01.CCM.0000202208.37364.7D pmid: 16505659
[13] Posteraro B, De Pascale G, Tumbarello M , et al. Early diagnosis of candidemia in intensive care unit patients with sepsis: a prospective comparison of (1→3)-β-D-glucan assay, Candida score, and colonization index[J]. Crit Care, 2011,15(5):R249.
doi: 10.1186/cc10507 pmid: 22018278
[14] Abe M, Kimura M, Araoka H , et al. Serum (1, 3)-beta-D-glucan is an inefficient marker of breakthrough candidemia[J]. Med Mycol, 2014,52(8):835-840.
doi: 10.1093/mmy/myu066 pmid: 25349254
[15] Singer M, Deutschman CS, Seymour CW , et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3)[J]. JAMA, 2016,315(8):801-810
doi: 10.1001/jama.2016.0287 pmid: 26903336
[16] 陈佰义 . 侵袭性念珠菌病早期经验治疗的临床思维[J]. 中华内科杂志, 2014,53(11):907-909
doi: 10.3760/cma.j.issn.0578-1426.2014.11.019
[17] Sims CR, Ostrosky-Zeichner L, Rex JH . Invasive candidiasis in immunocompromised hospitalized patients[J]. Arch Med Res, 2005,36(6):660-671
doi: 10.1016/j.arcmed.2005.05.015 pmid: 16216647
[18] Tragiannidis A, Tsoulas C, Kerl K , et al. Invasive candidiasis: update on current pharmacotherapy options and future perspectives[J]. Expert Opin Pharmacother, 2013,14(11):1515-1528.
doi: 10.1517/14656566.2013.805204 pmid: 23724798
[19] Ahmad S, Khan Z . Invasive candidiasis: a review of nonculture-based laboratory diagnostic methods[J]. Indian J Med Microbiol, 2012,30(3):264-269.
doi: 10.4103/0255-0857.99482 pmid: 22885190
[20] 谢剑锋, 杨毅 . 重症医学科患者念珠菌血症早期诊断的困境与思路[J]. 中华内科杂志, 2015,54(5):456-457.
doi: 10.3760/cma.j.issn.0578-1426.2015.05.016
[21] Del Bono V, Delfino E, Furfaro E , et al. Clinical performance of the (1, 3)-β-D-glucan assay in early diagnosis of nosocomial Candida bloodstream infections[J]. Clin Vaccine Immunol, 2011,18(12):2113-2117.
doi: 10.1128/CVI.05408-11 pmid: 21994353
[22] Jaijakul S, Vazquez JA, Swanson RN , et al.( 1, 3)-β-D-glucan as a prognostic marker of treatment response in invasive candidiasis[J]. Clin Infect Dis, 2012,55(4):521-526.
doi: 10.1093/cid/cis456 pmid: 22573851
[23] Lewis RE . Overview of the changing epidemiology of candidemia[J]. Curr Med Res Opin, 2009,25(7):1732-1740.
doi: 10.1185/03007990902990817 pmid: 19519284
[24] Pemán J, Cantón E, Miñana JJ , et al. Changes in the epidemiology of fungaemia and fluconazole susceptibility of blood isolates during the last 10 years in Spain: results from the FUNGEMYCA study[J]. Rev Iberoam Micol, 2011,28(2):91-99.
doi: 10.1016/j.riam.2011.02.005
[25] 吴吉芹, 朱利平, 区雪婷 , 等. 医院获得性念珠菌血症109例临床特点及预后分析[J]. 中华传染病杂志, 2011,29(4):206-210.
doi: 10.3760/cma.j.issn.1000-6680.2011.04.003
[26] Playford EG, Nimmo GR, Tilse M , et al. Increasing incidence of candidaemia: long-term epidemiological trends, Queensland, Australia, 1999-2008[J]. J Hosp Infect, 2010,76(1):46-51.
doi: 10.1016/j.jhin.2010.01.022 pmid: 20382444
[27] Pfaller MA, Messer SA, Moet GJ , et al. Candida bloodstream infections: comparison of species distribution and resistance to echinocandin and azole antifungal agents in intensive care unit (ICU) and non-ICU settings in the SENTRY Antimicrobial surveillance program (2008-2009)[J]. Int J Antimicrob Agents, 2011,38(1):65-69.
doi: 10.1016/j.ijantimicag.2011.02.016 pmid: 21514797
[28] Marriott DJ, Playford EG, Chen S , et al. Australian candidaemia study. Determinants of mortality in non-neutropenic ICU patients with candidaemia[J]. Crit Care, 2009,13(4):R115.
doi: 10.1186/cc7964 pmid: 19594912
[29] Tumbarello M, Posteraro B, Trecarichi EM , et al. Biofilm production by Candida species and inadequate antifungal therapy as predictors of mortality for patients with candidemia[J]. J Clin Microbiol, 2007,45(6):1843-1850.
doi: 10.1128/JCM.00131-07 pmid: 17460052
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