收稿日期: 2020-03-17
网络出版日期: 2021-05-14
基金资助
国家重点研发项目(2018YFC2000700);国家自然科学基金(81630086);中国科学院重点研究计划(ZDRW-ZS-2017-1);上海市教育委员会重大科技创新计划(2019-01-07-00-01-E00059);上海高校青年东方学者计划(QD2018016);上海浦江计划(18PJ1406600);上海交通大学医学与工程交叉学科研究基金(YG2020YQ06);上海交通大学医学院高水平地方高校创新团队(SSMU-ZLCX20180302)
Advances in epidemiology and treatment of invasive Candida infection in the immunocompromised population
Received date: 2020-03-17
Online published: 2021-05-14
Supported by
National Key Research and Development Program of China(2018YFC2000700);National Nature Science Foundation of China(81630086);Key Research Program of Chinese Academy of Sciences(ZDRW-ZS-2017-1);Major Science and Technology Innovation Program of Shanghai Municipal Education Commission(2019-01-07-00-01-E00059);Program for Young Eastern Scholar at Shanghai Institutions of Higher Learning(QD2018016);Shanghai Pujiang Program(18PJ1406600);Medicine and Engineering Interdisciplinary Research Fund of Shanghai Jiao Tong Univesity(YG2020YQ06);Innovative Research Team of High-level Local Universities in Shanghai(SSMU-ZLCX20180302)
随着器官移植等现代医学手段的大量开展、广谱抗生素和免疫抑制剂的广泛应用以及人类寿命的延长,免疫力低下人群的数量不断增多。侵袭性真菌感染在此类人群中的发病率和死亡率不断增高,已成为恶性肿瘤、器官移植等致死的直接原因。念珠菌是侵袭性真菌感染的首要致病真菌,它可侵入人体皮下组织、黏膜和全身各组织、器官,进而在血液中播散。念珠菌感染主要表现为念珠菌血症和深部念珠菌病,常预后不佳。目前,针对免疫力低下人群侵袭性念珠菌(invasive Candida,IC)感染的治疗方法仍以抗真菌感染为主,药物治疗是有效途径之一。临床常规抗真菌药物包括多烯类、唑类和棘白菌素类。其中,棘白菌素类是治疗IC的首选药物。然而,现有的治疗手段未能改善IC感染患者的预后,长期使用所致的耐药现象频发。目前可用的抗真菌药物数量极其有限。因此,为了解决上述问题,药物联合治疗、辅助免疫治疗、光动力治疗和激光治疗等为治疗IC感染提供了新的视角。该文就免疫力低下人群容易出现的IC感染的流行病学和治疗研究现状进行综述,深入讨论了国内外IC感染在重症住院患者、血液恶性肿瘤患者、实体器官移植患者、新生儿、老年人、人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者中的发病率、死亡率,主要致病念珠菌的菌种分布,以及新的研究方案的治疗潜力和局限性,并提出了未来的研究方向。
刘琳 , 王慧 , 刘宁宁 . 侵袭性念珠菌感染在免疫力低下人群中的流行病学和治疗进展[J]. 上海交通大学学报(医学版), 2021 , 41(4) : 525 -529 . DOI: 10.3969/j.issn.1674-8115.2021.04.018
With the development of modern medical technology, such as organ transplantation, the extensive application of broad-spectrum antibiotics and immunosuppressants and the prolongation of human life span, the number of people with low immunity is increasing. The morbidity and mortality of invasive fungal infection are increasing in these population. Invasive fungal infection has become the direct cause of death of critical diseases, such as malignant tumor and organ transplantation. Candida is the primary pathogenic fungi of invasive fungal infection. It can infect human subcutaneous tissue, mucous membrane, other tissues and organs of the whole body, and then spread in the blood. The main clinical manifestations of Candida infectionare candidemia and deep candidiasis, and the prognosis is often poor. At present, antifungal infection is still the main treatment for invasive Candida (IC) in immunocompromised population, and drug treatment is one of the effective ways. Clinical conventional antifungal drugs include polyenes, azoles and echinocandins. Among them, echinocandins is the first choice for the treatment of IC. However, the existing treatments fail to improve the prognosis of patients with IC infection, and drug resistance caused by long-term use frequently occurr. At present, the number of antifungal drugs available is extremely limited. Therefore, in order to solve the above problems, drug combination therapy, adjuvant immunotherapy, photodynamic therapy and laser therapy provide new perspectives for the treatment of IC. This article reviews the epidemiology and treatment of IC infetcion in the population with low immunity. In this paper, the incidence and mortality of IC infection in patients in intensive care unit, patients with hematological malignancies, solid organ transplant patients, neonates, the elderly, and human immunodeficiency virus (HIV)-infected people at home and abroad, and the distribution of main pathogenic Candida species, as well as the therapeutic potential and limitations of new research were discussed in depth. The future research direction was proposed.
1 | 扈东营, 姜伟伟, 李航, 等. 侵袭性念珠菌感染流行病学现状和治疗进展[J]. 世界临床药物, 2020, 41(05):323-28. |
2 | Enoch DA, Yang H, Aliyu SH, et al. The changing epidemiology of invasive fungal infections[J]. Methods Mol Biol, 2017, 1508:17-65. |
3 | Vincent JL, Sakr Y, Singer M, et al. Prevalence and outcomes of infection among patients in intensive care units in 2017[J]. JAMA, 2020, 323(15):1478-1487. |
4 | Chakrabarti A, Sood P, Rudramurthy SM, et al. Incidence, characteristics and outcome of ICU-acquired candidemia in India[J]. Intensive Care Med, 2015, 41(2):285-295. |
5 | Bassetti M, Giacobbe DR, Vena A, et al. Incidence and outcome of invasive candidiasis in intensive care units (ICUs) in Europe: results of the EUCANDICU project[J]. Crit Care, 2019, 23(1):219. |
6 | Guo FM, Yang Y, Kang Y, et al. Invasive candidiasis in intensive care units in China: a multicentre prospective observational study[J]. J Antimicrob Chemother, 2013, 68(7): 1660-1668. |
7 | Cortegiani A, Misseri G, Giarratano A, et al. The global challenge of Candida auris in the intensive care unit[J]. Crit Care, 2019, 23(1):150. |
8 | Keighley C, Chen SC, Marriott D, et al. Candidaemia and a risk predictive model for overall mortality: a prospective multicentre study[J]. BMC Infect Dis, 2019, 19(1):445. |
9 | Corzo-León DE, Satlin MJ, Soave R, et al. Epidemiology and outcomes of invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients in the era of antifungal prophylaxis: a single-centre study with focus on emerging pathogens[J]. Mycoses, 2015, 58(6):325-336. |
10 | Criscuolo M, Marchesi F, Candoni A, et al. Fungaemia in haematological malignancies: SEIFEM-2015 survey[J]. Eur J Clin Invest, 2019, 49(5):e13083. |
11 | Sun Y, Meng F, Han M, et al. Epidemiology, management, and outcome of invasive fungal disease in patients undergoing hematopoietic stem cell transplantation in China: a multicenter prospective observational study[J]. Biology Blood Marrow Transplantat, 2015, 21(6):1117-1126. |
12 | Chen CY, Tien FM, Sheng WH, et al. Clinical and microbiological characteristics of bloodstream infections among patients with haematological malignancies with and without neutropenia at a medical centre in northern Taiwan, 2008-2013[J]. Int J Antimicrob Agents, 2017, 49(3):272-281. |
13 | Andes DR, Safdar N, Baddley JW, et al. The epidemiology and outcomes of invasive Candida infections among organ transplant recipients in the United States: results of the Transplant-Associated Infection Surveillance Network (TRANSNET) [J]. Transpl Infect Dis, 2016, 18(6):921-931. |
14 | Fernández-Ruiz M, Cardozo C, Salavert M, et al. Candidemia in solid organ transplant recipients in Spain: epidemiological trends and determinants of outcome[J]. Transpl Infect Dis, 2019, 21(6):e13195. |
15 | Benedict K, Roy M, Kabbani S, et al. Neonatal and pediatric Candidemia: results from population-based active laboratory surveillance in four US locations, 2009-2015[J]. J Pediatric Infect Dis Soc, 2018, 7(3):e78-e85. |
16 | Warris A, Pana ZD, Oletto A, et al. Etiology and outcome of Candidemia in neonates and children in Europe: an 11-year multinational retrospective study[J]. Pediatric Infect Dis J, 2020, 39(2):114-120. |
17 | Hsu JF, Lai MY, Lee CW, et al. Comparison of the incidence, clinical features and outcomes of invasive candidiasis in children and neonates[J]. BMC Infect Dis, 2018, 18(1):194. |
18 | Toda M, Williams SR, Berkow EL, et al. Population-based active surveillance for culture-confirmed Candidemia-four sites, United States, 2012-2016[J]. MMWR Surveill Summ, 2019, 68(8):1-15. |
19 | Luzzati R, Cavinato S, Deiana ML, et al. Epidemiology and outcome of nosocomial candidemia in elderly patients admitted prevalently in medical wards[J]. Aging Cli Exp Res, 2015, 27(2):131-137. |
20 | Lerma A, Cantero E, Soriano M, et al. Clinical presentation of candidaemia in elderly patients: experience in a single institution[J]. Rev Esp Quimioter, 2017, 30(3):207-212. |
21 | Ramos-Martínez A, Vicente-López N, Sánchez-Romero I, et al. Epidemiology and prognosis of candidaemia in elderly patients[J]. Mycoses, 2017, 60(12):808-17. |
22 | Tang HJ, Liu WL, Lin HL, et al. Epidemiology and prognostic factors of candidemia in elderly patients[J]. Geriatr Gerontol Int, 2015, 15(6):688-693. |
23 | Taramasso L, Tatarelli P, Di Biagio A. Bloodstream infections in HIV-infected patients[J]. Virulence, 2016, 7(3):320-328. |
24 | Buchacz K, Lau B, Jing Y, et al. Incidence of AIDS-defining opportunistic infections in a multicohort analysis of HIV-infected persons in the United States and Canada, 2000-2010[J]. J Infect Dis, 2016, 214(6):862-872. |
25 | Pang W, Shang P, Li Q, et al. Prevalence of opportunistic infections and causes of death among hospitalized HIV-infected patients in Sichuan, China[J]. Tohoku J Exp Med, 2018, 244(3):231-242. |
26 | Katragkou A, McCarthy M, Meletiadis J, et al. In vitro combination therapy with isavuconazole against Candida spp.[J]. Med Mycol, 2017, 55(8):859-868. |
27 | Bidaud AL, Botterel F, Chowdhary A, et al. In vitro antifungal combination of flucytosine with amphotericin B, voriconazole, or micafungin against Candida auris shows no antagonism[J]. Antimicrob Agents Chemother, 2019, 63(12):e01393-19. |
28 | Shrestha SK, Fosso MY, Garneau-Tsodikova S. A combination approach to treating fungal infections[J]. Sci Rep, 2015, 5:17070. |
29 | Li H, Zhang C, Liu P, et al. In vitro interactions between fluconazole and minocycline against mixed cultures of Candida albicans and Staphylococcus aureus[J]. J Microbiol Immunol Infect, 2015, 48(6):655-661. |
30 | Li L, An M, Shen H, et al. The non-Geldanamycin Hsp90 inhibitors enhanced the antifungal activity of fluconazole[J]. Am J Transl Res, 2015, 7(12):2589-2602. |
31 | Jia W, Zhang H, Li C, et al. The calcineruin inhibitor cyclosporine a synergistically enhances the susceptibility of Candida albicans biofilms to fluconazole by multiple mechanisms[J]. BMC Microbiol, 2016, 16(1):113. |
32 | Pfaller MA, Rhomberg PR, Messer SA, et al. In vitro activity of a Hos2 deacetylase inhibitor, MGCD290, in combination with echinocandins against echinocandin-resistant Candida species[J]. Diagn Microbiol Infect Dis, 2015, 81(4):259-263. |
33 | Khan SN, Khan S, Misba L, et al. Synergistic fungicidal activity with low doses of eugenol and amphotericin B against Candida albicans[J]. Biochem Biophys Res Commun, 2019, 518(3):459-464. |
34 | Manoharan RK, Lee JH, Kim YG, et al. Inhibitory effects of the essential oils α-longipinene and linalool on biofilm formation and hyphal growth of Candida albicans[J]. Biofouling, 2017, 33(2):143-155. |
35 | Singh S, Uppuluri P, Mamouei Z, et al. The NDV-3A vaccine protects mice from multidrug resistant Candida auris infection[J]. PLoS Pathog, 2019, 15(8):e1007460. |
36 | Kamikawa Y, Fujisaki J, Nagayama T, et al. Use of Candida-specific chicken egg yolk antibodies to inhibit the adhering of Candida to denture base materials: prevention of denture stomatitis[J]. Gerodontology, 2016, 33(3):342-347. |
37 | Wan L, Zhang Y, Lai Y, et al. Effect of granulocyte-macrophage colony-stimulating factor on prevention and treatment of invasive fungal disease in recipients of allogeneic stem-cell transplantation: a prospective multicenter randomized phase IV trial[J]. J Clin Oncol, 2015, 33(34):3999-4006. |
38 | Fites JS, Gui M, Kernien JF, et al. An unappreciated role for neutrophil-DC hybrids in immunity to invasive fungal infections[J]. PLoS Pathog, 2018, 14(5):e1007073. |
39 | Freire F, Ferraresi C, Jorge AO, et al. Photodynamic therapy of oral Candida infection in a mouse model[J]. J Photochem Photobiol B, 2016, 159:161-168. |
40 | Seyedmousavi S, Hashemi SJ, Rezaie S, et al. Effects of low-level laser irradiation on the pathogenicity of Candida albicans: in vitro and in vivo study[J]. Photomed Laser Surg, 2014, 32(6): 322-329. |
/
〈 |
|
〉 |