恶性血液病侵袭性真菌感染的诊断与治疗
摘要
目的:近年研究表明,由于长期使用广谱抗生素、化疗药物、免疫抑制剂和造血干细胞移植的增加,使恶性血液病患者侵袭性真菌感染的发病率逐渐增加,侵袭性真菌感染已成为恶性血液病患者的常见并发症及致死原因。由于真菌感染症状的非特异性和临床表现的多样性,同时抗真菌药物毒副作用较大,且价格较昂贵,给侵袭性真菌感染诊断和治疗带来很大困难。通过文献综述总结恶性血液病患者侵袭性真菌感染的病原学和流行病学、易患因素、临床特征、检测方法、诊断过程和治疗药物。
方法:应用CNKI中文数据库、中国生物医学文献数据库、PubMed和Highwire press外文全文数据库进行文献的检索。
结果:恶性血液病患者患者侵袭性真菌感染的病原菌主要为念珠菌,曲霉菌;发病率在全球范围内迅速增加;恶性血液病患者侵袭性真菌感染的易患因素为疾病本身存在免疫缺陷和治疗因素如细胞毒药物,免疫抑制剂和抗生素的应用;恶性血液病患者侵袭性真菌感染中以呼吸系统真菌感染最常见;其次为中枢神经系统和消化系统;恶性血液病患者侵袭性真菌感染的病原学检测方法有形态学检查、血清学检查、分子生物学检查;恶性血液病患者侵袭性真菌感染的诊断依据宿主因素、临床表现、微生物资料进行分层诊断分别为确诊、临床诊断、拟诊;治疗原则分为预防治疗、经验性治疗、临床诊断治疗、确诊后治疗和联合治疗。抗真菌药物如两性霉素B脂质体、新一代咪唑类和棘白菌素类使抗真菌效果有了明显提高。
结论:
1恶性血液病患者侵袭性真菌感染的病原菌主要为念珠菌,曲霉菌,发病率在全球范围内迅速增加,感染部位主要是呼吸系统。
2真菌的检测方法依据形态学、血清学及分子生物学检查。
3诊断依据宿主因素、临床表现、微生物资料分层诊断为确诊、临床诊断、拟诊。治疗原则分为预防治疗、经验性治疗、临床诊断治疗、确诊后治疗和联合治疗。
Objective:In recent years,studies have shown that the incidence rate of invasive fungal infection in patients with haematologic malignancies have increased gradually,because of long-term use broad-spectrum antibiotics,chemotherapy drugs, immunosuppressor and hematopoietic stem cell transplant patients increasing.Invasive fungal infection has become the common complication and cause of death in patients with haematological malignancies.Invasive fungal infection has non-specificity symptom and variety of clinical manifestation, antifungal drugs have side effect and expensive in price,Which have resulted in great difficulty of invasive fungal infection diagnosis and treatment.In this paper,pathogeny epidemiology, susceptible factor,clinic characters,detecting methods,process of diagnosis and antifungal drugs of invasive fungal infection in patients with haematological malignancie were systemically reviewed.
Methods:To search the documents utilizing the CNKI and CBM databases,PubMed and Highwire press database.
Results:The major pathogenic fungis of invasive fungal infection in patients with haematological malignancies are Candida and aspergillus.The morbidity is greatly increasing in the world.The susceptible factor is closely related to the disease itself who exist immundeficiency and therapy factor such as the application of cytotoxic drug,immunosuppressor and broad-spectrum antibiotics.The most common site of infection is the respiratory system,followed by central nervous system and digestive system.The methods of pathogeny detecting are morphology,serology,molecular biology examination.The diagnosis of invasive fungal infection in patients with haematological malignancies was divided into three levels.They are final diagnosis,clinical diagnosis and possible diagnosis based on factor of host,clinical manifestation and microbiology criteria.Therapeutic principle may be categorized as prophy-lactic treatment,empiric treatment,clinical diagnosis treatment, final diagnosis treatment and combination therapy.The effect of several antifungal agents has improved such as lipid formulations of amphotercin B,new azoles and echinoca.
Conclusions:
1 The major species of fungal are candida and aspergillus of invasive fungal infection in patients with haematological malignancies.The morbidity is greatly increasing in the world. The most common site of infection was the respiratory system.
2 The methods of pathogeny detection are based upon morphology,serology and molecular biology examination.
3 Three levels of diagnosis are final diagnosis,clinical diagnosis and possible diagnosis of invasive fungal infection in patients with haematological malignancies.Therapeutic principle may be categorized as prophylactic treatment,empiric treatment, clinical diagnosis treatment,final diagnosis treatment and combination therapy.
方法:应用CNKI中文数据库、中国生物医学文献数据库、PubMed和Highwire press外文全文数据库进行文献的检索。
结果:恶性血液病患者患者侵袭性真菌感染的病原菌主要为念珠菌,曲霉菌;发病率在全球范围内迅速增加;恶性血液病患者侵袭性真菌感染的易患因素为疾病本身存在免疫缺陷和治疗因素如细胞毒药物,免疫抑制剂和抗生素的应用;恶性血液病患者侵袭性真菌感染中以呼吸系统真菌感染最常见;其次为中枢神经系统和消化系统;恶性血液病患者侵袭性真菌感染的病原学检测方法有形态学检查、血清学检查、分子生物学检查;恶性血液病患者侵袭性真菌感染的诊断依据宿主因素、临床表现、微生物资料进行分层诊断分别为确诊、临床诊断、拟诊;治疗原则分为预防治疗、经验性治疗、临床诊断治疗、确诊后治疗和联合治疗。抗真菌药物如两性霉素B脂质体、新一代咪唑类和棘白菌素类使抗真菌效果有了明显提高。
结论:
1恶性血液病患者侵袭性真菌感染的病原菌主要为念珠菌,曲霉菌,发病率在全球范围内迅速增加,感染部位主要是呼吸系统。
2真菌的检测方法依据形态学、血清学及分子生物学检查。
3诊断依据宿主因素、临床表现、微生物资料分层诊断为确诊、临床诊断、拟诊。治疗原则分为预防治疗、经验性治疗、临床诊断治疗、确诊后治疗和联合治疗。
Objective:In recent years,studies have shown that the incidence rate of invasive fungal infection in patients with haematologic malignancies have increased gradually,because of long-term use broad-spectrum antibiotics,chemotherapy drugs, immunosuppressor and hematopoietic stem cell transplant patients increasing.Invasive fungal infection has become the common complication and cause of death in patients with haematological malignancies.Invasive fungal infection has non-specificity symptom and variety of clinical manifestation, antifungal drugs have side effect and expensive in price,Which have resulted in great difficulty of invasive fungal infection diagnosis and treatment.In this paper,pathogeny epidemiology, susceptible factor,clinic characters,detecting methods,process of diagnosis and antifungal drugs of invasive fungal infection in patients with haematological malignancie were systemically reviewed.
Methods:To search the documents utilizing the CNKI and CBM databases,PubMed and Highwire press database.
Results:The major pathogenic fungis of invasive fungal infection in patients with haematological malignancies are Candida and aspergillus.The morbidity is greatly increasing in the world.The susceptible factor is closely related to the disease itself who exist immundeficiency and therapy factor such as the application of cytotoxic drug,immunosuppressor and broad-spectrum antibiotics.The most common site of infection is the respiratory system,followed by central nervous system and digestive system.The methods of pathogeny detecting are morphology,serology,molecular biology examination.The diagnosis of invasive fungal infection in patients with haematological malignancies was divided into three levels.They are final diagnosis,clinical diagnosis and possible diagnosis based on factor of host,clinical manifestation and microbiology criteria.Therapeutic principle may be categorized as prophy-lactic treatment,empiric treatment,clinical diagnosis treatment, final diagnosis treatment and combination therapy.The effect of several antifungal agents has improved such as lipid formulations of amphotercin B,new azoles and echinoca.
Conclusions:
1 The major species of fungal are candida and aspergillus of invasive fungal infection in patients with haematological malignancies.The morbidity is greatly increasing in the world. The most common site of infection was the respiratory system.
2 The methods of pathogeny detection are based upon morphology,serology and molecular biology examination.
3 Three levels of diagnosis are final diagnosis,clinical diagnosis and possible diagnosis of invasive fungal infection in patients with haematological malignancies.Therapeutic principle may be categorized as prophylactic treatment,empiric treatment, clinical diagnosis treatment,final diagnosis treatment and combination therapy.
引文
1 Pagano L,Caira M,Candoni A,et al.The epidemiology of fungal infections in patients with hematologic malignancies:theSEIFEM-2004study.Haematologica,2006,91(8):1068-1075
2 Singh N.Changing spectrum of invasive candidiasis and its therapeutic implications.Clin Microbiol Infect,2001,7 suppl 2:1-7
3 Maschmeye G.The changing epidemiology of invasive fungal infection:new threats.Int J Antimicrob Agents,2006,27suppl 1:3-6
4 Pfaller MA,Pappas PG,Wingard JR.Invasive fungal patho-gens:current epidemiological trends.Clinical Infectious Diseases,2006,43:S3-S14
5 McLintock LA,Jordanides NE,Allan EK,et al.The use of a risk group stratification in the management of invasive fungal infection:a prospective validation.British Journal Haematology,2004,124(3):403-404
6 Maertens J.Evaluating prophylaxis of invasive fungal infections in patients with haematologic malignancies.European Journal of Haematology,2007,78(4):275-282
7 Morgan J,Wannemuehler KA,Marr KA,et al.Incidence of invasive aspergillosis following hematopoietic stem cell and solid organ transplantation:interim results of a prospective multicenter surveillance program.Medical Mycology,2005,43 suppl 1:S49-S58
8 Marr KA,Carter RA,Boeckh M,et al.Invasive aspergillosis in allogeneic stem cell transplant recipientsxhanges in epidemiology and risk factors.Blood,2002,100(13):4358-4366
9 Holding K,Dworkin M,Wan P,et al.Aspergillosis among people infected with human immunodeficiency virus:incidence and survival.Adult and adolescent spectrum of HIV disease project.Clinical Infectious Diseases,2000,31(5):1253-1257
10 Cleri DJ,Moser RL,Villota FJ,et al.Pulmonary Aspergillosis and Central Nervous System Hemorrhage as Complications of Autoimmune Hemolytic Anemia Treated with Corticosteroids.Southern Medical Journal,2003,96 (6):592-595
11 Caillot D,Mannone L,Cuisenier B,et al.Role of early diagnosis and aggressive surgery in the management of invasive pulmonary aspergillosis in neutropenic patients.Clin Microbiol infect,2001,7 suppl 2:54-61
12 Pfaller MA,Diekema DJ,Gibbs DL,et al.Results from the ARTEMIS DISK Global Antifungal Surveillance Study,1997 to 2005.J Clin Microbiol,2007,45(6):1735-1745
13 Odabasi Z,Mattiuzzi G,Estey E,et al.β-D-glucan as a diagnostic adjunct for invasive fungal infections:validation, cutoff development,and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome.Clin Infect Dis,2004,39:199-205
14 纪宇,黄晓军.血清1,3-β-D葡聚糖检测用于造血干细胞移植后患者侵袭性真菌感染诊断的界值初探.中华血液学杂志,2008,29(6):405-407
15 Persat F,Ranque S,Derouin F,et al.Contribution of the(1,3)-beta-D-Glucan Assay for the Diagnosis of Invasive Fungal Infections.J Clin Microbiol,2008,46(3):1009-1013
16 Ali R,Ozkalemkas F,Ozcelik T,et al.Invasive pulm-onary aspergillosis:role of early diagnosis and surgical treatment in patients with acute leukemia.Ann Clin Micr-obiol Antimicrob,2006,5:17
17 Foy P,van Burik J,Weisdorf D,et al.Galactomannan Antigen Enzyme-Linked Immunosorbent Assay for Diag-nosis of Iinvasive Aspergillosis after Hematopoietic Stem Cell Transplantation.Biol Blood Marrow Transplant,2007,13(4):440-443
18 Jordanides NE,Allan EK,McLintock LA,et al.Aprospective study of real-time panfungal PCR for the early diagnosis of invasive fungal infection in haemato-oncology patients.Bone Marrow Trans plant,2005,35(4):389-395
19 KamiM,Fukui T,Ogawa S,et al.Use of real-time PCR on blood samples for diagnosis of invasive aspergillosis.Clin infect Dis,2001,33(9):1504-1512
20 Sanguinetti M,Posteraro B,Pagano L,et al.Comparison of real-time PCR,conventional PCR,and galactomannan antigen detection by enzyme-linked immunosorbent assay using bronchoalveolar lavage fluid samples from hematology patients for diagnosis of invasive pulmonary aspergillosis.J Clin Microbiol,2003,41(8):3922-3925
21 Buchheidt D,Hummel M,Schleiermacher D,et al.Prospective clinical evaluation of a lightcycler-mediated polymerase chain reaction assay,a nested-PCR assay,and a galactomannan enzyme-linked immunosorbent assay for detection of invasive aspergillosis in neutropenic cancer patients and haematological stem cell transplant recipients.Br J Haematol,2004,125(2):196-202
22 Spiess B,Buchheidt D,Baust C,et al.Development of a light cycler PCR Assay for Detection and Quantifucation of Aserpgillusfumigatus DNA in Clinical Samples f rom neut ropenic Patients.Clin Microbiol,2003,41 (5):1811-1818
23 Costa C,Costa JM,Desterke C,et al.Real-time PCR coupled with automated DNA extraction and detection of galactomannan antigen in serum by enzyme-linked immuneosorbent assay for diagnosis of invasive aspergillosis.J Clin Microbiol,2002,40(6):2224-2227
24 Musher B,Fredricks D,Leisenring W,et al.Aspergillus galactomannan enzyme immunoassay and quantitative PCR for diagnosis of invasive as pergillosis with bronchoalveolar lavage fluid.J Clin Microbiol,2004,42(12):5517-5522
25 de Valk HA,Meis JF,de Pauw BE,et al.Comparison of Two Highly Discriminatory Molecular Fingerprinting Assays for Analysis of Multiple Aspergillus fumigatus Isolates from Patients with Invasive Aspergillosis.J Clin Microbiol,2007,45(5):1415-1419
26 Schabereiter-Gurtner C,Selitsch B,Rotter ML,et al.Development of Novel Real-Time PCR Assays for Detection and Differentiation of Eleven Medically Important Aspergillus and Candida Species in Clinical Species in Clinial Specimens.J Clin Microb,2007,45(3):906-914
27 Spiess B,Seifarth W,Hummel M,et al.DNA Microarray-Based Detection and Identification of Fungal Pathogens in Clinical Samples from Neutropenic Patients.J Clin Microb,2007,45(11):3743-3753
28 Borlenghi E,Cattaneo C,Capucci MA,et al.Usefulness of the MSG/IFICG/EORTC diagnostic criteria of invasive pulmonary aspergillosis in the clinical management of patients with acute leukemia developing pumonary infiltrates.Ann hematol,2007,86(3):205-210
29 Ascioglu S,Rex JH,de Pauw B,et al.Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants:an international consensus.Clinical Infectious Diseases,2002,34(1):7-14
30 Robenshtok E,Gafter-Gvili A,Goldberg E,et al.Antifungal prophylaxis in cancer patients after chemotherapy or hematopoietic stem-cell transplantion systematic review and meta-analysis.J clin Oncol,2007,25(12):3851-3870
31 Maertens J.Evaluating prophylaxis of invasive fungal infections in patients with haematologic malignancies.Eur J Haematol,2007,78(4):275-282
32 刘庭波,祝亮方,站榕,等.两性霉素B治疗49例血液恶性肿瘤患者深部真菌感染分析.中国感染与化疗杂志,2007,7(1):38-40
33 佟红艳,张凤娟,肖峰,等.两性霉素B治疗血液病患者粒细胞缺乏合并真菌感染Ⅲ临床分析.中华血液学杂志,2008,29(7):472-475
34 王开泰,陆红娟.氟康唑治疗恶性血液病化疗后真菌感染21例.白血病·淋巴瘤,2008,17(3):212-213
35 赵万红,曹星梅,何爱丽,等.伊曲康唑注射液治疗恶性血液病侵袭性真菌感染的临床研究.白血病·淋巴瘤2007,15(2):242-243
36 纪宇,黄晓军.伊曲康唑治疗血液病患者侵袭性真菌感染的多中心回顾性分析.中华内科杂志,2008,47(12):1022-1025
37 Marchetti O,Cordonnier C,Calandra T,et al.Empirical antifungal therapy in neutropaenic cancer patients with persistent fever.European Journal of Cancer,(Supplememts 5)2007,5:32-42
38 Reboli A,Rotstein C,Pappas PG,et al.Anidulafungin versus fluconazole for invasive candidiasis.The New England Journal of Medicine,2007,356(24):2472-2482
39 Kuse ER,Chetchotisakd P,da Cunha CA,et al.Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis:a phase Ⅲ randomised double-blind trial.Lancet,2007,369(9572):1519-1527
40 朱丹,孟凡义,黄芬,等.卡泊芬净治疗侵袭性真菌感染27例临床研究.中华血液学杂志,2008,19(1):63-64
41 Maertens J,Raad I,Petrikkos Get al.Efficacy and safety of Caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy.Clin Infect Dis,2004,39(11):1563-1571
42 Joseph JM,Jain RJ,Danziger LH,et al.Micafungin:a new echinocandin antifungal pharmacotherapy,2007,27(1):53-67
43 Nakagawa Y,Ichii Y,Saeki Y,et al.Plasma concentration of Micafungin in patients with hematologic malignancies.Infect Chemother,2007,13(1):39-45.
44 Toubai T,Tanaka J,Ota S,et al.Efficacy safety of micafungin in febrile neutropenic patients treated for hematoloical malignancies.Intern Med,2007,46(1):3-9
45 姚金晓,魏旭东,房柏俊,等.米卡芬净治疗恶性血液病侵患者侵袭性真菌感染23例疗效分析.中华内科杂志,2008,47(9):758-759
2 Singh N.Changing spectrum of invasive candidiasis and its therapeutic implications.Clin Microbiol Infect,2001,7 suppl 2:1-7
3 Maschmeye G.The changing epidemiology of invasive fungal infection:new threats.Int J Antimicrob Agents,2006,27suppl 1:3-6
4 Pfaller MA,Pappas PG,Wingard JR.Invasive fungal patho-gens:current epidemiological trends.Clinical Infectious Diseases,2006,43:S3-S14
5 McLintock LA,Jordanides NE,Allan EK,et al.The use of a risk group stratification in the management of invasive fungal infection:a prospective validation.British Journal Haematology,2004,124(3):403-404
6 Maertens J.Evaluating prophylaxis of invasive fungal infections in patients with haematologic malignancies.European Journal of Haematology,2007,78(4):275-282
7 Morgan J,Wannemuehler KA,Marr KA,et al.Incidence of invasive aspergillosis following hematopoietic stem cell and solid organ transplantation:interim results of a prospective multicenter surveillance program.Medical Mycology,2005,43 suppl 1:S49-S58
8 Marr KA,Carter RA,Boeckh M,et al.Invasive aspergillosis in allogeneic stem cell transplant recipientsxhanges in epidemiology and risk factors.Blood,2002,100(13):4358-4366
9 Holding K,Dworkin M,Wan P,et al.Aspergillosis among people infected with human immunodeficiency virus:incidence and survival.Adult and adolescent spectrum of HIV disease project.Clinical Infectious Diseases,2000,31(5):1253-1257
10 Cleri DJ,Moser RL,Villota FJ,et al.Pulmonary Aspergillosis and Central Nervous System Hemorrhage as Complications of Autoimmune Hemolytic Anemia Treated with Corticosteroids.Southern Medical Journal,2003,96 (6):592-595
11 Caillot D,Mannone L,Cuisenier B,et al.Role of early diagnosis and aggressive surgery in the management of invasive pulmonary aspergillosis in neutropenic patients.Clin Microbiol infect,2001,7 suppl 2:54-61
12 Pfaller MA,Diekema DJ,Gibbs DL,et al.Results from the ARTEMIS DISK Global Antifungal Surveillance Study,1997 to 2005.J Clin Microbiol,2007,45(6):1735-1745
13 Odabasi Z,Mattiuzzi G,Estey E,et al.β-D-glucan as a diagnostic adjunct for invasive fungal infections:validation, cutoff development,and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome.Clin Infect Dis,2004,39:199-205
14 纪宇,黄晓军.血清1,3-β-D葡聚糖检测用于造血干细胞移植后患者侵袭性真菌感染诊断的界值初探.中华血液学杂志,2008,29(6):405-407
15 Persat F,Ranque S,Derouin F,et al.Contribution of the(1,3)-beta-D-Glucan Assay for the Diagnosis of Invasive Fungal Infections.J Clin Microbiol,2008,46(3):1009-1013
16 Ali R,Ozkalemkas F,Ozcelik T,et al.Invasive pulm-onary aspergillosis:role of early diagnosis and surgical treatment in patients with acute leukemia.Ann Clin Micr-obiol Antimicrob,2006,5:17
17 Foy P,van Burik J,Weisdorf D,et al.Galactomannan Antigen Enzyme-Linked Immunosorbent Assay for Diag-nosis of Iinvasive Aspergillosis after Hematopoietic Stem Cell Transplantation.Biol Blood Marrow Transplant,2007,13(4):440-443
18 Jordanides NE,Allan EK,McLintock LA,et al.Aprospective study of real-time panfungal PCR for the early diagnosis of invasive fungal infection in haemato-oncology patients.Bone Marrow Trans plant,2005,35(4):389-395
19 KamiM,Fukui T,Ogawa S,et al.Use of real-time PCR on blood samples for diagnosis of invasive aspergillosis.Clin infect Dis,2001,33(9):1504-1512
20 Sanguinetti M,Posteraro B,Pagano L,et al.Comparison of real-time PCR,conventional PCR,and galactomannan antigen detection by enzyme-linked immunosorbent assay using bronchoalveolar lavage fluid samples from hematology patients for diagnosis of invasive pulmonary aspergillosis.J Clin Microbiol,2003,41(8):3922-3925
21 Buchheidt D,Hummel M,Schleiermacher D,et al.Prospective clinical evaluation of a lightcycler-mediated polymerase chain reaction assay,a nested-PCR assay,and a galactomannan enzyme-linked immunosorbent assay for detection of invasive aspergillosis in neutropenic cancer patients and haematological stem cell transplant recipients.Br J Haematol,2004,125(2):196-202
22 Spiess B,Buchheidt D,Baust C,et al.Development of a light cycler PCR Assay for Detection and Quantifucation of Aserpgillusfumigatus DNA in Clinical Samples f rom neut ropenic Patients.Clin Microbiol,2003,41 (5):1811-1818
23 Costa C,Costa JM,Desterke C,et al.Real-time PCR coupled with automated DNA extraction and detection of galactomannan antigen in serum by enzyme-linked immuneosorbent assay for diagnosis of invasive aspergillosis.J Clin Microbiol,2002,40(6):2224-2227
24 Musher B,Fredricks D,Leisenring W,et al.Aspergillus galactomannan enzyme immunoassay and quantitative PCR for diagnosis of invasive as pergillosis with bronchoalveolar lavage fluid.J Clin Microbiol,2004,42(12):5517-5522
25 de Valk HA,Meis JF,de Pauw BE,et al.Comparison of Two Highly Discriminatory Molecular Fingerprinting Assays for Analysis of Multiple Aspergillus fumigatus Isolates from Patients with Invasive Aspergillosis.J Clin Microbiol,2007,45(5):1415-1419
26 Schabereiter-Gurtner C,Selitsch B,Rotter ML,et al.Development of Novel Real-Time PCR Assays for Detection and Differentiation of Eleven Medically Important Aspergillus and Candida Species in Clinical Species in Clinial Specimens.J Clin Microb,2007,45(3):906-914
27 Spiess B,Seifarth W,Hummel M,et al.DNA Microarray-Based Detection and Identification of Fungal Pathogens in Clinical Samples from Neutropenic Patients.J Clin Microb,2007,45(11):3743-3753
28 Borlenghi E,Cattaneo C,Capucci MA,et al.Usefulness of the MSG/IFICG/EORTC diagnostic criteria of invasive pulmonary aspergillosis in the clinical management of patients with acute leukemia developing pumonary infiltrates.Ann hematol,2007,86(3):205-210
29 Ascioglu S,Rex JH,de Pauw B,et al.Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants:an international consensus.Clinical Infectious Diseases,2002,34(1):7-14
30 Robenshtok E,Gafter-Gvili A,Goldberg E,et al.Antifungal prophylaxis in cancer patients after chemotherapy or hematopoietic stem-cell transplantion systematic review and meta-analysis.J clin Oncol,2007,25(12):3851-3870
31 Maertens J.Evaluating prophylaxis of invasive fungal infections in patients with haematologic malignancies.Eur J Haematol,2007,78(4):275-282
32 刘庭波,祝亮方,站榕,等.两性霉素B治疗49例血液恶性肿瘤患者深部真菌感染分析.中国感染与化疗杂志,2007,7(1):38-40
33 佟红艳,张凤娟,肖峰,等.两性霉素B治疗血液病患者粒细胞缺乏合并真菌感染Ⅲ临床分析.中华血液学杂志,2008,29(7):472-475
34 王开泰,陆红娟.氟康唑治疗恶性血液病化疗后真菌感染21例.白血病·淋巴瘤,2008,17(3):212-213
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