A randomized controlled trial of itraconazole versus fluconazole for the prevention of fungal infections in patients with haematological malignancies

被引:160
作者
Morgenstern, GR
Prentice, AG [1 ]
Prentice, HG
Ropner, JE
Schey, SA
Warnock, DW
机构
[1] Derriford Hosp, Dept Haematol, Plymouth PL6 8DH, Devon, England
[2] Christie Hosp & Holt Radium Inst, Manchester M20 9BX, Lancs, England
[3] Royal Free Hosp, London, England
[4] Sch Med, London, England
[5] Gloucestershire Royal NHS Trust, Gloucester, England
[6] Guys Hosp, London SE1 9RT, England
[7] Publ Hlth Lab, Mycol Reference Lab, Bristol, Avon, England
关键词
antifungal prophylaxis; itraconazole; fluconazole; Aspergillus; Candida;
D O I
10.1046/j.1365-2141.1999.01465.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Fluconazole is widely used as antifungal prophylaxis but it is ineffective against Aspergillus. Itraconazole has a broader spectrum of activity but the capsules give erratic bioavailability in neutropenic patients. We compared itraconazole oral solution (which has an improved pharmacokinetic profile) with fluconazole for antifungal prophylaxis. Adults with haematological malignancies receiving chemotherapy or bone marrow transplants were randomly allocated 5 mg/kg/d itraconazole (itra) solution (288 episodes) or 100 mg fluconazole suspension (flu) (293 episodes) from before the onset of neutropenia until neutrophil recovery or suspected fungal infection. Outcomes were assessed by independent reviewers unaware of the prophylaxis allocation. More proven systemic fungal infections occurred in flu (Aspergillus four, Candida tropicalis one, C. krusei one) than itra (C. albicans one) and more of these were fatal (four versus nil). This difference reached statistical significance when first study episodes were considered separately (six flu versus nil itra, P = 0.03). Significantly more deaths of presumed fungal origin occurred in flu than itra (seven versus nil, P = 0.024). There were significantly more cases of proven aspergillosis in flu than itra (six versus nil, P = 0.038, 5/6 cases were fatal) if those occurring outside the study period are included. Significantly more patients receiving flu required amphotericin B (58 v 39. P = 0.043) but this may have been affected by the fact that the study was not blinded. There were 11 proven mucosal candidal infections in flu and four in itra. Itraconazole solution and fluconazole provide effective prophylaxis against Candida but itraconazole affords greater protection against fatal aspergillosis.
引用
收藏
页码:901 / 911
页数:11
相关论文
共 49 条
[1]  
ALANGADEN G, 1994, BONE MARROW TRANSPL, V14, P919
[2]   OPPORTUNISTIC MYCOSES IN THE IMMUNOCOMPROMISED HOST - EXPERIENCE AT A CANCER CENTER AND REVIEW [J].
ANAISSIE, E .
CLINICAL INFECTIOUS DISEASES, 1992, 14 :S43-S53
[3]   SAFETY, PLASMA-CONCENTRATIONS, AND EFFICACY OF HIGH-DOSE FLUCONAZOLE IN INVASIVE MOLD INFECTIONS [J].
ANAISSIE, EJ ;
KONTOYIANNIS, DP ;
HULS, C ;
VARTIVARIAN, SE ;
KARL, C ;
PRINCE, RA ;
BOSSO, J ;
BODEY, GP .
JOURNAL OF INFECTIOUS DISEASES, 1995, 172 (02) :599-602
[4]   Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype [J].
Aversa, F ;
Tabilio, A ;
Velardi, A ;
Cunningham, I ;
Terenzi, A ;
Falzetti, F ;
Ruggeri, L ;
Barbabietola, G ;
Aristei, C ;
Latini, P ;
Reisner, Y ;
Martelli, MF .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (17) :1186-1193
[5]   RESPONSE RATES TO A STAGED ANTIBIOTIC REGIMEN IN FEBRILE NEUTROPENIC PATIENTS [J].
BARNES, RA ;
ROGERS, TR .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1988, 22 (05) :759-763
[6]  
BEHRE G, 1997, BLOOD S1, V90, pA598
[7]   FUNGAL-INFECTIONS IN CANCER-PATIENTS - AN INTERNATIONAL AUTOPSY SURVEY [J].
BODEY, G ;
BUELTMANN, B ;
DUGUID, W ;
GIBBS, D ;
HANAK, H ;
HOTCHI, M ;
MALL, G ;
MARTINO, P ;
MEUNIER, F ;
MILLIKEN, S ;
NAOE, S ;
OKUDAIRA, M ;
SCEVOLA, D ;
VANTWOUT, J .
EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES, 1992, 11 (02) :99-109
[8]  
BODEY GP, 1994, CANCER-AM CANCER SOC, V73, P2099, DOI 10.1002/1097-0142(19940415)73:8&lt
[9]  
2099::AID-CNCR2820730814&gt
[10]  
3.0.CO