Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy

被引:453
作者
Maertens, J
Raad, I
Petrikkos, G
Boogaerts, M
Selleslag, D
Petersen, FB
Sable, CA
Kartsonis, NA
Ngai, A
Taylor, A
Patterson, TF
Denning, DW
Walsh, TJ
机构
[1] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA
[2] Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium
[3] Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA
[4] Univ Athens, Laiko Gen Hosp, GR-10679 Athens, Greece
[5] AZ St Jan Brugge, Brugge, Belgium
[6] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT 84112 USA
[7] Merck Res Labs, West Point, PA USA
[8] Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA
[9] Univ Manchester, Manchester M13 9PL, Lancs, England
关键词
D O I
10.1086/423381
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Invasive aspergillosis (IA) is an important cause of morbidity and mortality among immuno-compromised patients. Echinocandins are novel antifungal molecules with in vitro and in vivo activity against Aspergillus species. Methods. We investigated the efficacy and safety of caspofungin in the treatment of IA. Ninety patients with IA who were refractory to or intolerant of amphotericin B, lipid formulations of amphotericin B, or triazoles were enrolled to receive caspofungin. Results. Efficacy was assessed for 83 patients who had infection consistent with definitions of IA and who received greater than or equal to1 dose of study drug. Common underlying conditions included hematologic malignancy ( 48% of patients), allogeneic blood and marrow transplantation (25% of patients), and solid-organ transplantation (11% of patients). Seventy-one patients (86%) were refractory to and 12 patients (14%) were intolerant of previous therapy. A favorable response to caspofungin therapy was observed in 37 (45%) of 83 patients, including 32 (50%) of 64 with pulmonary aspergillosis and 3 (23%) of 13 with disseminated aspergillosis. Two patients discontinued caspofungin therapy because of drug-related adverse events. Drug-related nephrotoxicity and hepatotoxicity occurred infrequently. Conclusion. Caspofungin demonstrated usefulness in the salvage treatment of IA.
引用
收藏
页码:1563 / 1571
页数:9
相关论文
共 42 条
  • [1] Efficacy of the echinocandin caspofungin against disseminated aspergillosis and candidiasis in cyclophosphamide-induced immunosuppressed mice
    Abruzzo, GK
    Gill, CJ
    Flattery, AM
    Kong, L
    Leighton, C
    Smith, JG
    Pikounis, VB
    Bartizal, K
    Rosen, H
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2000, 44 (09) : 2310 - 2318
  • [2] Evaluation of the echinocandin antifungal MK-0991 (L-743,872): Efficacies in mouse models of disseminated aspergillosis, candidiasis, and cryptococcosis
    Abruzzo, GK
    Flattery, AM
    Gill, CJ
    Kong, L
    Smith, JG
    Pikounis, VB
    Balkovec, JM
    Bouffard, AF
    Dropinski, JF
    Rosen, H
    Kropp, H
    Bartizal, K
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (11) : 2333 - 2338
  • [3] Aspergillosis: The most common community-acquired pneumonia with gram-negative bacilli as copathogens in stem cell transplant recipients with graft-versus-host disease
    Alangaden, GJ
    Wahiduzzaman, M
    Chandrasekar, PH
    [J]. CLINICAL INFECTIOUS DISEASES, 2002, 35 (06) : 659 - 664
  • [4] Refractory aspergillus pneumonia in patients with acute leukemia - Successful therapy with combination caspofungin and liposomal amphotericin
    Aliff, TB
    Maslak, PG
    Jurcic, JG
    Heaney, ML
    Cathcart, KN
    Sepkowitz, KA
    Weiss, MA
    [J]. CANCER, 2003, 97 (04) : 1025 - 1032
  • [5] OPPORTUNISTIC MYCOSES IN THE IMMUNOCOMPROMISED HOST - EXPERIENCE AT A CANCER CENTER AND REVIEW
    ANAISSIE, E
    [J]. CLINICAL INFECTIOUS DISEASES, 1992, 14 : S43 - S53
  • [6] Randomized, double-blind, Multicenter study of caspofungin versus amphotericin B for treatment of oropharyngeal and esophageal candidiases
    Arathoon, EG
    Gotuzzo, E
    Noriega, LM
    Berman, RS
    DiNubile, MJ
    Sable, CA
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2002, 46 (02) : 451 - 457
  • [7] In vitro synergy of caspofungin and amphotericin B against Aspergillus and Fusarium spp.
    Arikan, S
    Lozano-Chiu, M
    Paetznick, V
    Rex, JH
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2002, 46 (01) : 245 - 247
  • [8] Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: An international consensus
    Ascioglu, S
    Rex, JH
    de Pauw, B
    Bennett, JE
    Bille, J
    Crokaert, F
    Denning, DW
    Donnelly, JP
    Edwards, JE
    Erjavec, Z
    Fiere, D
    Lortholary, O
    Maertens, J
    Meis, JF
    Patterson, TF
    Ritter, J
    Selleslag, D
    Shah, PM
    Stevens, DA
    Walsh, TJ
    [J]. CLINICAL INFECTIOUS DISEASES, 2002, 34 (01) : 7 - 14
  • [9] A double-blind, randomized, controlled trial of amphotericin B colloidal dispersion versus amphotericin B for treatment of invasive aspergillosis in immunocompromised patients
    Bowden, R
    Chandrasekar, P
    White, MH
    Li, X
    Pietrelli, L
    Gurwith, M
    van Burik, JA
    Laverdiere, M
    Safrin, S
    Wingard, JR
    [J]. CLINICAL INFECTIOUS DISEASES, 2002, 35 (04) : 359 - 366
  • [10] Quantitative PCR assay to measure Aspergillus fumigatus burden in a murine model of disseminated aspergillosis:: Demonstration of efficacy of caspofungin acetate
    Bowman, JC
    Abruzzo, GK
    Anderson, JW
    Flattery, AM
    Gill, CJ
    Pikounis, VB
    Schmatz, DM
    Liberator, PA
    Douglas, CM
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2001, 45 (12) : 3474 - 3481