International, Open-label, Noncomparative, Clinical Trial of Micafungin Alone and in Combination for Treatment of Newly Diagnosed and Refractory Candidemia

Overview

Journal Eur J Clin Microbiol Infect Dis

Publisher Springer

Specialties Infectious Diseases
Microbiology

Date 2005 Nov 2

PMID 16261306

Citations 44

Authors

L Ostrosky-Zeichner

D Kontoyiannis

J Raffalli

K M Mullane

J Vazquez

E J Anaissie

J Lipton

P Jacobs

J H Jansen van Rensburg

J H Rex

W Lau

D Facklam

D N Buell

Affiliations

Soon will be listed here.

Abstract

Candida spp. are the fourth leading cause of bloodstream infections, and non-albicans species are increasing in importance. Micafungin is a new echinocandin antifungal agent with excellent in vitro activity against Candida spp. Pediatric, neonatal, and adult patients with new or refractory candidemia were enrolled into this open-label, noncomparative, international study. The initial dose of micafungin was 50 mg/d (1 mg/kg for patients <40 kg) for infections due to C. albicans and 100 mg/d (2 mg/kg for patients <40 kg) for infections due to other species. Dose escalation was allowed. Maximum length of therapy was 42 days. A total of 126 patients were evaluable (received at least five doses of micafungin). Success (complete or partial response) was seen in 83.3% patients overall. Success rates for treatment of infections caused by the most common Candida spp. were as follows: C. albicans 85.1%, C. glabrata 93.8%, C. parapsilosis 86.4%, and C. tropicalis 83.3%. Serious adverse events related to micafungin were uncommon. Micafungin shows promise as a safe and effective agent for the treatment of newly diagnosed and refractory cases of candidemia. Large-scale, randomized, controlled trials are warranted.

Citing Articles

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References

Anaissie E, Darouiche R, Abi-Said D, Uzun O, Mera J, Gentry L . Management of invasive candidal infections: results of a prospective, randomized, multicenter study of fluconazole versus amphotericin B and review of the literature. Clin Infect Dis. 1996; 23(5):964-72. DOI: 10.1093/clinids/23.5.964. View

Rex J, Pappas P, Karchmer A, Sobel J, Edwards J, Hadley S . A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects. Clin Infect Dis. 2003; 36(10):1221-8. DOI: 10.1086/374850. View

Pappas P, Rex J, Lee J, Hamill R, Larsen R, Powderly W . A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin Infect Dis. 2003; 37(5):634-43. DOI: 10.1086/376906. View

Colombo A, Nucci M, Salomao R, Branchini M, Richtmann R, Derossi A . High rate of non-albicans candidemia in Brazilian tertiary care hospitals. Diagn Microbiol Infect Dis. 1999; 34(4):281-6. DOI: 10.1016/s0732-8893(99)00042-5. View

Jarvis B, Figgitt D, Scott L . Micafungin. Drugs. 2004; 64(9):969-82. DOI: 10.2165/00003495-200464090-00004. View

Pappagianis D, Collins M, Hector R, Remington J . Development of resistance to amphotericin B in Candida lusitaniae infecting a human. Antimicrob Agents Chemother. 1979; 16(2):123-6. PMC: 352808. DOI: 10.1128/AAC.16.2.123. View

Hajjeh R, Sofair A, Harrison L, Lyon G, Arthington-Skaggs B, Mirza S . Incidence of bloodstream infections due to Candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program. J Clin Microbiol. 2004; 42(4):1519-27. PMC: 387610. DOI: 10.1128/JCM.42.4.1519-1527.2004. View

Ostrosky-Zeichner L, Rex J, Pappas P, Hamill R, Larsen R, Horowitz H . Antifungal susceptibility survey of 2,000 bloodstream Candida isolates in the United States. Antimicrob Agents Chemother. 2003; 47(10):3149-54. PMC: 201160. DOI: 10.1128/AAC.47.10.3149-3154.2003. View

Patterson T . Role of newer azoles in surgical patients. J Chemother. 2000; 11(6):504-12. DOI: 10.1179/joc.1999.11.6.504. View

10.

Pfaller M, Jones R, Doern G, Fluit A, Verhoef J, Sader H . International surveillance of blood stream infections due to Candida species in the European SENTRY Program: species distribution and antifungal susceptibility including the investigational triazole and echinocandin agents. SENTRY Participant Group.... Diagn Microbiol Infect Dis. 1999; 35(1):19-25. DOI: 10.1016/s0732-8893(99)00046-2. View

11.

Wiederhold N, Lewis R . The echinocandin antifungals: an overview of the pharmacology, spectrum and clinical efficacy. Expert Opin Investig Drugs. 2003; 12(8):1313-33. DOI: 10.1517/13543784.12.8.1313. View

12.

Odds F, Brown A, Gow N . Antifungal agents: mechanisms of action. Trends Microbiol. 2003; 11(6):272-9. DOI: 10.1016/s0966-842x(03)00117-3. View

13.

Perfect J, Marr K, Walsh T, Greenberg R, Dupont B, la Torre-Cisneros J . Voriconazole treatment for less-common, emerging, or refractory fungal infections. Clin Infect Dis. 2003; 36(9):1122-31. DOI: 10.1086/374557. View

14.

Garbino J, Kolarova L, Rohner P, Lew D, Pichna P, Pittet D . Secular trends of candidemia over 12 years in adult patients at a tertiary care hospital. Medicine (Baltimore). 2002; 81(6):425-33. DOI: 10.1097/00005792-200211000-00003. View

15.

Kuhn D, Ghannoum M . Candida biofilms: antifungal resistance and emerging therapeutic options. Curr Opin Investig Drugs. 2004; 5(2):186-97. View

16.

Ostrosky-Zeichner L, Oude Lashof A, Kullberg B, Rex J . Voriconazole salvage treatment of invasive candidiasis. Eur J Clin Microbiol Infect Dis. 2003; 22(11):651-5. DOI: 10.1007/s10096-003-1014-3. View

17.

Torres H, Kontoyiannis D, Rolston K . High-dose fluconazole therapy for cancer patients with solid tumors and candidemia: an observational, noncomparative retrospective study. Support Care Cancer. 2004; 12(7):511-6. DOI: 10.1007/s00520-004-0601-x. View

18.

Hobson R . The global epidemiology of invasive Candida infections--is the tide turning?. J Hosp Infect. 2003; 55(3):159-68. DOI: 10.1016/j.jhin.2003.08.012. View

19.

Ostrosky-Zeichner L, Marr K, Rex J, Cohen S . Amphotericin B: time for a new "gold standard". Clin Infect Dis. 2003; 37(3):415-25. DOI: 10.1086/376634. View

20.

Graybill J . Hitting a new target with echinocandins. Why chase something else?. Curr Opin Investig Drugs. 2001; 2(4):468-71. View