Comparison of Caspofungin and Amphotericin B for Invasive Candidiasis
Jorge Mora-Duarte, M.D., Robert Betts, M.D., Coleman Rotstein, M.D., Arnaldo Lopes Colombo, M.D., Luis Thompson-Moya, M.D., Juanita Smietana, B.S., Robert Lupinacci, M.S., Carole Sable, M.D., Nicholas Kartsonis, M.D., John Perfect, M.D., for the Caspofungin Invasive Candidiasis Study Group
Background Caspofungin is an echinocandin agent with fungicidalactivity against candida species. We performed a double-blindtrial to compare caspofungin with amphotericin B deoxycholatefor the primary treatment of invasive candidiasis.
Methods We enrolled patients who had clinical evidence of infectionand a positive culture for candida species from blood or anothersite. Patients were stratified according to the severity ofdisease, as indicated by the Acute Physiology and Chronic HealthEvaluation (APACHE II) score, and the presence or absence ofneutropenia and were randomly assigned to receive either caspofunginor amphotericin B. The study was designed to compare the efficacyof caspofungin with that of amphotericin B in patients withinvasive candidiasis and in a subgroup with candidemia.
Results Of the 239 patients enrolled, 224 were included in themodified intention-to-treat analysis. Base-line characteristics,including the percentage of patients with neutropenia and themean APACHE II score, were similar in the two treatment groups.A modified intention-to-treat analysis showed that the efficacyof caspofungin was similar to that of amphotericin B, with successfuloutcomes in 73.4 percent of the patients treated with caspofunginand in 61.7 percent of those treated with amphotericin B (differenceafter adjustment for APACHE II score and neutropenic status,12.7 percentage points; 95.6 percent confidence interval, 0.7to 26.0). An analysis of patients who met prespecified criteriafor evaluation showed that caspofungin was superior, with afavorable response in 80.7 percent of patients, as comparedwith 64.9 percent of those who received amphotericin B (difference,15.4 percentage points; 95.6 percent confidence interval, 1.1to 29.7). Caspofungin was as effective as amphotericin B inpatients who had candidemia, with a favorable response in 71.7percent and 62.8 percent of patients, respectively (difference,10.0 percentage points; 95.0 percent confidence interval, 4.5to 24.5). There were significantly fewer drug-related adverseevents in the caspofungin group than in the amphotericin B group.
Conclusions Caspofungin is at least as effective as amphotericinB for the treatment of invasive candidiasis and, more specifically,candidemia.
Source Information
From Neeman-ICIC and Hospital Mexico, C.C.S.S., San José, Costa Rica (J.M.-D.); the University of Rochester, Rochester, N.Y. (R.B.); McMaster University, Hamilton, Ont., Canada (C.R.); Escola Paulista de MedicinaUNIFESP, São Paulo, Brazil (A.L.C.); Clinica Santa Maria, Santiago, Chile (L.T.-M.); Merck Research Laboratories, West Point, Pa. (J.S., R.L., C.S., N.K.); and Duke University, Durham, N.C. (J.P.).
Address reprint requests to Dr. Perfect at Duke University Medical Center, P.O. Box 3353, Trent Dr., Rm. 1558, Duke South, Durham, NC 27710, or at perfe001{at}mc.duke.edu.
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(2004). {blacktriangledown}Caspofungin and {blacktriangledown}voriconazole for fungal infections. DTB
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Wingard, J. R., Nichols, W. G., McDonald, G. B.
(2004). Supportive Care. ASH Education Book
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Pfaller, M. A., Messer, S. A., Boyken, L., Rice, C., Tendolkar, S., Hollis, R. J., Diekema, D. J.
(2003). Caspofungin Activity against Clinical Isolates of Fluconazole-Resistant Candida. J. Clin. Microbiol.
41: 5729-5731
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Nichols, W. G.
(2003). Management of Infectious Complications in the Hematopoietic Stem Cell Transplant Recipient. J Intensive Care Med
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Ostrosky-Zeichner, L., Rex, J. H., Pappas, P. G., Hamill, R. J., Larsen, R. A., Horowitz, H. W., Powderly, W. G., Hyslop, N., Kauffman, C. A., Cleary, J., Mangino, J. E., Lee, J.
(2003). Antifungal Susceptibility Survey of 2,000 Bloodstream Candida Isolates in the United States. Antimicrob. Agents Chemother.
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(2003). ADDITIONAL ARTICLES ABSTRACTED IN ACP JOURNAL CLUB. Evid. Based Med.
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Graybill, J. R., Bocanegra, R., Najvar, L. K., Hernandez, S., Larsen, R. A.
(2003). Addition of Caspofungin to Fluconazole Does Not Improve Outcome in Murine Candidiasis. Antimicrob. Agents Chemother.
47: 2373-2375
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Brown, A. L., Greig, J. R., Kartsonis, N. A., Perfect, J., Walsh, T. J.
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Pfaller, M. A., Diekema, D. J., Messer, S. A., Hollis, R. J., Jones, R. N.
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(2003). Caspofungin: An Effective New Treatment for Invasive Candidiasis. JWatch Infect. Diseases
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O'Brien, S. N., Blijlevens, N. M.A., Mahfouz, T. H., Anaissie, E. J.
(2003). Infections in Patients with Hematological Cancer: Recent Developments. ASH Education Book
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(2002). Echinocandins -- An Advance in the Primary Treatment of Invasive Candidiasis. NEJM
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