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Factors related to survival and treatment success in invasive candidiasis or candidemia: a pooled analysis of two large, prospective, micafungin trials

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Abstract

Crude and attributable mortality rates in patients with candidemia and invasive candidiasis remain unacceptably high. It is important to reach a more complete understanding of the risk factors underlying poor outcomes in patients with invasive Candida infections. Micafungin therapy has been assessed in two phase 3 trials compared to either liposomal amphotericin B or caspofungin. The availability of this large dataset allows the analyses of non-drug factors associated with survival and treatment success. A multivariate regression analysis was performed on data from the two trials separately and as a pooled analysis (N = 1,070). Analysis outcomes were survival at 42 days post-initiation of therapy and treatment success. For the pooled analysis, treatment success was significantly more likely for candidemia than invasive candidiasis. Both survival and treatment success were significantly less likely for the non-removal of catheter versus removal, Asian-Indians versus Caucasians, APACHE II score >20 to ≤30 and >30 versus ≤20, age ≥70 years versus <50 years, baseline corticosteroids, and persistent neutropenia. Survival was also significantly less likely for treatment in other regions versus North America and for patients with renal failure at baseline. These findings help to define non-antifungal drug factors that may impact survival and treatment success in invasive candidiasis or candidemia.

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References

  1. Beck-Sagué C, Jarvis WR (1993) Secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980–1990. National Nosocomial Infections Surveillance System. J Infect Dis 167:1247–1251

    PubMed  Google Scholar 

  2. Edmond MB, Wallace SE, McClish DK, Pfaller MA, Jones RN, Wenzel RP (1999) Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin Infect Dis 29:239–244

    Article  CAS  PubMed  Google Scholar 

  3. Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB (2004) Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 39:309–317

    Article  PubMed  Google Scholar 

  4. Horn DL, Fishman JA, Steinbach WJ, Anaissie EJ, Marr KA, Olyaei AJ, Pfaller MA, Weiss MA, Webster KM, Neofytos D (2007) Presentation of the PATH Alliance registry for prospective data collection and analysis of the epidemiology, therapy, and outcomes of invasive fungal infections. Diagn Microbiol Infect Dis 59:407–414

    Article  PubMed  Google Scholar 

  5. Almirante B, Rodríguez D, Park BJ, Cuenca-Estrella M, Planes AM, Almela M, Mensa J, Sanchez F, Ayats J, Gimenez M, Saballs P, Fridkin SK, Morgan J, Rodriguez-Tudela JL, Warnock DW, Pahissa A (2005) Epidemiology and predictors of mortality in cases of Candida bloodstream infection: results from population-based surveillance, Barcelona, Spain, from 2002 to 2003. J Clin Microbiol 43:1829–1835

    Article  PubMed  Google Scholar 

  6. Wey SB, Mori M, Pfaller MA, Woolson RF, Wenzel RP (1988) Hospital-acquired candidemia. The attributable mortality and excess length of stay. Arch Intern Med 148:2642–2645

    Article  CAS  PubMed  Google Scholar 

  7. Pappas PG, Rex JH, Lee J, Hamill RJ, Larsen RA, Powderly W, Kauffman CA, Hyslop N, Mangino JE, Chapman S, Horowitz HW, Edwards JE, Dismukes WE (2003) A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin Infect Dis 37:634–643

    Article  PubMed  Google Scholar 

  8. Colombo AL, Guimarães T, Silva LR, de Almeida Monfardini LP, Cunha AK, Rady P, Alves T, Rosas RC (2007) Prospective observational study of candidemia in São Paulo, Brazil: incidence rate, epidemiology, and predictors of mortality. Infect Control Hosp Epidemiol 28:570–576

    Article  PubMed  Google Scholar 

  9. Fraser VJ, Jones M, Dunkel J, Storfer S, Medoff G, Dunagan WC (1992) Candidemia in a tertiary care hospital: epidemiology, risk factors, and predictors of mortality. Clin Infect Dis 15:414–421

    CAS  PubMed  Google Scholar 

  10. Komshian SV, Uwaydah AK, Sobel JD, Crane LR (1989) Fungemia caused by Candida species and Torulopsis glabrata in the hospitalized patient: frequency, characteristics, and evaluation of factors influencing outcome. Rev Infect Dis 11:379–390

    CAS  PubMed  Google Scholar 

  11. Yamamura DL, Rotstein C, Nicolle LE, Ioannou S (1999) Candidemia at selected Canadian sites: results from the Fungal Disease Registry, 1992–1994. Fungal Disease Registry of the Canadian Infectious Disease Society. CMAJ 160:493–499

    CAS  PubMed  Google Scholar 

  12. Tortorano AM, Peman J, Bernhardt H, Klingspor L, Kibbler CC, Faure O, Biraghi E, Canton E, Zimmermann K, Seaton S, Grillot R (2004) Epidemiology of candidaemia in Europe: results of 28-month European Confederation of Medical Mycology (ECMM) hospital-based surveillance study. Eur J Clin Microbiol Infect Dis 23:317–322

    Article  CAS  PubMed  Google Scholar 

  13. Poikonen E, Lyytikäinen O, Anttila VJ, Ruutu P (2003) Candidemia in Finland, 1995–1999. Emerg Infect Dis 9:985–990

    PubMed  Google Scholar 

  14. Tortorano AM, Kibbler C, Peman J, Bernhardt H, Klingspor L, Grillot R (2006) Candidaemia in Europe: epidemiology and resistance. Int J Antimicrob Agents 27:359–366

    Article  CAS  PubMed  Google Scholar 

  15. Gudlaugsson O, Gillespie S, Lee K, Vande Berg J, Hu J, Messer S, Herwaldt L, Pfaller M, Diekema D (2003) Attributable mortality of nosocomial candidemia, revisited. Clin Infect Dis 37:1172–1177

    Article  PubMed  Google Scholar 

  16. Zaoutis TE, Argon J, Chu J, Berlin JA, Walsh TJ, Feudtner C (2005) The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin Infect Dis 41:1232–1239

    Article  PubMed  Google Scholar 

  17. Abi-Said D, Anaissie E, Uzun O, Raad I, Pinzcowski H, Vartivarian S (1997) The epidemiology of hematogenous candidiasis caused by different Candida species. Clin Infect Dis 24:1122–1128

    Article  CAS  PubMed  Google Scholar 

  18. Antoniadou A, Torres HA, Lewis RE, Thornby J, Bodey GP, Tarrand JP, Han XY, Rolston KV, Safdar A, Raad II, Kontoyiannis DP (2003) Candidemia in a tertiary care cancer center: in vitro susceptibility and its association with outcome of initial antifungal therapy. Medicine (Baltimore) 82:309–321

    Article  CAS  Google Scholar 

  19. Blumberg HM, Jarvis WR, Soucie JM, Edwards JE, Patterson JE, Pfaller MA, Rangel-Frausto MS, Rinaldi MG, Saiman L, Wiblin RT, Wenzel RP (2001) Risk factors for candidal bloodstream infections in surgical intensive care unit patients: the NEMIS prospective multicenter study. The National Epidemiology of Mycosis Survey. Clin Infect Dis 33:177–186

    Article  CAS  PubMed  Google Scholar 

  20. Eggimann P, Garbino J, Pittet D (2003) Epidemiology of Candida species infections in critically ill non-immunosuppressed patients. Lancet Infect Dis 3:685–702

    Article  PubMed  Google Scholar 

  21. Hajjeh RA, Sofair AN, Harrison LH, Lyon GM, Arthington-Skaggs BA, Mirza SA, Phelan M, Morgan J, Lee-Yang W, Ciblak MA, Benjamin LE, Sanza LT, Huie S, Yeo SF, Brandt ME, Warnock DW (2004) 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 42:1519–1527

    Article  PubMed  Google Scholar 

  22. Marr KA, Seidel K, White TC, Bowden RA (2000) Candidemia in allogeneic blood and marrow transplant recipients: evolution of risk factors after the adoption of prophylactic fluconazole. J Infect Dis 181:309–316

    Article  CAS  PubMed  Google Scholar 

  23. Rangel-Frausto MS, Wiblin T, Blumberg HM, Saiman L, Patterson J, Rinaldi M, Pfaller M, Edwards JE Jr, Jarvis W, Dawson J, Wenzel RP (1999) National epidemiology of mycoses survey (NEMIS): variations in rates of bloodstream infections due to Candida species in seven surgical intensive care units and six neonatal intensive care units. Clin Infect Dis 29:253–258

    Article  CAS  PubMed  Google Scholar 

  24. Pfaller MA, Diekema DJ (2002) Role of sentinel surveillance of candidemia: trends in species distribution and antifungal susceptibility. J Clin Microbiol 40:3551–3557

    Article  CAS  PubMed  Google Scholar 

  25. Pittet D, Monod M, Suter PM, Frenk E, Auckenthaler R (1994) Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg 220:751–758

    Article  CAS  PubMed  Google Scholar 

  26. Wey SB, Mori M, Pfaller MA, Woolson RF, Wenzel RP (1989) Risk factors for hospital-acquired candidemia. A matched case–control study. Arch Intern Med 149:2349–2353

    Article  CAS  PubMed  Google Scholar 

  27. Edwards JE Jr, Bodey GP, Bowden RA, Büchner T, de Pauw BE, Filler SG, Ghannoum MA, Glauser M, Herbrecht R, Kauffman CA, Kohno S, Martino P, Meunier F, Mori T, Pfaller MA, Rex JH, Rogers TR, Rubin RH, Solomkin J, Viscoli C, Walsh TJ, White M (1997) International Conference for the Development of a Consensus on the Management and Prevention of Severe Candidal Infections. Clin Infect Dis 25:43–59

    Article  PubMed  Google Scholar 

  28. Bassetti M, Trecarichi EM, Righi E, Sanguinetti M, Bisio F, Posteraro B, Soro O, Cauda R, Viscoli C, Tumbarello M (2007) Incidence, risk factors, and predictors of outcome of candidemia. Survey in 2 Italian university hospitals. Diagn Microbiol Infect Dis 58:325–331

    Article  PubMed  Google Scholar 

  29. Morrell M, Fraser VJ, Kollef MH (2005) Delaying the empiric treatment of Candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Chemother 49:3640–3645

    Article  CAS  PubMed  Google Scholar 

  30. Kuse ER, Chetchotisakd P, da Cunha CA, Ruhnke M, Barrios C, Raghunadharao D, Sekhon JS, Freire A, Ramasubramanian V, Demeyer I, Nucci M, Leelarasamee A, Jacobs F, Decruyenaere J, Pittet D, Ullmann AJ, Ostrosky-Zeichner L, Lortholary O, Koblinger S, Diekmann-Berndt H, Cornely OA (2007) Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet 369:1519–1527

    Article  CAS  PubMed  Google Scholar 

  31. Pappas PG, Rotstein CM, Betts RF, Nucci M, Talwar D, De Waele JJ, Vazquez JA, Dupont BF, Horn DL, Ostrosky-Zeichner L, Reboli AC, Suh B, Digumarti R, Wu C, Kovanda LL, Arnold LJ, Buell DN (2007) Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. Clin Infect Dis 45:883–893

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was sponsored by Astellas Pharma Inc., and medical writing and editorial support was provided by Paul Hassan Ph.D. of Envision Pharma Ltd.

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Authors and Affiliations

  1. Clinical Research, Division of Infectious Diseases, Thomas Jefferson University, Suite 210, 211 South 9th Street, Philadelphia, PA, 19107, USA

    D. L. Horn

  2. University of Texas Medical School at Houston, 6431 Fannin, MSB 2.112, Houston, TX, 77030, USA

    L. Ostrosky-Zeichner

  3. University of Miami Miller School of Medicine, 1400 N.W. 10th Avenue, D90-A, Dominion Tower, #813A, Miami, FL, 33136, USA

    M. I. Morris

  4. III. Medizinische Klinik und Poliklinik, Klinikum der Johannes Gutenberg-Universität, Langenbeckstrasse 1, 55101, Mainz, Germany

    A. J. Ullmann

  5. Astellas Pharma Global Development Inc., 3 Parkway North, Deerfield, IL, 60015, USA

    C. Wu, D. N. Buell & L. L. Kovanda

  6. Klinik I für Innere Medizin, Zentrum für Klinische Studien (ZKS Köln; BMBF 01KN0706), Universität zu Köln, Kerpener Str. 62, 50937, Köln, Germany

    O. A. Cornely

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  1. D. L. Horn
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  2. L. Ostrosky-Zeichner
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  3. M. I. Morris
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  4. A. J. Ullmann
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  5. C. Wu
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  6. D. N. Buell
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  7. L. L. Kovanda
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  8. O. A. Cornely
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Correspondence to D. L. Horn.

Additional information

Presented in part at the following congresses:

18th Annual European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Barcelona, Spain, April 19–22, 2008;

Joint Meeting: 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy/46th Annual Meeting of the Infectious Diseases Society of America (ICAAC/IDSA), Washington, DC, USA, October 25–28, 2008;

38th Congress of the Society of Critical Care Medicine (SCCM), Nashville, TN, USA, January 31–February 4, 2009.

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Horn, D.L., Ostrosky-Zeichner, L., Morris, M.I. et al. Factors related to survival and treatment success in invasive candidiasis or candidemia: a pooled analysis of two large, prospective, micafungin trials. Eur J Clin Microbiol Infect Dis 29, 223–229 (2010). https://doi.org/10.1007/s10096-009-0843-0

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  • DOI: https://doi.org/10.1007/s10096-009-0843-0

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