Intensive Care Medicine

, Volume 35, Issue 5, pp 903–908

Caspofungin for prevention of intra-abdominal candidiasis in high-risk surgical patients

  • Laurence Senn
  • Philippe Eggimann
  • Riadh Ksontini
  • Andres Pascual
  • Nicolas Demartines
  • Jacques Bille
  • Thierry Calandra
  • Oscar Marchetti
Brief Report



Thirty to forty percent of patients with recurrent gastrointestinal perforation/anastomotic leakage or acute necrotizing pancreatitis develop intra-abdominal invasive candidiasis (IC). A corrected Candida colonization index (CCI) ≥0.4 is a powerful predictor of IC. Fluconazole prevents intra-abdominal IC in this setting, but azole-resistant Candida species are emerging. The aim of this study was to explore the efficacy and safety of caspofungin for prevention of intra-abdominal IC in high-risk surgical patients.


Prospective non-comparative single-center study in consecutive adult surgical patients with recurrent gastrointestinal perforation/anastomotic leakage or acute necrotizing pancreatitis. Preventive caspofungin therapy (70 mg, then 50 mg/day) was given until resolution of the surgical condition. Candida colonization index and CCI, occurrence of intra-abdominal IC and adverse events were monitored.


Nineteen patients were studied: 16 (84%) had recurrent gastrointestinal perforation/anastomotic leakage and 3 (16%) acute necrotizing pancreatitis. The median duration of preventive caspofungin therapy was 16 days (range 4–46). The colonization index decreased significantly during study therapy, and the CCI remained <0.4 in all patients. Caspofungin was successful for prevention of intra-abdominal IC in 18/19 patients (95%, 1 breakthrough IC 5 days after inclusion). No drug-related adverse event requiring caspofungin discontinuation occurred.


Caspofungin may be efficacious and safe for prevention of intra-abdominal candidiasis in high-risk surgical patients. This needs to be further investigated in randomized trials.


Caspofungin Prevention Surgery Pancreatitis Candidiasis Fungal infection 


  1. 1.
    Marchetti O, Bille J, Fluckiger U, Eggimann P, Ruef C, Garbino J, Calandra T, Glauser MP, Tauber MG, Pittet D (2004) Epidemiology of candidemia in Swiss tertiary care hospitals: secular trends, 1991–2000. Clin Infect Dis 38:311–320PubMedCrossRefGoogle Scholar
  2. 2.
    Bougnoux ME, Kac G, Aegerter P, d’Enfert C, Fagon JY (2008) Candidemia and candiduria in critically ill patients admitted to intensive care units in France: incidence, molecular diversity, management and outcome. Intensive Care Med 34:292–299PubMedCrossRefGoogle Scholar
  3. 3.
    Eggimann P, Francioli P, Bille J, Schneider R, Wu MM, Chapuis G, Chiolero R, Pannatier A, Schilling J, Geroulanos S, Glauser MP, Calandra T (1999) Fluconazole prophylaxis prevents intra-abdominal candidiasis in high-risk surgical patients. Crit Care Med 27:1066–1072PubMedCrossRefGoogle Scholar
  4. 4.
    De Waele JJ, Vogelaers D, Blot S, Colardyn F (2003) Fungal infections in patients with severe acute pancreatitis and the use of prophylactic therapy. Clin Infect Dis 37:208–213PubMedCrossRefGoogle Scholar
  5. 5.
    Calandra T, Bille J, Schneider R, Mosimann F, Francioli P (1989) Clinical significance of Candida isolated from peritoneum in surgical patients. Lancet 2:1437–1440PubMedCrossRefGoogle Scholar
  6. 6.
    Sandven P, Qvist H, Skovlund E, Giercksky KE (2002) Significance of Candida recovered from intraoperative specimens in patients with intra-abdominal perforations. Crit Care Med 30:541–547PubMedCrossRefGoogle Scholar
  7. 7.
    Calandra T, Marchetti O (2004) Clinical trials of antifungal prophylaxis among patients undergoing surgery. Clin Infect Dis 39(Suppl 4):S185–S192PubMedCrossRefGoogle Scholar
  8. 8.
    Pittet D, Monod M, Suter PM, Frenk E, Auckenthaler R (1994) Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg 220:751–758PubMedCrossRefGoogle Scholar
  9. 9.
    Rex JH, Sobel JD (2001) Prophylactic antifungal therapy in the intensive care unit. Clin Infect Dis 32:1191–1200PubMedCrossRefGoogle Scholar
  10. 10.
    Calandra T, Marchetti O (2002) Antifungal prophylaxis for intensive care unit patients: let’s fine tune it. Intensive Care Med 28:1698–1700PubMedCrossRefGoogle Scholar
  11. 11.
    Piarroux R, Grenouillet F, Balvay P, Tran V, Blasco G, Millon L, Boillot A (2004) Assessment of preemptive treatment to prevent severe candidiasis in critically ill surgical patients. Crit Care Med 32:2443–2449PubMedCrossRefGoogle Scholar
  12. 12.
    Shorr AF, Chung K, Jackson WL, Waterman PE, Kollef MH (2005) Fluconazole prophylaxis in critically ill surgical patients: a meta-analysis. Crit Care Med 33:1928–1935PubMedCrossRefGoogle Scholar
  13. 13.
    Prella M, Bille J, Pugnale M, Duvoisin B, Cavassini M, Calandra T, Marchetti O (2005) Early diagnosis of invasive candidiasis with mannan antigenemia and antimannan antibodies. Diagn Microbiol Infect Dis 51:95–101PubMedCrossRefGoogle Scholar
  14. 14.
    Ostrosky-Zeichner L, Sable C, Sobel J, Alexander BD, Donowitz G, Kan V, Kauffman CA, Kett D, Larsen RA, Morrison V, Nucci M, Pappas PG, Bradley ME, Major S, Zimmer L, Wallace D, Dismukes WE, Rex JH (2007) Multicenter retrospective development and validation of a clinical prediction rule for nosocomial invasive candidiasis in the intensive care setting. Eur J Clin Microbiol Infect Dis 26:271–276PubMedCrossRefGoogle Scholar
  15. 15.
    Leon C, Ruiz-Santana S, Saavedra P, Almirante B, Nolla-Salas J, Varez-Lerma F, Garnacho-Montero J, Leon MA (2006) A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization. Crit Care Med 34:730–737PubMedCrossRefGoogle Scholar
  16. 16.
    Pelz RK, Hendrix CW, Swoboda SM, Diener-West M, Merz WG, Hammond J, Lipsett PA (2001) Double-blind placebo-controlled trial of fluconazole to prevent candidal infections in critically ill surgical patients. Ann Surg 233:542–548PubMedCrossRefGoogle Scholar
  17. 17.
    Garbino J, Lew DP, Romand JA, Hugonnet S, Auckenthaler R, Pittet D (2002) Prevention of severe Candida infections in nonneutropenic, high-risk, critically ill patients: a randomized, double-blind, placebo-controlled trial in patients treated by selective digestive decontamination. Intensive Care Med 28:1708–1717PubMedCrossRefGoogle Scholar
  18. 18.
    Ho KM, Lipman J, Dobb GJ, Webb SA (2005) The use of prophylactic fluconazole in immunocompetent high-risk surgical patients: a meta-analysis. Crit Care 9:R710–R717PubMedCrossRefGoogle Scholar
  19. 19.
    Playford EG, Webster AC, Sorrell TC, Craig JC (2006) Antifungal agents for preventing fungal infections in non-neutropenic critically ill and surgical patients: systematic review and meta-analysis of randomized clinical trials. J Antimicrob Chemother 57:628–638PubMedCrossRefGoogle Scholar
  20. 20.
    Cruciani M, de Lalla F, Mengoli C (2005) Prophylaxis of Candida infections in adult trauma and surgical intensive care patients: a systematic review and meta-analysis. Intensive Care Med 31:1479–1487Google Scholar
  21. 21.
    Schuster MG, Edwards JE Jr, Sobel JD, Darouiche RO, Karchmer AW, Hadley S, Slotman G, Panzer H, Biswas P, Rex JH (2008) Empirical fluconazole versus placebo for intensive care unit patients: a randomized trial. Ann Intern Med 149:83–90PubMedGoogle Scholar
  22. 22.
    Pappas PG, Rex JH, Sobel JD, Filler SG, Dismukes WE, Walsh TJ, Edwards JE (2004) Guidelines for treatment of candidiasis. Clin Infect Dis 38:161–189PubMedCrossRefGoogle Scholar
  23. 23.
    Wingard JR, Merz WG, Rinaldi MG, Johnson TR, Karp JE, Saral R (1991) Increase in Candida krusei infection among patients with bone marrow transplantation and neutropenia treated prophylactically with fluconazole. N Engl J Med 325:1274–1277PubMedGoogle Scholar
  24. 24.
    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 24:1122–1128PubMedCrossRefGoogle Scholar
  25. 25.
    Eggimann P, Garbino J, Pittet D (2003) Epidemiology of Candida species infections in critically ill non-immunosuppressed patients. Lancet Infect Dis 3:685–702PubMedCrossRefGoogle Scholar
  26. 26.
    Shorr AF, Lazarus DR, Sherner JH, Jackson WL, Morrel M, Fraser VJ, Kollef MH (2007) Do clinical features allow for accurate prediction of fungal pathogenesis in bloodstream infections? Potential implications of the increasing prevalence of non-albicans candidemia. Crit Care Med 35:1077–1083PubMedCrossRefGoogle Scholar
  27. 27.
    Mora-Duarte J, Betts R, Rotstein C, Colombo AL, Thompson-Moya L, Smietana J, Lupinacci R, Sable C, Kartsonis N, Perfect J (2002) Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 347:2020–2029PubMedCrossRefGoogle Scholar
  28. 28.
    Clinical and Laboratory Standards Institute (2005) Performance standards for antimicrobial susceptibility testing: fifteenth informational supplement. Clinical and laboratory Standards Institute, Wayne, PAGoogle Scholar
  29. 29.
    Common Terminology Criteria for Adverse Events v3.0 (CTCAE) Published 9 August 2006., 2008
  30. 30.
    Charles PE, Dalle F, Aube H, Doise JM, Quenot JP, Aho LS, Chavanet P, Blettery B (2005) Candida spp. colonization significance in critically ill medical patients: a prospective study. Intensive Care Med 31:393–400PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Laurence Senn
    • 1
  • Philippe Eggimann
    • 2
  • Riadh Ksontini
    • 3
  • Andres Pascual
    • 1
  • Nicolas Demartines
    • 3
  • Jacques Bille
    • 1
    • 4
  • Thierry Calandra
    • 1
  • Oscar Marchetti
    • 1
  1. 1.Infectious Diseases Service, Department of MedicineCentre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL)LausanneSwitzerland
  2. 2.Adult Intensive Care ServiceCentre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL)LausanneSwitzerland
  3. 3.Visceral Surgery ServiceCentre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL)LausanneSwitzerland
  4. 4.Institute of MicrobiologyCentre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL)LausanneSwitzerland

Personalised recommendations