Skip to main content
Top
Published in: European Journal of Medical Research 4/2011

01-12-2011 | Research

Treatment and prophylaxis of invasive candidiasis with anidulafungin, caspofungin and micafungin and its impact on use and costs - review of the literature

Author: MH Wilke

Published in: European Journal of Medical Research | Issue 4/2011

Login to get access

Abstract

Invasive fungal infections are on the rise. Echinocandins are a relatively new class of antifungal drugs that act by inhibition of a key enzyme necessary for integrity of the fungal cell wall. Currently there are three available agents: caspofungin, micafungin and anidulafungin.
While the individual echinocandin antifungals have a different spectrum of licensed indications, basically all of them are available for the treatment of candidemia and invasive candidiasis. Antifungal treatment modalities basically include in therapy for suspected or proven infection and prophylaxis. All three drugs are comparatively expensive. Therefore a systematic review of the literature was performed to investigate the following aspects:
  • General aspects of cost-effectiveness in the treatment of invasive fungal infections
  • Cost-effectiveness of the treatment with the above-mentioned antifungals
  • Cost-effectiveness in two settings: therapy and prophylaxis
Early initiation of antifungal therapy, adjustment after availability of microbiological results, duration of therapy, success and occurrence of severe complications (e.g renal failure) are the most important cost drivers in antifungal therapy.
Considering the specific antifungals, for caspofungin the best evidence for cost-effectiveness is found in treatment of invasive candidiasis and in empiric therapy of suspected infections. Favourable economic data are available for micafungin as a cost-effective alternative to LAmB for prophylaxis in patients with hematopoietic stem cell transplantation (HSCT). For anidulafungin, cost-effectiveness was demostrated in a pharmacoeconomic model. Net savings - yet not significant - were observed in a retrospective chart review of 234 patients. Generally, however, most analyses are still based on pharmacoeconomic modelling rather than direct analysis of trial data or real-life clinical populations.
As an overall conclusion, using caspofungin, micafungin, or anidulafungin is not more expensive than using other established therapies. Micafungin has proven to be cost-effective in prophylaxis if the local fungal epidemiology indicates a high level of resistance to fluconazole. Switch strategies involving early initiation of broadly active therapy with switch to cheaper alternatives according to microbiology results and clinical status and early initiation of an appropriate therapy have been proven to be cost-efficient independent of the antifungal agent.
Literature
1.
go back to reference Grover ND: Echinocandins: A ray of hope in antifungal drug therapy. Indian journal of pharmacology 42: 9–11. Grover ND: Echinocandins: A ray of hope in antifungal drug therapy. Indian journal of pharmacology 42: 9–11.
2.
go back to reference Hasssan I, Powell G, Sidhu M, Hart WM, Denning DW: Excess mortality, length of stay and cost attributable to candidaemia. J Infect 2009, 59: 360–5. 10.1016/j.jinf.2009.08.020CrossRef Hasssan I, Powell G, Sidhu M, Hart WM, Denning DW: Excess mortality, length of stay and cost attributable to candidaemia. J Infect 2009, 59: 360–5. 10.1016/j.jinf.2009.08.020CrossRef
3.
go back to reference Hennen CR: Pharmacoeconomic evaluations of antifungal therapies. Curr Med Res Opin 2009, 25: 1751–8.PubMed Hennen CR: Pharmacoeconomic evaluations of antifungal therapies. Curr Med Res Opin 2009, 25: 1751–8.PubMed
4.
go back to reference Alexander BD, Ashley ED, Reller LB, Reed SD: Cost savings with implementation of PNA FISH testing for identification of Candida albicans in blood cultures. Diagn Microbiol Infect Dis 2006, 54: 277–82. 10.1016/j.diagmicrobio.2005.10.011PubMedCrossRef Alexander BD, Ashley ED, Reller LB, Reed SD: Cost savings with implementation of PNA FISH testing for identification of Candida albicans in blood cultures. Diagn Microbiol Infect Dis 2006, 54: 277–82. 10.1016/j.diagmicrobio.2005.10.011PubMedCrossRef
5.
go back to reference Al-Badriyeh D, Liew D, Stewart K, Kong DC: Economic impact of caspofungin as compared with liposomal amphotericin B for empirical therapy in febrile neutropenia in Australia. The Journal of antimicrobial chemotherapy 63: 1276–85. Al-Badriyeh D, Liew D, Stewart K, Kong DC: Economic impact of caspofungin as compared with liposomal amphotericin B for empirical therapy in febrile neutropenia in Australia. The Journal of antimicrobial chemotherapy 63: 1276–85.
6.
go back to reference Golan Y, Wolf MP, Pauker SG, Wong JB, Hadley S: Empirical anti-Candida therapy among selected patients in the intensive care unit: a cost-effectiveness analysis. Annals of internal medicine 143: 857–69. Golan Y, Wolf MP, Pauker SG, Wong JB, Hadley S: Empirical anti-Candida therapy among selected patients in the intensive care unit: a cost-effectiveness analysis. Annals of internal medicine 143: 857–69.
7.
go back to reference Gagne JJ, Breitbart RE, Maio V, et al.: Costs associated with candidemia in a hospital setting. Pharmacol Ther 2006, 31: 586–619. Gagne JJ, Breitbart RE, Maio V, et al.: Costs associated with candidemia in a hospital setting. Pharmacol Ther 2006, 31: 586–619.
8.
go back to reference Zaoutis TE, Argon J, Chu J, Berlin JA, Walsh TJ, Feudtner C: The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin Infect Dis 2005, 41: 1232–9. 10.1086/496922PubMedCrossRef Zaoutis TE, Argon J, Chu J, Berlin JA, Walsh TJ, Feudtner C: The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin Infect Dis 2005, 41: 1232–9. 10.1086/496922PubMedCrossRef
9.
go back to reference Gagne JJ, Goldfarb NI: Candidemia in the in-patient setting: treatment options and economics. Expert Opin Pharmacother 2007, 8: 1643–50. 10.1517/14656566.8.11.1643PubMedCrossRef Gagne JJ, Goldfarb NI: Candidemia in the in-patient setting: treatment options and economics. Expert Opin Pharmacother 2007, 8: 1643–50. 10.1517/14656566.8.11.1643PubMedCrossRef
10.
go back to reference Rentz AM, Halpern MT, Bowden R: The impact of candidemia on length of hospital stay, outcome, and overall cost of illness. Clin Infect Dis 1998, 27: 781–8. 10.1086/514955PubMedCrossRef Rentz AM, Halpern MT, Bowden R: The impact of candidemia on length of hospital stay, outcome, and overall cost of illness. Clin Infect Dis 1998, 27: 781–8. 10.1086/514955PubMedCrossRef
11.
go back to reference Forrest GN, Mankes K, Jabra-Rizk MA, et al.: Peptide nucleic acid fluorescence in situ hybridization-based identification of Candida albicans and its impact on mortality and antifungal therapy costs. Journal of clinical microbiology 44: 3381–3. Forrest GN, Mankes K, Jabra-Rizk MA, et al.: Peptide nucleic acid fluorescence in situ hybridization-based identification of Candida albicans and its impact on mortality and antifungal therapy costs. Journal of clinical microbiology 44: 3381–3.
12.
go back to reference Fdci DR, Dos SRP, Wirth F, Goldani LZ: Continuous infusion of amphotericin B deoxycholate: an innovative, low-cost strategy in antifungal treatment. Mycoses Fdci DR, Dos SRP, Wirth F, Goldani LZ: Continuous infusion of amphotericin B deoxycholate: an innovative, low-cost strategy in antifungal treatment. Mycoses
13.
go back to reference Wingard JR, Leather HL, Wood CA, et al.: Pharmacoeconomic analysis of caspofungin versus liposomal amphotericin B as empirical antifungal therapy for neutropenic fever. American journal of health-system pharmacy : AJHP: official journal of the American Society of Health-System Pharmacists 64: 637–43. Wingard JR, Leather HL, Wood CA, et al.: Pharmacoeconomic analysis of caspofungin versus liposomal amphotericin B as empirical antifungal therapy for neutropenic fever. American journal of health-system pharmacy : AJHP: official journal of the American Society of Health-System Pharmacists 64: 637–43.
14.
go back to reference Hsu DI, Nguyen M, Nguyen L, Law A, Wong-Beringer A: A multicentre study to evaluate the impact of timing of caspofungin administration on outcomes of invasive candidiasis in non-immunocompromised adult patients. The Journal of antimicrobial chemotherapy 65: 1765–70. Hsu DI, Nguyen M, Nguyen L, Law A, Wong-Beringer A: A multicentre study to evaluate the impact of timing of caspofungin administration on outcomes of invasive candidiasis in non-immunocompromised adult patients. The Journal of antimicrobial chemotherapy 65: 1765–70.
15.
go back to reference Kaskel P, Tuschy S, Wagner A, et al.: Economic evaluation of caspofungin vs liposomal amphotericin B for empirical therapy of suspected systemic fungal infection in the German hospital setting. Annals of hematology 87: 311–9. Kaskel P, Tuschy S, Wagner A, et al.: Economic evaluation of caspofungin vs liposomal amphotericin B for empirical therapy of suspected systemic fungal infection in the German hospital setting. Annals of hematology 87: 311–9.
16.
go back to reference Zilberberg MD, Kothari S, Shorr AF: Cost-effectiveness of micafungin as an alternative to fluconazole empiric treatment of suspected ICU-acquired candidemia among patients with sepsis: a model simulation. Critical care (London, England) 2009, 13: R94. 10.1186/cc7924CrossRef Zilberberg MD, Kothari S, Shorr AF: Cost-effectiveness of micafungin as an alternative to fluconazole empiric treatment of suspected ICU-acquired candidemia among patients with sepsis: a model simulation. Critical care (London, England) 2009, 13: R94. 10.1186/cc7924CrossRef
17.
go back to reference Earnshaw SR GC, Gasper S: Cost-effectiveness of Anidulafungin in confirmed candidemia and other forms of invasive candidiasis. In In 47th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Chicago, Ill.; 2007. Earnshaw SR GC, Gasper S: Cost-effectiveness of Anidulafungin in confirmed candidemia and other forms of invasive candidiasis. In In 47th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Chicago, Ill.; 2007.
18.
go back to reference Reboli AC RC, Kett DH, Schorr A, Hux M, Maschio M, Chambers R, Tarallo M: Economic Evaluation of anidulafungin (Eraxis(R)/ECALTA(R)) versus intravenous fluconazole in the treatment of hospital inpatients diagnosed with candidemia an other forms of invasive candidiasis (C/IC). In: 19th ECCMID. Helsinki, Finland; 2009. Reboli AC RC, Kett DH, Schorr A, Hux M, Maschio M, Chambers R, Tarallo M: Economic Evaluation of anidulafungin (Eraxis(R)/ECALTA(R)) versus intravenous fluconazole in the treatment of hospital inpatients diagnosed with candidemia an other forms of invasive candidiasis (C/IC). In: 19th ECCMID. Helsinki, Finland; 2009.
19.
go back to reference Williams A: The role of health economics in clinical decision-making: is it ethical? Respiratory medicine 85(Suppl B):3–5. Williams A: The role of health economics in clinical decision-making: is it ethical? Respiratory medicine 85(Suppl B):3–5.
20.
go back to reference Brouwer WB, Koopmanschap MA: On the economic foundations of CEA. Ladies and gentlemen, take your positions! Journal of health economics 19: 439–59. Brouwer WB, Koopmanschap MA: On the economic foundations of CEA. Ladies and gentlemen, take your positions! Journal of health economics 19: 439–59.
21.
go back to reference Schwalm A, Danner M, Seidl A, Volz F, Dintsios CM, Gerber A: Wo steht die Kosten-Nutzen-Bewertung des IQWiG : Abgleich mit einem internationalen Referenzszenario? IQWiG's methods for the cost-benefit assessment : Comparison with an international reference scenario]. Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz 53: 615–22. Schwalm A, Danner M, Seidl A, Volz F, Dintsios CM, Gerber A: Wo steht die Kosten-Nutzen-Bewertung des IQWiG : Abgleich mit einem internationalen Referenzszenario? IQWiG's methods for the cost-benefit assessment : Comparison with an international reference scenario]. Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz 53: 615–22.
22.
go back to reference Brazier JE, Dixon S, Ratcliffe J: The role of patient preferences in cost-effectiveness analysis: a conflict of values? PharmacoEconomics 2009, 27: 705–12. 10.2165/11314840-000000000-00000PubMedCrossRef Brazier JE, Dixon S, Ratcliffe J: The role of patient preferences in cost-effectiveness analysis: a conflict of values? PharmacoEconomics 2009, 27: 705–12. 10.2165/11314840-000000000-00000PubMedCrossRef
23.
go back to reference Wingard JR, Wood CA, Sullivan E, Berger ML, Gerth WC, Mansley EC: Caspofungin versus amphotericin B for candidemia: a pharmacoeconomic analysis. Clin Ther 2005, 27: 960–9. 10.1016/j.clinthera.2005.06.023PubMedCrossRef Wingard JR, Wood CA, Sullivan E, Berger ML, Gerth WC, Mansley EC: Caspofungin versus amphotericin B for candidemia: a pharmacoeconomic analysis. Clin Ther 2005, 27: 960–9. 10.1016/j.clinthera.2005.06.023PubMedCrossRef
24.
go back to reference Sidhu MK, van EAK, Kleintjens J, Schoeman O, Palazzo M: Cost-effectiveness analysis of micafungin versus caspofungin for treatment of systemic Candida infections in the UK. Current medical research and opinion 25: 2049–59. Sidhu MK, van EAK, Kleintjens J, Schoeman O, Palazzo M: Cost-effectiveness analysis of micafungin versus caspofungin for treatment of systemic Candida infections in the UK. Current medical research and opinion 25: 2049–59.
25.
go back to reference Stam WB, Aversa F, Kumar RN, Jansen JP: Economic evaluation of caspofungin versus liposomal amphotericin B for empiric antifungal treatment in patients with neutropenic fever in Italy. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research 2008, 11: 830–41.CrossRef Stam WB, Aversa F, Kumar RN, Jansen JP: Economic evaluation of caspofungin versus liposomal amphotericin B for empiric antifungal treatment in patients with neutropenic fever in Italy. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research 2008, 11: 830–41.CrossRef
26.
go back to reference Bruynesteyn K, Gant V, McKenzie C, et al.: A cost-effectiveness analysis of caspofungin vs. liposomal amphotericin B for treatment of suspected fungal infections in the UK. European journal of haematology 78: 532–9. Bruynesteyn K, Gant V, McKenzie C, et al.: A cost-effectiveness analysis of caspofungin vs. liposomal amphotericin B for treatment of suspected fungal infections in the UK. European journal of haematology 78: 532–9.
27.
go back to reference Cornely OA, Sidhu M, Odeyemi I, van E'AK, van dWJM, Schoeman O: Economic analysis of micafungin versus liposomal amphotericin B for treatment of candidaemia and invasive candidiasis in Germany. Current medical research and opinion 24: 1743–53. Cornely OA, Sidhu M, Odeyemi I, van E'AK, van dWJM, Schoeman O: Economic analysis of micafungin versus liposomal amphotericin B for treatment of candidaemia and invasive candidiasis in Germany. Current medical research and opinion 24: 1743–53.
28.
go back to reference Nomura K, Kawasugi K, Morimoto T: Cost-effectiveness analysis of antifungal treatment for patients on chemotherapy. European journal of cancer care 15: 44–50. Nomura K, Kawasugi K, Morimoto T: Cost-effectiveness analysis of antifungal treatment for patients on chemotherapy. European journal of cancer care 15: 44–50.
29.
go back to reference Sohn HS, Lee TJ, Kim J, Kim D: Cost-effectiveness analysis of micafungin versus fluconazole for prophylaxis of invasive fungal infections in patients undergoing hematopoietic stem cell transplantation in Korea. Clinical therapeutics 31: 1105–15. discussion 066–8 Sohn HS, Lee TJ, Kim J, Kim D: Cost-effectiveness analysis of micafungin versus fluconazole for prophylaxis of invasive fungal infections in patients undergoing hematopoietic stem cell transplantation in Korea. Clinical therapeutics 31: 1105–15. discussion 066–8
30.
go back to reference Schonfeld W, Wang CJ, Tong KB, Seifeldin R: Cost-effectiveness analysis of antifungal prophylaxis in patients undergoing hematopoietic stem cell transplantation. Clinical therapeutics 30: 964–73. Schonfeld W, Wang CJ, Tong KB, Seifeldin R: Cost-effectiveness analysis of antifungal prophylaxis in patients undergoing hematopoietic stem cell transplantation. Clinical therapeutics 30: 964–73.
31.
go back to reference Garcia : Pharmaco-economic evaluation of currently available echinocandins in a spanish hospital setting. In 12th Annual European Congress of the International Society for Pharmacoeconomics and Outcomes Research. Paris; 2009. Garcia : Pharmaco-economic evaluation of currently available echinocandins in a spanish hospital setting. In 12th Annual European Congress of the International Society for Pharmacoeconomics and Outcomes Research. Paris; 2009.
32.
go back to reference Reboli AC, Rotstein C, Kett DH, et al.: Resource utilisation and cost of treatment with anidulafungin or fluconazole for candidaemia and other forms of invasive candidiasis: focus on critically ill patients. Pharmacoeconomics [in press] 2011. Reboli AC, Rotstein C, Kett DH, et al.: Resource utilisation and cost of treatment with anidulafungin or fluconazole for candidaemia and other forms of invasive candidiasis: focus on critically ill patients. Pharmacoeconomics [in press] 2011.
33.
go back to reference Reboli AC, Rotstein C, Pappas PG, et al.: Anidulafungin versus fluconazole for invasive candidiasis. The New England journal of medicine 356: 2472–82. Reboli AC, Rotstein C, Pappas PG, et al.: Anidulafungin versus fluconazole for invasive candidiasis. The New England journal of medicine 356: 2472–82.
34.
go back to reference Vehreschild JJ, Kummerle T, Karthaus M, Cornely OA: Anidulafungin-state of affairs from a clinical perspective. Mycoses 2007,50(Suppl 1):38–43.PubMedCrossRef Vehreschild JJ, Kummerle T, Karthaus M, Cornely OA: Anidulafungin-state of affairs from a clinical perspective. Mycoses 2007,50(Suppl 1):38–43.PubMedCrossRef
35.
go back to reference Estes KE, Penzak SR, Calis KA, Walsh TJ: Pharmacology and antifungal properties of anidulafungin, a new echinocandin. Pharmacotherapy 2009, 29: 17–30. 10.1592/phco.29.1.17PubMedCrossRef Estes KE, Penzak SR, Calis KA, Walsh TJ: Pharmacology and antifungal properties of anidulafungin, a new echinocandin. Pharmacotherapy 2009, 29: 17–30. 10.1592/phco.29.1.17PubMedCrossRef
36.
go back to reference Bates DW, Su L, Yu Dt, et al.: Mortality and costs of acute renal failure associated with amphotericin B therapy. Clin Infect Dis 2001, 32: 686–93. 10.1086/319211PubMedCrossRef Bates DW, Su L, Yu Dt, et al.: Mortality and costs of acute renal failure associated with amphotericin B therapy. Clin Infect Dis 2001, 32: 686–93. 10.1086/319211PubMedCrossRef
37.
go back to reference Raymond S, Henon T, Grenouillet F, et al.: [Clinical audit on the use of expensive systemic antifungals in the Besancon University Hospital]. Med Mal Infect 2009, 39: 125–32. 10.1016/j.medmal.2008.09.028PubMedCrossRef Raymond S, Henon T, Grenouillet F, et al.: [Clinical audit on the use of expensive systemic antifungals in the Besancon University Hospital]. Med Mal Infect 2009, 39: 125–32. 10.1016/j.medmal.2008.09.028PubMedCrossRef
38.
go back to reference Arnold HM, Micek ST, Shorr AF, et al.: Hospital resource utilization and costs of inappropriate treatment of candidemia. Pharmacotherapy 2010, 30: 361–8. 10.1592/phco.30.4.361PubMedCrossRef Arnold HM, Micek ST, Shorr AF, et al.: Hospital resource utilization and costs of inappropriate treatment of candidemia. Pharmacotherapy 2010, 30: 361–8. 10.1592/phco.30.4.361PubMedCrossRef
39.
go back to reference Wang P: Rapid differentiation of Candida albicans from non-C. albicans directly in a variety of clinical specimens using fluorescent in situ hybridisation. Mycoses Wang P: Rapid differentiation of Candida albicans from non-C. albicans directly in a variety of clinical specimens using fluorescent in situ hybridisation. Mycoses
40.
go back to reference Wang JL, Chang CH, Young-Xu Y, Chan KA: Systematic review and meta-analysis of the tolerability and hepatotoxicity of antifungals in empirical and definitive therapy for invasive fungal infection. Antimicrobial agents and chemotherapy 54: 2409–19. Wang JL, Chang CH, Young-Xu Y, Chan KA: Systematic review and meta-analysis of the tolerability and hepatotoxicity of antifungals in empirical and definitive therapy for invasive fungal infection. Antimicrobial agents and chemotherapy 54: 2409–19.
41.
42.
go back to reference Erjavec Z, Kluin-Nelemans H, Verweij PE: Trends in invasive fungal infections, with emphasis on invasive aspergillosis. Clin Microbiol Infect 2009, 15: 625–33. 10.1111/j.1469-0691.2009.02929.xPubMedCrossRef Erjavec Z, Kluin-Nelemans H, Verweij PE: Trends in invasive fungal infections, with emphasis on invasive aspergillosis. Clin Microbiol Infect 2009, 15: 625–33. 10.1111/j.1469-0691.2009.02929.xPubMedCrossRef
43.
go back to reference Hosseini-Moghaddam SM, Husain S: Fungi and molds following lung transplantation. Semin Respir Crit Care Med 2010, 31: 222–33. 10.1055/s-0030-1249118PubMedCrossRef Hosseini-Moghaddam SM, Husain S: Fungi and molds following lung transplantation. Semin Respir Crit Care Med 2010, 31: 222–33. 10.1055/s-0030-1249118PubMedCrossRef
44.
go back to reference Playford EG, Lipman J, Sorrell TC: Prophylaxis, empirical and preemptive treatment of invasive candidiasis. Curr Opin Crit Care 2010, 16: 470–4. 10.1097/MCC.0b013e32833e10e8PubMedCrossRef Playford EG, Lipman J, Sorrell TC: Prophylaxis, empirical and preemptive treatment of invasive candidiasis. Curr Opin Crit Care 2010, 16: 470–4. 10.1097/MCC.0b013e32833e10e8PubMedCrossRef
Metadata
Title
Treatment and prophylaxis of invasive candidiasis with anidulafungin, caspofungin and micafungin and its impact on use and costs - review of the literature
Author
MH Wilke
Publication date
01-12-2011
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 4/2011
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/2047-783X-16-4-180

Other articles of this Issue 4/2011

European Journal of Medical Research 4/2011 Go to the issue