Copyright (c) 2025 Maryam Mahmoodan
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
An Update on Safety and Efficacy of Echinocandins in Antifungal Therapy
Corresponding Author(s) : Maryam Mahmoodan
International Journal of Allied Medical Sciences and Clinical Research,
Vol. 5 No. 3 (2017): 2017 Volume 5- Issue -3
Abstract
The echinocandins are important and exciting agents because of their novel mechanism of action, low incidence of serious adverse effects, and low potential for drug–drug interactions. In vitro and in vivo, the echinocandins are rapidly fungicidal against most Candida species and fungistatic against Aspergillus species.It is also a treatment option for serious fungal infections. Pharmacokinetic–pharmacodynamic studies in animals have demonstrated superior efficacy, defined as maximal microbial kill, when compared to fluconazole. Anidulafungin exhibits a unique pharmacokinetic profile, and limited cases have shown a potential for activity in isolates with increased minimum inhibitory concentrations to caspofungin and micafungin. Caspofungin appears to have a slightly higher incidence of side effects and potential for drug–drug interactions. Micafungin appears to be very similar to caspofungin, with very few obvious differences between the two agents and also have similar safety and efficacy profile in patients with fungal infections. Adverse events are generally mild, including (for caspofungin) local phlebitis, fever, abnormal liver function tests, and mild haemolysis. Anidulafungin is economical and have dominant efficacy compared with micafungin and caspofungin in patients with candidemia and/or invasive candidiasis. All three echinocandins are generally well-tolerated. Echinocandins provide safe, uncomplicated and highly active therapy for invasive Candida infections with potentially superior efficacy versus fluconazole and better tolerability compared to formulations like amphotericin B, making them the agents of choice for moderate to severely ill patients with invasive candidiasis.
Keywords
Echinocandin
Anti-fungal therapy
Safety and efficacy
Drug interaction
Candidiasis
References
-
Neoh CF, Liew D, Slavin M, Marriott D, Chen SC, Morrissey O, Stewart K, Kong D. Cost-effectiveness
analysis of anidulafungin versus fluconazole for the treatment of invasive candidiasis. Journal of antimicrobial
chemotherapy, 66(8), 2011, 1906-15.
[2]. Kauffman CA, Marr KA, Thorner AR. Treatment of candidemia and invasive candidiasis in adults. UpToDate,
Waltham, MA. 2012.
[3]. Gafter-Gvili A, Vidal L, Goldberg E, Leibovici L, Paul M. Treatment of invasive candidal infections:
systematic review and meta-analysis. InMayo Clinic Proceedings 83(9), 2008, 1011-1021. Elsevier.
[4]. Denning DW. Echinocandins: a new class of antifungal. Journal of Antimicrobial Chemotherapy. 49(6), 2002,
889-91.
[5]. Stone EA, Fung HB, Kirschenbaum HL. Caspofungin: an echinocandin antifungal agent. Clinical therapeutics.
24(3), 2002, 351-77.
[6]. Dannaoui E, Lortholary O, Raoux D, Bougnoux ME, Galeazzi G, Lawrence C, Moissenet D, Poilane I, Hoinard
D, Dromer F, YEASTS Group. Comparative in vitro activities of caspofungin and micafungin, determined
using the method of the European Committee on Antimicrobial Susceptibility Testing, against yeast isolates
obtained in France in 2005-2006. Antimicrobial agents and chemotherapy. 52(2), 2008, 778-81.
Maryam M et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-5(3) 2017 [716-723]
722
[7]. 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(6), 2010, 2409-19. [8]. FDA Approves New Treatment for Fungal Infections". FDA News Release. Food and Drug Administration. Archived from the original on Retrieved 2009, 08-01. [9]. Wagner C, Graninger W, Presterl E, Joukhadar C. The echinocandins: comparison of their pharmacokinetics, pharmacodynamics and clinical applications. Pharmacology. 78(4), 2006, 161-77. [10]. Pfaller MA, Boyken L, Hollis RJ, Messer SA, Tendolkar S, Diekema DJ. Global surveillance of in vitro activity of micafungin against Candida: a comparison with caspofungin by CLSI-recommended methods. Journal of clinical microbiology. 44(10), 2006, 3533-8. [11]. Arendrup MC, Perlin DS, Jensen RH, Howard SJ, Goodwin J, Hope W. Differential in vivo activities of anidulafungin, caspofungin, and micafungin against Candida glabrata isolates with and without FKS resistance mutations. Antimicrobial agents and chemotherapy. 56(5), 2012, 2435-42. [12]. Sabol K, Gumbo T. Anidulafungin in the treatment of invasive fungal infections. Therapeutics and clinical risk management. 4(1), 2008, 71. [13]. Chandrasekar PH, Sobel JD. Micafungin: a new echinocandin. Clinical infectious diseases. 42(8), 2006, 1171-8. [14]. Glöckner A. Treatment and prophylaxis of invasive candidiasis with anidulafungin, caspofungin and micafungin-review of the literature. European journal of medical research. 16(4), 2011, 167.
[15]. Caspofungin package insert. Whitehouse Station, NJ: Merck & Co.; 2005. [16]. Eschenauer G, DePestel DD, Carver PL. Comparison of echinocandin antifungals. Therapeutics and clinical risk management. 3(1), 2007, 71. [17]. Denning, David W. "Echinocandin antifungal drugs." The Lancet 362.9390, 2003, 1142-1151. [18]. Denning DW. Echinocandins: a new class of antifungal. Journal of Antimicrobial Chemotherapy. 49(6), 2002, 889-91.
[19]. Cancidas PI 2005. Cancidas package insert [online]. Rahway, NJ: Merck. 2006 [20]. Perea S, Gonzalez G, Fothergill AW, Kirkpatrick WR, Rinaldi MG, Patterson TF. In vitro interaction of caspofungin acetate with voriconazole against clinical isolates of Aspergillus spp. Antimicrobial Agents and Chemotherapy. 46(9), 2002, 3039-41.
[21]. Caspofungin acetate. FDA advisory committee meeting background. http://www.fda.gov/ohrms/dockets/ac/01/briefing/3676b1_02.pdf (accessed 2002). [22]. Chen YL, Lehman VN, Averette AF, Perfect JR, Heitman J. Posaconazole exhibits in vitro and in vivo synergistic antifungal activity with caspofungin or FK506 against Candida albicans. PloS one. 8(3), 2013, 57672. [23]. Townsend R, Hebert M, Wisemandle W, Bekersky I. Concomitant pharmacokinetics (PK) of micafungin, an echinocandin antifungal, and tacrolimus in healthy volunteers. InJOURNAL OF CLINICAL PHARMACOLOGY 42(9), 2002, 1055-1055. 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA: SAGE PUBLICATIONS INC.
[24]. European Medicines agency MycamineR summary of product characteristics. 2010
[25]. Mycamine [package insert]. Deerfield, IL: Astellas Pharma US, 2005. [26]. Katragkou A, McCarthy M, Alexander EL, Antachopoulos C, Meletiadis J, Jabra-Rizk MA, Petraitis V, Roilides E, Walsh TJ. In vitro interactions between farnesol and fluconazole, amphotericin B or micafungin against Candida albicans biofilms. Journal of Antimicrobial Chemotherapy. 70(2), 2015, 470-8. [27]. Thye D, Kilfoil T, Kilfoil G, Henkel T. Anidulafungin: safety and pharmacokinetics in subjects receiving concomitant cyclosporine. InProgram and abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy 2002. [28]. Seyedmousavi S, Brüggemann RJ, Melchers WJ, Rijs AJ, Verweij PE, Mouton JW. Efficacy and pharmacodynamics of voriconazole combined with anidulafungin in azole-resistant invasive aspergillosis. Journal of Antimicrobial Chemotherapy. 68(2), 2013, 385-93. [29]. Kofla G, Ruhnke M. Pharmacology and metabolism of anidulafungin, caspofungin and micafungin in the treatment of invasive candidosis-review of the literature. European journal of medical research. 16(4), 2011, 159.
Maryam M et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-5(3) 2017 [716-723]
723
[30]. Wang JF, Xue Y, Zhu XB, Fan H. Efficacy and safety of echinocandins versus triazoles for the prophylaxis and treatment of fungal infections: a meta-analysis of RCTs. European Journal of Clinical Microbiology & Infectious Diseases. 34(4), 2015, 651-9. [31]. Grau S, Pozo JC, Romá E, Salavert M, Barrueta JA, Peral C, Rodriguez I, Rubio-Rodríguez D, Rubio-Terrés C. Cost-effectiveness of three echinocandins and fluconazole in the treatment of candidemia and/or invasive candidiasis in nonneutropenic adult patients. ClinicoEconomics and outcomes research: CEOR.7, 2015, 527.
References
Neoh CF, Liew D, Slavin M, Marriott D, Chen SC, Morrissey O, Stewart K, Kong D. Cost-effectiveness
analysis of anidulafungin versus fluconazole for the treatment of invasive candidiasis. Journal of antimicrobial
chemotherapy, 66(8), 2011, 1906-15.
[2]. Kauffman CA, Marr KA, Thorner AR. Treatment of candidemia and invasive candidiasis in adults. UpToDate,
Waltham, MA. 2012.
[3]. Gafter-Gvili A, Vidal L, Goldberg E, Leibovici L, Paul M. Treatment of invasive candidal infections:
systematic review and meta-analysis. InMayo Clinic Proceedings 83(9), 2008, 1011-1021. Elsevier.
[4]. Denning DW. Echinocandins: a new class of antifungal. Journal of Antimicrobial Chemotherapy. 49(6), 2002,
889-91.
[5]. Stone EA, Fung HB, Kirschenbaum HL. Caspofungin: an echinocandin antifungal agent. Clinical therapeutics.
24(3), 2002, 351-77.
[6]. Dannaoui E, Lortholary O, Raoux D, Bougnoux ME, Galeazzi G, Lawrence C, Moissenet D, Poilane I, Hoinard
D, Dromer F, YEASTS Group. Comparative in vitro activities of caspofungin and micafungin, determined
using the method of the European Committee on Antimicrobial Susceptibility Testing, against yeast isolates
obtained in France in 2005-2006. Antimicrobial agents and chemotherapy. 52(2), 2008, 778-81.
Maryam M et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-5(3) 2017 [716-723]
722
[7]. 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(6), 2010, 2409-19. [8]. FDA Approves New Treatment for Fungal Infections". FDA News Release. Food and Drug Administration. Archived from the original on Retrieved 2009, 08-01. [9]. Wagner C, Graninger W, Presterl E, Joukhadar C. The echinocandins: comparison of their pharmacokinetics, pharmacodynamics and clinical applications. Pharmacology. 78(4), 2006, 161-77. [10]. Pfaller MA, Boyken L, Hollis RJ, Messer SA, Tendolkar S, Diekema DJ. Global surveillance of in vitro activity of micafungin against Candida: a comparison with caspofungin by CLSI-recommended methods. Journal of clinical microbiology. 44(10), 2006, 3533-8. [11]. Arendrup MC, Perlin DS, Jensen RH, Howard SJ, Goodwin J, Hope W. Differential in vivo activities of anidulafungin, caspofungin, and micafungin against Candida glabrata isolates with and without FKS resistance mutations. Antimicrobial agents and chemotherapy. 56(5), 2012, 2435-42. [12]. Sabol K, Gumbo T. Anidulafungin in the treatment of invasive fungal infections. Therapeutics and clinical risk management. 4(1), 2008, 71. [13]. Chandrasekar PH, Sobel JD. Micafungin: a new echinocandin. Clinical infectious diseases. 42(8), 2006, 1171-8. [14]. Glöckner A. Treatment and prophylaxis of invasive candidiasis with anidulafungin, caspofungin and micafungin-review of the literature. European journal of medical research. 16(4), 2011, 167.
[15]. Caspofungin package insert. Whitehouse Station, NJ: Merck & Co.; 2005. [16]. Eschenauer G, DePestel DD, Carver PL. Comparison of echinocandin antifungals. Therapeutics and clinical risk management. 3(1), 2007, 71. [17]. Denning, David W. "Echinocandin antifungal drugs." The Lancet 362.9390, 2003, 1142-1151. [18]. Denning DW. Echinocandins: a new class of antifungal. Journal of Antimicrobial Chemotherapy. 49(6), 2002, 889-91.
[19]. Cancidas PI 2005. Cancidas package insert [online]. Rahway, NJ: Merck. 2006 [20]. Perea S, Gonzalez G, Fothergill AW, Kirkpatrick WR, Rinaldi MG, Patterson TF. In vitro interaction of caspofungin acetate with voriconazole against clinical isolates of Aspergillus spp. Antimicrobial Agents and Chemotherapy. 46(9), 2002, 3039-41.
[21]. Caspofungin acetate. FDA advisory committee meeting background. http://www.fda.gov/ohrms/dockets/ac/01/briefing/3676b1_02.pdf (accessed 2002). [22]. Chen YL, Lehman VN, Averette AF, Perfect JR, Heitman J. Posaconazole exhibits in vitro and in vivo synergistic antifungal activity with caspofungin or FK506 against Candida albicans. PloS one. 8(3), 2013, 57672. [23]. Townsend R, Hebert M, Wisemandle W, Bekersky I. Concomitant pharmacokinetics (PK) of micafungin, an echinocandin antifungal, and tacrolimus in healthy volunteers. InJOURNAL OF CLINICAL PHARMACOLOGY 42(9), 2002, 1055-1055. 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA: SAGE PUBLICATIONS INC.
[24]. European Medicines agency MycamineR summary of product characteristics. 2010
[25]. Mycamine [package insert]. Deerfield, IL: Astellas Pharma US, 2005. [26]. Katragkou A, McCarthy M, Alexander EL, Antachopoulos C, Meletiadis J, Jabra-Rizk MA, Petraitis V, Roilides E, Walsh TJ. In vitro interactions between farnesol and fluconazole, amphotericin B or micafungin against Candida albicans biofilms. Journal of Antimicrobial Chemotherapy. 70(2), 2015, 470-8. [27]. Thye D, Kilfoil T, Kilfoil G, Henkel T. Anidulafungin: safety and pharmacokinetics in subjects receiving concomitant cyclosporine. InProgram and abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy 2002. [28]. Seyedmousavi S, Brüggemann RJ, Melchers WJ, Rijs AJ, Verweij PE, Mouton JW. Efficacy and pharmacodynamics of voriconazole combined with anidulafungin in azole-resistant invasive aspergillosis. Journal of Antimicrobial Chemotherapy. 68(2), 2013, 385-93. [29]. Kofla G, Ruhnke M. Pharmacology and metabolism of anidulafungin, caspofungin and micafungin in the treatment of invasive candidosis-review of the literature. European journal of medical research. 16(4), 2011, 159.
Maryam M et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-5(3) 2017 [716-723]
723
[30]. Wang JF, Xue Y, Zhu XB, Fan H. Efficacy and safety of echinocandins versus triazoles for the prophylaxis and treatment of fungal infections: a meta-analysis of RCTs. European Journal of Clinical Microbiology & Infectious Diseases. 34(4), 2015, 651-9. [31]. Grau S, Pozo JC, Romá E, Salavert M, Barrueta JA, Peral C, Rodriguez I, Rubio-Rodríguez D, Rubio-Terrés C. Cost-effectiveness of three echinocandins and fluconazole in the treatment of candidemia and/or invasive candidiasis in nonneutropenic adult patients. ClinicoEconomics and outcomes research: CEOR.7, 2015, 527.
analysis of anidulafungin versus fluconazole for the treatment of invasive candidiasis. Journal of antimicrobial
chemotherapy, 66(8), 2011, 1906-15.
[2]. Kauffman CA, Marr KA, Thorner AR. Treatment of candidemia and invasive candidiasis in adults. UpToDate,
Waltham, MA. 2012.
[3]. Gafter-Gvili A, Vidal L, Goldberg E, Leibovici L, Paul M. Treatment of invasive candidal infections:
systematic review and meta-analysis. InMayo Clinic Proceedings 83(9), 2008, 1011-1021. Elsevier.
[4]. Denning DW. Echinocandins: a new class of antifungal. Journal of Antimicrobial Chemotherapy. 49(6), 2002,
889-91.
[5]. Stone EA, Fung HB, Kirschenbaum HL. Caspofungin: an echinocandin antifungal agent. Clinical therapeutics.
24(3), 2002, 351-77.
[6]. Dannaoui E, Lortholary O, Raoux D, Bougnoux ME, Galeazzi G, Lawrence C, Moissenet D, Poilane I, Hoinard
D, Dromer F, YEASTS Group. Comparative in vitro activities of caspofungin and micafungin, determined
using the method of the European Committee on Antimicrobial Susceptibility Testing, against yeast isolates
obtained in France in 2005-2006. Antimicrobial agents and chemotherapy. 52(2), 2008, 778-81.
Maryam M et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-5(3) 2017 [716-723]
722
[7]. 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(6), 2010, 2409-19. [8]. FDA Approves New Treatment for Fungal Infections". FDA News Release. Food and Drug Administration. Archived from the original on Retrieved 2009, 08-01. [9]. Wagner C, Graninger W, Presterl E, Joukhadar C. The echinocandins: comparison of their pharmacokinetics, pharmacodynamics and clinical applications. Pharmacology. 78(4), 2006, 161-77. [10]. Pfaller MA, Boyken L, Hollis RJ, Messer SA, Tendolkar S, Diekema DJ. Global surveillance of in vitro activity of micafungin against Candida: a comparison with caspofungin by CLSI-recommended methods. Journal of clinical microbiology. 44(10), 2006, 3533-8. [11]. Arendrup MC, Perlin DS, Jensen RH, Howard SJ, Goodwin J, Hope W. Differential in vivo activities of anidulafungin, caspofungin, and micafungin against Candida glabrata isolates with and without FKS resistance mutations. Antimicrobial agents and chemotherapy. 56(5), 2012, 2435-42. [12]. Sabol K, Gumbo T. Anidulafungin in the treatment of invasive fungal infections. Therapeutics and clinical risk management. 4(1), 2008, 71. [13]. Chandrasekar PH, Sobel JD. Micafungin: a new echinocandin. Clinical infectious diseases. 42(8), 2006, 1171-8. [14]. Glöckner A. Treatment and prophylaxis of invasive candidiasis with anidulafungin, caspofungin and micafungin-review of the literature. European journal of medical research. 16(4), 2011, 167.
[15]. Caspofungin package insert. Whitehouse Station, NJ: Merck & Co.; 2005. [16]. Eschenauer G, DePestel DD, Carver PL. Comparison of echinocandin antifungals. Therapeutics and clinical risk management. 3(1), 2007, 71. [17]. Denning, David W. "Echinocandin antifungal drugs." The Lancet 362.9390, 2003, 1142-1151. [18]. Denning DW. Echinocandins: a new class of antifungal. Journal of Antimicrobial Chemotherapy. 49(6), 2002, 889-91.
[19]. Cancidas PI 2005. Cancidas package insert [online]. Rahway, NJ: Merck. 2006 [20]. Perea S, Gonzalez G, Fothergill AW, Kirkpatrick WR, Rinaldi MG, Patterson TF. In vitro interaction of caspofungin acetate with voriconazole against clinical isolates of Aspergillus spp. Antimicrobial Agents and Chemotherapy. 46(9), 2002, 3039-41.
[21]. Caspofungin acetate. FDA advisory committee meeting background. http://www.fda.gov/ohrms/dockets/ac/01/briefing/3676b1_02.pdf (accessed 2002). [22]. Chen YL, Lehman VN, Averette AF, Perfect JR, Heitman J. Posaconazole exhibits in vitro and in vivo synergistic antifungal activity with caspofungin or FK506 against Candida albicans. PloS one. 8(3), 2013, 57672. [23]. Townsend R, Hebert M, Wisemandle W, Bekersky I. Concomitant pharmacokinetics (PK) of micafungin, an echinocandin antifungal, and tacrolimus in healthy volunteers. InJOURNAL OF CLINICAL PHARMACOLOGY 42(9), 2002, 1055-1055. 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA: SAGE PUBLICATIONS INC.
[24]. European Medicines agency MycamineR summary of product characteristics. 2010
[25]. Mycamine [package insert]. Deerfield, IL: Astellas Pharma US, 2005. [26]. Katragkou A, McCarthy M, Alexander EL, Antachopoulos C, Meletiadis J, Jabra-Rizk MA, Petraitis V, Roilides E, Walsh TJ. In vitro interactions between farnesol and fluconazole, amphotericin B or micafungin against Candida albicans biofilms. Journal of Antimicrobial Chemotherapy. 70(2), 2015, 470-8. [27]. Thye D, Kilfoil T, Kilfoil G, Henkel T. Anidulafungin: safety and pharmacokinetics in subjects receiving concomitant cyclosporine. InProgram and abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy 2002. [28]. Seyedmousavi S, Brüggemann RJ, Melchers WJ, Rijs AJ, Verweij PE, Mouton JW. Efficacy and pharmacodynamics of voriconazole combined with anidulafungin in azole-resistant invasive aspergillosis. Journal of Antimicrobial Chemotherapy. 68(2), 2013, 385-93. [29]. Kofla G, Ruhnke M. Pharmacology and metabolism of anidulafungin, caspofungin and micafungin in the treatment of invasive candidosis-review of the literature. European journal of medical research. 16(4), 2011, 159.
Maryam M et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-5(3) 2017 [716-723]
723
[30]. Wang JF, Xue Y, Zhu XB, Fan H. Efficacy and safety of echinocandins versus triazoles for the prophylaxis and treatment of fungal infections: a meta-analysis of RCTs. European Journal of Clinical Microbiology & Infectious Diseases. 34(4), 2015, 651-9. [31]. Grau S, Pozo JC, Romá E, Salavert M, Barrueta JA, Peral C, Rodriguez I, Rubio-Rodríguez D, Rubio-Terrés C. Cost-effectiveness of three echinocandins and fluconazole in the treatment of candidemia and/or invasive candidiasis in nonneutropenic adult patients. ClinicoEconomics and outcomes research: CEOR.7, 2015, 527.