Caspofungin: a review of its use in the treatment of fungal infections.

Caspofungin (Cancidas) is the first of a new class of antifungal agents, the echinocandins, that inhibit the synthesis of the fungal cell wall component beta-(1,3)-D-glucan. Caspofungin is administered once daily by slow intravenous infusion and is used to treat infections caused by Candida spp. and Aspergillus spp. Caspofungin is a valuable new antifungal agent with a novel mechanism of action. In comparative clinical trials, caspofungin was no less effective than liposomal amphotericin B in the empirical treatment of neutropenic patients with persistent fever, amphotericin B deoxycholate in the treatment of invasive candidiasis or fluconazole in the treatment of oesophageal candidiasis. Caspofungin also displayed broadly similar efficacy to amphotericin B deoxycholate in oesophageal or oropharyngeal candidiasis and was effective as salvage therapy in patients with invasive aspergillosis who were refractory to or intolerant of standard therapy. The tolerability profile of caspofungin was similar to that of fluconazole and superior to that of amphotericin B deoxycholate and liposomal amphotericin B. Therefore, in the appropriate indications, caspofungin is a viable alternative to amphotericin B deoxycholate, liposomal amphotericin B or fluconazole.

[1]  M. Klepser.  Antifungal Resistance Among Candida Species , 2001, Pharmacotherapy.

[2]  A. Sterrett,et al.  Single- and Multiple-Dose Pharmacokinetics of Caspofungin in Healthy Men , 2002, Antimicrobial Agents and Chemotherapy.

[3]  C. Gill,et al.  Efficacy of the Echinocandin Caspofungin against Disseminated Aspergillosis and Candidiasis in Cyclophosphamide-Induced Immunosuppressed Mice , 2000, Antimicrobial Agents and Chemotherapy.

[4]  J. Graybill,et al.  Treatment of murine disseminated candidiasis with L-743,872 , 1997, Antimicrobial agents and chemotherapy.

[5]  K. Kuchler,et al.  The Candida albicans Cdr2p ATP‐binding cassette (ABC) transporter confers resistance to caspofungin , 2003, Molecular microbiology.

[6]  M. Klepser,et al.  Postantifungal Effects of Echinocandin, Azole, and Polyene Antifungal Agents against Candida albicans andCryptococcus neoformans , 2000, Antimicrobial Agents and Chemotherapy.

[7]  A. Francesconi,et al.  Antifungal Efficacy of Caspofungin (MK-0991) in Experimental Pulmonary Aspergillosis in Persistently Neutropenic Rabbits: Pharmacokinetics, Drug Disposition, and Relationship to Galactomannan Antigenemia , 2002, Antimicrobial Agents and Chemotherapy.

[8]  A. Ullmann.  Review of the safety, tolerability, and drug interactions of the new antifungal agents caspofungin and voriconazole , 2003, Current medical research and opinion.

[9]  E. Gotuzzo,et al.  Randomized, Double-Blind, Multicenter Study of Caspofungin versus Amphotericin B for Treatment of Oropharyngeal and Esophageal Candidiases , 2002, Antimicrobial Agents and Chemotherapy.

[10]  Xin Xu,et al.  Disposition of Caspofungin: Role of Distribution in Determining Pharmacokinetics in Plasma , 2004, Antimicrobial Agents and Chemotherapy.

[11]  D. Denning,et al.  Practice Guidelines for Diseases Caused by Aspergillus , 2000 .

[12]  S. Waldman,et al.  Potential for Interactions between Caspofungin and Nelfinavir or Rifampin , 2004, Antimicrobial Agents and Chemotherapy.

[13]  J. Sobel.  Practice guidelines for the treatment of fungal infections. For the Mycoses Study Group. Infectious Diseases Society of America. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[14]  J. Vazquez,et al.  Multiechinocandin- and Multiazole-Resistant Candida parapsilosis Isolates Serially Obtained during Therapy for Prosthetic Valve Endocarditis , 2005, Antimicrobial Agents and Chemotherapy.

[15]  A. Espinel-Ingroff.  Evaluation of Broth Microdilution Testing Parameters and Agar Diffusion Etest Procedure for Testing Susceptibilities of Aspergillus spp. to Caspofungin Acetate (MK-0991) , 2003, Journal of Clinical Microbiology.

[16]  M. Rinaldi,et al.  In Vitro Activity of the New Echinocandin Antifungal, MK-0991, against Common and Uncommon Clinical Isolates of Candida Species , 1999, European Journal of Clinical Microbiology and Infectious Diseases.

[17]  D. Denning,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group. Microbiology Standards of Care British Society for Medical Mycology Proposed Standards of Care for Patients with Invasive Fungal Infections , 2022 .

[18]  J. Smietana,et al.  A randomized double-blind study of caspofungin versus fluconazole for the treatment of esophageal candidiasis. , 2002, The American journal of medicine.

[19]  J. Rex,et al.  In Vitro Susceptibility Testing Methods for Caspofungin against Aspergillus andFusarium Isolates , 2001, Antimicrobial Agents and Chemotherapy.

[20]  D. MacCallum,et al.  Need for Early Antifungal Treatment Confirmed in Experimental Disseminated Candida albicans Infection , 2004, Antimicrobial Agents and Chemotherapy.

[21]  D. Schmatz,et al.  Quantitative PCR Assay To MeasureAspergillus fumigatus Burden in a Murine Model of Disseminated Aspergillosis: Demonstration of Efficacy of Caspofungin Acetate , 2001, Antimicrobial Agents and Chemotherapy.

[22]  M. Pfaller,et al.  Geographic Variation in the Susceptibilities of Invasive Isolates of Candida glabrata to Seven Systemically Active Antifungal Agents: a Global Assessment from the ARTEMIS Antifungal Surveillance Program Conducted in 2001 and 2002 , 2004, Journal of Clinical Microbiology.

[23]  A. Groll,et al.  Caspofungin: pharmacology, safety and therapeutic potential in superficial and invasive fungal infections , 2001, Expert opinion on investigational drugs.

[24]  E. Stone,et al.  Caspofungin: an echinocandin antifungal agent. , 2002, Clinical therapeutics.

[25]  D. Perlin,et al.  Caspofungin Uptake Is Mediated by a High-Affinity Transporter in Candida albicans , 2004, Antimicrobial Agents and Chemotherapy.

[26]  Xin Xu,et al.  HEPATIC UPTAKE OF THE NOVEL ANTIFUNGAL AGENT CASPOFUNGIN , 2005, Drug Metabolism and Disposition.

[27]  A. Saah,et al.  Salvage therapy with caspofungin for invasive aspergillosis: results from the caspofungin compassionate use study. , 2005, The Journal of infection.

[28]  D. Schmatz,et al.  The Antifungal Echinocandin Caspofungin Acetate Kills Growing Cells of Aspergillus fumigatus In Vitro , 2002, Antimicrobial Agents and Chemotherapy.

[29]  D. Figgitt,et al.  Caspofungin , 2012, Drugs.

[30]  E. Gotuzzo,et al.  A randomized double-blind study of caspofungin versus amphotericin for the treatment of candidal esophagitis. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[31]  J. Onishi,et al.  Morphological effects of lipopeptides against Aspergillus fumigatus correlate with activities against (1,3)-beta-D-glucan synthase , 1994, Antimicrobial Agents and Chemotherapy.

[32]  Richard Sylvester,et al.  Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. , 2002, The New England journal of medicine.

[33]  C. Girmenia,et al.  New antifungal drugs and new clinical trials: interpreting results may be difficult , 2003, Current opinion in oncology.

[34]  Thomas J Walsh,et al.  Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. , 2004, The New England journal of medicine.

[35]  T. Patterson,et al.  Efficacy of Caspofungin Alone and in Combination with Voriconazole in a Guinea Pig Model of Invasive Aspergillosis , 2002, Antimicrobial Agents and Chemotherapy.

[36]  M. Pfaller,et al.  Multicenter Comparison of the Sensititre YeastOne Colorimetric Antifungal Panel with the NCCLS M27-A2 Reference Method for Testing New Antifungal Agents against Clinical Isolates of Candida spp , 2004, Journal of Clinical Microbiology.

[37]  G. Papanicolaou,et al.  Retrospective study of the hepatic safety profile of patients concomitantly treated with caspofungin and cyclosporin A , 2004, Transplant infectious disease : an official journal of the Transplantation Society.

[38]  J. Sobel,et al.  Guidelines for treatment of candidiasis. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[39]  J. Sobel,et al.  In vitro activity of a new pneumocandin antifungal, L-743,872, against azole-susceptible and -resistant Candida species , 1997, Antimicrobial agents and chemotherapy.

[40]  C. Solano,et al.  Safety of the concomitant use of caspofungin and cyclosporin A in patients with invasive fungal infections , 2004, Bone Marrow Transplantation.

[41]  D. Pittet,et al.  Nosocomial bloodstream infections. Secular trends in rates, mortality, and contribution to total hospital deaths. , 1995, Archives of internal medicine.

[42]  M. Feldmesser.  New and Emerging Antifungal Agents , 2003, American journal of respiratory medicine : drugs, devices, and other interventions.

[43]  M. Pfaller,et al.  Further Standardization of Broth Microdilution Methodology for In Vitro Susceptibility Testing of Caspofungin against Candida Species by Use of an International Collection of More than 3,000 Clinical Isolates , 2004, Journal of Clinical Microbiology.

[44]  J. Perfect,et al.  Interlaboratory Comparison of Results of Susceptibility Testing with Caspofungin against Candida and Aspergillus Species , 2004, Journal of Clinical Microbiology.

[45]  D. Denning,et al.  Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[46]  Steve A. Hernandez,et al.  Caspofungin Resistance in Candida albicans: Correlating Clinical Outcome with Laboratory Susceptibility Testing of Three Isogenic Isolates Serially Obtained from a Patient with Progressive Candida Esophagitis , 2004, Antimicrobial Agents and Chemotherapy.

[47]  T. Sorrell,et al.  Guidelines for the use of antifungal agents in the treatment of invasive Candida and mould infections , 2004, Internal medicine journal.

[48]  M. Pfaller,et al.  Rare and Emerging Opportunistic Fungal Pathogens: Concern for Resistance beyond Candida albicans and Aspergillus fumigatus , 2004, Journal of Clinical Microbiology.

[49]  D. Stevens,et al.  Paradoxical Effect of Caspofungin: Reduced Activity against Candida albicans at High Drug Concentrations , 2004, Antimicrobial Agents and Chemotherapy.

[50]  T. Calandra,et al.  Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer , 2002 .

[51]  J. Smith,et al.  Evaluation of the echinocandin antifungal MK-0991 (L-743,872): efficacies in mouse models of disseminated aspergillosis, candidiasis, and cryptococcosis , 1997, Antimicrobial agents and chemotherapy.

[52]  Vincent H Tam,et al.  Pharmacodynamics of caspofungin in a murine model of invasive pulmonary aspergillosis: evidence of concentration-dependent activity. , 2004, The Journal of infectious diseases.

[53]  T. C. White,et al.  Studies of the paradoxical effect of caspofungin at high drug concentrations. , 2005, Diagnostic microbiology and infectious disease.

[54]  D. Denning.  Echinocandin antifungal drugs , 2003, The Lancet.

[55]  J. Baddley,et al.  Emerging fungal resistance. , 2004, Clinics in laboratory medicine.

[56]  B. Plikaytis,et al.  Trends in mortality due to invasive mycotic diseases in the United States, 1980-1997. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[57]  M. Pfaller,et al.  Activities of Caspofungin, Itraconazole, Posaconazole, Ravuconazole, Voriconazole, and Amphotericin B against 448 Recent Clinical Isolates of Filamentous Fungi , 2003, Journal of Clinical Microbiology.

[58]  J. Cleary,et al.  Antifungal Susceptibility Survey of 2,000 Bloodstream Candida Isolates in the United States , 2003, Antimicrobial Agents and Chemotherapy.

[59]  H. Einsele,et al.  Treatment of fungal infections in hematology and oncology , 2003, Annals of Hematology.

[60]  E. Manavathu,et al.  A comparative study of the post-antifungal effect (PAFE) of amphotericin B, triazoles and echinocandins on Aspergillus fumigatus and Candida albicans. , 2004, The Journal of antimicrobial chemotherapy.

[61]  J. Perfect,et al.  Comparison of caspofungin and amphotericin B for invasive candidiasis. , 2002, The New England journal of medicine.

[62]  J. Smith,et al.  In vitro preclinical evaluation studies with the echinocandin antifungal MK-0991 (L-743,872) , 1997, Antimicrobial agents and chemotherapy.

[63]  M. Pfaller,et al.  Caspofungin Activity against Clinical Isolates of Fluconazole-Resistant Candida , 2003, Journal of Clinical Microbiology.

[64]  T. Baillie,et al.  Metabolites of caspofungin acetate, a potent antifungal agent, in human plasma and urine. , 2000, Drug metabolism and disposition: the biological fate of chemicals.

[65]  M. Klepser,et al.  In vitro pharmacodynamic properties of MK-0991 determined by time-kill methods. , 1999, Diagnostic microbiology and infectious disease.

[66]  K. Holmes,et al.  Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America. , 2004, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[67]  S. Holland,et al.  Efficacies of Fluconazole, Caspofungin, and Amphotericin B in Candida glabrata-Infected p47phox−/− Knockout Mice , 2002, Antimicrobial Agents and Chemotherapy.

[68]  J. Rex,et al.  Glucan synthase inhibitors as antifungal agents. , 2001, Advances in protein chemistry.

[69]  J. Graybill,et al.  Treatment of murine Candida krusei or Candida glabrata infection with L-743,872 , 1997, Antimicrobial agents and chemotherapy.