ECHINOCANDINS - NEW ANTIFUNGAL AGENTS

Authors

  • Catalina Daniela STAN University of Medicine and Pharmacy “Grigore T. Popa” - Iaşi
  • Cristina TUCHILUS University of Medicine and Pharmacy “Grigore T. Popa” - Iaşi
  • C. I. STAN University of Medicine and Pharmacy “Grigore T. Popa” - Iaşi

Abstract

Over the past 10-15 years, the number of clinically available antifungal agents has increased substantially, due to rise in the number of invasive fungal infections, which are a real problem for specialists. Echinocandins are the new class of antifungal agents available for clinical use. This class comprises over 20 natural echinocandins and several semisynthetic ones. Natural echinocandins are not of clinical utility due to their toxicity and low water-solubility (which does not allow obtaining parenteral pharmaceutical forms), although they have good antifungal activity against Candida species. Consequently, semisynthetic echinocandins with minimal toxicity, good antifungal activity and high water-solubility were obtained. All echinocandins inhibit β-1,3-glucan-synthase, an essential component of the fungal cell wall. Echinocandins exhibit potent antifungal activity against key pathogenic fungi, including Candida species, Aspergillus species and Pneumocystis carinii. The available echinocandins lack in vitro activity against Cryptococcus neoformans. The semisynthetic echinocandins have great advantages, among which low toxicity, fast antifungal activity, favorable pharmacokinetics that allow once-daily administration. The echinocandins recently available for clinical use are: caspofungin, micafungin and anidulafungin.

Author Biographies

  • Catalina Daniela STAN, University of Medicine and Pharmacy “Grigore T. Popa” - Iaşi

    Faculty of Pharmacy
    Drug Industry and Pharmaceutical Biotechnology Department

  • Cristina TUCHILUS, University of Medicine and Pharmacy “Grigore T. Popa” - Iaşi

    Faculty of Medicine
    Microbiology Department

  • C. I. STAN, University of Medicine and Pharmacy “Grigore T. Popa” - Iaşi

    Faculty of Medicine                                                                                                                                                              Anatomy Department

References

1. Stan CD. Biotehnologii farmaceutice. Antibiotice. Iaşi: Editura Arslonga, 2007.
2. Denning DW. Echinocandins: a new class of antifungal. J Antimicrob Chemother 2002; 49: 889-891.
3. Walsh TJ. Echinocandins - An advance in the primary treatment of invasive candidiasis. New Eng J Med 2002; 347(25): 2070-2072.
4. Wisplinghoff H, Bischoff T, Tallent SM et al. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 2004; 39: 309-317.
5. Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 2007; 20: 133-163.
6. Garcia-Vidal C, Upton A, Kirby KA et al. Epidemiology of invasive mold infections in allogeneic stem cell transplant recipients: biological risk factors for infection according to time after transplantation. Clin Microbiol Rev 2008; 47: 1041-1050.
7. Clancy CJ. Huang H. Cheng S et al. Characterizing the effects of Caspofungin on Candida albicans, Candida parapsilosis and Candida glabrata isolates by simultaneous time-kill and postantifungal-effect experiments. Antimicrob Agents Chemother 2006; 50: 2569-2572.
8. Pound MW, Townsend ML, Drew RH. Echinocandin pharmacodynamics: review and clinical impli-cations. J Antimicrob Chemother 2010; 65(6): 1108-1118.
9. Chen SC, Slavin MA, Sorrell TC. Echinocandin antifungal drugs in fungal infections: a comparison. Drugs 2011; 71(1): 11-41.
10. Nagappan V, Boikov D, Vazquez JA. Assessment of the in vitro kinetic activity of Caspofungin against Candida glabrata. Antimicrob Agents Chemother 2010; 54(1): 522-525.
11. Rocha EMF, Garcia-Effron G, Park S, Perlin DS. A ser678Pro substitution in Fks1p confers resistance to echinocandin drugs in Aspergillus fumigates. Antimicrob Agents Chemother 2007; 51(11): 4174-4176.
12. Bizerra FC, Melo AS, Katchburian E et al. Changes in cell wall synthesis and ultrastructure during paradoxical growth effect of caspofungin on four different Candida species. Antimicrob Agents Chemother 2011; 55(1): 302-310.
13. Bouyer S, Imbert C, Daniault GE et al. Effect of caspofungin on trophozoites and cysts of three species of Acanthamoeba. J Antimicrob Chemother 2007; 59(1): 122-124.
14. Kofla G, Ruhnke M. Pharmacology and metabolism of anidulafungin, caspofungin and micafungin in the treatment of invasive candidosis- review of the literature. Eur J Med Res 2011; 16: 159-166.
15. Abruzzo GK, Gill CJ, Flattery AM et al. Efficacy of the echinocandin Caspofungin against dissemi-nated aspergillosis and candidiasis in cyclophosphamide-induced immunosuppressed mice. Antimicrob Agents Chemother 2000; 44: 2310-2318.
16. Villanueva A, Gotuzzo E, Arathoon EG et al. A randomized double-blind study of Caspofungin versus Fluconazole for the treatment of esophageal candidiasis. Am J Med 2002; 113: 294-299.
17. Mora-Duarte J, Betts R, Rotstein C et al. Comparison of Caspofungin and Amphotericin B for invasive candidiasis. New Eng J Med 2002; 347: 2020-2029.
18. Brown AL, Greig JR, Kartsonis NA et al. Caspofungin versus Amphotericin B for invasive candidia-sis. New Eng J Med 2003; 348: 1287-1288.
19. Glasmacher A, Cornely OA, Orlopp K et al. Caspofungin treatment in severely ill, immunocompro-mised patients: a case-documentation study of 118 patients. J Antimicrob Chemother 2006; 57(1): 127-134.
20. Kuse ER, Chetchotisakd P, da Cunha CA et al. Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet 2007; 369(9572): 1519-1527.
21. Wiederhold NP, Cota JM, Frei CR. Micafungin in the treatment of invasive candidiasis and invasive aspergillosis. Infect Drug Res 2008; 1: 63–77.
22. Mehta PA, Vinks AA, Filipovich A et al. Alternate-day micafungin antifungal prophylaxis in pediatric patients undergoing hematopoietic stem cell transplantation: a pharmacokinetic study. Biol Blood Marrow Transplant 2010; 16(10): 1458-1462.
23. Krause DS, Reinhardt J, Vazquez JA et al. Evaluating the safety and efficacy of Anidulafungin in invasive candidiasis and candidemia. Antimicrob Agents Chemother 2004; 48: 2021-2024.
24. Reboli AC, Rotstein C, Pappas PG et al. Anidulafungin versus Fluconazole for invasive candidiasis. New Eng J Med 2007; 356: 2472-2482.

Additional Files

Published

2018-05-09