Korean J Lab Med.  2006 Aug;26(4):275-281. 10.3343/kjlm.2006.26.4.275.

In Vitro Susceptibilities to Caspofungin and Micafungin of Clinical Isolates of Candida Species

• Choi HW
• Shin JH
• Lee JS
• Cho D
• Shin MG
• Suh SP
• Ryang DW

• KMID: 2238835
• DOI: http://doi.org/10.3343/kjlm.2006.26.4.275

Abstract

BACKGROUND: Caspofungin and micafungin are echinochandins with potent activities against Candida species. However, in vitro susceptibility to these agents of clinical Candida isolates in Korea has not been fully surveyed. We determined minimum inhibitory concentrations (MICs) of caspofungin and micafungin against clinical isolates of Candida species.
METHODS
A total of 107 blood isolates of Candida species (24 C. albicans, 25 C. tropicalis, 24 C. glabrata, 20 C. parapsilosis, 8 C. krusei, and 6 other Candida species) were tested by using the National Committee for Clinical Laboratory Standards M27-A2 broth microdilution methods. The in vitro antifungal activities and spectrum of caspofungin and micafungin were compared with those of amphotericin B, fluconazole, and itraconazole.
RESULTS
Caspofungin and micafungin exhibited a broad-spectrum activity against Candida species: caspofungin MIC ranged from 0.125 to 1 microgram/mL and micafungin MIC from < or =0.03 to 1 microgram/mL. C. albicans, C. tropicalis and C. glabrata showed high susceptibility to caspofungin (MIC90, 0.25 to 0.5 microgram/mL) and micafungin (MIC90 , < or =0.03 microgram/mL), whereas C. parapsilosis was less susceptible to both echinocandins (MIC90, 1 microgram/mL). The MIC50 for caspofungin, micafungin, amphotericin B, fluconazole, and itraconazole were 0.25, < or =0.03, 0.5, 1, and 0.125 microgram/mL, respectively. Caspofungin MIC50 of C. glabrata and C. krusei isolates with decreased susceptibility to azoles were 0.25 and 0.5 microgram/mL, respectively, and micafungin MIC50 were < or =0.03 and 0.125 microgram/mL, respectively.
CONCLUSIONS
These data showed an excellent in vitro activity of caspofungin and micafungin against clinical strains of Candida species, including isolates with reduced susceptibility to azoles.

Keyword

Caspofungin; Micafungin; Candida; Antifungal susceptibility testing

MeSH Terms

Amphotericin B
Azoles
Candida*
Danazol
Echinocandins
Fluconazole
Itraconazole
Korea
Microbial Sensitivity Tests
Amphotericin B
Azoles
Danazol
Echinocandins
Fluconazole
Itraconazole

Reference

References

1. Chae MJ, Shin JH, Cho D, Kee SJ, Kim SH, Shin MG, et al. Antifungal susceptibilities and distribution of Candida species recovered from blood cultures over an 8-year period. Korean J Lab Med. 2003; 23:329–35.

2. Kao AS, Brandt ME, Pruitt WR, Conn LA, Perkins BA, Stephens DS, et al. The epidemiology of candidemia in two United States cities: results of a population-based active surveillance. Clin Infect Dis. 1999; 29:1164–70.

3. Jarvis WR. Epidemiology of nosocomial fungal infections, with emphasis on Candida species. Clin Infect Dis. 1995; 20:1526–30.

4. Pfaller MA. Nosocomial candidiasis: emerging species, reservoirs, and modes of transmission. Clin Infect Dis. 1996; 22:S89–94.

5. Verduyn Lunel FM, Meis JF, Voss A. Nosocomial fungal infections: candidemia. Diagn Microbiol Infect Dis. 1999; 34:213–20.

6. Shin JH, Kee SJ, Shin MG, Kim SH, Shin DH, Lee SK, et al. Biofilm production by isolates of Candida species recovered from nonneutropenic patients: comparison of bloodstream isolates with isolates from other sources. J Clin Microbiol. 2002; 40:1244–8.

7. Thomas AH. Suggested mechanisms for the antimycotic activity of the polyene antibiotics and the N-substituted imidazoles. J Antimicrob Chemother. 1986; 17:269–79.

8. Ellis D. Amphotericin B: spectrum and resistance. J Antimicrob Chemother. 2002; 49:S7–10.

9. Hitchcock CA, Pye GW, Troke PF, Johnson EM, Warnock DW. Fluconazole resistance in Candida glabrata. Antimicrob Agents Chemother. 1993; 37:1962–5.

10. Rex JH, Rinaldi MG, Pfaller MA. Resistance of Candida species to fluconazole. Antimicrob Agents Chemother. 1995; 39:1–8.

11. Tawara S, Ikeda F, Maki K, Morishita Y, Otomo K, Teratani N, et al. In vitro activities of a new lipopeptide antifungal agent, FK463, against a variety of clinically important fungi. Antimicrob Agents Chemother. 2000; 44:57–62.

12. Denning DW. Echinocandin antifungal drugs. Lancet. 2003; 362:1142–51.

13. Onishi J, Meinz M, Thompson J, Curotto J, Dreikorn S, Rosenbach M, et al. Discovery of novel antifungal (1,3)-beta-D-glucan synthase inhibitors. Antimicrob Agents Chemother. 2000; 44:368–77.

14. Ostrosky-Zeichner L, Rex JH, Pappas PG, Hamill RJ, Larsen RA, Horowitz HW, et al. Antifungal susceptibility survey of 2,000 bloodstream Candida isolates in the United States. Antimicrob Agents Chemother. 2003; 47:3149–54.

15. Takakura S, Fujihara N, Saito T, Kudo T, Iinuma Y, Ichiyama S. National surveillance of species distribution in blood isolates of Candida species in Japan and their susceptibility to six antifungal agents including voriconazole and micafungin. J Antimicrob Chemother. 2004; 53:283–9.

16. Higashiyama Y, Kohno S. Micafungin: a therapeutic review. Expert Rev Anti Infect Ther. 2004; 2:345–55.

17. Keating GM, Jarvis B. Caspofungin. Drugs. 2001; 61:1121–9.

18. Kartsonis N, Killar J, Mixson L, Hoe CM, Sable C, Bartizal K, et al. Caspofungin susceptibility testing of isolates from patients with esophageal candidiasis or invasive candidiasis: Relationship of MIC to Treatment Outcome. Antimicrob Agents Chemother. 2005; 49:3616–23.

19. Pfaller MA, Diekema DJ, Messer SA, Hollis RJ, Jones RN. In vitro activities of caspofungin compared with those of fluconazole and itraconazole against 3,959 clinical isolates of Candida spp., Including 157 fluconazole-resistant isolates. Antimicrob Agents Chemother. 2003; 47:1068–71.

20. National Committee for Clinical Laboratory Standards. Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard M27-A2. Villanova, Pa: National Committee for Clinical Laboratory Standards;2002.

21. Arthington-Skaggs BA, Lee-Yang W, Ciblak MA, Frade JP, Brandt ME, Hajjeh RA, et al. Comparison of visual and spectrophotometric methods of broth microdilution MIC end point determination and evaluation of a sterol quantitation method for in vitro susceptibility testing of fluconazole and itraconazole against trailing and nontrailing Candida isolates. Antimicrob Agents Chemother. 2002; 46:2477–81.

22. Samra Z, Yardeni M, Peled N, Bishara J. Species distribution and antifungal susceptibility of Candida bloodstream isolates in a tertiary medical center in Israel. Eur J Clin Microbiol Infect Dis. 2005; 24:592–5.

23. Ikeda F, Wakai Y, Matsumoto S, Maki K, Watabe E, Tawara S, et al. Efficacy of FK463, a new lipopeptide antifungal agent, in mouse models of disseminated candidiasis and aspergillosis. Antimicrob Agents Chemother. 2000; 44:614–8.

24. Petraitis V, Petraitiene R, Groll AH, Roussillon K, Hemmings M, Lyman CA, et al. Comparative antifungal activities and plasma pharmacokinetics of micafungin (FK463) against disseminated candidiasis and invasive pulmonary aspergillosis in persistently neutropenic rabbits. Antimicrob Agents Chemother. 2002; 46:1857–69.

25. Pettengell K, Mynhardt J, Kluyts T, Lau W, Facklam D, Buell D; FK463 South African Study Group. Successful treatment of oesophageal candidiasis by micafungin: a novel systemic antifungal agent. Aliment Pharmacol Ther. 2004; 20:475–81.

26. Bartizal C, Odds FC. Influences of methodological variables on susceptibility testing of caspofungin against Candida species and Aspergillus fumigatus. Antimicrob Agents Chemother. 2003; 47:2100–7.

27. Klepser ME, Ernst EJ, Ernst ME, Messer SA, Pfaller MA. Evaluation of end points for antifungal susceptibility determinations with LY303366. Antimicrob Agents Chemother. 1998; 42:1387–91.

28. Pfaller MA, Messer SA, Boyken L, Rice C, Tendolkar S, Hollis RJ, 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. J Clin Microbiol. 2004; 42:3117–9.

29. Odds FC, Motyl M, Andrade R, Bille J, Canton E, Cuenca-Estrella M, et al. Interlaboratory comparison of results of susceptibility testing with caspofungin against Candida and Aspergillus species. J Clin Microbiol. 2004; 42:3475–82.

30. Cuenca-Estrella M, Rodriguez D, Almirante B, Morgan J, Planes AM, Almela M, et al. In vitro susceptibilities of bloodstream isolates of Candida species to six antifungal agents: results from a population-based active surveillance programme, Barcelona, Spain, 2002–2003. J Antimicrob Chemother. 2005; 55:194–9.

31. Laverdiere M, Hoban D, Restieri C, Habel F. In vitro activity of three new triazoles and one echinocandin against Candida bloodstream isolates from cancer patients. J Antimicrob Chemother. 2002; 50:119–23.