1887

Abstract

Killing rates () of 1–32 µg ml caspofungin were determined in RPMI-1640 and in 50 % serum using time–kill methodology against three (MICs of all three isolates 0.25 µg ml in RPMI-1640 and 2 µg ml in serum) and three clinical isolates (MIC ranges 0.06–0.12 µg ml in RPMI-1640 and 0.25–0.5 µg ml in serum), against ATCC 6258 and against one isolate that was resistant to echinocandins (MIC 8 µg ml in RPMI-1640 and 32 µg ml in serum). In RPMI-1640, the highest mean values were observed at 4 (−1.05 h) and 16 (−0.27 h) μg ml caspofungin for and clinical isolates, respectively. In 50 % serum, mean value ranges at 1–32 and 4–32 µg ml concentrations for and were −1.12 to −1.44 and −0.42 to −0.57 h, respectively. While values against in RPMI-1640 and 50 % serum were comparable, serum significantly increased the killing rate against (<0.0003 for all tested concentrations). In a neutropenic murine model, daily caspofungin at 1, 2, 3, 5 and 15 mg kg significantly decreased the fungal tissue burden of in the kidneys (<0.05–0.001). Against , doses of 3, 5 and 15 mg kg caspofungin were effective (<0.05–0.01). All effective doses were comparably efficacious for both species. Only the highest 15 mg kg caspofungin dose was effective even against the echinocandin-resistant isolate. In 50 % serum, killing was concentration independent at effective concentrations (≥4 and ≥1 µg ml for and , respectively), suggesting that the efficacy of dose escalation is questionable. These results were also supported by the murine model.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.066381-0
2014-02-01
2019-12-11
Loading full text...

Full text loading...

/deliver/fulltext/jmm/63/2/186.html?itemId=/content/journal/jmm/10.1099/jmm.0.066381-0&mimeType=html&fmt=ahah

References

  1. Andes D. , Diekema D. J. , Pfaller M. A. , Bohrmuller J. , Marchillo K. , Lepak A. . ( 2010; ). In vivo comparison of the pharmacodynamic targets for echinocandin drugs against Candida species. . Antimicrob Agents Chemother 54:, 2497–2506. [CrossRef] [PubMed]
    [Google Scholar]
  2. Betts R. F. , Nucci M. , Talwar D. , Gareca M. , Queiroz-Telles F. , Bedimo R. J. , Herbrecht R. , Ruiz-Palacios G. , Young J. A. . & other authors ( 2009; ). A multicenter, double-blind trial of a high-dose caspofungin treatment regimen versus a standard caspofungin treatment regimen for adult patients with invasive candidiasis. . Clin Infect Dis 48:, 1676–1684. [CrossRef] [PubMed]
    [Google Scholar]
  3. Cantón E. , Pemán J. , Valentín A. , Espinel-Ingroff A. , Gobernado M. . ( 2009; ). In vitro activities of echinocandins against Candida krusei determined by three methods: MIC and minimal fungicidal concentration measurements and time-kill studies. . Antimicrob Agents Chemother 53:, 3108–3111. [CrossRef] [PubMed]
    [Google Scholar]
  4. Cantón E. , Espinel-Ingroff A. , Pemán J. , del Castillo L. . ( 2010; ). In vitro fungicidal activities of echinocandins against Candida metapsilosis, C. orthopsilosis, and C. parapsilosis evaluated by time-kill studies. . Antimicrob Agents Chemother 54:, 2194–2197. [CrossRef] [PubMed]
    [Google Scholar]
  5. Chen S. C. , Slavin M. A. , Sorrell T. C. . ( 2011; ). Echinocandin antifungal drugs in fungal infections: a comparison. . Drugs 71:, 11–41. [CrossRef] [PubMed]
    [Google Scholar]
  6. Chiller T. , Farrokhshad K. , Brummer E. , Stevens D. A. . ( 2000; ). Influence of human sera on the in vitro activity of the echinocandin caspofungin (MK-0991) against Aspergillus fumigatus . . Antimicrob Agents Chemother 44:, 3302–3305. [CrossRef] [PubMed]
    [Google Scholar]
  7. CLSI ( 2008; ). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard, 3rd edn, M27-A3. . Wayne, PA:: Clinical and Laboratory Standards Institute;.
  8. Cornely O. A. , Vehreschild J. J. , Vehreschild M. J. , Würthwein G. , Arenz D. , Schwartz S. , Heussel C. P. , Silling G. , Mahne M. . & other authors ( 2011; ). Phase II dose escalation study of caspofungin for invasive Aspergillosis . . Antimicrob Agents Chemother 55:, 5798–5803. [CrossRef] [PubMed]
    [Google Scholar]
  9. Földi R. , Szilágyi J. , Kardos G. , Berényi R. , Kovács R. , Majoros L. . ( 2012a; ). Effect of 50% human serum on the killing activity of micafungin against eight Candida species using time-kill methodology. . Diagn Microbiol Infect Dis 73:, 338–342. [CrossRef] [PubMed]
    [Google Scholar]
  10. Földi R. , Kovács R. , Gesztelyi R. , Kardos G. , Berényi R. , Juhász B. , Szilágyi J. , Mózes J. , Majoros L. . ( 2012b; ). Comparison of in vitro and vivo efficacy of caspofungin against Candida parapsilosis, C. orthopsilosis, C. metapsilosis and C. albicans . . Mycopathologia 174:, 311–318. [CrossRef] [PubMed]
    [Google Scholar]
  11. Garcia-Effron G. S. , Park S. , Perlin D. S. . ( 2011; ). Improved detection of Candida sp. fks hot spot mutants by using the method of the CLSI M27-A3 document with the addition of bovine serum albumin. . Antimicrob Agents Chemother 55:, 2245–2255. [CrossRef] [PubMed]
    [Google Scholar]
  12. Ishikawa J. , Maeda T. , Matsumura I. , Yasumi M. , Ujiie H. , Masaie H. , Nakazawa T. , Mochizuki N. , Kishino S. , Kanakura Y. . ( 2009; ). Antifungal activity of micafungin in serum. . Antimicrob Agents Chemother 53:, 4559–4562. [CrossRef] [PubMed]
    [Google Scholar]
  13. Majoros L. , Kardos G. , Belák Á. , Maráz A. , Asztalos L. , Csánky E. , Barta Z. , Szabó B. . ( 2003; ). Restriction enzyme analysis of ribosomal DNA shows that Candida inconspicua clinical isolates can be misidentified as Candida norvegensis with traditional diagnostic procedures. . J Clin Microbiol 41:, 5250–5253. [CrossRef] [PubMed]
    [Google Scholar]
  14. Mukherjee P. K. , Sheehan D. , Puzniak L. , Schlamm H. , Ghannoum M. A. . ( 2011; ). Echinocandins: are they all the same. ? J Chemother 23:, 319–325.[PubMed] [CrossRef]
    [Google Scholar]
  15. Nasar A. , Ryan L. , Frei C. R. , Cota J. M. , Wiederhold N. P. . ( 2013; ). Influence of serum and albumin on echinocandin in vitro potency and pharmacodynamics. . Curr Fungal Infect Rep 7:, 89–95. [CrossRef]
    [Google Scholar]
  16. Odabasi Z. , Paetznick V. , Rex J. H. , Ostrosky-Zeichner L. . ( 2007; ). Effects of serum on in vitro susceptibility testing of echinocandins. . Antimicrob Agents Chemother 51:, 4214–4216. [CrossRef] [PubMed]
    [Google Scholar]
  17. Paderu P. , Garcia-Effron G. , Balashov S. , Delmas G. , Park S. , Perlin D. S. . ( 2007; ). Serum differentially alters the antifungal properties of echinocandin drugs. . Antimicrob Agents Chemother 51:, 2253–2256. [CrossRef] [PubMed]
    [Google Scholar]
  18. Pappas P. G. , Rotstein C. M. F. , Betts R. F. , Nucci M. , Talwar D. , De Waele J. J. , Vazquez J. A. , Dupont B. F. , Horn D. L. . & other authors ( 2007; ). Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. . Clin Infect Dis 45:, 883–893. [CrossRef] [PubMed]
    [Google Scholar]
  19. Pappas P. G. , Kauffman C. A. , Andes D. , Benjamin D. K. Jr , Calandra T. F. , Edwards J. E. Jr , Filler S. G. , Fisher J. F. , Kullberg B. J. . & other authors ( 2009; ). Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. . Clin Infect Dis 48:, 503–535. [CrossRef] [PubMed]
    [Google Scholar]
  20. Pfaller M. A. , Diekema D. J. . ( 2007; ). Epidemiology of invasive candidiasis: a persistent public health problem. . Clin Microbiol Rev 20:, 133–163. [CrossRef] [PubMed]
    [Google Scholar]
  21. Pfaller M. A. , Diekema D. J. , Andes D. , Arendrup M. C. , Brown S. D. , Lockhart S. R. , Motyl M. , Perlin D. S. . CLSI Subcommittee for Antifungal Testing ( 2011; ). Clinical breakpoints for the echinocandins and Candida revisited: integration of molecular, clinical, and microbiological data to arrive at species-specific interpretive criteria. . Drug Resist Updat 14:, 164–176. [CrossRef] [PubMed]
    [Google Scholar]
  22. Pfaller M. A. , Neofytos D. , Diekema D. , Azie N. , Meier-Kriesche H. U. , Quan S. P. , Horn D. . ( 2012; ). Epidemiology and outcomes of candidemia in 3648 patients: data from the Prospective Antifungal Therapy (PATH Alliance®) registry, 2004–2008. . Diagn Microbiol Infect Dis 74:, 323–331. [CrossRef] [PubMed]
    [Google Scholar]
  23. Sirohi B. , Powles R. L. , Chopra R. , Russell N. , Byrne J. L. , Prentice H. G. , Potter M. , Koblinger S. . ( 2006; ). A study to determine the safety profile and maximum tolerated dose of micafungin (FK463) in patients undergoing haematopoietic stem cell transplantation. . Bone Marrow Transplant 38:, 47–51. [CrossRef] [PubMed]
    [Google Scholar]
  24. Spreghini E. , Orlando F. , Tavanti A. , Senesi S. , Giannini D. , Manso E. , Barchiesi F. . ( 2012; ). In vitro and in vivo effects of echinocandins against Candida parapsilosis sensu stricto, Candida orthopsilosis and Candida metapsilosis . . J Antimicrob Chemother 67:, 2195–2202. [CrossRef] [PubMed]
    [Google Scholar]
  25. Szilágyi J. , Földi R. , Bayegan S. , Kardos G. , Majoros L. . ( 2012a; ). Effect of nikkomycin Z and 50% human serum on the killing activity of high-concentration caspofungin against Candida species using time-kill methodology. . J Chemother 24:, 18–25. [CrossRef] [PubMed]
    [Google Scholar]
  26. Szilágyi J. , Földi R. , Gesztelyi R. , Bayegan S. , Kardos G. , Juhász B. , Majoros L. . ( 2012b; ). Comparison of the kidney fungal burden in experimental disseminated candidiasis by species of the Candida parapsilosis complex treated with fluconazole, amphotericin B and caspofungin in a temporarily neutropenic murine model. . Chemotherapy 58:, 159–164. [CrossRef] [PubMed]
    [Google Scholar]
  27. Tortorano A. M. , Prigitano A. , Dho G. , Grancini A. , Passera M. . ECMM-FIMUA Study Group ( 2012; ). Antifungal susceptibility profiles of Candida isolates from a prospective survey of invasive fungal infections in Italian intensive care units. . J Med Microbiol 61:, 389–393. [CrossRef] [PubMed]
    [Google Scholar]
  28. Wiederhold N. P. , Najvar L. K. , Bocanegra R. , Molina D. , Olivo M. , Graybill J. R. . ( 2007; ). In vivo efficacy of anidulafungin and caspofungin against Candida glabrata and association with in vitro potency in the presence of sera. . Antimicrob Agents Chemother 51:, 1616–1620. [CrossRef] [PubMed]
    [Google Scholar]
  29. Wiederhold N. P. , Najvar L. K. , Bocanegra R. A. , Kirkpatrick W. R. , Patterson T. F. . ( 2011; ). Caspofungin dose escalation for invasive candidiasis due to resistant Candida albicans . . Antimicrob Agents Chemother 55:, 3254–3260. [CrossRef] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.066381-0
Loading
/content/journal/jmm/10.1099/jmm.0.066381-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error