Skip to main content
SpringerLink
Log in

Comparison of Killing Activity of Micafungin Against Six Candida Species Isolated from Peritoneal and Pleural Cavities in RPMI-1640, 10 and 30% Serum

  • Original Paper
  • Published:
Mycopathologia Aims and scope Submit manuscript

Abstract

Currently echinocandins are recommended in Candida peritonitis and pleuritis. We determined micafungin killing rates (k values) at therapeutic concentrations (0.25–2 mg/L) in RPMI-1640 with and without 10 and 30% serum mimicking in vivo conditions against six Candida species isolated from peritoneal and pleural fluid. In RPMI-1640, micafungin was fungicidal against C. glabrata, C. krusei and C. kefyr within 2.27 ± 10.68, 2.69 ± 10.29 and 3.10 ± 4.41 h, respectively, while was fungistatic against C. albicans, C. tropicalis and C. parapsilosis. In 10% serum, ≥ 0.25, ≥ 0.5, ≥ 0.5 and ≥ 1 mg/L micafungin produced positive k values (killing) for all C. albicans, C. glabrata, C. kefyr and C. krusei, respectively. In 30% serum, 2 mg/L micafungin produced killing against all C. albicans, C. glabrata and C. kefyr isolates, but was ineffective against C. krusei, C. parapsilosis and 2 of 3 C. tropicalis. Micafungin exposure should be increased against non-albicans species to eradicate fungi from peritoneal and pleural cavities.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Perlin DS. Echinocandin resistance, susceptibility testing and prophylaxis: implications for patient management. Drugs. 2014;74:1573–85.

    Article  CAS  Google Scholar 

  2. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical practice guideline for the management of candidiasis: update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:e1–50.

    Article  Google Scholar 

  3. Nasar A, Ryan L, Frei CR, Cota JM, Wiederhold NP. Influence of serum and albumin on echinocandin in vitro potency and pharmacodynamics. Curr Fungal Infect Rep. 2013;7:89–95.

    Article  Google Scholar 

  4. Saleh Q, Kovács R, Kardos G, Gesztelyi R, Kardos T, Bozó A, et al. Decreased killing activity of micafungin against Candida guilliermondii, Candida lusitaniae, and Candida kefyr in the presence of human serum. Microb Drug Resist. 2017;23:764–70.

    Article  CAS  Google Scholar 

  5. Földi R, Szilágyi J, Kardos G, Berényi R, Kovács R, Majoros L. Effect of 50% human serum on the killing activity of micafungin against eight Candida species using time-kill methodology. Diagn Microbiol Infect Dis. 2012;73:338–42.

    Article  Google Scholar 

  6. Kovács R, Gesztelyi R, Berényi R, Domán M, Kardos G, Juhász B, et al. Killing rates exerted by caspofungin in 50% serum and its correlation with in vivo efficacy in a neutropenic murine model against Candida krusei and C. inconspicua. J Med Microbiol. 2014;63:186–94.

    Article  Google Scholar 

  7. Földi R, Kovács R, Gesztelyi R, Kardos G, Berényi R, Juhász B, et al. Comparison of in vitro and in vivo efficacy of caspofungin against Candida parapsilosis, C. orthopsilosis, C. metapsilosis and C. albicans. Mycopathologia. 2012;174:311–8.

    Article  Google Scholar 

  8. Szilágyi J, Földi R, Bayegan S, Kardos G, Majoros L. 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. 2012;24:18–25.

    Article  Google Scholar 

  9. Kovács R, Saleh Q, Bozó A, Tóth Z, Gesztelyi R, Kardos T, Kardos G, Takacs I, Majoros L. Killing activity of micafungin against Candida albicans, C. dubliniensis and Candida africana in the presence of human serum. Mycopathologia. 2017;182:979–87.

    Article  Google Scholar 

  10. Yamada N, Kumada K, Kishino S, Mochizuki N, Ohno K, Ogura S. Distribution of micafungin in the tissue fluids of patients with invasive fungal infections. J Infect Chemother. 2011;17:731–4.

    Article  CAS  Google Scholar 

  11. Grau S, Luque S, Campillo N, Samsó E, Rodríguez U, García-Bernedo CA, et al. Plasma and peritoneal fluid population pharmacokinetics of micafungin in post-surgical patients with severe peritonitis. J Antimicrob Chemother. 2015;70:2854–61.

    Article  CAS  Google Scholar 

  12. García-de-Lorenzo A, Luque S, Grau S, Agrifoglio A, Cachafeiro L, Herrero E, et al. Comparative population plasma and tissue pharmacokinetics of micafungin in critically ill patients with severe burn injuries and patients with complicated intra-abdominal infection. Antimicrob Agents Chemother. 2016;60:5914–21.

    Article  Google Scholar 

  13. Zhao Y, Prideaux B, Nagasaki Y, Lee MH, Chen PY, Blanc L, et al. Unraveling drug penetration of echinocandin antifungals at the site of infection in an intra-abdominal abscess model. Antimicrob Agents Chemother. 2017;61:e01009–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Moriyama B, Ditullio M, Wilson E, Henning SA, Penzak SR, Danner RL, et al. Pharmacokinetics of anidulafungin in pleural fluid during the treatment of a patient with Candida empyema. Antimicrob Agents Chemother. 2011;55:2478–80.

    Article  CAS  Google Scholar 

  15. Clinical and Laboratory Standards Institute. 2008: Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard, 3rd ed. M27-A3. Clinical and Laboratory Standards Institute, Wayne, PA.

  16. Huang LL, Xia HH, Zhu SL. Ascitic fluid analysis in the differential diagnosis of ascites: focus on cirrhotic ascites. J Clin Transl Hepatol. 2014;2:58–64.

    PubMed  PubMed Central  Google Scholar 

  17. Ferreiro L, Porcel JM, Valdés L. Diagnosis and management of pleural transudates. Arch Bronconeumol. 2017;53:629–36.

    PubMed  Google Scholar 

  18. Porcel JM, Light RW. Diagnostic approach to pleural effusion in adults. Am Fam Physician. 2006;73:1211–20.

    PubMed  Google Scholar 

  19. Tarn AC, Lapworth R. Biochemical analysis of ascitic (peritoneal) fluid: what should we measure? Ann Clin Biochem. 2010;47:397–407.

    Article  CAS  Google Scholar 

  20. Wahidi MM, Willner DA, Snyder LD, Hardison JL, Chia JY, Palmer SM. Diagnosis and outcome of early pleural space infection following lung transplantation. Chest. 2009;135:484–91.

    Article  Google Scholar 

  21. Davies HE, Davies RJ, Davies CW, BTS Pleural Disease Guideline Group. Management of pleural infection in adults: British Thoracic Society Pleural Disease Guideline 2010. Thorax. 2010;65(Suppl 2):ii41–53.

    Article  Google Scholar 

  22. Srinivasnakshatri VK, Subramani P, Venkateshwaraprasad KN, Varma P. A fatal case of fungal empyema due to Candida krusei and Candida tropicalis: a rare occurrence with an atypical presentation. J Clin Diagn Res. 2014;8:DD01–2.

    PubMed  PubMed Central  Google Scholar 

  23. Pfaller MA, Castanheira M, Diekema DJ, Messer SA, Jones RN. Triazole and echinocandin MIC distributions with epidemiological cutoff values for differentiation of wild-type strains from non-wild-type strains of six uncommon species of Candida. J Clin Microbiol. 2011;49:3800–4.

    Article  CAS  Google Scholar 

  24. Vergidis P, Clancy CJ, Shields RK, Park SY, Wildfeuer BN, Simmons RL, et al. Intra-abdominal candidiasis: the importance of early source control and antifungal treatment. PLoS ONE. 2016;11:e0153247.

    Article  Google Scholar 

  25. Bassetti M, Righi E, Ansaldi F, Merelli M, Scarparo C, Antonelli M, Garnacho-Montero J, et al. A multicenter multinational study of abdominal candidiasis: epidemiology, outcomes and predictors of mortality. Intensive Care Med. 2015;41:1601–10.

    Article  Google Scholar 

  26. Montravers P, Mira JP, Gangneux JP, Leroy O, Lortholary O, The AmarCand study group. A multicentre study of antifungal strategies and outcome of Candida spp. peritonitis in intensive-care units. Clin Microbiol Infect. 2011;17:1061–7.

    Article  CAS  Google Scholar 

  27. Ko SC, Chen KY, Hsueh PR, Luh KT, Yang PC. Fungal empyema thoracis: an emerging clinical entity. Chest. 2000;117:1672–8.

    Article  CAS  Google Scholar 

  28. Lin HS, Chao CM, Lin WT, Lai CC. Candida empyema thoracis at a hospital in Taiwan. Surg Infect (Larchmt). 2014;15:540–3.

    Article  Google Scholar 

  29. Nigo M, Vial MR, Munita JM, Jiang Y, Tarrand J, Jimenez CA, et al. Fungal empyema thoracis in cancer patients. J Infect. 2016;72:615–21.

    Article  Google Scholar 

  30. Pemán J, Aguilar G, Valía JC, Salavert M, Navarro D, Zaragoza R, et al. Jávea consensus guidelines for the treatment of Candida peritonitis and other intra-abdominal fungal infections in non-neutropenic critically ill adult patients. Rev Iberoam Micol. 2017;34:130–42.

    Article  Google Scholar 

  31. Bordallo-Cardona MÁ, Escribano P, Marcos-Zambrano LJ, Díaz-García J, de la Pedrosa EG, Cantón R, et al. Low and constant micafungin concentrations may be sufficient to lead to resistance mutations in FKS2 gene of Candida glabrata. Med Mycol. 2017. https://doi.org/10.1093/mmy/myx124.

    Article  Google Scholar 

  32. Shields RK, Nguyen MH, Press EG, Clancy CJ. Abdominal candidiasis is a hidden reservoir of echinocandin resistance. Antimicrob Agents Chemother. 2014;58:7601–5.

    Article  Google Scholar 

  33. Fekkar A, Meyer I, Brossas JY, Dannaoui E, Palous M, Uzunov M, et al. Rapid emergence of echinocandin resistance during Candida kefyr fungemia treatment with caspofungin. Antimicrob Agents Chemother. 2013;57:2380–2.

    Article  CAS  Google Scholar 

  34. Xiao M, Fan X, Hou X, Chen SC, Wang H, Kong F, et al. Clinical characteristics of the first cases of invasive candidiasis in China due to pan-echinocandin-resistant Candida tropicalis and Candida glabrata isolates with delineation of their resistance mechanisms. Infect Drug Resist. 2018;11:155–61.

    Article  Google Scholar 

Download references

Acknowledgements

L. Majoros received conference travel grants from MSD, Astellas and Pfizer.

Author information

Authors and Affiliations

  1. Faculty of Medicine, Medical Microbiology, University of Debrecen, Nagyerdei krt. 98, Debrecen, 4032, Hungary

    Zoltán Tóth, Tamás Kardos, Renátó Kovács, Gábor Kardos, Fruzsina Nagy, Eszter Prépost & László Majoros

  2. Department of Pulmonology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

    Tamás Kardos

  3. Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary

    Renátó Kovács

  4. Department of Infectology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

    Zsolt Barta

  5. Faculty of Health, University of Miskolc, Miskolc, Hungary

    István Takacs

Authors
  1. Zoltán Tóth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tamás Kardos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Renátó Kovács
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gábor Kardos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fruzsina Nagy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eszter Prépost
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zsolt Barta
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. István Takacs
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. László Majoros
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to László Majoros.

Additional information

Handling Editor: Ana Alastruey-Izquierdo.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tóth, Z., Kardos, T., Kovács, R. et al. Comparison of Killing Activity of Micafungin Against Six Candida Species Isolated from Peritoneal and Pleural Cavities in RPMI-1640, 10 and 30% Serum. Mycopathologia 183, 905–912 (2018). https://doi.org/10.1007/s11046-018-0302-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11046-018-0302-5

Keywords

Search

Navigation