Empirical anidulafungin therapy increases the treatment efficacy in invasive candidiasis: ERA study results (EraxisR in the Russian Federation)
https://doi.org/10.17650/1818-8346-2019-14-3-90-97
Abstract
The objective of the study was to evaluate the effectiveness of empirical therapy with anidulafungin in patients with invasive candidiasis in real clinical practice in Russian healthcare institutions.
Materials and methods. In a prospective multicenter (n = 23) ERA study in 2015–2017, 92 adult patients with invasive candidiasis were included. Depending on the type of anidulafungin administration, patients were divided into 2 comparable demographic groups. In the 1st group (n = 52; median age 50.5 ± 13.9 years (19–75 years); men ‒ 62 %), invasive candidiasis was microbiologically confirmed after the initiation of empirical anidulafungin therapy. In the 2nd group (n = 40; median age 47.15 ± 18.01 years (18–98 years); men — 65 %), patients received anidulafungin only after microbiological confirmation of invasive candidiasis. The groups did not statistically differ in risk factors, etiology of invasive candidiasis, the frequency of various organs damage, and also in APACHE II and SOFA score at the time of anidulafungin administration.
Results and conclusion. Overall survival on the 30th day after laboratory confirmation of invasive candidiasis was statistically significantly higher in the empirical therapy group (66 % vs 58 %; p = 0.04 416). In addition, the empirical anidulafungin therapy was lead to a significant decrease in the duration of stay in intensive care units (13.5 ± 19.7 days vs 21 ± 15 days) and the total treatment time (22 ± 18 days vs 29 ± 21 days).
Supporting agencies: The study was supported by Pfizer Innovation LLC
About the Author
N. N. Klimko
I. I. Mechnikov North-Western State Medical University, Ministry of Health of Russia
Russian Federation
Russian Federation
Department of Clinical Mycology, Allergology and Immunology
41 Kirochnaya St., Saint-Petersburg 191015
References
1. Klimko N.N., Kozlova Ya.I., Khostelidi S.N. et al. The prevalence of serious and chronic fungal diseases in Russian Federation on LIFE Program model. Problemy meditsinskoy mikologii = Problems of Medical Mycology 2014;16(1): 3–7. (In Russ.).
2. Bongomin F., Gago S., Oladele R.O., Denning D.W. Global and multi-national prevalence of fungal diseases – estimate precision. J Fung 2017;3(4):1–29. DOI: 10.3390/jof3040057.
3. Yakovlev S.V., Suvorova M.P., Beloborodov V.B. et al. Prevalence and clinical significance of nosocomial infections in Russian medical institutions: ERGINI study. Antibiotiki i khimioterapiya = Antibiotics and Chemotherapy 2016;61:5–6. (In Russ.).
4. Shagdileeva E.V., Raush E.R., Bogomolova T.S. et al. The results of the invasive candidiasis study in Saint-Petersburg. Problemy meditsinskoy mikologii = Problems of Medical Mycology 2015;17(2):148–9. (In Russ.).
5. Klimko N., Vasilyeva N, Chernenkaya T. et al. Invasive candidiasis in intensive care units: results of prospective multicenter study in Russia. ECCMID 2015.
6. Pfaller M.A., Boyken I., Hollis R.J. et al. In vitro activities of anidulafungin against more than 2,500 clinical isolates of Candida spp., including 315 isolates resistant to fluconazole. J Clin Microbiol 2005;43(11):5425–7. DOI: 10.1128/JCM.43.11.5425-5427.2005.
7. Reboli A.C., Rotstein C., Pappas P.G. et al. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med 2007;356(24):2472–82. DOI: 10.1056/NEJMoa066906.
8. Ruhnke M., Paiva J.A., Meersseman W. et al. Anidulafungin for the treatment of candidaemia/invasive candidiasis in selected critically ill patients. Clin Microbiol Infect 2012;18(7):680–7. DOI: 10.1111/j.1469-0691.2012.03784.x.
9. Reboli A.C., Shorr A.F., Rotstein C. et al. Anidulafungin compared with fluconazole for treatment of candidemia and other forms of invasive candidiasis caused by Candida albicans: a multivariate analysis of factors associated with improved outcome. BMC Infect Dis 2011;11:261. DOI: 10.1186/1471-2334-11-261.
10. Nucci M., Colombo A.L., Petti M. et al. An open-label study of anidulafungin for the treatment of candidaemia/invasive candidiasis in Latin America. Mycoses 2014;57(1):12–8. DOI: 10.1111/myc.12094.
11. Kullberg B., Vasquez J., Mootsikapun P. et al. Efficacy of anidulafungin in 539 patients with invasive candidiasis: a patientlevel pooled analysis of six clinical trials. J Antimicrob Chemother 2017;72(8):2368– 77. DOI: 10.1093/jac/dkx116.
12. Klimko N.N., Rubinchik V.E., Sobol M.M. et al. Prospective multicenter study results of anidulafungin therapy ‒ ERA (Eraxis in the Russian Federation). Problemy meditsinskoy mikologii = Problems of Medical Mycology 2018;(3):21‒5. (In Russ.).
13. Eggimann P, Ostrosky-Zeichner L. Early antifungal intervention strategies in ICU patients. Curr Opin Crit Care 2010; 16:465–9.
14. Ostrosky-Zeichner L., Kullberg B.J., Bow E.J. et al. Early treatment of candidemia in adults: a review. Med Mycol 2011;49(2):113–20. DOI: 10.3109/13693786.2010.512300.
15. Kollef M., Micek S., Hampton N. et al. Septic shock attributed to Candida infection: importance of empiric therapy and source control. Clin Infect Dis 2012;54(12):1739–46. DOI: 10.1093/cid/cis305.
16. Diagnosis and treatment of mycoses in intensive care units. Russian recommendations. Ed.: N.N. Klimko Moscow: Farmtek, 2015, P. 95. (In Russ.).
17. De Pauw B., Walsh T., Donnelly J. et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008;46(12):1813–21. DOI: 10.1086/588660.
18. Vasilyeva N.V., Raush E.R., Rudneva M.V. et al. Etiology of invasive candidosis agents in Russia: a multicenter epidemiological survey. Front Med 2018;12(1):84–91. DOI: 10.1007/s11684-017-0612-x.
19. Cornely O., Bassetti M., Calandra T. et al. ESCMID guideline for the diagnosis and management of candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 2012;18(Suppl 7):19–37. DOI: 10.1111/1469-0691.12039.
20. Pappas P.G., Kauffman C.A., David R. et al. Clinical practice guideline for the management of candidiasis: 2016 update by the infectious diseases society of America. Clin Infect Dis 2016;62(4):e1–50. DOI: 10.1093/cid/civ933.
21. Andes D.R., Safdar N., Baddley J.W. et al. Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patient-level quantitative review of randomized trials. Clin Infect Dis 2012;54(8):1110–22. DOI: 10.1093/cid/cis021.
22. Garey K.W., Rege M., Pai M.P. et al. Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis 2006;43(1):25–31. DOI: 10.1086/504810.
23. Farmakiotis D., Kyvernitakis A., Tarrand, J.J., Kontoyiannis D.P. Early initiation of appropriate treatment is associated with increased survival in cancer patients with Candida glabrata fungaemia: a potential benefit from infectious disease consultation. Clin Microbiol Infect 2015;21(1):79– 86. DOI: 10.1016/j.cmi.2014.07.006.
24. Wissing H., Ballus J., Bingold T.M. et al. Intensive care unit-related fluconazole use in Spain and Germany: patient characteristics and outcomes of a prospective multicenter longitudinal observational study. Infect Drug Resist 2013;6:15–25. DOI: 10.2147/IDR.S38945.
25. Leroy O., Bailly S., Gangneux J.P. et al. Systemic antifungal therapy for proven or suspected invasive candidiasis: the AmarCAND 2 study. Ann Intensive Care 2016;6(1):2. DOI: 10.1186/s13613-0150103-7.
26. Clancy C.J., Nguyen M.H. Finding the “missing 50 %” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis 2013;56(9):1284–92. DOI: 10.1093/cid/cit006.
27. Pfeiffer C.D., Samsa G.P., Schell W.A. et al. Quantitation of Candida CFU in initial positive blood cultures. J Clin Microbiol 2011;49(8):2879–83. DOI: 10.1128/JCM.00609-11.
28. León C., Ruiz-Santana S., Saavedra P. et al. Contribution of Candida biomarkers and DNA detection for the diagnosis of invasive candidiasis in ICU patients with severe abdominal conditions. Crit Care 2016;20(1):149. DOI: 10.1186/s13054016-1324-3.
29. Held J., Kohlberger I., Rappold E. et al. Comparison of (1-3)-b-D-glucan, mannan/ anti-mannan antibodies, and CandTec Candida antigen as serum biomarkers for candidemia. J Clin Microbiol 2013;51:1158–64.
30. Mikulska M., Calandra T., Sanguinetti M. et al. The use of mannan antigen and antimannan antibodies in the diagnosis of invasive candidiasis: recommendations from the Third European Conference on Infections in Leukemia. Crit Care 2010;14(6):R222. DOI: 10.1186/cc9365.
31. Karageorgopoulos D.E., Vouloumanou E.K., Ntziora F. et al. beta-D-glucan assay for the diagnosis of invasive fungal infections: a meta-analysis. Clin Infect Dis 2011;52(6):750–70. DOI: 10.1093/cid/ciq206.
32. Avni T., Leibovici L., Paul M. PCR diagnosis of invasive candidiasis: systematic review and meta-analysis. J Clin Microbiol 2011;49(2):665–70. DOI: 10.1128/JCM.01602-10.
33. Mylonakis E., Clancy C.J., OstroskyZeichner L. et al. T2magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial. Clin Infect Dis 2015;60(6):892–9. DOI: 10.1093/cid/ciu959.
34. Knitsch W., Vincent J.L., Utzolino S. et al. A randomized, placebo-controlled trial of preemptive antifungal therapy for the prevention of invasive candidiasis following gastrointestinal surgery for intra-abdominal infections. Clin Infect Dis 2015;61(11):1671–8. DOI: 10.1093/cid/civ707.
35. Ostrosky-Zeichner L., Shoham S., Vazquez J. et al. MSG-01: a randomized, double-blind, placebo-controlled trial of caspofungin prophylaxis followed by preemptive therapy for invasive candidiasis in high-risk adults in the critical care setting. Clin Infect Dis 2014;58(9):1219–26. DOI: 10.1093/cid/ciu074.
36. Hsu D.I., Nguyen M., Nguyen L. et al. A multicentre study to evaluate the impact of timing of caspofungin administration on outcomes of invasive candidiasis in non-immunocompromised adult patients. J Antimicrob Chemother 2010;65(8):1765–70. DOI: 10.1093/jac/dkq216.
37. Puig-Asensio M., Peman J., Zaragoza R. et al. Impact of therapeutic strategies on the prognosis of candidemia in the ICU. Crit Care Med 2014;42(6):1423–32. DOI: 10.1097/CCM.0000000000000221
Review
For citations:
Klimko N.N. Empirical anidulafungin therapy increases the treatment efficacy in invasive candidiasis: ERA study results (EraxisR in the Russian Federation). Oncohematology. 2019;14(3):90-97. (In Russ.) https://doi.org/10.17650/1818-8346-2019-14-3-90-97
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