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Rita Wilson Dib
Ray Hachem
Anne-Marie P Chaftari
Issam I Raad


Candidemia, non-nuetropenic patients, intravenous treatment


In this review we have analyzed the available literature pertaining to the total duration of intravenous (IV) therapy and the appropriate timing of step down to oral therapy in the management of candidemia. Overview of the guidelines and literature seem to indicate that a minimum of 14 days of antifungal therapy is required in the treatment of candidemia without deep seated infection. However, this was never based on evidence. Furthermore, step down to oral therapy seems to be dependent on the clinical stability criteria of the patient with candidemia after 4 to 7 days of IV therapy.  Further studies are required to evaluate the appropriate total duration of IV therapy, appropriate timing of step down to oral therapy and to validate the clinical criteria that would allow the switch to happen.


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1. Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302(21):2323-9. doi: 10.1001/jama.2009.1754. PubMed PMID: 19952319.

2. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. New Engl J Med. 2003;348(16):1546-54. doi: DOI 10.1056/NEJMoa022139. PubMed PMID: WOS:000182248900005.

3. Gudlaugsson O, Gillespie S, Lee K, Vande Berg J, Hu J, Messer S, et al. Attributable mortality of nosocomial candidemia, revisited. Clin Infect Dis. 2003;37(9):1172-7. doi: 10.1086/378745. PubMed PMID: 14557960.

4. Pappas PG, Rex JH, Lee J, Hamill RJ, Larsen RA, Powderly W, et al. A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin Infect Dis. 2003;37(5):634-43. doi: 10.1086/376906. PubMed PMID: 12942393.

5. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, 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. PubMed PMID: 26679628; PubMed Central PMCID: PMCPMC4725385.

6. Kuse ER, Chetchotisakd P, da Cunha CA, Ruhnke M, Barrios C, Raghunadharao D, et al. Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet. 2007;369(9572):1519-27. doi: 10.1016/S0140-6736(07)60605-9. PubMed PMID: 17482982.

7. Rex JH, Bennett JE, Sugar AM, Pappas PG, Vanderhorst CM, Edwards JE, et al. A Randomized Trial Comparing Fluconazole with Amphotericin-B for the Treatment of Candidemia in Patients without Neutropenia. New Engl J Med. 1994;331(20):1325-30. doi: Doi 10.1056/Nejm199411173312001. PubMed PMID: WOS:A1994PR21600001.

8. Pappas PG, Rotstein CM, Betts RF, Nucci M, Talwar D, De Waele JJ, et al. Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. Clin Infect Dis. 2007;45(7):883-93. doi: 10.1086/520980. PubMed PMID: 17806055.

9. Betts RF, Nucci M, Talwar D, Gareca M, Queiroz-Telles F, Bedimo RJ, et al. 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. 2009;48(12):1676-84. doi: 10.1086/598933. PubMed PMID: 19419331.

10. Morrell M, Fraser VJ, Kollef MH. Delaying the empiric treatment of Candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Ch. 2005;49(9):3640-5. doi: 10.1128/Aac.49.9.3640-3645.2005. PubMed PMID: WOS:000231542900006.

11. Oude Lashof AM, Rothova A, Sobel JD, Ruhnke M, Pappas PG, Viscoli C, et al. Ocular manifestations of candidemia. Clin Infect Dis. 2011;53(3):262-8. doi: 10.1093/cid/cir355. PubMed PMID: 21765074.

12. Blennow O, Tallstedt L, Hedquist B, Gardlund B. Duration of treatment for candidemia and risk for late-onset ocular candidiasis. Infection. 2013;41(1):129-34. doi: 10.1007/s15010-012-0369-8. PubMed PMID: 23212461.

13. Cornely OA, Bassetti M, Calandra T, Garbino J, Kullberg BJ, Lortholary O, 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. PubMed PMID: 23137135.

14. Reboli AC, Rotstein C, Pappas PG, Chapman SW, Kett DH, Kumar D, et al. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med. 2007;356(24):2472-82. doi: 10.1056/NEJMoa066906. PubMed PMID: 17568028.

15. Nucci M, Colombo AL, Petti M, Magana M, Abreu P, Schlamm HT, 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. PubMed PMID: 23710653.

16. Vazquez J, Reboli AC, Pappas PG, Patterson TF, Reinhardt J, Chin-Hong P, et al. Evaluation of an early step-down strategy from intravenous anidulafungin to oral azole therapy for the treatment of candidemia and other forms of invasive candidiasis: results from an open-label trial. BMC Infect Dis. 2014;14:97. doi: 10.1186/1471-2334-14-97. PubMed PMID: 24559321; PubMed Central PMCID: PMCPMC3944438.

17. Kullberg BJ, Sobel JD, Ruhnke M, Pappas PG, Viscoli C, Rex JH, et al. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial. Lancet. 2005;366(9495):1435-42. doi: 10.1016/S0140-6736(05)67490-9. PubMed PMID: 16243088.

18. Glockner A, Cornely OA. Practical considerations on current
guidelines for the management of non-neutropenic adult patients with candidaemia. Mycoses. 2013;56(1):11-20. doi: 10.1111/j.1439-0507.2012.02208.x. PubMed PMID: 22574925.

19. Zaoutis TE, Argon J, Chu J, Berlin JA, Walsh TJ, Feudtner C. The
epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin Infect Dis. 2005;41(9):1232-9. doi: 10.1086/496922. PubMed PMID: 16206095.

20. Reboli AC, Shorr AF, Rotstein C, Pappas PG, Kett DH, Schlamm HT, 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. PubMed PMID: 21961941; PubMed Central PMCID: PMCPMC3203347.

21. Pfaller MA, Boyken L, Hollis RJ, Kroeger J, Messer SA, Tendolkar S, et al. In vitro susceptibility of invasive isolates of Candida spp. to anidulafungin, caspofungin, and micafungin: six years of global surveillance. J Clin Microbiol. 2008;46(1):150-6. doi: 10.1128/JCM.01901-07. PubMed PMID: 18032613; PubMed Central PMCID: PMCPMC2224271.

22. Pfaller MA, Boyken L, Hollis RJ, Kroeger J, Messer SA, Tendolkar S, et al. Wild-type MIC distributions and epidemiological cutoff values for the echinocandins and Candida spp. J Clin Microbiol. 2010;48(1):52-6. doi: 10.1128/JCM.01590-09. PubMed PMID: 19923478; PubMed Central PMCID: PMCPMC2812271.

23. Mora-Duarte J, Betts R, Rotstein C, Colombo AL, Thompson-Moya L, Smietana J, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002;347(25):2020-9. doi: 10.1056/NEJMoa021585. PubMed PMID: 12490683.

24. Bassetti M, Righi E, Montravers P, Cornely OA. What has changed in the treatment of invasive candidiasis? A look at the past 10 years and ahead. J Antimicrob Chemother. 2018;73(suppl_1):i14-i25. doi: 10.1093/jac/dkx445. PubMed PMID: 29304208.

25. Kontoyiannis DP, Vaziri I, Hanna HA, Boktour M, Thornby J, Hachem R, et al. Risk Factors for Candida tropicalis fungemia in patients with cancer. Clin Infect Dis. 2001;33(10):1676-81. doi: 10.1086/323812. PubMed PMID: 11568858.

26. Farmakiotis D, Tarrand JJ, Kontoyiannis DP. Drug-resistant Candida glabrata infection in cancer patients. Emerg Infect Dis. 2014;20(11):1833-40. doi: 10.3201/eid2011.140685. PubMed PMID: 25340258; PubMed Central PMCID: PMCPMC4214312.

27. Masterton RG, Casamayor M, Musingarimi P, van Engen A, Zinck R, Odufowora-Sita O, et al. De-escalation from micafungin is a cost-effective alternative to traditional escalation from fluconazole in the treatment of patients with systemic Candida infections. J Med Econ. 2013;16(11):1344-56. doi: 10.3111/13696998.2013.839948. PubMed PMID: 24003830.

28. Chen D, Wan X, Kruger E, Chen C, Yue X, Wang L, et al. Cost-effectiveness of de-escalation from micafungin versus escalation from fluconazole for invasive candidiasis in China. J Med Econ. 2018;21(3):301-7. doi: 10.1080/13696998.2017.1417312. PubMed PMID: 29303621.

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