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Outcomes associated with routine systemic antifungal therapy in critically ill patients with Candida colonization

David Ferreira| Frederic Grenouillet| Gilles Blasco| Emmanuel Samain| Thierry Hénon| Alain Dussaucy| Laurence Millon| Mariette Mercier| Sebastien Pili-Floury
Original
Volume 41, Issue 6 / June , 2015

Pages 1077 - 1088

Abstract

Purpose

To assess the evolution of patient deep colonization by Candida spp. in a surgical ICU over an 8-year period.

Methods

This retrospective, observational study included all patients hospitalized for more than 2 days in a surgical and trauma ICU of a university hospital, from 2005 to 2012. Mycological samples were monitored weekly from five sites (oropharyngeal, rectal, gastric, tracheal and urinary). Preemptive fluconazole therapy was started in patients highly colonized with Candida albicans. The evolution in Candida spp. involved in the deep colonization sites distribution over the study period (main outcome measure, trend chi-square and time-series analysis), antifungal consumption, ICU-acquired candidemia and mortality were determined.

Results

Among the 3029 patients with ICU stay >48 h, 2651 had at least one set of mycological sampling. Thirty percent of the 31,171 samples were positive to Candida spp. Caspofungin consumption increased over the years, whereas fluconazole consumption decreased. No trend in C. albicans colonization was observed, after adjusting on colonization risk-factors. A significant increase of acquired C. glabrata colonization was observed, whereas the clearing of C. parapsilosis colonization significantly decreased. No significant shift of colonization to other Candida spp. and mortality was observed.

Conclusions

Preemptive strategy of antifungal drug prescriptions in highly colonized ICU patients induced an increase in C. glabrata colonization without significant shift of colonization to other Candida spp. in surgical ICU patients. However, the potential detrimental impact of fluconazole on Candida ecology in ICU and/or on Candida susceptibility to antifungal drugs should be considered, and deserves further studies.

Keywords

References

  1. Eggimann P, Garbino J, Pittet D (2003) Epidemiology of Candida species infections in critically ill non-immunosuppressed patients. Lancet Infect Dis 3:685–702
    • View reference on PubMed
    • View reference on publisher's website
  2. Bassetti M, Merelli M, Righi E et al (2013) Epidemiology, species distribution, antifungal susceptibility, and outcome of candidemia across five sites in Italy and Spain. J Clin Microbiol 51:4167–4172. doi:10.1128/jcm.01998-13
    • View reference on PubMed
    • View reference on publisher's website
  3. Pfaller MA, Diekema DJ (2007) Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 20:133–163. doi:10.1128/cmr.00029-06
    • View reference on PubMed
    • View reference on publisher's website
  4. Arendrup MC, Sulim S, Holm A, Nielsen L, Nielsen SD, Knudsen JD, Drenck NE, Christensen JJ, Johansen HK (2011) Diagnostic issues, clinical characteristics, and outcomes for patients with fungemia. J Clin Microbiol 49:3300–3308. doi:10.1128/jcm.00179-11
    • View reference on PubMed
    • View reference on publisher's website
  5. Puig-Asensio M, Peman J, Zaragoza R, Garnacho-Montero J, Martin-Mazuelos E, Cuenca-Estrella M, Almirante B (2014) Impact of therapeutic strategies on the prognosis of candidemia in the ICU. Crit Care Med 42:423–432. doi:10.1097/ccm.0000000000000221
    • View reference on publisher's website
  6. Pappas PG, Kauffman CA, Andes D et al (2009) Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 48:503–535. doi:10.1086/596757
    • View reference on PubMed
    • View reference on publisher's website
  7. Voss A, Hollis RJ, Pfaller MA, Wenzel RP, Doebbeling BN (1994) Investigation of the sequence of colonization and candidemia in nonneutropenic patients. J Clin Microbiol 32:975–980
    • View reference on PubMed
  8. Leon C, Ostrosky-Zeichner L, Schuster M (2014) What’s new in the clinical and diagnostic management of invasive candidiasis in critically ill patients. Intensive Care Med 40:808–819. doi:10.1007/s00134-014-3281-0
  9. Pittet D, Monod M, Suter PM, Frenk E, Auckenthaler R (1994) Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg 220:751–758
    • View reference on PubMed
    • View reference on publisher's website
  10. Eggimann P, Pittet D (2014) Candida colonization index and subsequent infection in critically ill surgical patients: 20 years later. Intensive Care Med 40:1429–1448. doi:10.1007/s00134-014-3355-z
  11. Bassetti M, Marchetti M, Chakrabarti A et al (2013) A research agenda on the management of intra-abdominal candidiasis: results from a consensus of multinational experts. Intensive Care Med 39:2092–2106. doi:10.1007/s00134-013-3109-3
  12. Cornely OA, Bassetti M, Calandra T et al (2012) ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 18(Suppl 7):19–37. doi:10.1111/1469-0691.12039
    • View reference on PubMed
    • View reference on publisher's website
  13. Piarroux R, Grenouillet F, Balvay P, Tran V, Blasco G, Millon L, Boillot A (2004) Assessment of preemptive treatment to prevent severe candidiasis in critically ill surgical patients. Crit Care Med 32:2443–2449
    • View reference on PubMed
    • View reference on publisher's website
  14. Paramythiotou E, Frantzeskaki F, Flevari A, Armaganidis A, Dimopoulos G (2014) Invasive fungal infections in the ICU: how to approach, how to treat. Molecules 19:1085–1119. doi:10.3390/molecules19011085
    • View reference on PubMed
    • View reference on publisher's website
  15. Eggimann P, Francioli P, Bille J et al (1999) Fluconazole prophylaxis prevents intra-abdominal candidiasis in high-risk surgical patients. Crit Care Med 27:1066–1072
    • View reference on PubMed
    • View reference on publisher's website
  16. Garbino J, Lew DP, Romand JA, Hugonnet S, Auckenthaler R, Pittet D (2002) Prevention of severe Candida infections in nonneutropenic, high-risk, critically ill patients: a randomized, double-blind, placebo-controlled trial in patients treated by selective digestive decontamination. Intensive Care Med 28:1708–1717. doi:10.1007/s00134-002-1540-y
  17. Pelz RK, Hendrix CW, Swoboda SM, Diener-West M, Merz WG, Hammond J, Lipsett PA (2001) Double-blind placebo-controlled trial of fluconazole to prevent Candidal infections in critically ill surgical patients. Ann Surg 233:542–548
    • View reference on PubMed
    • View reference on publisher's website
  18. Shorr AF, Chung K, Jackson WL, Waterman PE, Kollef MH (2005) Fluconazole prophylaxis in critically ill surgical patients: a meta-analysis. Crit Care Med 33:1928–1935
    • View reference on PubMed
    • View reference on publisher's website
  19. Schuster MG, Edwards JE Jr, Sobel JD et al (2008) Empirical fluconazole versus placebo for intensive care unit patients: a randomized trial. Ann Intern Med 149:83–90
    • View reference on PubMed
    • View reference on publisher's website
  20. Albert M, Williamson D, Muscedere J, Lauzier F, Rotstein C, Kanji S, Jiang X, Hall M, Heyland D (2014) Candida in the respiratory tract secretions of critically ill patients and the impact of antifungal treatment: a randomized placebo controlled pilot trial (CANTREAT study). Intensive Care Med 40:1313–1322. doi:10.1007/s00134-014-3352-2
  21. De Pascale G, Antonelli M (2014) Candida colonization of respiratory tract: to treat or not to treat, will we ever get an answer? Intensive Care Med 40:1381–1384. doi:10.1007/s00134-014-3364-y
  22. Ostrosky-Zeichner L, Shoham S, Vazquez J et al (2014) 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 58:1219–1226. doi:10.1093/cid/ciu074
    • View reference on PubMed
    • View reference on publisher's website
  23. Lortholary O, Desnos-Ollivier M, Sitbon K, Fontanet A, Bretagne S, Dromer F (2011) Recent exposure to caspofungin or fluconazole influences the epidemiology of candidemia: a prospective multicenter study involving 2,441 patients. Antimicrob Agents Chemother 55:532–538. doi:10.1128/aac.01128-10
    • View reference on PubMed
    • View reference on publisher's website
  24. Azoulay E, Dupont H, Tabah A, Lortholary O, Stahl JP, Francais A, Martin C, Guidet B, Timsit JF (2012) Systemic antifungal therapy in critically ill patients without invasive fungal infection*. Crit Care Med 40:813–822. doi:10.1097/CCM.0b013e318236f297
    • View reference on PubMed
    • View reference on publisher's website
  25. Gleason TG, May AK, Caparelli D, Farr BM, Sawyer RG (1997) Emerging evidence of selection of fluconazole-tolerant fungi in surgical intensive care units. Arch Surg 132:1197–1201 (discussion 1202)
    • View reference on PubMed
    • View reference on publisher's website
  26. Rocco TR, Reinert SE, Simms HH (2000) Effects of fluconazole administration in critically ill patients: analysis of bacterial and fungal resistance. Arch Surg 135:160–165
    • View reference on PubMed
    • View reference on publisher's website
  27. Dimopoulos G, Velegraki A, Falagas ME (2009) A 10-year survey of antifungal susceptibility of candidemia isolates from intensive care unit patients in Greece. Antimicrob Agents Chemother 53:1242–1244. doi:10.1128/aac.01368-08
    • View reference on PubMed
    • View reference on publisher's website
  28. Playford EG, Nimmo GR, Tilse M, Sorrell TC (2010) Increasing incidence of candidaemia: long-term epidemiological trends, Queensland, Australia, 1999–2008. J Hosp Infect 76:46–51. doi:10.1016/j.jhin.2010.01.022
    • View reference on PubMed
    • View reference on publisher's website
  29. WHO collaborating centre for drug statistics methodology (2014) Guidelines for ATC classification and DDD assignment, 2015. Oslo. http://www.whocc.no/atc_ddd_publications/guidelines/
  30. Wingard JR, Merz WG, Rinaldi MG, Johnson TR, Karp JE, Saral R (1991) Increase in Candidakrusei infection among patients with bone marrow transplantation and neutropenia treated prophylactically with fluconazole. N Engl J Med 325:1274–1277. doi:10.1056/nejm199110313251803
    • View reference on PubMed
    • View reference on publisher's website
  31. Fournier P, Schwebel C, Maubon D et al (2011) Antifungal use influences Candida species distribution and susceptibility in the intensive care unit. J Antimicrob Chemother 66:2880–2886. doi:10.1093/jac/dkr394
    • View reference on PubMed
    • View reference on publisher's website
  32. Kunova A, Trupl J, Demitrovicova A et al (1997) Eight-year surveillance of non-albicans Candida spp. in an oncology department prior to and after fluconazole had been introduced into antifungal prophylaxis. Microb Drug Resist 3:283–287
    • View reference on PubMed
    • View reference on publisher's website
  33. Montagna MT, Lovero G, Borghi E et al (2014) Candidemia in intensive care unit: a nationwide prospective observational survey (GISIA-3 study) and review of the European literature from 2000 through 2013. Eur Rev Med Pharmacol Sci 18:661–674
    • View reference on PubMed
  34. Maubon D, Garnaud C, Calandra T, Sanglard D, Cornet M (2014) Resistance of Candida spp. to antifungal drugs in the ICU: where are we now? Intensive Care Med 40:1241–1255. doi:10.1007/s00134-014-3404-7
  35. Leon C, Ruiz-Santana S, Saavedra P, Almirante B, Nolla-Salas J, Alvarez-Lerma F, Garnacho-Montero J, Leon MA (2006) A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization. Crit Care Med 34:730–737. doi:10.1097/01.ccm.0000202208.37364.7d
    • View reference on PubMed
    • View reference on publisher's website
  36. Tissot F, Lamoth F, Hauser PM et al (2013) beta-glucan antigenemia anticipates diagnosis of blood culture-negative intraabdominal candidiasis. Am J Respir Crit Care Med 188:1100–1109. doi:10.1164/rccm.201211-2069OC
    • View reference on PubMed
    • View reference on publisher's website
  37. Lortholary O, Renaudat C, Sitbon K, Madec Y, Denoeud-Ndam L, Wolff M, Fontanet A, Bretagne S, Dromer F (2014) Worrisome trends in incidence and mortality of candidemia in intensive care units (Paris area, 2002–2010). Intensive Care Med 40:1303–1312. doi:10.1007/s00134-014-3408-3
  38. Shemer R, Weissman Z, Hashman N, Kornitzer D (2001) A highly polymorphic degenerate microsatellite for molecular strain typing of Candidakrusei. Microbiology 147:2021–2028
    • View reference on PubMed
  39. Grenouillet F, Millon L, Bart JM, Roussel S, Biot I, Didier E, Ong AS, Piarroux R (2007) Multiple-locus variable-number tandem-repeat analysis for rapid typing of Candidaglabrata. J Clin Microbiol 45:3781–3784. doi:10.1128/jcm.01603-07
    • View reference on PubMed
    • View reference on publisher's website

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