Skip to main content
Top
Published in: Annals of Intensive Care 1/2016

Open Access 01-12-2016 | Research

Systemic antifungal therapy for proven or suspected invasive candidiasis: the AmarCAND 2 study

Authors: Olivier Leroy, Sébastien Bailly, Jean-Pierre Gangneux, Jean-Paul Mira, Patrick Devos, Hervé Dupont, Philippe Montravers, Pierre-François Perrigault, Jean-Michel Constantin, Didier Guillemot, Elie Azoulay, Olivier Lortholary, Caroline Bensoussan, Jean-François Timsit, AmarCAND2 study group

Published in: Annals of Intensive Care | Issue 1/2016

Login to get access

Abstract

Background

In the context of recent guidelines on invasive candidiasis (IC), how French intensive care units (ICUs) are managing IC?

Methods

This is a prospective observational multicenter cohort study. During 1 year (2012–2013), 87 French ICUs enrolled consecutive patients with suspected or proven IC (SIC or PIC) and receiving systemic antifungal therapy (SAT). Data were collected up to 28 days after inclusion.

Results

We studied 835 patients, 291 with PIC and 544 with SIC. At SAT initiation, patients with SIC were significantly more severe (SAPS II 50.1 ± 18.7 vs. 46.2 ± 18.0). Severe sepsis or septic shock prompted to initiate empiric SAT in 70 % of SIC. Within 4 days in median, the initial SAT was modified in 49 % of patients with PIC vs. 33 % patients with SIC. Modifications were most often motivated by mycological results, and de-escalation was the most frequent change. Regarding compliance to IC management guidelines, echinocandin was used for 182 (62.5 %) patients with PIC, and 287 (52.7 %) of those with SIC; central venous catheter was removed in 87 (54.3 %) of patients with candidaemia, and 43 of the remaining patients received echinocandin; and de-escalation was undertaken after 5 days of SAT in 142 patients, after 10 days in 13 patients. As 20.6 % of SIC were secondarily documented, 403/835 (48 %) patients had finally a proven IC. Candida albicans was the main pathogen (65.3 %), then Candida glabrata (15.9 %). The 28-day mortality rates were 40.0 % in candidaemia, 25.4 % in cIAI, and 26.7 % in deep-seated candidiasis. In the overall population of patients with proven IC, four independent prognostic factors were identified: immunosuppression (Odds Ratio (OR) = 1.977: 1.03–3.794 95 % confidence interval (CI), p = 0.04), age (OR = 1.035; 1.017–1.053 95 % CI; p < 0.001), SAPS >46 on ICU admission (OR = 2.894; 1.81–4.626 95 % CI; p < 0.001), and surgery just before or during ICU stay (OR = 0.473; 0.29–0.77 95 % CI; p < 0.001).

Conclusion

When SAT is initiated in French ICUs, the IC is ultimately proven for 48 % of patients. Empiric SAT is initiated in severely ill ICU patients. The initial SAT is often adapted, with de-escalation to fluconazole when possible. Mortality rate remains high.
Appendix
Available only for authorised users
Literature
1.
go back to reference Vincent JL, Rello J, Marshall J, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302:2323–9.PubMedCrossRef Vincent JL, Rello J, Marshall J, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302:2323–9.PubMedCrossRef
2.
go back to reference Kett DH, Azoulay E, Echeverria PM, et al. Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study. Crit Care Med. 2011;39:665–70.PubMedCrossRef Kett DH, Azoulay E, Echeverria PM, et al. Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study. Crit Care Med. 2011;39:665–70.PubMedCrossRef
3.
go back to reference Cornely OA, 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.PubMedCrossRef Cornely OA, 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.PubMedCrossRef
4.
go back to reference Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;48:503–35.PubMedCrossRef Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;48:503–35.PubMedCrossRef
5.
go back to reference Tabah A, Koulenti D, Laupland K, et al. Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study. Intensive Care Med. 2012;38:1930–45.PubMedCrossRef Tabah A, Koulenti D, Laupland K, et al. Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study. Intensive Care Med. 2012;38:1930–45.PubMedCrossRef
6.
go back to reference Blot S, Charles PE. Fungal sepsis in the ICU: are we doing better? Trends in incidence, diagnosis, and outcome. Minerva Anestesiol. 2013;79:1396–405.PubMed Blot S, Charles PE. Fungal sepsis in the ICU: are we doing better? Trends in incidence, diagnosis, and outcome. Minerva Anestesiol. 2013;79:1396–405.PubMed
7.
go back to reference Leon C, Ostrosky-Zeichner L, Schuster M. What’s new in the clinical and diagnostic management of invasive candidiasis in critically ill patients. Intensive Care Med. 2014;40:808–19.PubMedCrossRef Leon C, Ostrosky-Zeichner L, Schuster M. What’s new in the clinical and diagnostic management of invasive candidiasis in critically ill patients. Intensive Care Med. 2014;40:808–19.PubMedCrossRef
8.
go back to reference Cuenca-Estrella M, Verweij PE, Arendrup MC, et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures. Clin Infect Dis. 2012;18(Suppl 7):9–18.CrossRef Cuenca-Estrella M, Verweij PE, Arendrup MC, et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures. Clin Infect Dis. 2012;18(Suppl 7):9–18.CrossRef
9.
go back to reference Nguyen MH, Wissel MC, Shields RK, et al. Performance of Candida real-time polymerase chain reaction, beta-D-glucan assay, and blood cultures in the diagnosis of invasive candidiasis. Clin Infect Dis. 2012;54:1240–8.PubMedCrossRef Nguyen MH, Wissel MC, Shields RK, et al. Performance of Candida real-time polymerase chain reaction, beta-D-glucan assay, and blood cultures in the diagnosis of invasive candidiasis. Clin Infect Dis. 2012;54:1240–8.PubMedCrossRef
10.
go back to reference 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;54:1739–46.PubMedCrossRef 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;54:1739–46.PubMedCrossRef
11.
go back to reference Garey KW, Rege M, Pai MP, et al. Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis. 2006;43:25–31.PubMedCrossRef Garey KW, Rege M, Pai MP, et al. Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis. 2006;43:25–31.PubMedCrossRef
12.
go back to reference 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 Chemother. 2005;49:3640–5.PubMedPubMedCentralCrossRef 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 Chemother. 2005;49:3640–5.PubMedPubMedCentralCrossRef
13.
go back to reference Colombo AL, Guimaraes T, Sukienik T, et al. Prognostic factors and historical trends in the epidemiology of candidemia in critically ill patients: an analysis of five multicenter studies sequentially conducted over a 9-year period. Intensive Care Med. 2014;40:1489–98.PubMedPubMedCentralCrossRef Colombo AL, Guimaraes T, Sukienik T, et al. Prognostic factors and historical trends in the epidemiology of candidemia in critically ill patients: an analysis of five multicenter studies sequentially conducted over a 9-year period. Intensive Care Med. 2014;40:1489–98.PubMedPubMedCentralCrossRef
14.
go back to reference Arendrup MC, Sulim S, Holm A, et al. Diagnostic issues, clinical characteristics, and outcomes for patients with fungemia. J Clin Microbiol. 2011;49:3300–8.PubMedPubMedCentralCrossRef Arendrup MC, Sulim S, Holm A, et al. Diagnostic issues, clinical characteristics, and outcomes for patients with fungemia. J Clin Microbiol. 2011;49:3300–8.PubMedPubMedCentralCrossRef
15.
go back to reference Puig-Asensio M, Padilla B, Garnacho-Montero J, et al. Epidemiology and predictive factors for early and late mortality in Candida bloodstream infections: a population-based surveillance in Spain. Clin Microbiol Infect. 2014;20:O245–54.PubMedCrossRef Puig-Asensio M, Padilla B, Garnacho-Montero J, et al. Epidemiology and predictive factors for early and late mortality in Candida bloodstream infections: a population-based surveillance in Spain. Clin Microbiol Infect. 2014;20:O245–54.PubMedCrossRef
16.
go back to reference Leon C, Ruiz-Santana S, Saavedra P, et al. Usefulness of the “Candida score” for discriminating between Candida colonization and invasive candidiasis in non-neutropenic critically ill patients: a prospective multicenter study. Crit Care Med. 2009;37:1624–33.PubMedCrossRef Leon C, Ruiz-Santana S, Saavedra P, et al. Usefulness of the “Candida score” for discriminating between Candida colonization and invasive candidiasis in non-neutropenic critically ill patients: a prospective multicenter study. Crit Care Med. 2009;37:1624–33.PubMedCrossRef
17.
go back to reference Ostrosky-Zeichner L, Pappas PG, Shoham S, et al. Improvement of a clinical prediction rule for clinical trials on prophylaxis for invasive candidiasis in the intensive care unit. Mycoses. 2009;54:46–51.CrossRef Ostrosky-Zeichner L, Pappas PG, Shoham S, et al. Improvement of a clinical prediction rule for clinical trials on prophylaxis for invasive candidiasis in the intensive care unit. Mycoses. 2009;54:46–51.CrossRef
18.
go back to reference Eggimann P, Pittet D. Candida colonization index and subsequent infection in critically ill surgical patients: 20 years later. Intensive Care Med. 2014;40:1429–48.PubMedPubMedCentralCrossRef Eggimann P, Pittet D. Candida colonization index and subsequent infection in critically ill surgical patients: 20 years later. Intensive Care Med. 2014;40:1429–48.PubMedPubMedCentralCrossRef
19.
go back to reference Leroy O, Gangneux JP, Montravers P, et al. Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005–2006). Crit Care Med. 2009;37:1612–8.PubMedCrossRef Leroy O, Gangneux JP, Montravers P, et al. Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005–2006). Crit Care Med. 2009;37:1612–8.PubMedCrossRef
20.
go back to reference Azoulay E, Dupont H, Tabah A, et al. Systemic antifungal therapy in critically ill patients without invasive fungal infection. Crit Care Med. 2012;40:813–22.PubMedCrossRef Azoulay E, Dupont H, Tabah A, et al. Systemic antifungal therapy in critically ill patients without invasive fungal infection. Crit Care Med. 2012;40:813–22.PubMedCrossRef
21.
go back to reference Parmeland L, Gazon M, Guerin C, et al. Candida albicans and non-Candida albicans fungemia in an institutional hospital during a decade. Med Mycol. 2013;51:33–7.PubMedCrossRef Parmeland L, Gazon M, Guerin C, et al. Candida albicans and non-Candida albicans fungemia in an institutional hospital during a decade. Med Mycol. 2013;51:33–7.PubMedCrossRef
22.
go back to reference Arendrup MC, Dzajic E, Jensen RH, et al. Epidemiological changes with potential implication for antifungal prescription recommendations for fungaemia: data from a nationwide fungaemia surveillance programme. Clin Microbiol Infect. 2013;19:E343–53.PubMedCrossRef Arendrup MC, Dzajic E, Jensen RH, et al. Epidemiological changes with potential implication for antifungal prescription recommendations for fungaemia: data from a nationwide fungaemia surveillance programme. Clin Microbiol Infect. 2013;19:E343–53.PubMedCrossRef
23.
go back to reference Das I, Nightingale P, Patel M, et al. Epidemiology, clinical characteristics, and outcome of candidemia: experience in a tertiary referral center in the UK. Int J Infect Dis. 2011;15:e759–63.PubMedCrossRef Das I, Nightingale P, Patel M, et al. Epidemiology, clinical characteristics, and outcome of candidemia: experience in a tertiary referral center in the UK. Int J Infect Dis. 2011;15:e759–63.PubMedCrossRef
24.
go back to reference Ericsson J, Chryssanthou E, Klingspor L, et al. Candidaemia in Sweden: a nationwide prospective observational survey. Clin Microbiol Infect. 2013;19:E218–21.PubMedCrossRef Ericsson J, Chryssanthou E, Klingspor L, et al. Candidaemia in Sweden: a nationwide prospective observational survey. Clin Microbiol Infect. 2013;19:E218–21.PubMedCrossRef
25.
go back to reference Pfaller MA, Andes DR, Diekema DJ, et al. Epidemiology and outcomes of invasive candidiasis due to non-albicans species of Candida in 2,496 patients: data from the Prospective Antifungal Therapy (PATH) registry 2004–2008. PLoS One. 2014;9:e101510.PubMedPubMedCentralCrossRef Pfaller MA, Andes DR, Diekema DJ, et al. Epidemiology and outcomes of invasive candidiasis due to non-albicans species of Candida in 2,496 patients: data from the Prospective Antifungal Therapy (PATH) registry 2004–2008. PLoS One. 2014;9:e101510.PubMedPubMedCentralCrossRef
26.
go back to reference Lortholary O, Renaudat C, Sitbon K, et al. Worrisome trends in incidence and mortality of candidemia in intensive care units (Paris area, 2002–2010). Intensive Care Med. 2014;40:1303–12.PubMedPubMedCentralCrossRef Lortholary O, Renaudat C, Sitbon K, et al. Worrisome trends in incidence and mortality of candidemia in intensive care units (Paris area, 2002–2010). Intensive Care Med. 2014;40:1303–12.PubMedPubMedCentralCrossRef
27.
go back to reference Paugam A, Ancelle T, Lortholary O, et al. Longer incubation times for yeast fungemia: importance for presumptive treatment. Diag Microbiol Infect Dis. 2014;80:119–21.CrossRef Paugam A, Ancelle T, Lortholary O, et al. Longer incubation times for yeast fungemia: importance for presumptive treatment. Diag Microbiol Infect Dis. 2014;80:119–21.CrossRef
28.
go back to reference Guery BP, Arendrup MC, Auzinger G, et al. Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: part I Epidemiology and diagnosis. Intensive Care Med. 2009;35:55–62.PubMedCrossRef Guery BP, Arendrup MC, Auzinger G, et al. Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: part I Epidemiology and diagnosis. Intensive Care Med. 2009;35:55–62.PubMedCrossRef
29.
go back to reference Bruyere R, Quenot JP, Prin S, Dalle F, Vigneron C, Aho S, et al. Empirical antifungal therapy with an echinocandin in critically-ill patients: prospective evaluation of a pragmatic Candida score-based strategy in one medical ICU. BMC Infect Dis. 2014;14:385.PubMedPubMedCentralCrossRef Bruyere R, Quenot JP, Prin S, Dalle F, Vigneron C, Aho S, et al. Empirical antifungal therapy with an echinocandin in critically-ill patients: prospective evaluation of a pragmatic Candida score-based strategy in one medical ICU. BMC Infect Dis. 2014;14:385.PubMedPubMedCentralCrossRef
30.
go back to reference Wisplinghoff H, Seifert H, Tallent SM, et al. Nosocomial bloodstream infections in pediatric patients in United States hospitals: epidemiology, clinical features and susceptibilities. Ped Infect Dis J. 2003;22:686–91.CrossRef Wisplinghoff H, Seifert H, Tallent SM, et al. Nosocomial bloodstream infections in pediatric patients in United States hospitals: epidemiology, clinical features and susceptibilities. Ped Infect Dis J. 2003;22:686–91.CrossRef
31.
go back to reference Charles PE, Doise JM, Quenot JP, Aube H, Dalle F, Chavanet P, et al. Candidemia in critically ill patients: difference of outcome between medical and surgical patients. Intensive Care Med. 2003;29(12):2162–9.PubMedCrossRef Charles PE, Doise JM, Quenot JP, Aube H, Dalle F, Chavanet P, et al. Candidemia in critically ill patients: difference of outcome between medical and surgical patients. Intensive Care Med. 2003;29(12):2162–9.PubMedCrossRef
Metadata
Title
Systemic antifungal therapy for proven or suspected invasive candidiasis: the AmarCAND 2 study
Authors
Olivier Leroy
Sébastien Bailly
Jean-Pierre Gangneux
Jean-Paul Mira
Patrick Devos
Hervé Dupont
Philippe Montravers
Pierre-François Perrigault
Jean-Michel Constantin
Didier Guillemot
Elie Azoulay
Olivier Lortholary
Caroline Bensoussan
Jean-François Timsit
AmarCAND2 study group
Publication date
01-12-2016
Publisher
Springer Paris
Published in
Annals of Intensive Care / Issue 1/2016
Electronic ISSN: 2110-5820
DOI
https://doi.org/10.1186/s13613-015-0103-7

Other articles of this Issue 1/2016

Annals of Intensive Care 1/2016 Go to the issue