Antifungal therapy for patients with proven or suspected Candida peritonitis: Amarcand2, a prospective cohort study in French intensive care units

P Montravers; P F Perrigault; J F Timsit; J P Mira; O Lortholary; O Leroy; J P Gangneux; D Guillemot; C Bensoussan; S Bailly; E Azoulay; J M Constantin; H Dupont; AmarCAND2 Study Group

doi:10.1016/j.cmi.2016.10.001

Antifungal therapy for patients with proven or suspected Candida peritonitis: Amarcand2, a prospective cohort study in French intensive care units

Clin Microbiol Infect. 2017 Feb;23(2):117.e1-117.e8. doi: 10.1016/j.cmi.2016.10.001. Epub 2016 Oct 13.

Authors

P Montravers¹, P F Perrigault², J F Timsit³, J P Mira⁴, O Lortholary⁵, O Leroy⁶, J P Gangneux⁷, D Guillemot⁸, C Bensoussan⁹, S Bailly¹⁰, E Azoulay¹¹, J M Constantin¹², H Dupont¹³; AmarCAND2 Study Group

Collaborators

AmarCAND2 Study Group:
A Aait Hssain, M Adda, B Allaouchiche, N Ammenouche, G Angel, L Argaud, C Badetti, O Baldesi, M C Barthet, O Bastien, F Baudin, F Bellec, G Blasco, P E Bollaert, A Bonadona, C Bretonniere, E Brocas, S Brua, N Bruder, G Brunin, P Cabaret, D Carpentier, J C Cartier, C Cerf, R Chabanne, P E Charles, C Cheval, R Cinotti, Y Cohen, J Cousson, E Delpierre, D Demory, E Diconne, D Du Cheyron, C Dubost, A S Dumenil, M Durand, E Duroy, J M Forel, A L Foucher-Lezla, S Fratea, J Gally, P Gaudard, P Geffe, S Gergaud, S Gette, C Girault, B Goubaux, P Gouin, R Grenot, G Grossmith, D Guelon, A M Guerin-Robardey, C Guervilly, D Hayl-Slayman, G Hilbert, H Houissa, S Hraiech, P Ichai, B Jung, M Kaidomar, P Karoubi, A Kherchache, F Lambiotte, L Lamhaut, A Launoy, F Lebreton, J Y Lefrant, C Lemaire, A Lepape, T Lepoivre, O Lesieur, B Levy, C E Luyt, P J Mahe, P Mahul, P Mateu, B Megarbane, J C Merle, A Montcriol, Y Mootien, J C Navellou, A Ouattara, B Page, F Petitpas, G Plantefeve, A Quinart, H Quintard, B Ragonnet, A Roquilly, J Ruiz, F Saliba, D Samba, Z Schmitt, P Seguin, C Sejourne, A C Tellier, F Thevenot, J M Tonnelier, N Van Grunderbeek, J F Vincent, S Wiramus, E Zogheib

Affiliations

¹ Paris Diderot Sorbonne Cite University, and Anesthesiology and Critical Care Medicine, Bichat-Claude Bernard University Hospital, HUPNSV, AP-HP, Paris, France. Electronic address: philippe.montravers@aphp.fr.
² Medical-surgical ICU, Montpellier University Hospital, Montpellier, France.
³ Medical ICU, Paris Diderot University, and Bichat University Hospital, HUPNVS, AP-HP, Paris, France.
⁴ Medical ICU, Cochin University Hospital, HUPC, AP-HP, and Paris Descartes, Sorbonne Paris Cité University, Paris, France.
⁵ University Paris Descartes, Necker Pasteur Centre for Infectious Diseases, HUNEM, AP-HP, IHU Imagine, Paris, France; Pasteur Institute, National Reference Centre for Invasive Mycoses and Antifungals, CNRS URA3012, Paris, France.
⁶ Medical ICU, Chatilliez Hospital, Tourcoing, France.
⁷ Mycology, Rennes University Hospital, Rennes, France.
⁸ Inserm UMR 1181 « Biostatistics, Biomathematics, Pharmaco-epidemiology and Infectious Diseases » (B2PHI), F-75015 Paris, France.
⁹ Medical Affairs, Therapy Area Hospital, MSD France, Courbevoie, France.
¹⁰ Inserm UMR 1137 - IAME Team 5 - DeSCID: Decision SCiences in Infectious Diseases, Control and Care INSERM/Paris Diderot, Sorbonne Paris Cité University, Paris, France.
¹¹ Medical ICU, Saint-Louis University Hospital, HUSLLFW, AP-HP, Paris, France.
¹² Perioperative Medicine Department, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.
¹³ Surgical ICU, Amiens University Hospital, Amiens, France.

PMID: 27746395
DOI: 10.1016/j.cmi.2016.10.001

Abstract

Objective: The clinical characteristics and prognosis of patients treated for Candida peritonitis (CP) were compared according to the type of systemic antifungal therapy (SAT), empiric (EAF) or targeted (TAF) therapies, and the final diagnosis of infection.

Methods: Patients in intensive care units (ICU) treated for CP were selected among the AmarCAND2 cohort, to compare patients receiving EAF for unconfirmed suspicion of CP (EAF/nonCP), to those with suspected secondarily confirmed CP (EAF/CP), or with primarily proven CP receiving TAF.

Results: In all, 279 patients were evaluated (43.4% EAF/nonCP, 29.7% EAF/CP and 25.8% TAF patients). At SAT initiation, the severity of illness was similar among EAF/nonCP and EAF/CP patients, lower among TAF patients (median Simplified Acute Physiology Score II (SAPS II) 49 and 51 versus 35, respectively; p 0.001). Candida albicans was involved in 67%, Candida glabrata in 15.6%. All strains were susceptible to echinocandin; 84% to fluconazole. Echinocandin was administered to 51.2% EAF/nonCP, 49% EAF/CP and 40% TAF patients. At day 28, 72%, 76% and 75% of EAF/nonCP, EAF/CP and TAF patients, respectively, were alive. An increased mortality was observed in patients with a Sequential Organ Failure Assessment (SOFA) score <7 if SAT was delayed by ≥6 days (p 0.04). Healthcare-associated CP (OR 3.82, 95% CI 1.52-9.64, p 0.004), SOFA ≥8 at ICU admission (OR 2.61, 95% CI 1.08-6.34; p 0.03), and SAPS II ≥45 at SAT initiation (OR 5.08, 95% CI 1.04-12.67; p 0.001) impacted the 28-day mortality.

Conclusions: In summary, only 56.6% of ICU patients receiving SAT had CP. Most strains were susceptible to SAT. A similar 28-day mortality rate was observed among groups; the late administration of SAT significantly worsened the prognosis of patients with less severe CP.

Keywords: Antifungal agents; Candida peritonitis; Candida score; Critically ill patients; Empiric antifungal therapy; Invasive candidiasis; Peritonitis score; Targeted antifungal therapy.

MeSH terms

Aged
Antifungal Agents / pharmacology
Antifungal Agents / therapeutic use*
Candida*
Candidiasis / diagnosis
Candidiasis / drug therapy*
Candidiasis / microbiology*
Candidiasis / mortality
Comorbidity
France
Humans
Intensive Care Units*
Middle Aged
Odds Ratio
Peritonitis / diagnosis
Peritonitis / drug therapy*
Peritonitis / microbiology*
Peritonitis / mortality
Prospective Studies
ROC Curve
Risk Factors
Severity of Illness Index
Treatment Outcome

Substances

Antifungal Agents