title: Antifungal therapy for patients with proven or suspected Candida peritonitis: Amarcand2, a prospective cohort study in French intensive care units.
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.
authors.affiliation: 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.
authors.forename: P
authors.initials: P
authors.lastname: Montravers
authors.affiliation: Medical-surgical ICU, Montpellier University Hospital, Montpellier, France.
authors.forename: P F
authors.initials: PF
authors.lastname: Perrigault
authors.affiliation: Medical ICU, Paris Diderot University, and Bichat University Hospital, HUPNVS, AP-HP, Paris, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Timsit
authors.affiliation: Medical ICU, Cochin University Hospital, HUPC, AP-HP, and Paris Descartes, Sorbonne Paris Cité University, Paris, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Mira
authors.affiliation: 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.
authors.forename: O
authors.initials: O
authors.lastname: Lortholary
authors.affiliation: Medical ICU, Chatilliez Hospital, Tourcoing, France.
authors.forename: O
authors.initials: O
authors.lastname: Leroy
authors.affiliation: Mycology, Rennes University Hospital, Rennes, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Gangneux
authors.affiliation: Inserm UMR 1181 « Biostatistics, Biomathematics, Pharmaco-epidemiology and Infectious Diseases » (B2PHI), F-75015 Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Guillemot
authors.affiliation: Medical Affairs, Therapy Area Hospital, MSD France, Courbevoie, France.
authors.forename: C
authors.initials: C
authors.lastname: Bensoussan
authors.affiliation: Inserm UMR 1137 - IAME Team 5 - DeSCID: Decision SCiences in Infectious Diseases, Control and Care INSERM/Paris Diderot, Sorbonne Paris Cité University, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Bailly
authors.affiliation: Medical ICU, Saint-Louis University Hospital, HUSLLFW, AP-HP, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Azoulay
authors.affiliation: Perioperative Medicine Department, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Constantin
authors.affiliation: Surgical ICU, Amiens University Hospital, Amiens, France.
authors.forename: H
authors.initials: H
authors.lastname: Dupont
mesh_terms: D000368:Aged; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002175:Candida; D002177:Candidiasis / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology* / Q000401:mortality; D015897:Comorbidity; D005602:France; D006801:Humans; D007362:Intensive Care Units; D008875:Middle Aged; D016017:Odds Ratio; D010538:Peritonitis / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology* / Q000401:mortality; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents
keywords: Antifungal agents; Candida peritonitis; Candida score; Critically ill patients; Empiric antifungal therapy; Invasive candidiasis; Peritonitis score; Targeted antifungal therapy