title: Invasive candidiasis treated in the intensive care unit: observations from a randomized clinical trial.
abstract: OBJECTIVE
  The objectives of this study were to contrast risk factors, microbiology, and outcomes in patients with invasive candidiasis treated in an intensive care unit (ICU) with those in patients with invasive candidiasis treated outside an ICU and to describe therapeutic results with caspofungin in ICU patients.
  
  
  METHODS
  We retrospectively identified patients with documented invasive candidiasis who received their first dose of the study drug in the ICU as part of a double-blind randomized trial. Participants were not stratified at entry by their ICU status. Patients received caspofungin (50 mg/d after a 70-mg loading dose) or conventional amphotericin B (0.6-1.0 mg/kg per day) for 10 to 14 days. A favorable response required resolution of signs and symptoms as well as eradication of Candida pathogens.
  
  
  RESULTS
  Of the 224 patients, 97 (43%) received their first dose of the study drug in the ICU. Most patients had well-recognized risk factors for invasive candidiasis, including broad-spectrum antibiotics, central venous catheters, and hyperalimentation. Recent surgery was more common whereas malignancy, neutropenia, and immunosuppression were less common among ICU patients than among non-ICU patients. Candidemia was demonstrated in 81% of ICU patients and in 84% of non-ICU patients. Favorable response rates in the ICU patients vs the non-ICU patients were 68% (95% confidence interval [CI] = 53%, 82%) vs 77% (95% CI = 67%, 87%) for caspofungin and 56% (95% CI = 43%, 69%) vs 67% (95% CI = 55%, 79%) for amphotericin B. After accounting for differences in APACHE (Acute Physiology and Chronic Health Evaluation) II score, neutropenia status, and geographic region, we found that patients initiating the study therapy in an ICU were still more likely to die than patients initiating study therapy outside an ICU. For ICU patients, all-cause mortality rates were 45% (95% CI = 30%, 60%) for caspofungin recipients and 40% (95% CI = 28%, 53%) for amphotericin B recipients, whereas candidiasis-attributable mortality rates were 5% (95% CI = 0%, 12%) for caspofungin recipients and 11% (95% CI = 3%, 19%) for amphotericin B recipients. Overall, drug-related adverse events were reported less often among the ICU patients than among the non-ICU patients.
  
  
  CONCLUSIONS
  In ICU patients treated with antifungal therapy, invasive candidiasis is associated with substantial mortality, but most deaths cannot be directly attributed to this infection.
authors.affiliation: Department of Medical Communication, Merck Research Laboratories, West Point, PA 19486, USA. mark_dinubile@merck.com
authors.forename: Mark J
authors.initials: MJ
authors.lastname: DiNubile
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lupinacci
authors.forename: Kim M
authors.initials: KM
authors.lastname: Strohmaier
authors.forename: Carole A
authors.initials: CA
authors.lastname: Sable
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Kartsonis
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002177:Candidiasis / Q000188:drug therapy* / Q000401:mortality*; D000077336:Caspofungin; D064420:Drug-Related Side Effects and Adverse Reactions; D054714:Echinocandins / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D016469:Fungemia / Q000188:drug therapy*; D006801:Humans; D007362:Intensive Care Units; D055666:Lipopeptides; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000666:Amphotericin B; D000077336:Caspofungin