A randomized, placebo-controlled trial of preemptive antifungal therapy for the prevention of invasive candidiasis following gastrointestinal surgery for intra-abdominal infections.
BACKGROUND
Patients undergoing emergency gastrointestinal surgery for intra-abdominal infection are at risk of invasive candidiasis (IC) and candidates for preemptive antifungal therapy.


METHODS
This exploratory, randomized, double-blind, placebo-controlled trial assessed a preemptive antifungal approach with micafungin (100 mg/d) in intensive care unit patients requiring surgery for intra-abdominal infection. Coprimary efficacy variables were the incidence of IC and the time from baseline to first IC in the full analysis set; an independent data review board confirmed IC. An exploratory biomarker analysis was performed using logistic regression.


RESULTS
The full analysis set comprised 124 placebo- and 117 micafungin-treated patients. The incidence of IC was 8.9% for placebo and 11.1% for micafungin (difference, 2.24%; [95% confidence interval, -5.52 to 10.20]). There was no difference between the arms in median time to IC. The estimated odds ratio showed that patients with a positive (1,3)-β-d-glucan (ßDG) result were 3.66 (95% confidence interval, 1.01-13.29) times more likely to have confirmed IC than those with a negative result.


CONCLUSIONS
This study was unable to provide evidence that preemptive administration of an echinocandin was effective in preventing IC in high-risk surgical intensive care unit patients with intra-abdominal infections. This may have been because the drug was administered too late to prevent IC coupled with an overall low number of IC events. It does provide some support for using ßDG to identify patients at high risk of IC.


BACKGROUND
NCT01122368.
Department of General, Visceral and Transplantation Surgery, Hanover Medical School.
Wolfgang
W
Knitsch
Department of Intensive Care Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
Jean-Louis
JL
Vincent
Department of General and Visceral Surgery, University of Freiburg, Freiburg im Breisgau.
Stefan
S
Utzolino
Inserm CIC 1435/Medical-Surgical Intensive Care Unit, Centre Hospitalier Universitaire Dupuytren, Limoges.
Bruno
B
François
Institute of Surgery, University of Debrecen, Hungary.
Tamás
T
Dinya
2nd Intensive Care Department, University Hospital Attikon, Athens, Greece.
George
G
Dimopoulos
Department of Clinical Microbiology and Infectious Diseases, Eskisehir Osmangazi University Faculty of Medicine, Turkey.
İlhan
İ
Özgüneş
Servicio de Anestesia y Reanimación, Hospital General Universitario, Valencia.
Juan Carlos
JC
Valía
Adult Intensive Care Service, Department of Interdisciplinary Centers and Logistics, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland.
Philippe
P
Eggimann
Intensive Care Unit, Valme University Hospital, University of Seville, Spain.
Cristóbal
C
León
Département d'Anesthésie Réanimation Chirurgicale, Centre Hospitalier Universitaire Bichat Claude Bernard and University Denis Diderot Sorbonne Cité, Paris, France.
Philippe
P
Montravers
Chiltern International, Leiden, The Netherlands.
Stephen
S
Phillips
Astellas Pharma EMEA Medical Affairs, Chertsey, United Kingdom.
Lorraine
L
Tweddle
Astellas Pharma EMEA Medical Affairs, Chertsey, United Kingdom.
Andreas
A
Karas
Astellas Pharma Global Medical Affairs, Northbrook, Illinois.
Malcolm
M
Brown
Department I of Internal Medicine, Clinical Trials Centre Cologne, German Centre for Infection Research, and Cologne Excellence Custer on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Germany.
Oliver A
OA
Cornely
D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D058365:Candidiasis, Invasive / Q000188:drug therapy / Q000517:prevention & control*; D004311:Double-Blind Method; D054714:Echinocandins / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D059413:Intraabdominal Infections / Q000188:drug therapy / Q000517:prevention & control / Q000601:surgery*; D055666:Lipopeptides / Q000008:administration & dosage; D008297:Male; D000077551:Micafungin; D008875:Middle Aged; D011183:Postoperative Complications / Q000517:prevention & control*; D065129:Pre-Exposure Prophylaxis; D011509:Proteoglycans; D055815:Young Adult; D047071:beta-Glucans / Q000097:blood
D000935:Antifungal Agents; D015415:Biomarkers; D054714:Echinocandins; D055666:Lipopeptides; D011509:Proteoglycans; D047071:beta-Glucans; C010770:polysaccharide-K; D000077551:Micafungin
Preemptive antifungal therapy; gastrointestinal surgery; intensive care; invasive candidiasis; micafungin