A randomized, placebo-controlled trial of preemptive antifungal therapy for the prevention of invasive candidiasis following gastrointestinal surgery for intra-abdominal infections

Wolfgang Knitsch, Jean-Louis Vincent, Stefan Utzolino, Bruno François, Tamás Dinya, George Dimopoulos, İlhan Özgüneş, Juan Carlos Valía, Philippe Eggimann, Cristóbal León, Philippe Montravers, Stephen Phillips, Lorraine Tweddle, Andreas Karas, Malcolm Brown, Oliver A Cornely, Wolfgang Knitsch, Jean-Louis Vincent, Stefan Utzolino, Bruno François, Tamás Dinya, George Dimopoulos, İlhan Özgüneş, Juan Carlos Valía, Philippe Eggimann, Cristóbal León, Philippe Montravers, Stephen Phillips, Lorraine Tweddle, Andreas Karas, Malcolm Brown, Oliver A Cornely

Abstract

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.

Clinical trials registration: NCT01122368.

Keywords: Preemptive antifungal therapy; gastrointestinal surgery; intensive care; invasive candidiasis; micafungin.

© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Patient flow through the study. In the full analysis set (FAS), 30.7% of patients had either violated the protocol (10.4% had received concurrent antifungal agents and 12.9% were outside the drug study window) or had received treatment for

Figure 2.

Kaplan–Meier failure curves of time…

Figure 2.

Kaplan–Meier failure curves of time to independent data review board (IDRB)-confirmed invasive candidiasis…

Figure 2.
Kaplan–Meier failure curves of time to independent data review board (IDRB)-confirmed invasive candidiasis (IC) (full analysis set).

Figure 3.

Incidence of confirmed cases of…

Figure 3.

Incidence of confirmed cases of invasive candidiasis (IC) by higher-risk subgroups (full analysis…

Figure 3.
Incidence of confirmed cases of invasive candidiasis (IC) by higher-risk subgroups (full analysis set, modified according to who assessed for IC at baseline; cases were confirmed by independent data review board and/or investigator). Abbreviations: CI, confidence interval; NAI, nosocomially acquired infection.
Figure 2.
Figure 2.
Kaplan–Meier failure curves of time to independent data review board (IDRB)-confirmed invasive candidiasis (IC) (full analysis set).
Figure 3.
Figure 3.
Incidence of confirmed cases of invasive candidiasis (IC) by higher-risk subgroups (full analysis set, modified according to who assessed for IC at baseline; cases were confirmed by independent data review board and/or investigator). Abbreviations: CI, confidence interval; NAI, nosocomially acquired infection.

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Source: PubMed

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