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Caspofungin may be effective as pre-emptive strategy in ICU patients
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Caspofungin did not significantly reduce the incidence of invasive candidiasis when used as a prophylactic approach, according to recent data published in Clinical Infectious Diseases.
“While the study was probably underpowered to give a clear answer about prophylaxis, we found that caspofungin was safe and tended to reduce the incidence of invasive candidiasis in high-risk ICU patients,” Luis Ostrosky-Zeichner, MD, professor of medicine and epidemiology at University of Texas Medical School at Houston, told Infectious Disease News. “Perhaps the more attractive finding is the proof of concept for beta-glucan monitoring and pre-emptive therapy. We also validated a clinical prediction rule that appears to identify patients at risk for this disease.”
Luis Ostrosky-Zeichner
In a multicenter, randomized, double blind, placebo-controlled trial, the researchers compared caspofungin (Cancidas, Merck) with placebo as antifungal prophylaxis among adults who were in the ICU for at least 3 days. The primary objective was the efficacy of caspofungin as prophylaxis for invasive candidiasis. When this endpoint was reached, the researchers also evaluated the effectiveness of caspofungin as a pre-emptive therapy approach.
The incidence of proven and probable invasive candidiasis among 186 patients in the analysis was 9.8% among those who received caspofungin prophylaxis vs. 16.7% among those who received placebo. When the primary endpoint was met, those who were receiving placebo began therapy with caspofungin and the researchers evaluated a pre-emptive approach.
In this analysis, which included 219 patients, the researchers used beta-glucan levels to guide pre-emptive therapy. The incidence of proven and probable invasive candidiasis was 18.8% for caspofungin vs. 30.4% for placebo. The mean beta-glucan levels were higher among patients with proven or probable invasive candidiasis. In addition, patients with proven or probable invasive candidiasis had a significantly longer length of stay in the ICU.
In both the prophylaxis and pre-emptive analyses, there were no differences in antifungal drug use within 7 days, all-cause mortality within 7 days, and time to invasive candidiasis or length of ICU or hospital stay between the groups. There were also no differences in adverse events between the caspofungin and placebo groups.
“We hope that clinicians will use our clinical prediction rule to identify patients who are at high risk for this infection and who may benefit from increased monitoring or protocolized prophylaxis,” Ostrosky-Zeichner said. “Now that we have established the proof of concept of pre-emptive therapy, future studies should focus on this and be powered to look at outcomes such as mortality and resource utilization.” – by Emily Shafer
Luis Ostrosky-Zeichner, MD, can be reached at the University of Texas Medical School at Houston, 6431 Fannin St., MSB 2.112, Houston, TX 77030; email: luis.ostrosky-zeichner@uth.tmc.edu.
Disclosure: This study was an investigator-initiated study funded by Merck. Ostrosky-Zeichner has received research funding from Astellas, Associates of Cape Cod, Merck and Pfizer, and is a speaker or consultant for Astellas, Merck and Pfizer.
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