A randomized study comparing fluconazole with amphotericin B/5-flucytosine for the treatment of systemicCandida infections in intensive care patients

Abstract

In this prospective, randomized study fluconazole and amphotericin B/5-flucytosine were compared in the treatment of systemic candidiasis. Seventy-two non-neutropenic intensive care patients with systemic Candida infections were enrolled. Thirty-six patients were randomly assigned to receive fluconazole (400 mg on the first day then 200 mg) and 36 were randomized to amphotericin B/5-flucytosine (1.0-1.5 mg/kg body weight every other day and 3 x 2.5 g flucytosine/day) for 14 days following the diagnosis. There was no statistically significant difference in clinical outcome in regard to the treatment of pneumonia and sepsis: 18/28 of the patients were treated successfully with fluconazole and 17/27 with amphotericin B/5-flucytosine. For the treatment of peritonitis, however, amphotericin B/5-flucytosine was more effective than fluconazole (55% vs. 25%). Furthermore, amphotericin B/5-flucytosine was found to be superior to fluconazole with regard to pathogen eradication (86% vs. 50%). Fluconazole was associated with less toxicity than amphotericin B/5-flucytosine.

Fungicidal versus fungistatic therapy of invasive Candida infection in non-neutropenic adults: a meta-analysis

“…A total of 1335 eligible subjects were enrolled in the eight included trials (Kujath et al 1993; Rex et al 1994, 2003; Abele-Horn et al 1996; Anaissie et al 1996; Phillips et al 1997; Kullberg et al 2005; Reboli et al 2007) (Table 2). All of the studies were published in peer-reviewed, English-language journals between 1993 and 2014.…”

“…Three studies enrolled only adults (age 18 years or more) (Kujath et al 1993; Abele-Horn et al 1996; Phillips et al 1997). The others enrolled adults and older children with the study by Kullberg et al (2005) enrolling children as young as 12.…”

“…Candidemia was the enrolment criterion in four of the trials (Rex et al 1994, 2003; Phillips et al 1997; Kullberg et al 2005); the others allowed entry on the basis of invasive candidiasis without documented candidemia (Kujath et al 1993; Abele-Horn et al 1996; Anaissie et al 1996; Reboli et al 2007). Five of the studies specifically excluded neutropenic subjects (Rex et al 1994, 2003; Abele-Horn et al 1996; Phillips et al 1997; Kullberg et al 2005). In one study, invasive Candida cases associated with neutropenia (polymorphonuclear leucocyte count <1000/μL) were removed from the data set with only the remaining cases retained for analysis (Anaissie et al 1996).…”

“…In seven trials, the fungistatic therapy utilised was fluconazole (Kujath et al 1993; Rex et al 1994, 2003; Abele-Horn et al 1996; Anaissie et al 1996; Phillips et al 1997; Reboli et al 2007); the remaining study utilised voriconazole (Kullberg et al 2005). Seven of the eight studies used standard amphotericin B deoxycholate as the fungicidal therapy (Kujath et al 1993; Rex et al 1994, 2003; Abele-Horn et al 1996; Anaissie et al 1996; Phillips et al 1997; Kullberg et al 2005); the other study used the echinocandin, anidulafungin (Reboli et al 2007).…”

“…No trial utilised lipid-modified amphotericin B preparations. In two cases, amphotericin B deoxycholate was supplemented with flucytosine for a variable duration (Kujath et al 1993; Abele-Horn et al 1996). In one case, amphotericin B was supplemented by fluconazole at the same dose used in the fungistatic therapy arm (Rex et al 2003).…”