Management of Invasive Candidal Infections: Results of a Prospective, Randomized, Multicenter Study of Fluconazole Versus Amphotericin B and Review of the Literature

Anaissie, Elias; Darouiche, Rabih O.; Abi-Said, Dima; Uzun, Ömrüm; Mera, Jorge; Gentry, Layne O.; Williams, Temple W.; Kontoyiannis, Dimitrios P.; Karl, Cynthia; Bodey, Gerald P.

doi:10.1093/clinids/23.5.964

Cited by 255 publications

(149 citation statements)

References 22 publications

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“…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.…”

Section: Search Resultsmentioning

confidence: 99%

“…The total number of eligible subjects in the studies ranged from 40 to 370. Of the eight studies, half enrolled more than 100 eligible patients (Rex et al 1994, 2003; Kullberg et al 2005; Reboli et al 2007) and 6 were multicentre (Rex et al 1994, 2003; Anaissie et al 1996; Phillips et al 1997; Kullberg et al 2005; Reboli et al 2007). Although all studies were randomised, only two claimed blinding through the study (Rex et al 2003; Reboli et al 2007).…”

Section: Search Resultsmentioning

confidence: 99%

“…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).…”

Section: Search Resultsmentioning

confidence: 99%

“…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 another study, only non-neutropenic (post-surgery) subjects appear to have been enrolled although an absence of neutropenia was not an explicit study requirement (Kujath et al 1993).…”

Section: Search Resultsmentioning

confidence: 99%

“…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).…”

Section: Search Resultsmentioning

confidence: 99%

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

et al. 2018

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The purpose of this study was to determine whether fungicidal versus fungistatic pharmacotherapy of invasive candidiasis/candidemia yields superior outcomes.Data sources included MEDLINE (1966–June 2017), EMBASE (1980–June 2017), PubMed (1966–June 2017), Global Health-Ovid (inception to June 2017), LILACS Virtual Health Library (inception to June 2017) and the Cochrane Central Register of Controlled Trials (to 2nd quarter 2017). The ClinicalTrial.gov database, the SCOPUS database, SIGLE (System for Information on Grey Literature) and Google Scholar were also utilised to search for relevant studies.Randomised studies of any pharmacotherapy of invasive candidiasis including candidemia using a fungicidal (amphotericin B or echinocandin compound) versus a fungistatic (triazole) compound in adolescent or adult non-neutropenic patients. Eight studies met the inclusion criteria.Pooled odds ratios demonstrated an advantage of fungicidal therapy with respect to early therapeutic success (OR 1.61, 95% CI 1.27–2.03, p < 0.0001, I2 = 0%) and persistence or recurrence of infection (OR 0.51, 95% CI 0.35–0.74, p = 0.0005, I2 = 0%) but no advantage for late survival (OR 0.97, 95% CI 0.77–1.21, p = 0.77, I2 = 0%).Fungicidal therapy of invasive candidiasis and candidemia is associated with a higher probability of early therapeutic success and decreased probability of persistent or recurrent infection. However, there is no improvement in survival.

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Section: Search Resultsmentioning

confidence: 99%

Section: Search Resultsmentioning

confidence: 99%

Section: Search Resultsmentioning

confidence: 99%

Section: Search Resultsmentioning

confidence: 99%

Section: Search Resultsmentioning

confidence: 99%

See 3 more Smart Citations

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

et al. 2018

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Predictive Factors of Mortality Due to Polymicrobial Peritonitis With Candida Isolation in Peritoneal Fluid in Critically Ill Patients

Paugam–Burtz²,

et al. 2002

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Problems in the Design and Reporting of Trials of Antifungal Agents Encountered During Meta-analysis

Johansen

Gøtzsche²

1999

JAMA

109

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Meta-analyses may become biased if the reported data in the individual trials are biased and if overlap among trials cannot be identified. We describe the unanticipated problems we encountered in collecting data for a meta-analysis comparing a new antifungal agent, fluconazole, with amphotericin B in patients with cancer complicated by neutropenia. In 3 large trials that comprised 43% of the patients identified for the meta-analysis, results for amphotericin B were combined with results for nystatin in a "polyene" group. Because nystatin is recognized as an ineffective drug in these circumstances, this approach creates a bias in favor of fluconazole. Furthermore, 79% of the patients were randomized to receive oral amphotericin B, which is poorly absorbed and not an established treatment, in contrast to intravenous amphotericin B, which was administered in 4 of 5 placebo-controlled trials, or 86% of patients. It was unclear whether there was overlap among the "polyene" trials, and it is possible that results from single-center trials were included in multicenter trial reports. We were unable to obtain information to clarify these issues from the trial authors or the manufacturer of fluconazole. Two of 11 responding authors replied that the data were with the drug manufacturer and two indicated that they did not have access to their data because of change of affiliation. In the meta-analyses, fluconazole and amphotericin B (mostly given orally) had similar effects (13 trials), whereas nystatin was no better than placebo (3 trials). Since individual trials are rarely conclusive, investigators, institutions, and pharmaceutical companies should provide essential details about their work to ensure that meta-analyses can accurately reflect the studies conducted and that patients will realize maximum benefits from treatments. We recommend that investigators keep copies of their trial data to help facilitate accurate and unbiased meta-analyses.

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Management of Invasive Candidal Infections: Results of a Prospective, Randomized, Multicenter Study of Fluconazole Versus Amphotericin B and Review of the Literature

Cited by 255 publications

References 22 publications

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

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

Predictive Factors of Mortality Due to Polymicrobial Peritonitis With Candida Isolation in Peritoneal Fluid in Critically Ill Patients

Problems in the Design and Reporting of Trials of Antifungal Agents Encountered During Meta-analysis

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