Isavuconazole Versus Caspofungin in the Treatment of Candidemia and Other Invasive Candida Infections: The ACTIVE Trial

Kullberg, Bart Jan; Viscoli, Claudio; Pappas, Peter G.; Vázquez, José Antonio; Ostrosky-Zeichner, Luis; Rotstein, Coleman; Sobel, Jack D.; Herbrecht, Raoul; Rahav, Galia; Jaruratanasirikul, Sutep; Chetchotisakd, Ploenchan; Wijngaerden, Eric Van; Waele, Jan J. De; Lademacher, Christopher; Engelhardt, Marc; Kovanda, Laura; Croos‐Dabrera, Rodney; Fredericks, Christine; Thompson, George R.

doi:10.1093/cid/ciy827

Cited by 145 publications

(100 citation statements)

References 22 publications

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“…Reports have suggested that as many as one-third of all patients with disseminated Candida infections fail to respond to antifungal therapy (10,(36)(37)(38)(39). Both intrinsic and acquired mechanisms of antifungal drug resistance are known to reduce the chances of successful treatment of IFIs (11).…”

Section: Discussionmentioning

confidence: 99%

A Systematic Screen Reveals a Diverse Collection of Medications That Induce Antifungal Resistance in Candida Species

Butts

Reitler

Nishimoto

et al. 2019

Antimicrob Agents Chemother

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The increasing incidence of and high mortality rates associated with invasive fungal infections (IFIs) impose an enormous clinical, social, and economic burden on humankind. In addition to microbiological resistance to existing antifungal drugs, the large number of unexplained treatment failures is a serious concern. Due to the extremely limited therapeutic options available, it is critical to identify and understand the various causes of treatment failure if patient outcomes are to improve. In this study, we examined one potential source of treatment failure: antagonistic drug interactions. Using a simple screen, we systematically identified currently approved medications that undermine the antifungal activity of three major antifungal drugs-fluconazole, caspofungin, and amphotericin B-on four prevalent human fungal pathogens-Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis. This revealed that a diverse collection of structurally distinct drugs exhibit antagonistic interactions with fluconazole. Several antagonistic agents selected for follow-up studies induce azole resistance through a mechanism that depends on Tac1p/Pdr1p zinc-cluster transcription factors, which activate the expression of drug efflux pumps belonging to the ABC-type transporter family. Few antagonistic interactions were identified with caspofungin or amphotericin B, possibly reflecting their cell surface mode of action that should not be affected by drug efflux mechanisms. Given that patients at greatest risk of IFIs usually receive a multitude of drugs to treat various underlying conditions, these studies suggest that chemically inducible azole resistance may be much more common and important than previously realized.

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Section: Discussionmentioning

confidence: 99%

A Systematic Screen Reveals a Diverse Collection of Medications That Induce Antifungal Resistance in Candida Species

Butts

Reitler

Nishimoto

et al. 2019

Antimicrob Agents Chemother

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“…Even if Candida spp. Are sensitive to azoles, therapy with an echinocandin is recommended as it was shown to be superior in a septic ICU population with invasive candidiasis and candidaemia [53,54]. Several population pharmacokinetic studies in a general ICU population suggested that echinocandins are probably underdosed and no dose reduction is required for patients on CRRT [55,56].…”

Section: De-escalationmentioning

confidence: 99%

Management of infected pancreatic necrosis in the intensive care unit: a narrative review

Wolbrink

Kolwijck

Oever

et al. 2020

Clinical Microbiology and Infection

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“…179 Echinocandins appear to be as effective as and better tolerated than amphotericin B formulations 180,181 and, in two randomized trials, more effective than azoles. 182,183 Particularly, in one of these trials including 245 patients with IC (89% of them with candidemia only) anidulafungin treatment resulted in superior combined clinical and microbiological response compared with fluconazole (at 2 weeks 65 vs. 49%), although no differences were observed at 60-day mortality rates. 182 The use of echinocandins is further supported by a quantitative review of RCTs (1,915 patients, seven studies) showing that treatment with echinocandins led to decreased mortality (OR: 0.65; 95% CI: 0.45-0.94) and increased treatment success (OR: 2.33; 95% CI: 1.27-4.35).…”

Section: Treatmentmentioning

confidence: 99%

Diagnosis and Treatment of Candidemia in the Intensive Care Unit

Bassetti

Giacobbe

Vena

et al. 2019

Semin Respir Crit Care Med

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Candidemia is the fourth most frequent health care-associated bloodstream infection, and the most frequent severe fungal infection developing in critically ill patients in intensive care units (ICUs). Diagnosis of candidemia in ICU patients is a complex task made of both early and late assessments involving both conventional diagnostic methods and novel rapid tests. Management strategies to optimize treatment of candidemia can be challenging and include starting early adequate therapy, use of an adequate dose and duration of therapy, de-escalating treatment whenever possible, and early discontinuation of useless antifungals in those with no definitive diagnosis of fungal infection. Herein, we will discuss recent epidemiological data on candidemia in ICUs and current diagnostic techniques before concentrating on antifungal treatments.

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Isavuconazole Versus Caspofungin in the Treatment of Candidemia and Other Invasive Candida Infections: The ACTIVE Trial

Abstract: In a phase 3, randomized, double-blind, multinational clinical trial comparing isavuconazole to caspofungin for primary treatment of patients with proven candidemia or invasive candidiasis, isavuconazole failed to demonstrate noninferiority compared with caspofungin.

Cited by 145 publications

References 22 publications

A Systematic Screen Reveals a Diverse Collection of Medications That Induce Antifungal Resistance in Candida Species

A Systematic Screen Reveals a Diverse Collection of Medications That Induce Antifungal Resistance in Candida Species

Management of infected pancreatic necrosis in the intensive care unit: a narrative review

Diagnosis and Treatment of Candidemia in the Intensive Care Unit

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