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Kidney Week

Abstract: FR-PO0515

Oral Voriconazole vs. Amphotericin B Plus Flucytosine for Fungal Peritonitis in Peritoneal Dialysis: A Multicenter Randomized Noninferiority Trial with Stratification by Fungal Type

Session Information

Category: Dialysis

  • 802 Dialysis: Home Dialysis and Peritoneal Dialysis

Authors

  • Puapatanakul, Pongpratch, Division of Nephrology, Department of Medicine and Center of Excellence in Kidney Metabolic Disorders, Faculty of Medicine, Chulalongkorn University, Pathum Wan, Bangkok, Thailand
  • Kanjanabuch, Talerngsak, Division of Nephrology, Department of Medicine and Center of Excellence in Kidney Metabolic Disorders, Faculty of Medicine, Chulalongkorn University, Pathum Wan, Bangkok, Thailand
  • Tungsanga, Somkanya, Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Pathum Wan, Bangkok, Thailand
  • Vanichanan, Jakapat, Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Pathum Wan, Bangkok, Thailand
  • Johnson, David W., Department of Kidney and Transplant Services, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
Background

Fungal peritonitis is a life-threatening complication of peritoneal dialysis (PD), yet robust evidence to guide empiric antifungal therapy is lacking. This multicenter, randomized controlled trial assessed the noninferiority of oral voriconazole vs. intravenous amphotericin B plus oral flucytosine for initial treatment of fungal peritonitis.

Methods

In this open-label, muti-centered trial (TCTR20210316001), 91 PD patients with confirmed fungal peritonitis were randomized 1:1 to voriconazole or combination therapy within 24 hours of timely PD catheter removal (within 3 days). Randomization was stratified by fungal type (yeast vs. mold) and site. The primary outcome was peritonitis-related death within 30 days. Secondary outcomes included clinical response, recurrence, mortality, and HD transfer. Analyses followed intention-to-treat principles using risk differences (RD), risk ratios (RR), and Kaplan-Meier survival.

Results

Peritonitis-related death occurred in 11% of the voriconazole group vs. 24% with combination therapy (RD -13.6%; 95% CI -29.0%, 1.9%), meeting the 15% noninferiority margin. Kaplan-Meier survival curves trended in favor of voriconazole (HR 0.40; 95% CI 0.14, 1.16). Primary response was higher with voriconazole (87% vs. 71%; RD 15.8%, 95% CI -0.6%, 32.3%), whilst recurrence was lower (2.2% vs. 8.9%). Long-term mortality was numerically lower in the voriconazole group at 12 months (22% vs. 36%; RD -13.8%, 95% CI -32.2%, 4.6%) (Figure 1). Adverse events and PD resumption rates were comparable. Hyaline molds predominated (65%) over yeasts (35%), with no difference in treatment responses by fungal type. Notably, 30% of isolates were voriconazole-resistant, associated with poorer response and possibly required initial combination therapy.

Conclusion

Voriconazole monotherapy was noninferior to amphotericin B plus flucytosine for initial management of PD-associated fungal peritonitis. Its oral formulation, favorable safety profile, and outpatient feasibility suggest it may be a viable first-line alternative. Further studies are needed to assess efficacy in patients with drug-resistant fungi.

Funding

  • Government Support – Non-U.S.

Digital Object Identifier (DOI)