Treatment of Fungal Peritonitis with a Combination of Intravenous Amphotericin B and Oral Flucytosine, and Delayed Catheter Replacement in Continuous Ambulatory Peritoneal Dialysis

Abstract

Background Fungal peritonitis (FP) is associated with significant mortality and high risk of peritoneal failure. The optimum treatment for peritoneal dialysis (PD)-associated FP remains unclear. Since January 2000 we have been treating FP with a combination of intravenous amphotericin B and oral flucytosine, together with deferred catheter replacement. We examined the clinical course and outcome of the FP patients treated with this approach (study group). An outcome comparison was also made to an alternatively treated historic cohort (control group). Methods This was a single-center retrospective study. The clinical course and outcome of 13 consecutive episodes of FP occurring in 13 patients treated between January 2000 and April 2005 with the study approach were examined. The patients were treated with an incremental dose of intravenous amphotericin B to a target dose of 0.75 – 1 mg/kg body weight/day, and oral flucytosine 1 g/day upon a diagnosis of FP at 3.77 ± 0.93 days from presentation. Replacement of the peritoneal catheter was intended after complete clearing of effluent, after which, antifungal chemotherapy was continued for another 1 – 2 weeks. Their outcome was compared with 14 historic controls that were treated between April 1995 and December 1999. Results Mean age of the study group was 58.7 ± 13.2 years; male-to-female ratio was 2:11; 6 (46.1%) were diabetic. All FP were caused by Candida species ( C. albicans, 2; C. parapsilosis, 8; C. glabrata, 3). Two (15.4%) patients died before resolution of the peritonitis. The dialysate effluent cleared in 11 patients (84.6%) after 13.2 ± 3.3 days of treatment, but 2 patients died of acute myocardial infarction before catheter replacement. Nine patients had their catheters replaced at day 26.7 ± 7.7 of treatment; all 9 returned to PD after a total of 31 ± 12.2 days of antifungal chemotherapy. Reversible liver dysfunction was common with this regimen. When compared with the 14 cases in the historic control group ( Candida species, 13; Trichosporon, 1), who were treated with amphotericin B, fluconazole, or a combination of the two, and the majority (78.6%) of whose catheters were removed before day 10 of presentation, the study group appeared to have a lower technique failure rate (30.8% vs 78.6%, p = 0.013) and similar all-cause mortality (30.7% vs 28.5%, p = NS), FP-related mortality (15.4% vs 28.5%, p = NS), and length of hospitalization (48.5 ± 30.2 vs 57.0 ± 37.7 days, p = NS). However, a significantly earlier commencement of antifungal treatment in the study group (3.8 ± 0.9 vs 5.8 ± 2.4 days, p = 0.012) could be an important confounder of outcome. Conclusions Combination of intravenous amphotericin B and oral flucytosine with deferred catheter replacement appears to be associated with a relatively low incidence of PD technique failure, without affecting mortality in patients suffering from FP due to yeasts in this preliminary study. Nonetheless, drug-induced hepatic dysfunction was common; close monitoring during treatment is of paramount importance. The reasons accounting for the observed distinctive outcome remain unclear and further study is required to confirm the results and to investigate for the underlying mechanism.

Seeking Clarity within Cloudy Effluents: Differentiating Fungal from Bacterial Peritonitis in Peritoneal Dialysis Patients

“…In the present study, increased mortality was noted in those with retained catheters, emphasising the importance of prompt catheter removal when managing fungal peritonitis [3] . Although late (especially after 5 days following diagnosis) catheter removal has been associated with poorer survival [6] , [21] , this was not found in this and several other studies, perhaps due to the high rates of catheter removal at the outset and prompt initiation of antifungal therapy [4] , [22] . This may have also accounted for the equivalent mortality rates between fungal and bacterial peritonitis that was observed, in contrast to previous reports of higher mortality rates for fungal peritonitis [3] , [6] .…”

Fungal peritonitis in peritoneal dialysis: a 34-year single centre evaluation

“…Other groups recommend drug treatment of FP and delaying catheter removal until the dialysate effluent has become clear [ 43 ]. The current literature suggests that this approach is recommended only for elderly or frail patients with little capacity to support a shift to haemodialysis [ 44 ]. The PD catheter was removed in all our patients after a median time of 4 days from the onset of peritonitis.…”

Peritoneal dialysis-related peritonitis: challenges and solutions

“…If flucytosine is used, trough serum levels should be measured with a target level of 25-50 μg/mL to avoid toxicity. 66 Voriconazole is a newer triazole antifungal that is active on many fluconazole-resistant strains. 67 There is little experience using voriconazole to treat Candida peritonitis, but it has been used successfully in the treatment of peritonitis caused by filamentous fungi at a dose of 200 mg intraperitoneally once daily or 200 mg orally twice a day.…”

“…Wang et al treated 13 Candida peritonitis patients with IV amphotericin B and oral fluconazole, leaving the catheter in place until the effluent cleared. 66 These patients were treated with antifungals for 1-2 more weeks, followed by catheter replacement about 4 weeks after the onset of treatment. However, of these 13 patients, none successfully returned to PD.…”