title: 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.
authors.affiliation: Renal Unit, Department of Medicine & Geriatrics, Kwong Wah Hospital, Hong Kong SAR, China. apnwong@alumni.cuhk.net
authors.forename: Ping-Nam
authors.initials: PN
authors.lastname: Wong
authors.forename: Kin-Yee
authors.initials: KY
authors.lastname: Lo
authors.forename: Gensy M W
authors.initials: GM
authors.lastname: Tong
authors.forename: Shuk-Fan
authors.initials: SF
authors.lastname: Chan
authors.forename: Man-Wai
authors.initials: MW
authors.lastname: Lo
authors.forename: Siu-Ka
authors.initials: SK
authors.lastname: Mak
authors.forename: Andrew K M
authors.initials: AK
authors.lastname: Wong
mesh_terms: D000284:Administration, Oral; D000666:Amphotericin B / Q000008:administration & dosage*; D000935:Antifungal Agents / Q000008:administration & dosage*; D002177:Candidiasis / Q000188:drug therapy*; D002408:Catheters, Indwelling; D020878:Device Removal; D004359:Drug Therapy, Combination; D005260:Female; D005437:Flucytosine / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010538:Peritonitis / Q000188:drug therapy*
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B; D005437:Flucytosine