Overview

Biliary Candidiasis refers to the infection of the gallbladder and/or the biliary tree caused by Candida spp. Even when Candida is isolated from the bile drained during gallbladder surgeries, such recovery is not enough proof that Candida plays a pathogenic role [274]. However, Candida spp. have been clearly implicated in some cases of biliary diseases:

  1. Cholecystitis [10, 843, 1043, 1423, 2054, 2084, 2216, 2380]. The majority of these cases were acalculous cholecystitis.
  2. Biliary tract obstruction (fungus ball) [955, 1412, 1435].
  3. Cholangitis [592].

These forms of biliary candidiasis are related to invasive candidiasis in the sense that candidemia or other deep organ involvement may occur simultaneously [322, 865, 1043, 1098, 1412, 2380]. The series by Diebel et. al studied 27 patients from whom Candida spp. had been isolated from gallbladder and other biliary tract sources. Eleven percent of these patients also had candidemia [592]. However, in other cases biliary candidiasis seems to occur by itself [10, 326, 955].

Epidemiology

Limited data are available regarding the incidence of biliary candidiasis. Most of the published literature consist of case reports [10, 322, 326, 843, 955, 1043, 1098, 1369, 1412, 1423, 1435, 2059, 2084, 2216, 2277, 2380]. The one exception is the study by Dieble et. al of 27 cases over a 10 year period [592].

Risk factors

Most patients have several of the usual risk factors for invasive candidiasis, even though some present with biliary candidiasis as their primary and only candidal infection. Populations at major risk would appear to be immunocompromised hosts:

  1. The most common type of immunosuppression related to the occurrence of biliary candidiasis is chemotherapy-induced neutropenia [10, 1412, 2059].
  2. Two cases have been reported of candidal cholecystitis in patients with AIDS [326, 406].
  3. Cases in patients with diabetes mellitus have also been published [322, 1369, 2380].

In addition, endoscopic retrograde cholecystopancreatogram (ERCP) [2216] and external biliary shunt/endoprosthesis [592] have been linked to the occurrence of biliary candidiasis.

Candida species and Biliary Candidiasis

All data are from case reports, and this may produce a major bias (e.g, rare species could be more frequently reported). Despite this, the prevalence of Candida albicans is evident [10, 322, 326, 955, 1043, 1098, 1369, 1412, 1435, 2084]. Two cases of biliary candidiasis caused by Candida glabrata and one by Candida parapsilosis, have also been published [1423, 2277, 2380].

Clinical Manifestations

Candidal cholecystitis presents with such classic biliary symptoms and signs as right quadrant tenderness, intolerance of oral feeding, nausea and vomiting, and fever. Post-cholecystectomy biliary tract obstruction presents also with classic obstructive signs and symptoms of abdominal pain, jaundice, and abdominal distension [955].

Specific Diagnostic Strategies

Besides the classic biochemical abnormalities seen in biliary tract obstruction or gallbladder inflammatory processes, the diagnosis of biliary candidiasis is usually based on the isolation of Candida from the gallbladder or biliary sources. Ideally, histopathologic confirmation of tissue invasion would be obtained [1412], but this is not always feasible or necessary. Several cases published in the literature have used data such as pure or persistent growth of Candida spp. from biliary sources [326, 955, 1369] plus clinical response only after a complete course of antifungal therapy [1369] as guides to the diagnosis.

Therapies

In view of the rarity of biliary candidiasis, limited data on therapeutic strategies are available. Medical and surgical therapy are often combined.

Surgical procedures

Some authors have reported cures when using surgical drainage alone [1435, 2054, 2380]. Evidence in favor of combining surgery with an antifungal agent is mostly anecdotal. Hiatt et. al reported 50% mortality due to ongoing sepsis in a group of 4 patients with acalculous cholecystitis who were treated with percutaneous cholecystostomy and interval cholecystectomy [1043].

Antifungal therapy

Effective antifungal therapy appears to be necessary. The following agents have been used:

  1. Amphotericin B. After intravenous administration of regular standard doses of 0.5 mg/kg/day, high concentrations of this drug in the biliary tract are obtained [10]. Successful results have been reported when using amphotericin B after surgery [1412, 2059]. Precise doses and length of therapy have not been studied, but we would recommend doses of 0.5mg/kg/day for 10-14 days.
  2. Ketoconazole. A single published case on the use of this agent emphasized the failure of 400mg/day given orally for 9 days [322]. This particular patient also had invasive candidiasis/candidemia. Oral therapy with an agent with such unreliable absorption as ketoconazole is definitively inappropriate by current standards.
  3. Fluconazole. A few reports of the use of fluconazole in candidal cholecystitis have been published [312, 1369]. Bozzette et al. measured levels of fluconazole in the bile by gas chromatography and found that they were were the same as those in the blood during the first 8 hours after an intravenous dose [312]. Further studies are needed to define the efficacy, dose and length of therapy with this agent on the treatment of biliary candidiasis.