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Biliary Candidiasis
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:
- Cholecystitis [10, 843, 1043, 1423, 2054, 2084, 2216, 2380]. The majority of these cases were acalculous cholecystitis.
- Biliary tract obstruction (fungus ball) [955, 1412, 1435].
- 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].
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:
- The most common type of immunosuppression related to the occurrence of biliary candidiasis is chemotherapy-induced neutropenia [10, 1412, 2059].
- Two cases have been reported of candidal cholecystitis in patients with AIDS [326, 406].
- 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].
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].
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.
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:
- 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.
- 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.
- 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.
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References
10. Adamson, P. C., M. G. Rinaldi, P. A. Pizzo, and T. J. Walsh. 1989. Amphotericin B in treatment of Candida cholecystitis. Pediatr. Infect. Dis. J. 8:408-411.
274. Bodey, G. P., and J. D. Sobel. 1993. Lower gastrointestinal candidiasis, p. 205-222. In G. P. Bodey (ed.), Candidiasis: Pathogenesis, Diagnosis, and Treatment. Raven Press, Ltd., New York.
312. Bozzette, S. A., R. L. Gordon, A. Yen, M. Rinaldi, M. K. Ito, and J. Fierer. 1992. Biliary concentrations of fluconazole in a patient with candidal cholecystitis: case report. Clin Infect Dis. 15:701-3.
322. Brooks, B. J., W. L. Williams, C. V. Sanders, and R. L. Marier. 1982. Apparent ketoconazole failure in candidal cholecystitis. Arch. Intern. Med. 142:1934-1935.
326. Brown, H., M. Talamini, and W. H. Westra. 1996. Xanthogranulomatous cholecystitis due to invasive Candida albicans in a patient with AIDS. Clin. Infect. Dis. 22:186-187.
406. Cervia, J. S., and H. W. Murray. 1990. Fungal cholecystitis and AIDS. J Infect Dis. 161:358.
592. Diebel, L. N., A. M. Raafat, S. A. Dulchavsky, and W. J. Brown. 1996. Gallbladder and biliary tract candidiasis. Surgery. 120:760-4; discussion 764-5.
843. Gips, M., M. Halpern, and Y. Wolloch. 1992. Acalculous Candida cholecystitis. Eur J Surg. 158:251-2.
865. Gomez-Mateos, J. M., A. Sanchez Porto, D. Martinez Parra, A. Royo Balbontin, A. Lesmes Serrano, and J. Aguilar Luque. 1988. Disseminated candidiasis and gangrenous cholecystitis due to Candida spp. J Infect Dis. 158:653-4.
955. Gupta, N. M., A. Chaudhary, and P. Talwar. 1985. Candidial obstruction of the common bile duct. British Journal of Surgery. 72:13.
1043. Hiatt, J. R., M. R. Kobayashi, J. E. Doty, and K. P. Ramming. 1991. Acalculous candida cholecystitis: a complication of critical surgical illness. Am Surg. 57:825-9.
1098. Irani, M., and L. D. Truong. 1986. Candidiasis of the extrahepatic biliary tract. Arch Pathol Lab Med. 110:1087-90.
1369. Lopez Onrubia, P., M. T. Bastida Vila, J. A. Martinez Martinez, J. R. Montfort, and N. Jove Vidal. 1995. Acute cholecystitis and wound infection due to Candida albicans. Eur. J. Clin. Microbiol. Infect. Dis. 14:253.
1412. Magnussen, C. R., J. P. Olson, F. V. Ona, and A. J. Graziani. 1979. Candida fungus balls in the common bile duct. Unusual manifestation of disseminated candidiasis. Arch. Intern. Med. 139:821-2.
1423. Mandak, J. S., B. Pollack, N. O. Fishman, E. E. Furth, M. L. Kochman, M. A. Acker, and G. R. Lichtenstein. 1995. Acalculous candidal cholecystitis: a previously unrecognized complication after cardiac transplantation. Am J Gastroenterol. 90:1333-7.
1435. Marcucci, R. A., H. Whitely, and D. Armstrong. 1978. Common bile duct obstruction secondary to infection with Candida. J Clin Microbiol. 7:490-2.
2054. Schneiderman, J., A. Bass, and B. Morag. 1987. Cryptogenic Candida albicans cholecystitis. Br J Surg. 74:649.
2059. Schreiber, M., l. bLACK, Z. Noah, S. T. Shulman, R. Yogev, and F. R. Venezio. 1982. Gallbladder candidiasis in a leukemic child. Am J Dis Child. 136:462-463.
2084. Shah, M. D., W. F. Berman, M. A. Turner, and T. M. Kerkering. 1993. Candida albicans cholecystitis. Am J Gastroenterol. 88:1792-3.
2216. Takano, H., T. Yoshikawa, K. Nishida, Y. Terasawa, M. Fujii, A. Yamaguchi, B. Nishioka, and M. Kondo. 1996. Candida cholecystitis as an unusual complication of endoscopic retrograde cholangiography. Endoscopy. 28:790-1.
2277. Valainis, G. T., R. A. Sachitano, and G. A. Pankey. 1987. Cholecystitis due to Torulopsis glabrata. J Infect Dis. 156:244-5.
2380. Warren, G. H., and S. Marsh. 1982. Granulomatous Torulopsis glabrata cholecystitis in a diabetic. Am J Clin Pathol. 78:406-10.
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