A novel treatment of candidal cholecystitis using amphotericin B cholecystostomy irrigation

May 25, 2007
Surgical Rounds®, August 2006, Volume 0, Issue 0

Shalini R. Anne, Thoracic Surgery Fellow, SUNY Upstate Medical Center, Syracuse, NY; Peter L. Faries, Site Chief of Vascular Surgery, Division of Vascular Surgery, New York-Presbyterian Hospital, New York, NY; Gregg S. Landis, Director of Endovascular Surgery, Department of Surgery, New York Hospital Queens, Flushing, NY

Shalini R. Anne, MD

Thoracic Surgery

Fellow

SUNY Upstate Medical

Center

Syracuse, NY

Peter L. Faries, MD

Site Chief of Vascular

Surgery

Division of Vascular

Surgery

New York-Presbyterian

Hospital

New York, NY

Gregg S. Landis, MD

Director of

Endovascular Surgery

Department of Surgery

New York Hospital

Queens

Flushing, NY

Candidal infection of the gallbladder is an uncommon cause of cholecystitis. Most cases are found in acutely ill patients with acalculous cholecystitis. These patients often have disseminated candidiasis, thought to occur as a secondary infection of the biliary tree. Patients with candidal cholecystitis are often septic, immunocompromised, and have multiorgan dysfunction. We report the case of a patient whose candidal cholecystitis was refractory to intravenous (IV) antifungal agents but was treated successfully with percutaneous instillation of amphotericin B directly into the gallbladder.

Case report

A 33-year-old man came to the emergency department with multiple stab wounds to his abdomen. The patient was in extremis from hemorrhage and had to be resuscitated. During abdominal exploration, multiple enterotomies were repaired and several lacerations to bleeding mesenteric arteries were ligated. Gross peritoneal soilage was noted. Postoperatively, the patient required substantial fluid resuscitation and ventilatory support. On postoperative days 4, 6, 11, 19, and 26, the patient underwent re-exploration of the abdomen to drain multiple fluid collections and control a pancreatic fistula.

Several positive bacterial cultures were obtained from these intra-abdominal fluid collections and from infected central venous access lines. Over a 4-week span, the patient was treated with multiple courses of IV antibiotics, including ampicillin, gentamicin, metro-nidazole, vancomycin, and ciprofloxacin.

Candida parapsilosis

C parapsilosis

On postoperative day 35, the patient showed renewed signs of sepsis, including pyrexia and hypotension, with concomitant elevation in his liver function tests. Blood cultures were positive for , sensitive to amphotericin B. A computed tomography scan of his abdomen suggested acalculous cholecystitis. Abdominal ultrasonography showed pericholecystic fluid and thickening of the gallbladder wall. Dense, prohibitive, right upper quadrant adhesions had been noted during the previous abdominal surgeries, and percutaneous cholecystostomy was undertaken. The patient’s bile cultures grew , sensitive to amphotericin B, and an IV regimen of amphotericin B was initiated.

Candida

After 10 days of IV amphotericin B therapy and the removal of all vascular and urinary indwelling catheters, the patient’s blood and bile cultures continued to test positive for candidemia. Despite the presence of a draining cholecystostomy tube, the patient continued to have ultrasonographic findings consistent with cholecystitis. Because the gallbladder was the putative source of the ongoing candidemia, we elected to irrigate the cholecystostomy tube with amphotericin B. Three aliquots of 25 mL of amphotericin B solution (5 mg in 10 mL of 5% dextrose sterile water) were instilled into the cholecystostomy tube and allowed to dwell for 30 minutes. This process was repeated three times daily for 7 days. By day 5 of this treatment, the patient showed no signs of sepsis and his blood and bile cultures were negative for . The cholecystostomy remained in place, growing no new fungi for the remainder of the patient’s hospitalization. The patient died of unrelated pulmonary complications approximately 2 months later.

Discussion

Candida albicans

Candidiasis is being identified with increasing frequency in immunocompromised patients who are hospitalized due to trauma, malignancy, diabetes, corticosteroid use, chemotherapy, or sepsis. Fungal infections of the biliary tree, however, are uncommon. Morris and colleagues estimated the rate of candidal biliary tract disease to be 0.01% of hospitalizations.1 Of the 692 cholecystectomies addressed in their study, 1.3% harbored candidal infection. It is unclear whether these isolates represented invasive infections or simple colonization. There have been reports of nearly all pathogenic fungal species infecting the biliary tree, with being the most common.1 The biliary tree is usually seeded as a result of disseminated candidiasis from primary sources such as the urinary bladder and indwelling vascular catheters. Despite advancements in critical care and antifungal therapies, candidal cholecystitis is associated with a near 100% mortality rate in intensive care unit patients.2

Cholecystectomy is curative in patients whose infections are limited to the gallbladder. Morris and colleagues’ internal series and literature review found that in the absence of extravesicular infection, parenteral antifungals were probably not required and good outcomes were noted.1 Yet, many critically ill patients cannot undergo cholecystectomy without significant risk. In our patient, the dense adhesions precluded cholecystectomy.

Treating candiduria with amphotericin B urinary bladder irrigation has been proved safe and effective. Although bladder irrigation is used less often than oral and IV antifungal agents for treating symptomatic candiduria, it remains an important modality in patients with refractory candiduria. Greater concentrations of amphotericin B can be achieved through instillation directly into the urinary bladder. Given our patient’s lack of response to parenteral antifungal agents, we sought to produce similarly elevated luminal concentrations of amphotericin B in the gallbladder.

Intravenously delivered amphotericin B is partially excreted into bile at 2 to 7 times the serum concentration.3 This likely contributes to its efficacy in treating fungal cholecystitis. Yet in our patient, it proved ineffective in eradicating either the gallbladder infection or the candidemia. The presence of a luminal fungus ball, similar to that described by Reeves and associates, could have confounded the parenteral treatment, but none of this case’s imaging studies found luminal filling defects.4 Our patient’s poor hepatic performance at the time may have also limited his body’s ability to concentrate the antifungal agents adequately. Only amphotericin B cholecystostomy irrigation succeeded in eradicating fungi from this patient’s bile and blood cultures.

Conclusion

The technique presented in this case report offers an alternative to parenteral therapy in refractory cases. Given the excessive morbidity and mortality rates associated with candidal cholecystitis, prompt treatment via a percutaneous cholecystostomy is an attractive alternative to open cholecystectomy for critically ill and surgically prohibitive patients.

References

1. Morris AB, Sands ML, Shiraki M, et al. Gallbladder and biliary tract candidiasis: nine cases and review. Rev Infect Dis. 1990;12(3): 483-489.

2. Diebel LN, Raafat AM, Dulchavsky SA, et al. Gallbladder and biliary tract candidiasis. Surgery. 1996;120(4): 760-764.

3. Adamson PC, Rinaldi MG, Pizzo PA, et al. Amphotericin B in the treatment of Candida cholecystitis. Pediatr Infect Dis J. 1989;8(6):408-411.

4. Reeves AR, Johnson MS, Stine S. Percutaneous diagnosis and treatment of biliary candidiasis. J Vasc Interv Radiol. 2000;11(1):107-109.