Secondary pancreatic infections develop in only about 5% of cases of acute pancreatitis; however, this complication accounts for a disproportionately high percentage of morbidity and mortality.^1-14 Pancreatic infections have recently been subdivided into pancreatic abscess, infected pancreatic necrosis, and infected pseudocyst.^12-14 All three types of secondary pancreatic infections are usually due to bacterial organisms and typically involve enteric flora. Less commonly, Candida albicans has been cultured from pancreatic infections, almost always as part of a polymicrobial infection.^{4,6,9,10,15-17} In the following case, C albicans was the sole microorganism isolated from an infected pancreatic pseudocyst. Factors that may have predisposed the patient to this condition are discussed.

CASE REPORT
A 40-year-old white man was hospitalized after having severe abdominal pain, nausea, and vomiting for 1 day. He had a history of calcific pancreatitis, alcoholic cirrhosis, atherosclerotic heart disease with congestive heart failure, and insulin-dependent diabetes mellitus. He admitted to continued alcohol abuse. Initial laboratory evaluation revealed serum amylase of 652 U/L (normal, 24 to 134 U/L) and serum lipase of 7,960 U/dL (normal, 4 to 24 U/dL).

The patient's condition deteriorated rapidly after admission and included respiratory failure requiring mechanical ventilation. He had multiple electrolyte abnormalities and marked leukocytosis. During the first 48 hours of hospitalization, the patient had eight of RansonÕs prognostic criteria.18 Before he was treated with broad spectrum antibiotics, multiple cultures were done, all of which were negative for organisms. Total parenteral nutrition was begun on hospital day 9. Abdominal ultrasonography revealed no gallstones or biliary dilatation. Computed tomography (CT) revealed edematous pancreatitis with some calcification and a moderate amount of ascites. Paracentesis revealed a white blood cell (WBC) count of 5,600/mm3 with 69% polymorphonuclear neutrophil leukocytes (PMNs), protein of 0.9 g/dL, and amylase of 431 U/L. Serum amylase at that time was 67 U/L. Ascites cultures were repeatedly negative for organisms.

Despite a stormy course, the patient slowly improved. Intermittent low-grade fever prompted several courses of antibiotics given empirically, despite repeatedly negative cultures. Serial CT scans revealed severe, edematous pancreatitis, which evolved into a pancreatic phlegmon complicated by portal vein thrombosis. Multiple pancreatic pseudocysts were seen on follow-up CT on hospital day 43 .

Because of intermittent fever, on hospital day 48, the largest pancreatic fluid collection was aspirated under CT guidance, with placement of a drainage catheter. Approximately 70 mL of cloudy, green, odorless fluid and debris was obtained. Analysis of the pseudocyst fluid revealed RBC 55,000/mm3 and WBC 38,000/mm3 with 26% PMNs, 44% lymphocytes, and 30% degenerated cells. Gram's stain of the fluid revealed 3+ yeast with no bacteria. Cultures of the fluid grew pure Candida albicans, which was also isolated from a pleural fluid specimen obtained 3 days later. Candida had been cultured from a single sputum specimen about 1 month earlier.

Therapy with amphotericin B was begun and broad spectrum antibiotics were continued. Follow-up CT revealed several smaller pancreatic pseudocysts that were not drained by the single percutaneous catheter. The patient was thought to be unfit for open surgical drainage due to his poor general medical condition.

One week after the pseudocyst aspiration, the patient had hypotension attributed to sepsis. Mechanical ventilation and blood pressure support were again required. His course was further complicated by acute renal failure and esophageal variceal bleeding. He slowly improved, though C albicans alone was repeatedly cultured from both pleural and pancreatic fluid despite amphotericin B therapy. On hospital day 75, pleural fluid cultures revealed Enterococcus faecalis and methicillin-resistant Staphylococcus aureus. Four days later, the patient was unresponsive after apparent vomiting with aspiration. He was successfully resuscitated but remained unresponsive. Progressive hypotension developed and the patient died. Postmortem examination revealed severe acute pancreatitis with saponification, fat necrosis, and hemorrhage into the adjacent omentum. A pseudocyst containing greenish exudate was found between the pancreas and stomach. Histologic examination of the pancreas revealed Candida organisms. Micronodular cirrhosis and bilateral pneumonia were also seen.

Postmortem blood cultures grew E faecalis, methicillin-resistant S aureus, and Enterobacter sakazakii. Cultures of lung tissue grew methicillin-resistant S aureus only. Unfortunately, the pseudocyst fluid was not cultured postmortem.

DISCUSSION
Secondary infection of the pancreas is a dreaded complication of acute pancreatitis due to its high rate of associated morbidity and mortality. In one review, the average surgical mortality rate was 39.3%.12 Death is most often due to persistent or recurrent sepsis, gastrointestinal tract bleeding, or multiple organ system failure. Emphasis has been given to differentiating pancreatic abscess from other types of secondary pancreatic infections, ie, infected pancreatic necrosis and infected pseudocysts.12-14 Fedorak et al14 reported a statistically significant difference in mortality for separate categories of infection: 9% for infected pseudocyst, 25% for pancreatic abscess, and 48% for infected pancreatic necrosis. Nonetheless, these entities have several important features in common. Infectious complications occur most frequently in patients with severe pancreatitis who tend to have a greater number of Ranson's prognostic criteria than do patients without pancreatic infections.5,6,10 These infections usually become apparent 2 to 3 weeks (or longer) after the onset of pancreatitis.7,9,12-14,19 Abdominal pain, tenderness, nausea and vomiting, leukocytosis, and fever are all commonly present, but each is nonspecific.

Gerzof et al20 showed that when there is a high clinical suspicion of pancreatic bacterial infection, CT-guided aspiration is a safe and accurate means of identifying such an infection. However, these authors found that this procedure was indicated in only 5% of all patients with acute pancreatitis based on their selection criteria of fever, leukocytosis, and a pancreatic inflammatory mass. In the case reported here, it is possible that aspiration at an earlier date would have more quickly led to the diagnosis of candidal pancreatic infection. This was not done, since the patient was already receiving broad spectrum antibiotics, even before a pancreatic phlegmon had developed. As discussed by Richter et al,21 even if a culture positive for Candida is obtained from a pancreatic abscess, the significance of such an isolate may not be immediately appreciated, leading to delayed antifungal therapy.

Pancreatic infections are nearly always bacterial, are commonly polymicrobial, and are most often due to gut flora. Though many series do not provide details of the bacteriologic isolates, C albicans is the fungus that has most frequently been reported in pancreatic infections. Candida has almost always been found in association with concomitant bacte- rial infection.6,9,10,15-17,21 C albicans or other fungal isolates have been reported in 4.5% to 10.9% of patients with pancreatic abscess.4,6,7,9,10,14 However, C albicans infection of the pancreas in the absence of bacterial coinfection is much less common. During this review, only 10 previous reports of other such cases were found.4,7,21-26 There have also been reports of pancreatic fungal infections due to Aspergillus27 and Torulopsis glabrata.7,28

A number of factors have been identified that predispose patients to disseminated candidiasis, several of which were present in our patient. Primary is the use of systemic antibiotics, which may lead to candidal overgrowth.29,30 Other predisposing conditions include immunosuppressive therapy, parenteral hyperalimentation, malignancy, gastrointestinal tract surgery, and intravenous catheters. Diabetes mellitus predisposes patients to mucocutaneous candidiasis but not to systemic candidiasis.29,30

Though Candida infection will no doubt remain a rare complication of acute pancreatitis, the predisposing factors seen in our patient are commonly present in many patients with severe, acute pancreatitis. In retrospect, the only possible clue to systemic C albicans infection in our patient was a sputum culture positive for Candida a month earlier. Because he had diabetes, this was attributed to sputum colonization. Multiple blood cultures over a period of 6 weeks were all consistently negative for bacteria, as was the pseudocyst aspirate, suggesting that Candida was the only microorganism present in the pseudocyst. Eradication of a preceding pancreatic bacterial infection is unlikely, since antibiotics alone are believed to be insufficient to cure such infections.19

Of the 11 reported cases of pancreatic infection due to C albicans alone, 3 patients died, 5 survived, and outcome was not specified in 3. All of the reported survivors received amphotericin B and 4 required surgical drainage.21,22,25,26 Percutaneous drainage without surgery was successful in only 1 case.24 Although very few patients with this condition have been described, mortality from candidal pancreatic infections is likely to be high, as in any case of severe pancreatitis complicated by infection. Since factors that might predispose a patient to disseminated candidiasis are present in most patients with severe pancreatitis, the possibility of candidal involvement must considered in any patient with suspected pancreatic infection.

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