International Journal of Pancreatology, vol. 25, no. 1, 59–63, February 1999 © Copyright 1999 by Humana Press Inc. All rights of any nature whatsoever reserved. 0169-4197/99/25:59–63/$11.25

Case Report

Stenotrophomonas (Xanthomonas) maltophilia Infection in Necrotizing Pancreatitis Klaus E. Mönkemüller,1 Desiree E. Morgan,2 and Todd H. Baron*,3 1

University of Alabama at Birmingham, Birmingham, AL; 2Department of Radiology, University of Alabama at Birmingham, Birmingham, AL; and 3Departments of Medicine, Divisions of Gastroenterology and Hepatology, Mayo Medical School, Rochester, MN

Summary Conclusion: Although the therapy of infected pancreatic collections or organized pancreatic necrosis remains surgical, we have demonstrated that infected organized pancreatic necrosis can be treated endoscopically. Background: Stenotrophomonas (Xanthomonas) maltophilia has been increasingly recognized as a nosocomial pathogen associated with meningitis, pneumonia, conjunctivitis, soft tissue infections, endocarditis, and urinary tract infections. This organism is consistently resistant to imipenem, a drug commonly employed in patients with necrotizing pancreatitis to prevent local and systemic infections. Methods and Results: We report the first case of infected pancreatic necrosis by S. (X.) maltophilia. Our patient was treated successfully with endoscopic drainage of the pancreatic fluid collection and appropriate antibiogram-based antibiotic therapy. Endoscopic drainage has emerged as one of the treatment modalities for pancreatic fluid collections. Key Words: Pancreatitis; necrotizing pancreatitis; Stenotrophomonas; Xanthomonas; Imipenem; endoscopic therapy.

ventilation, prolonged stay in the intensive care unit (ICU), iv drug abuse, indwelling catheters, and previous antibiotic exposure (3–5). S. maltophilia has been associated with meningitis, pneumonia, conjunctivitis, soft tissue infections, endocarditis, and urinary tract infections (3,6,7). This organism is consistently resistant to third-generation cephalosporins and imipenem-cilastatin. The latter antibiotic is commonly given prophylactically in patients with necrotizing pancreatitis to prevent infection of the pancreatic collection (8). Trimethoprimsulfamethoxazole (TMP-SMX) has traditionally been the most active agent against S. maltophilia. Synergistic combinations of TMP-SMX with ciprofloxacin or ticarcillin-clavulanate appear promising in the eradication of this organism.

Introduction Stenotrophomonas (Xanthomonas) maltophilia, a multidrug-resistant organism, has been increasingly recognized as an important cause of nosocomial infection (1,2). The organism more commonly infects patients with predisposing risk factors, such as malignancy, immunosuppression, mechanical

Received August 31, 1998; Revised November 5, 1998; Accepted November 13, 1998 *Author to whom all correspondence and reprint requests should be addressed: Division of Gastroenterology and Hepatology, 200 First Street SW, Rochester, MN, 55905. E-mail: [email protected]

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60 We report a patient with acute necrotizing pancreatitis whose organized pancreatic fluid collection became infected with S. maltophilia. The patient was treated successfully with endoscopic drainage and antibiogram-based antibiotic therapy. Endoscopic drainage has emerged as one of the treatment modalities for pancreatic fluid collections. Although the therapy of infected pancreatic collections or organized pancreatic necrosis remains surgical, it has been previously demonstrated that endoscopic drainage may be a suitable option (9). To our knowledge, this is the first documented case of infection of a pancreatic collection by S. maltophilia. The isolation of this organism from necrotic pancreatic collection is alarming, because imipenem-cilastatin is commonly used as a prophylactic antibiotic in patients with necrotizing pancreatitis (8). This organism should be added to the list of potential pathogens that can affect patients with severe necrotizing pancreatitis, especially after prolonged stay in the ICU, immunosupression, or previous antibiotic exposure.

Case Report A 55-yr-old male was transferred to our hospital with severe acute necrotizing pancreatitis 72 h after the onset of illness. He had undergone a kidney transplant 2 yr prior and was maintained on daily prednisone, azathioprine, and cyclosporine. On physical exam, he was morbidly obese (body mass index 43 kg/m2), his temperature was 102°F, heart rate was 96, and blood pressure was 115/72. Abdominal examination revealed decreased bowel sounds, with diffuse tenderness, but no rebound. Admission laboratory values were: white blood count (WBC) 16,400/mm 3, hemoglobin 13.6 g/dL, platelets 237,000/mm3, glucose 260 mg/dL, and lactate dehydrogenase (LDH) 476 IU/L. Although the etiology of the patient’s pancreatitis was gallstones, liver enzymes were normalizing by the time of transfer (aspartate aminotransferase [AST] 45 IU/L, alkaline phosphatase 178 U/dL, total bilirubin 1.3 mg/dL). Ranson’s score was 6 (10), and admission APACHE II score was 12 (11). Dynamic iv contrast-enhanced helical abdominal CT scanning (CECT) revealed 30–50% pancreatic necrosis and grade D pancreatitis; the CT severity index was 7 (12) (Fig. 1). The patient was treated in the ICU. Imipenem-cilastatin (Primaxin®) was administered iv for 28 d to prevent infection of necrosis (8). From d 25 to 53, the patient International Journal of Pancreatology

Mönkemüller, Morgan, and Baron

Fig. 1. Dynamic iv and oral contrast-enhanced helical CT scan of the abdomen at the level of the celiac axis demonstrates diffuse low attenuation throughout the pancreatic glandular tissue in the body region, consistent with necrosis.

also was treated with iv vancomycin for two successive infections with Staphylococcus (line-related S. epidermidis infection and methicillin-resistant S. aureus-bacteremia). The patient’s hospital course was complicated by upper gastrointestinal bleeding from a duodenal ulcer, renal insufficiency, systemic toxicity, persistent fever, abdominal pain, nausea, and vomiting. A fine-needle aspiration of the collection performed on d 19 of the illness was sterile. On d 40, the necrotic pancreatic collection had reached 24 cm in maximal antero–posterior diameter, compromising the gastric lumen and producing complete gastric outlet obstruction (Fig. 2). Other indications for drainage of the pancreatic fluid collection were abdominal pain and persistent systemic toxicity as evidenced by fever (101.8°F), tachycardia (102/min) and leukocytosis (17,400/mm 3). Because of the patient’s poor operative status, the decision to proceed with endoscopic management of pancreatic necrosis was made by the multidisciplinary team caring for the patient (gastroenterologists, abdominal radiologists, nephrologists, pancreatic, and transplant surgeons). The patient and family gave informed consent for the procedure. Endoscopic transmural drainage of the collection was accomplished through the posterior wall of the stomach using the Seldinger technique as previously described (13). The collection was localized and Volume 25, 1999

Stenotrophomonas maltophilia Infection punctured with an 18-gage endoscopic needle (GAN-18, Wilson-Cook, Winston-Salem, NC) and an aspirate was sent for microbiological analysis. After creating the cystgastrostomy, 5800 mL of dark-chocolate brown-colored fluid containing visible solid necrotic debris was drained. The amylase level of the fluid was 38,940 IU/L. The cystgastrostomy patency was maintained with two 10Fr, 3 cm double-pigtail catheters. A 7Fr nasopancreatic (NP) lavage catheter (ENBD-7-Liguory, WilsonCook) was placed through the same transgastric tract into the collection for vigorous irrigation. The collection was irrigated via the NP catheter with 200 cc 0.4% sodium oxychlorosene solution (Clorpactin WCS-90, Guardian Laboratories, Hauppauge, NY) every 2 h, until CT documentation of collapse (Fig. 3). The drains were removed on d 51 after initial endoscopic drainage. Gram stain of the organized pancreatic fluid revealed the presence of Gram-negative bacilli and large number of polymorphonuclear leukocytes. The fluid cultures grew abundant S. maltophilia (McConkey and Blood/chocolate agars, Remel, Lenexa, KS). The anaerobic cultures (Columbia sheep blood, Bacteroides fragilis ID media and the chop-meat-broth, Remel) were sterile. The antibiotic susceptibility report (antibiogram) revealed that the organism was resistant to imipemem, tobramycin, and ceftazidime, and sensitive to TMP-SMX, ticarcillin/clavulanate, and piperacillin. Antibiotic therapy was changed to ticarcillin/clavulanate. One month after endoscopic pancreatic drainage, the patient underwent cholecystectomy for acute cholecystitis. The gallbladder wall was thickened, edematous, and friable. Cultures of the gallbladder revealed abundant S. maltophilia. Antibiogram at this time revealed susceptibility only to TMP-SMX. Oral antibiotic therapy with TMP-SMX was continued until removal of all endoscopic drains. The patient was discharged home on d 55 following initial presentation and has gradually recovered. Follow-up CECT 50 d following initial endoscopic drainage documented resolution of the collection.

Discussion S. maltophilia is a Gram-negative, nonenterobacteriacea, nonfermentative, aerobic bacillus (14) that International Journal of Pancreatology

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Fig. 2. Abdominal predrainage CT scan with oral, but without iv contrast material demonstrates progression of the pancreatic and retroperitoneal fat necrosis to a large homogeneous low-attenuation collection. The stomach is displaced anteriorly.

Fig. 3. Dynamic iv and oral contrast-enhanced helical CT scan of the abdomen at drainage conclusion demonstrates complete collapse of the necrotic pancreatic collection around the catheters.

was formerly classified in the genus Xanthomonas (15). In general, the organism is opportunistic, and colonizes or infects patients with predisposing risk factors, such as malignancy, immunosuppression, mechanical ventilation, iv drug abuse (3), previous antibiotic exposure (5), and indwelling catheters, such as urinary catheters, endotracheal tubes, Tenckhoff catheter, and Ommaya reservoir for treatment Volume 25, 1999

62 of meningeal carcinomatosis (4,16). The most common infections reported with this organism include meningitis, pneumonia, conjunctivitis, soft tissue infections, and endocarditis (2,3,5–7). Five cases of cholangitis in patients with biliary malignancies have been described (17). Therapy of this organism is complicated by its high resistance to multiple broad-spectrum antibiotics, including thirdgeneration cephalosporins and imipemem-cilastatin (18). S. maltophilia is sensitive to TMP-SMX or synergistic combinations of TMP-SMX with ciprofloxacin or ticarcillin-clavulanate (1,17). This case report is important for several reasons. We have shown that S. maltophilia can be a cause of infected pancreatic necrosis. To date, few studies have evaluated the microbiology of infected pancreatic fluid collections (19). The most common organisms reported to infect pancreatic fluid collections include Escherichia coli, Klebsiella pneumoniae, Enterococcus spp, and Pseudomonas aeruginosa (19); S. maltophilia has never been reported in association with pancreatic necrosis. S. maltophilia has been reported as a cause of biliary sepsis (17). In all cases, the patients had obstructive jaundice secondary to hepatobiliary malignancy and had undergone biliary tract instrumentation. This organism can easily colonize the biliary tract, especially when biliary catheters are in place (17). The source of S. maltophilia in our patient is unknown, but it likely originated from the biliary tree during the initial attack of gallstone pancreatitis. The presence of S. maltophilia in the cultures of the resected gallbladder supports this possibility, but our patient had other risk factors associated with the occurrence of this organism, such as immunosuppression, prolonged ICU stay, and previous use of broadspectrum antibiotics (3–5). The isolation of S. maltophilia from a pancreatic collection associated with necrotizing pancreatitis has important clinical implications. Previous reports have shown that the prophylactic administration of imipenem in patients with acute necrotizing pancreatitis may prevent bacterial infection of necrotic pancreatic tissue and, thus, improving patient outcome (8). S. maltophilia is a multidrug-resistant organism that is highly resistant against cephalosporins and carbapemems, such as imipenemcilastatin (18). The resistance results from the production of a β-lactamase enzyme by S. maltophilia International Journal of Pancreatology

Mönkemüller, Morgan, and Baron that destroys imipemem. In addition, the use of imipemem has been considered to confer greater risk for the acquisition of S. maltophilia, although this has not been proven in other studies (20). This organism does not need to be routinely included in the spectrum of pathogens against which prophylactic antibiotics should be used in patients with acute necrotizing pancreatitis. However, this case suggests that patients with pancreatic necrosis who continue to do poorly despite prophylaxis with imipenem may benefit from repeat culturing of the necrosis, especially in the setting of immunosuppression and prolonged ICU stay. Because the experience with S. maltophiliaassociated biliary and pancreatic infections has been limited, it is difficult to make therapeutic recommendations. Nevertheless, S. maltophilia bacterobilia need not be treated prophylactically in patients with functioning biliary catheters or in patients without symptoms and signs of infection, because prophylactic antibiotic therapy does not eliminate the bacteria from the bile (17). However, when infection does develop, prompt institution of effective antibiotic therapy with TMP-SMX and biliary tract decompression may result in a favorable outcome (17). We want to emphasize that the mainstay of therapy for infected pancreatic collections is prompt drainage. In general, pancreatic necrosis, whether sterile or infected, is considered to be definitively treated using only surgical techniques (21). However, recent reports have documented the feasibility of draining infected and noninfected organized pancreatic fluid collections, including abscesses and pancreatic necrosis endoscopically and percutaneously (22,23). Endoscopic drainage has emerged as one of the treatment modalities for pancreatic fluid collections (13,22). Our patient was treated successfully with endoscopic drainage of the organized pancreatic fluid collection, and therefore, we have demonstrated with this case that an infected organized pancreatic necrosis can be treated endoscopically. When caring for patients with necrotizing pancreatitis, physicians should keep in mind that S. maltophilia may superinfect the necrosis, despite the prophylactic use of imipenem-cilastatin. This article should serve as an impetus for further studies to confirm the association of this organism with pancreatic necrosis. Volume 25, 1999

Stenotrophomonas maltophilia Infection

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