YALE JOURNAL OF BIOLOGY AND MEDICINE 75 (2002), pp. 285-291. Copyright @2003. All rghts reserved. MEDICAL REVIEW Staphylococcus aureus Cholecystitis: A Report of Three Cases with Review of the Literature Shehzad S. Merchanta and Ann R. FalseyaAb7c aDepartment of Medicine, Rochester General Hospital and bUniversity of Rochester School of Medicine and Dentistry, Rochester, New York Infection of the hepatobiliary system is most commonly dtue to enteric bacteria. We report three unusual cases of acute cholecystitis in which Staphylococcus aureus was the primary pathogen. Infection of the gallbladder with this organism has been rarely described and may be associated with gallstones and obstnrctive disease as well as acalculous cholecystitis in the setting ofstaphylococcal bacteremia and endocarditis. Two ofourpatients had multiple chronic medical conditions and were infected with oxacillin-resistant S. aureus (ORSA) suggesting nosocomial acquisition. Including our cases with a review ofthe literature, three ofnine reports ofS. aureus cholecvstitis were associated with infectious endocarditis. Thus, thefinding ofS. aureus cholecystitis with bacteremia is rare and shouldpromnpt an investigation for a possible endovascularfocus ofinfection. INTRODUCTION primary mechanism by which bacteria Acute cholecystitis is most commonly enter the bile. The organisms most com- associated with obstruction of the cystic monly isolated in biliary tract infections duct leading to ischemia and inflammation are Escherichia coli, Klebsiella species [1]. In normal individuals the biliary tract (Sp.)d, Enterococcus sp. and aniaerobes [5, is sterile, however, 20 to 50 percent of 6]. Staphylococci are usually associated patients with chronic cholecystitis and 40 with infections of the skin and soft tissues to 75 percent of patients with acute chole- and are rarely reported as pathogens in dis- cystitis have positive bile cultures [2, 3]. eases of the gallbladder. In this report, we Several modes of infection have been pos- describe three patients with Staphylococ- tulated, including ascending infection due cus aureus acute cholecystitis seen over a to reflux ofduodenal contents, blood-borne two-year period and summarize the pub- infection and infection spread through the lished English literature on staphylococcal portal-venous channels [4]. Ascending infec- infections of the gallbladder. tion from the duodenum is felt to be the CTo whom all correspondence should be addressed: Ann R. Falsey, M.D., Rochester General Hospital, 1425 Portland Avenue, Rochester, NY 14621. Tel.: 585-922-4339; Fax: 585-922-5168; E-mail: [email protected]. dAbbreviations: CT, computed tomography; IV, intravenous; NIDDM, non-insulin dependent diabetes mellitus; ORSA, oxacillin-resistant S. aureus; sp., species; TEE, transesophageal echocardiogram; WBC, white blood cell. Received: August 10, 2002; Returned for revisions: November 12, 2002; Accepted: March 17, 2003 285 286 Merchant and Falsey: Staphylococcus aureus cholecystitis METHODS discontinued. By hospital day eight, the S aureus was isolated from blood or patient became afebrile, abdominal tender- bile cultures by the Rochester General ness resolved and the WBC count returned Hospital Clinical Microbiology Laboratory. to normal. Trans-esophageal echocardiogram Identification ofstaphylococci was initially (TEE) revealed normal cardiac valves. She based on colony morphology and Gram was discharged on a three-week course of stain with confirmation by positive cata- nafcillin and did well. lase reaction. Suspected S. aureus isolates Patient two was a 73-year-old female were confirmed by positive coagulase tube admitted to the hospital with one day of test. Antibiotic susceptibility was performed severe epigastric pain, melena, and nausea. with the Vitek automated system (bioMerieux She had an extensive past medical history Vitek Inc., Hazelwood, Missouri). Oxacillin that included diverticular bleeding, coronary resistance was confirmed by growth of the artery disease, aortic valve replacement, isolate on Mueller-Hinton agar plates con- hypertension, atrial fibrillation, menin- taining 6 ,ug/ml of oxacillin. gioma, psoriasis, and non-insulin depen- dent diabetes mellitus (NIDDM). She had a recent prolonged hospital admission for CASE REPORTS gastrointestinal bleeding and a hip fracture. Patient one was a 64-year-old woman During that time she had no S. aureus infec- admitted with right upper quadrant pain, tions or active skin problems. fever and nausea for 48 hours. Her history On admission she was afebrile. Cardiac was significant for cholelithiasis, hyper- exam revealed a 3/6 systolic murmur, and tension, hypothyroidism, and pernicious her abdomen was tender in the epigastrium anemia. She had no history of diabetes and left upper quadrant. Because of poor mellitus, recent infections, skin disorders, venous access, a central venous catheter was or antibiotic use. On admission her tem- placed. She was treated with IV fluids alnd perature was 101.4'F and her abdomen antibiotics. Endoscopy on hospital day two was tender in the right upper quadrant. No showed no evidence of bleeding. Her ini- cardiac munrur was heard. White blood tial hospital course was complicated by cell (WBC) count was 17.4 x 109 cells/L Clostridium difficile colitis that responded and liver function tests (serum bilirubin, to oral metronidazole. Blood cultures at that alkaline phosphatase and transaminases) time were sterile. On hospital day 13, her IV were with in normal limits. Abdominal catheter site was noted to be purulent and ultrasound showed a distended gall bladder the central line was removed. The catheter tip with pericholic fluid. Despite intravenous grew S. aureus resistant to oxacillin, clin- (IV) fluids and ampicillin-sulbactam, she damycin, erythromycin, and quinolones. remained symptomatic and underwent The following day, the patient became cholecystectomy on hospital day two. The febrile and lethargic, and she was begun on gallbladder contained many stones, and IV vancomycin. She required intubation histopathologic evaluation showed acute and transfer to the medical intensive care and chronic inflammation. Tissue Gram stain unit on hospital day 15. Two sets of blood was not done. The postoperative course was cultures grew ORSA with the same antibi- complicated by delirium and high fever. ogram as the catheter tip. A TEE revealed Admission blood cultures grew oxacillin- a normal mechanical valve and no vegeta- sensitive S. aureus in one of four bottles, tions. Blood cultures were persistently pos- and culture ofthe gallbladder was positive itive one week after removal ofthe catheter, for 3+ £. aureus and 3+ alpha-hemolytic and gentamicin and rifampin were added. streptococci. On hospital day five, nafcillin Gradually, the patient improved and by hos- was given and previous antibiotics were pital day 20 fevers resolved and blood cul- Merchant and Falsey: Staphylococcus aureus cholecystitis 287 tures became sterile. On hospital day 22, sage of gallstones and that were managed she developed fever, right upper quadrant medically. During an episode ofpancreatitis tenderness, elevated levels ofserum alkaline three months earlier, he underwent endo- phosphatase (225 U/L [39-117, normal]) scopic retrograde cholangio-pancreatography and gammaglutamyl transpeptidase (212 with sphincterotomy. He had no history of U/L [1-64 normal]) and WBC of 14.0 x staphylococcal infections or skin problems 109 cells/L. Abdominal computed tomog- during previous admissions. raphy (CT) revealed a distended, thick- On admission, the patient appeared walled gallbladder, pericholic fluid, and a uncomfortable and had mild icterus. He was calculus in the cystic duct. Under ultra- afebrile. The abdomen was tender in the sound guidance, a percutaneous cholecys- right upper quadrant. The remainder ofthe tomy tube was placed, and thick fluid with exam was unremarkable. Total bilirubin several stones was drained. Gram stain of was 2.1 mg/dL (0-1.0, normal range), alkaline the bile showed many Gram-positive cocci phosphatase was 165 U/L (39-117), and in clusters and cultures grew 4+ ORSA. SGOT was 107 U/L (7-37). Abdominal Blood cultures at the time ofthe procedure ultrasound revealed a distended, thick were negative. After drainage, fever and walled gallbladder with stones and sludge. abdominal tenderness resolved. Gentamicin The patient was started on ampicillin-sul- was discontinued after two weeks, and she bactam and ciprofloxacin. He was felt to be completed six weeks of vancomycin and high risk for surgery, and medical manage- rifampin for presumed endovascular infec- ment was undertaken. On hospital day two, tion given her prolonged bacteremia. On admission blood cultures grew Gram-posi- hospital day 70, the gallbladder drain was tive cocci in clusters, and IV vancomycin dislodged. Over the next two months, the was added. The organism was subsequently patient developed progressive azotemia identified as ORSA with resistance to ery- requiring hemodialysis. In her fifth month thromycin, clindamycin, and quinolones. of hospitalization, she again developed Transthoracic echocardiogram showed no right upper quadrant tenderness and blood vegetations, and TEE was not performed cultures grew ORSA. Abdominal ultra- because of esophageal varices. Abdominal sound did not reveal stones or obstruction. CT confirmed a distended gallbladder with She was re-started on antibiotics, however, pericholecystic fluid. The liver was enlarged her family decided against aggressive treat-