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Cholecystitis Related to Brucella melitensis: A Rare Presentation

Gunal, Esen Kasapoglu MD; Topkaya, Aynur Eren MD; Arisoy, Ayse MD; Aydiner, Omer MD; Gökçen, Gökhan MD; Aksungar, Fehime Benli MD; Karabulut, Murat MD; Tulbek, M. Yasar MD; Aytug, O. Necip MD

Infectious Diseases in Clinical Practice: March 2008 - Volume 16 - Issue 2 - pp 134-136
doi: 10.1097/IPC.0b013e318146896b
Case Reports

Although human brucellosis is a multisystemic disease, cholecystitis due to Brucella species is a rare manifestation. Here we present a 64-year-old woman with Brucella cholecystitis who was admitted to the hospital with fever and arthralgias for the last 10 days. Her complete blood count and blood chemistry were unremarkable other than C-reactive protein: 3.08 mg/dL (<0.5 mg/dL), aspartate transaminase: 70 U/L (<65 U/L), alanine transaminase: 71 U/L (<37 U/L), γ-glutamyl transferase: 748 U/L (<85 U/L), and alkaline phosphatase: 285 U/L (<136 U/L). On the second day of hospitalization, she complained of diffuse abdominal pain, and physical examination revealed Murphy sign. Abdominal ultrasonography was consistent with acute cholecystitis. She was given ciprofloxacin because she refused cholecystectomy. On the 10th day of admission, she still had fevers, and Brucella melitensis was recovered from blood culture specimens. Brucella agglutination tests were also found to be positive. She was symptom free after the fifth day of introduction of streptomycin, doxycycline, and rifampicin.

Division of Rheumatology, Department of Internal Medicine, Maltepe University Medical Faculty, Maltepe, Istanbul, Turkey.

Address correspondence and reprint requests to Esen Kasapoglu Gunal, MD, Division of Rheumatology, Department of Internal Medicine, Maltepe University Medical Faculty, Maltepe, Istanbul, 34843 Turkey. E-mail:

Brucellosis is a zoonosis due to Brucella melitensis1 and endemic especially in Mediterranean areas, parts of south and Central America, and east and western Africa.2,3 Human brucellosis usually presents with fever, arthritis, arthralgia, and malaise, and granulomatous hepatitis is common among gastrointestinal complications. Wide-range clinical symptoms such as cholecystitis, endocarditis, and meningitis can also be seen, although rarely.2,4 Here we present a 64-year-old woman with Brucella cholecystitis.

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A 64-year-old woman was admitted to the rheumatology outpatient clinic with complaints of fever accompanied by chills, malaise, and arthralgias for the last 10 days. Physical examination was unremarkable other than body temperature of 39°C on the first day of hospitalization. Laboratory investigations were as follows: hemoglobin, 11.6 g/dL; hematocrit, 36.3%; white blood count, 6800 cells/μL; thrombocytes, 118,000/μL; erythrocyte sedimentation rate, 28 mm/h; C-reactive protein, 3.08 mg/dL (<0.5 mg/dL); blood urea nitrogen, 7 mg/dL, creatinine, 0.8 mg/dL; aspartate transaminase, 70 U/L (<65 U/L); alanine transaminase, 71 U/L (<37 U/L); γ-glutamyl transferase, 748 U/L (<85 U/L); alkaline phosphatase, 285 U/L (<136 U/L); total protein, 7.2 g/dL; albumin, 3.5 g/dL; total bilirubin, 0.7 mg/dL; and direct bilirubin, 0.28 mg/dL. Viral hepatitis markers (hepatitis B surface antigen, anti-hepatitis C virus) were negative. On the second day of hospitalization, she complained of diffuse abdominal pain. Physical examination revealed Murphy sign. Abdominal ultrasonography showed hepatomegaly (167 mm), and there were small-sized polypoid lesions in the gallbladder which were regarded to be associated with chronic inflammation (Fig. 1). The patient was considered as having acute cholecystitis, and on refusing cholecystectomy, she was given ciprofloxacin 2 × 200 mg/d intravenously, after blood culture had been taken in BACTEC 9050 blood culture media (Becton Dickinson and Co, Sparks, Md). Because she still had fever after 5 days of initiation of antibiotherapy, ciprofloxacin was changed to cefotaxime sodium 3 × 2 g/d intravenously and ornidazole 2 × 500 mg/d orally. Abdominal magnetic resonance imaging showed that gallbladder wall thickness was minimally increased because of pericholecystic collection and debris-forming air-fluid level (Fig. 2).

On the third day of incubation, preparate with positive signaling in radiometric system was stained with Gram staining. Gram-negative, small coccobacilli were detected. The specimen was subcultured both in chocolate agar and 5% sheep blood agar and incubated in 10% CO2 environment at 35°C temperature. Colonies were small, bright, and S-shaped, and both catalase and oxidase tests were positive. As the coccobacilli reproduced both with and without CO2, urease test positive after 2 hours, and not producing H2S, it was regarded as B. melitensis on the 10th day of antibiotherapy. This finding was validated by positive rose bengal, Wright (1/320) (Veterinary Control and Research Institute, Istanbul, Turkey), and Wright with Coombs tests in the preserved serum specimens taken on the day of hospitalization. On 10th day of antibiotherapy, she still had fever. She stated about consuming homemade cheese on questioning. She was diagnosed as having B.melitensis-related cholecystitis, and antibiotherapy was changed to streptomycin (1 × 1 g intramuscularly for 2 weeks), doxycycline (2 × 100 mg orally for 2 months), and rifampicin (600 mg orally for 2 months). She was symptom-free after 5 days of appropriate antibiotherapy. Abdominal ultrasonography was unremarkable after 2 months. After 90 days, Wright test was negative (1/80), and abdominal ultrasonography was still unremarkable.

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More than 90% of acute cholecystitis cases are related to gallstones and microorganisms from normal intestinal flora, such as Escherichia coli, Klebsiella, and Enterobacter, and anaerobics are usually the etiologic agents. Brucella as the cause of cholecystitis is very rare and presented only as case reports.4,5 To our knowledge, there are 20 cases of cholecystitis due to Brucella species, excluding this case (Table 1).1,6 Thirteen of the patients with cholecystitis due to Brucella species in the literature were male, mean age was 48 years (6-72 years), and only 3 had risk factor for brucellosis (2 shepherds, 1 microbiologist, present case consumed homemade cheese also). All of the patients presented with clinical symptoms, and results of physical examination were consistent with acute cholecystitis. All patients experienced fever for days to weeks. Only 2 patients with cholecystitis due to Brucella species had not undergone cholecystectomy. Before the case reported in 1947 by Hewlett and Ernstene,7 the patients had not been given antibiotherapy for brucellosis after cholecystectomy. The etiologic organism according to bile or blood cultures was B.melitensis in 10 patients excluding this case, Brucella abortus in 3, and Brucella suis in only 1 patient. In 5 patients, Brucella species could not be differentiated, and in 1 patient, neither blood nor bile culture was available. Ten patients with cholecystitis due to Brucella species in the literature have gallstones.4,6 Gallstones could not be detected in our Brucella cholecystitis patient also.

Our patient with cholecystitis due to Brucella species did not undergo cholecystectomy because she refused. After 60 days of antibiotherapy, she was still symptom-free, Wright test was negative, and abdominal ultrasonography was unremarkable; therefore, the indication of cholecystectomy was also debatable.

Combination of antimicrobials is recommended owing to the unacceptably high rate of relapse with single-drug therapy for brucellosis. Doxycycline (200 mg/d) in combination with rifampicin (600-900 mg/d) for 6 weeks is the most common therapy regimen. The use of doxycycline with 1 or more drugs for 6 to 9 months is recommended in treatment of brucellosis with complications such as endocarditis or meningitis.2,8

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Although cholecystitis due to Brucella species is a rare manifestation, Brucella species should be considered especially in patients who is experiencing fever even after cholecystectomy, visited endemic areas, and reveals risk factors for brucellosis.

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© 2008 Lippincott Williams & Wilkins, Inc.