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CASE REPORT

Pyogenic Liver Caused by Burkhoderia pseudomallei in Taiwan Yu-Lin Lee, Susan Shin-Jung Lee, Hung-Chin Tsai, Yao-Shen Chen, Shue-Ren Wann, Chih-Hsiang Kao, Yung-Ching Liu*

Pyogenic liver abscess in Taiwan is a well-known disease entity, commonly associated with a single , pneumoniae. is an endemic disease in Taiwan that can manifest as multiple in sites including the liver. We report three cases of liver abscesses caused by Burkholderia pseudomallei. The first patient was a 54-year-old diabetic woman, who presented with liver abscess and a left subphrenic abscess resulting from a ruptured splenic abscess, co-infected with K. pneumoniae and B. pseudomallei. The second patient, a 58-year-old diabetic man, developed bacteremic over the left lower lung due to B. pseudomallei with acute respiratory distress syndrome, and relapsed 5 months later with bacteremic abscesses of the liver, spleen, prostate and , due to lack of compliance with prescribed therapy. The third patient was a 61-year-old diabetic man with a history of travel to Thailand, who presented with jaundice and fever of unknown origin. Liver and splenic abscesses due to B. pseudomallei were diag- nosed. A high clinical alertness to patients’ travel history, underlying diseases, and the presence of concomi- tant splenic abscess is essential to early detection of the great mimicker, melioidosis. The treatment of choice is intravenous ceftazidime for at least 14 days or more. An adequate duration of maintenance oral therapy, withwith -clavulanate or -sultrimethoprim-sulfamethoxazolefamethoxazole forfor 12–20 weeks, is necessary to preventprevent relapse. Liver abscess in Taiwan is most commonly due to K. pneumoniae, but clinicians should keep in mind that this may be a presenting feature of melioidosis. [J Formos Med Assoc 2006;105(8):689–693]

Key Words: Burkholderia pseudomallei, , liver abscess, melioidosis, spleen abscess

Pyogenic liver abscess is the most common intra- geographically located in similar latitudes, but abdominal visceral abscess,1 which may arise was not regarded as an endemic area until from contiguous or hematogenously. indigenous cases were reported in 1992.6 Melioi- Ascending infection from biliary tract dosis is known for its propensity to cause is the most common and is usually polymicro- abscesses,7 and may cause liver abscesses, with bial.2 However, in Taiwan, liver abscess caused concomitant splenic abscesses in up to 56% of by Klebsiella pneumoniae is a frequently described patients. It often develops in diabetic patients entity, especially in diabetic patients.3 in whom it is associated with a higher mortality Melioidosis is a systemic infection caused and relapse rate. by Burkholderia pseudomallei, contracted mainly We report three cases of liver abscess caused by inoculation or inhalation.4 This disease is by B. pseudomallei as a reminder that melioidosis endemic in Southeast Asia and northern Australia, should be included in the differential diagnosis especially during the rainy season.5 Taiwan is of patients with liver abscess in Taiwan.

©2006 Elsevier & Formosan Medical Association ...... Section of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General , Kaohsiung, Taiwan.

Received: June 6, 2005 *Correspondence to: Dr Yung-Ching Liu, Section of Infectious Diseases, Department of Medicine, Revised: July 7, 2005 Kaohsiung Veterans General Hospital, 386, Ta-Chung 1st Road, Kaohsiung 813, Taiwan. Accepted: October 4, 2005 E-mail: [email protected]

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Case Reports

Case 1 A 54-year-old diabetic woman presented with fever and chills for 10 days. She reported no travel history to China. Physical examination showed an acutely ill appearance and knocking tenderness was elicited over the left upper quad- rant of the abdomen. Sonogram and computed tomography (CT) scan of the abdomen showed multifocal hypo- Fiigure. Computedhfhbdhd tomography of the abdomen shows densities in the left lobe (S4) of the liver and multiple abscesses over both lobes of the liver, spleen and splenic abscess with rupture to the left sub- prostate. phrenic space. Culture of the aspirated iso- lated K. pneumoniae and B. pseudomallei. Blood culture showed no growth. Ceftazidime 2 g was the right shoulder, proximal humerus, proximal given every 8 hours for 30 days, followed by oral femur and left femoral head. Relapse of septicemic minocycline with amoxicillin-clavulanate for 28 B. pseudomallei with multiple organ (liver, spleen, days. treatment was then switched to prostate, bone) involvement due to incomplete trimethoprim/sulfamethoxazole (TMP/SMX) for maintenance treatment was diagnosed. Ceftazi- a total of 8 months at the outpatient clinic. She dime 2 g every 8 hours was given for a total of 18 was well at follow-up 2 months later, and there days and then changed to amoxicillin-clavulanate was no relapse over the next 2 years. two tablets every 8 hours for 4 months. He was well at follow-up at the outpatient clinic 1 year later. Case 2 A 58-year-old diabetic man presented with fever, Case 3 and for 3 days. He also had A 61-year-old diabetic man presented with epigas- hypertension and chronic B. He had tralgia, fever and progressive jaundice for 1 week. wworked as a fisherman in the sea around Indonesia Asymptomatic gallstone had been found during and the Philippines. a routine health check up 1 year previously. He Five months before this admission, bac- had traveled to Thailand 2 years previously and teremic B. pseudomallei pneumonia over the left suffered from fever of unknown cause upon return lower lung complicated with acute respiratory to Taiwan. distress syndrome (ARDS) was diagnosed and he He visited a regional hospital initially, where was treated with ceftazidime 2 g every 8 hours for gallstone with acute was diagnosed. 3 weeks and oral TMP/SMX (TMP 80 mg; SMX Laparoscopic cholecystectomy was performed, 400 mg) two tablets every 6 hours for 6 weeks. but jaundice and fever persisted. He was then He was lost to follow-up thereafter. admitted to our hospital. During presentation, he appeared acutely ill CT of the abdomen disclosed at least three low- with impaired liver and renal function. Physical density areas over the right lobe of the liver with examination elicited local tenderness over the peripheral enhancement, and one low-density right upper quadrant of the abdomen. CT of the area within the spleen. The pus from the postop- abdomen disclosed multiple abscesses over both erative drainage tube grew B. pseudomallei. Four lobes of the liver, spleen, and prostate (Figure). sets of blood culture were negative. Cefazolin, gen- Two sets of blood culture grew B. pseudomallei. tamicin and metronidazole were given initiallyfor Osteomyelitis scan showed increased uptake over the treatment of intra-abdominal infection, but

690 J Formos Med Assoc | 2006 • Vol 105 • No 8 Melioidosis presenting as liver abscess his fever persisted. Ceftazidime 2 g every 8 hours empyema.13 The response is so slow that physi- was given for a total of 14 days, and then it was cians who have no clinical experience with this switched to oral amoxicillin-clavulanate (375 mg; disease often tend to change antibiotic regimens amoxicillin trihydrate 250 mg + due to fear of and treatment fail- 125 mg) two tablets every 8 hours for a total of 6 ure. The is about 37% in acute sep- months. He was well without relapse at follow- ticemia, but only 4% in nonsepticemic cases.14 up 1 year later. The relapse rate is about 10%, and rises to 30% if maintenance agents are not given for at least 5 months.15 Both mortality and relapse Discussion rates of melioidosis are higher than K. pneumoniae liver abscess. Therefore, in cases of liver abscess Pyogenic liver abscess is an uncommon compli- not due to K. pneumoniae, it is important to keep cation of intra-abdominal infection, usually aris- in mind the possibility of melioidosis as a cause ing from a biliary source in around 30–35% of of liver abscess in Taiwan. Concurrent infection cases.2 The etiology is often polymicrobial, with with K. pneumoniae and B. pseudomallei has not , the most often cultured , been reported previously and is of uncertain signi- accounting for about 35–40% of the cases.8 ficance. However, mellitus is a predispos- In Taiwan, liver abscess is most often caused by ing factor for both . The clinical course a single pathogen, K. pneumoniae. This pathogen and outcome of Case 1 in this report are typical. accounted for 30% of liver abscesses in the 1980s K. pneumoniae causing liver abscess in Taiwan to 80% in the 1990s.9 The estimated incidence is is usually susceptible to many antibiotics (most over 200 cases annually in Taiwan. Melioidosis is β-lactams, sulfamethoxazole-trimethoprim and a systemic infection due to B. pseudomallei, which ) except and ticar- often causes multiple abscesses. Taiwan was not cillin.14 However, B. pseudomallei is intrinsicallyy considered an endemic area until 2001,7 after resistant to penicillins other than ureidopenicillins, publication of the first two indigenous cases in first- and second-generation , mac- 1996.6 Liver abscess is not an infrequent manifes- rolides, rifampins and aminoglycosides,15 and is tation of melioidosis; however, only two cases of only susceptible to , tetracyclines, this condition have been previously reported in trimethoprim-sulfamethoxazole, ureidopenicillins, TTaiwan.10 ,11 Both K. pneumoniae liver abscess and third-generation cephalosporins, and melioidosis are associated with diabetes mellitus. amoxicillin-clavulanate. This difference in anti- Other reported risk factors of melioidosis are microbial susceptibility will result in treatment renal disease, liver cirrhosis, thalassemia, alco- failure when melioidosis is empirically treated holism, use of immunosuppressive agents, cystic as K. pneumoniae or other community-acquired, fibrosis and kava consumption.12 enteric Gram-negative bacteria. Resistance to K. pneumoniae liver abscess has a good progno- aminoglycosides in an oxidase-positive, Gram- sis when treated with adequate drainage and com- negative rod is a useful clue, since B. pseudomallei bination antimicrobial therapy for 2–3 weeks. is frequently misidentified as Pseudomonas spp. Poorer outcome is associated with the occurrence other than .16 of metastatic infections, rupture of abscess or Ceftazidime (40 mg/kg every 8 hours) is the severe , with a mortality rate of 18% and antibiotic of choice for melioidosis17 and otherr relapse rate of 7%.13 In contrast, melioidosis is third-generation cephalosporins should not be difficult to treat, with a slow clinical response to used despite evidence of good in vitro susceptibil- high dose parenteral antibiotics. The median time ity due to increased mortality rate.18 Imipenem for resolution of fever was 9 days, and may be (20 mg/kg every 8 hours) or intravenous amoxi- even longer in the presence of a large abscess or cillin-claavulanate are also alternative choices.19–21

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Parenteral antibiotics should be continued for References at least 10–14 days, until clear improvement is noted and the patient is able to take oral medica- 1. Huang CJ, Pitt HA, Lipsett PA, et al. Pyogenic hepatic tions. Oral maintenance therapy with amoxicillin- abscess: changing trends over 42 years. Ann Surg 1996; clavulanate (amoxicillin 27 mg/kg day divided 223:600–7. 2.Frey CF, Zhu Y, Suzuki M, et al. Liver abscess. Surg Clin into three doses) or trimethoprim-sulfamethoxa- North Am 1989;69:259–71. zole (trimethoprim 8 mg/kg/day and sulfamethox- 3. Wang JH, Liu YC, Lee SSJ, et al. Primary liver abscess due azole 40 mg/kg/day) should be given for at least to Klebsiella pneumoniae in Taiwan. Clin Infect Dis 1998; 20 weeks.22 26:1434. The characteristic features of melioidotic liver 4. Whitmore A, Krishnaswami CS. An account of the discov- ery of a hitherto undescribed infective disease occurring abscess on ultrasound or CT are the presence of among the population of Rangoon. Indian Med Gaz 1912; multiple, small cavities, appearing like Swiss 47:262–7. cheese, and the involvement of other visceral or- 5.Wuthiekanun V, Smith MD, Dance DA, et al. The isolation gans. The spleen is the most common site.23,24 of pseudomonas pseudomallei from soil in Northeastern The gold standard for diagnosis is culture of spu- Thailand. Trans R Soc Trop Med Hyg 1995;89:41–3. 6. Lee SSJ, Liu YC, Chen YS, et al. Melioidosis: two indi- tum, blood or aspirated pus, which takes several genous cases in Taiwan. J Formos Med Assoc 1996;95: days. B. pseudomallei can be cultured aerobically 562–6. 15 in most agar media within 24 hours at 37°C. 7. Hsueh PR, Teng LJ, Lee LN, et al. Melioidosis: an emerg- TThroat swab has 90% sensitivity compared to ing infection in Taiwan? Emerg Infect Dis 2001;7:428–33. , especially in a child or patient whose 8. Seeto RK, Rockey DC. Pyogenic liver abscess: change in sputum is not available. Rapid diagnosis may be etiology, management, and outcome. Medicine 1996;75: 99–113. achieved by methods including Gram or Wright 9. Lau YJ, Hu BS, Wu WL, et al. Identification of a major stain of the sputum or pus, which will disclose cluster of Klebsiella pneumoniae isolates from patients Gram-negative rods with bipolar staining, shaped with liver abscess in Taiwan. J Clin Microbiol 2000;38: like safety pins. Direct immunofluorescence micro- 412–4. scopy is 98% specific and 70% sensitive com- 10. Wang CZ, Hung MZ. Liver melioidosis: case report and literature review. Taiwan Med J 2004;47:32–4. pared to culture. Other rapid diagnostic methods [In Chinese] include serology tests, such as indirect hemag- 11. Ben RJ, Tsai YY, Chen JC, et al. Non-septicemic Burkholderia 12 glutination assay. pseudomallei liver abscess in a young man. J Microbiol In conclusion, K. pneumoniae is the most com- Immunol Infect 2004;37:254–7. mon cause of liver abscess in Taiwan in patients 12. White NJ. Melioidosis. Lancet 2003;361:1715–22. without biliary tract abnormalities. However, in 13. Cheng DL, Liu YC, Yen MY, et al. Septic metastatic lesions of pyogenic liver abscess. Arch Intern Med 1991;151: cases not due to K. pneumoniae, B. pseudomallei 1557–9. should be kept in mind as a possible pathogen, 14. Currie BJ, Fisher DA, Howard DM, et al. Endemic melioi- since misdiagnosis results in treatment failure and dosis in tropical northern Australia: a ten year prospective a high mortality rate. Distinguishing clinical char- study and review of the literature. Clin Infect Dis 2000; acteristics include travel history to endemic areas 31:981–6. 15. Chaowagul W, Suputtamongkol Y, Dance DA, et al. (in imported cases), bipolar staining on a Wright Relapse in melioidosis: incidence and risk factors. J Infect stain, slow response to treatment, multiple small Dis 1993;168:1181–5. abscesses on imaging, concomitant involvement 16. Dance DA. Melioidosis as an emerging global problem. of other visceral organs, especially the spleen, un- Acta Trop 2000;74:115–9. usual resistance to aminoglycosides and a higher 17. White NJ, Dance DA, Chaowagul W, et al. Halving of mor- mortality and relapse rate. Taiwan is now consid- tality of severe melioidosis by ceftazidime. Lancet 1989;2: 697–701. ered an endemic area for melioidosis, and physi- 18. Chaowagul W, Simpson AJ, Suputtamongkol Y, et al. cians should include melioidosis in the differential Empirical treatment in melioidosis. Clin diagnosis of pyogenic liver abscess in Taiwan. Infec Dis 1999;28:1328.

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