□ ORIGINAL ARTICLE □ Clinical and Microbiological Features of Shewanella Bacteremia in Patients with Hepatobiliary Disease Po-Yu Liu 1,2, Chin-Fu Lin 3,4, Kwong-Chung Tung 2, Ching-Lin Shyu 2, Ming-Ju Wu 1, Jai-Wen Liu 5, Chi-Sen Chang 1, Kun-Wei Chan 6, Jin-An Huang 7 and Zhi-Yuan Shi 1,8 Abstract Objective Shewanella bacteremia is an uncommon but potentially fatal disease. Although hepatobiliary dis- eases have been proposed to be risk factors for various Shewanella infections, little is known about the fea- tures of Shewanella bacteremia in patients with hepatobiliary diseases. This study aims to characterize the presentation and risk factors of Shewanella bacteremia in patients with hepatobiliary diseases. Methods We retrospectively investigated the clinical features, microbiology and outcomes of patients with Shewanella bacteremia who were admitted to a tertiary medical center between January 2001 and December 2010. All isolates were confirmed to the species level using 16S rRNA sequencing analyses. The English lan- guage medical literature was searched for previously published reports. Results Fifty-nine cases of Shewanella bacteremia, including nine at the hospital, were identified, 28 (47.4%) of which involved underlying hepatobiliary diseases, representing an important risk factor. In 12 of the 28 cases, the infections involved the hepatobiliary system; with a tendency towards an Asian origin. In our case series of nine patients, Shewanella haliotis was isolated in five patients. The majority of our patients lived in coastal areas, consumed seafood regularly and developed bacteremia during the summer season. Conclusion It is recommended that the possibility for Shewanella infection be considered in patients with bacteremia and also underlying hepatobiliary diseases, particularly if patients present with hepatobiliary infec- tions, a history of seafood, or development of the disease during the summer. Key words: bacteremia, cholangitis, biliary tract diseases, liver cirrhosis, seafood, Shewanella (Intern Med 52: 431-438, 2013) (DOI: 10.2169/internalmedicine.52.8152) critical care and antimicrobial therapy, rapid fatal cases are Introduction still reported (3). The genus Shewanella includes 59 recognized species at Shewanella is a non-fermentative Gram-negative bacilli the time of this writing (http://www.bacterio.cict.fr/s/ found in aquatic environments throughout the world. Bac- shewanella.html). Most reported human infections are teremia caused by Shewanella is an uncommon but poten- caused by Shewanella algae and Shewanella putrefaciens. tially fatal disease. The mortality rate of Shewanella bactere- However, it is often difficult to identify the microbes at the mia is 28% (1). However, the mortality may rise to more species level using conventional microbiologic culture and than 50% in patients with underlying hepatobiliary dis- biochemical analyses. In addition, many automated identifi- eases (2). Moreover, despite the administration of aggressive cation systems include only S. putrefaciens in their database. １Department of Internal Medicine, Taichung Veterans General Hospital, Taiwan, ２Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taiwan, ３Microbiology Section of the Medical Laboratory Department, Taichung Veterans General Hospital, Taiwan, ４Department of Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taiwan, ５De- partment of Emergency Medicine, Chung Shan Medical University Hospital, Taiwan, ６Department of Veterinary Medicine, National Chiayi Uni- versity, Chiayi, Taiwan, School of Medicine, Chung-Shan Medical University, Taiwan, ７Department of Emergency Medicine, Taichung Veterans General Hospital, Taiwan and ８National Yang-Ming University, Taiwan Received for publication May 15, 2012; Accepted for publication November 7, 2012 Correspondence to Dr. Zhi-Yuan Shi, [email protected] 431 Intern Med 52: 431-438, 2013 DOI: 10.2169/internalmedicine.52.8152 DNA sequencing provides an opportunity for definitive tion using the Basic Local Alignment Search Tool (BLAST) identification (4). By incorporating 16S rRNA gene se- algorithm. The closest matches and GenBank accession quencing into the identification of Shewanella, more She- numbers were obtained. wanella species can be recognized as pathogenic organ- The minimum inhibitory concentrations (MICs) for am- isms (5-7). picillin/sulbactam, piperacillin, piperacillin/tazobactam, cefa- Shewanella is primarily an opportunistic pathogen that zolin, cefoxitin, ceftazidime, ceftriaxone, cefepime, causes three patterns of infection: soft tissue infection, bac- ciprofloxacin, imipenem, gentamicin, and trimethoprim- teremia and neonatal sepsis (3). In the majority of cases, the sulfamethoxazole were determined using the VITEK II auto- organism is cultured from and related to soft tissue infec- mated system (bioMérieux, France). Next, the disk-diffusion tions, primarily in patients with associated underlying ill- method was used as a confirmatory tool. There are no rec- nesses. Sea water exposure is a common environmental fac- ognized Clinical and Laboratory Standards Institute (CLSI) tor linked with soft tissue infections. Recently, the number MIC interpretive standards specified for this bacterial genus, of case reports of severe Shewanella bacteremia has in- and the MIC breakpoints of cefazolin, cefoxitin and ampicil- creased. Many of these patients were reported to have un- lin/sulbactam for non-fermentative Gram-negative bacilli are derlying hepatobiliary diseases and were from Asian re- also lacking in the CLSI database. In the present report, the gions (3, 8, 9). Previous analyses also suggest that hepato- MIC breakpoints of piperacillin (susceptible, !16 μg/mL; in- biliary diseases are a risk factor for the development of vari- termediate, 32-64 μg/mL; resistant, "128 μg/mL), piperacil- ous Shewanella infections; however, little is known about lin/tazobactam (susceptible, !16/4 μg/mL; intermediate, 32/ the roles of predisposing factors in bacteremia. The predis- 4-64/4 μg/mL; resistant, "128/4 μg/mL), ceftazidime (sus- posing factors, clinical presentation, treatments and out- ceptible, !8 μg/mL; intermediate, 16 μg/mL; resistant, "32 comes of Shewanella infection are poorly characterized. μg/mL), ceftriaxone (susceptible, !8 μg/mL; intermediate, We therefore conducted a 10-year retrospective study to 16-32 μg/mL; resistant, !64 μg/mL), cefepime (susceptible, review cases of Shewanella bacteremia occurring at our in- !8 μg/mL; intermediate, 16 μg/mL; resistant, "32 μg/mL), stitution. The aim of this study was to investigate the clini- ciprofloxacin (susceptible, !1 μg/mL; intermediate, 2 μg/mL; cal and microbiologic characteristics of Shewanella bactere- resistant, "4 μg/mL), imipenem (susceptible, !4 μg/mL; in- mia, especially in patients with hepatobiliary diseases. All termediate, 8 μg/mL; resistant, "16 μg/mL), gentamicin (sus- isolates were confirmed to the species level using 16S rRNA ceptible, !4 μg/mL; intermediate, 8 μg/mL; resistant, "16 sequencing analyses. The susceptibility of the Shewanella μg/mL) and trimethoprim-sulfamethoxazole (susceptible, !2/ isolates to various antibiotics was determined. In this report, 38 μg/mL; resistant, "4/76 μg/mL) were interpreted using we also review similar cases reported elsewhere in order to CLSI approved standard M100-S22 categories for other non- summarize the important features of this disease. Enterobacteriaceae in accordance with previous re- ports (7, 9, 14). In addition, the standards recommended by Materials and Methods the U.S. Food and Drug Administration (FDA) for ampicil- lin/sulbactam (susceptible, !8 μg/mL; intermediate, 16 μg/ This retrospective study was conducted at Taichung Veter- mL; resistant, "32 μg/mL), cefazolin (susceptible, !16 μg/ ans General Hospital, a tertiary medical center in central mL; resistant, "64 μg/mL) and cefoxitin (susceptible, !8μg/ Taiwan. All patients included were diagnosed with Shewan- mL; intermediate, 16 μg/mL; resistant, "32 μg/mL) were ella bacteremia between January 2001 and December 2010. used. The patients were identified using the computerized database Previously published cases of Shewanella bacteremia in of the institution. Clinical, laboratory and microbiologic data adults were reviewed. The English language medical litera- were retrieved from the medical records of the patients. A ture was searched using the online bibliographic database of standardized case record form was used by two experienced the National Library of Medicine (MEDLINE, PubMed). physicians to record the demographic profile, underlying The search terms included “Pseudomonas putrefaciens,” condition, clinical presentation, therapy and outcome of each “Shewanella,” “Shewanella putrefaciens,” “Shewanella patient. alga,” “Shewanella algae,” “bacteremia” and “bloodstream All isolates from patients with Shewanella bacteremia infection.” All studies identified were reviewed, as were the were re-identified using Gram staining, colony morphology references cited in the articles found in the original search. and biochemical characteristics (10). The organisms were Fisher’s exact test was used to compare categorical vari- further confirmed with 16S rRNA gene sequence analy- ables. Continuous variables were compared using the Wil- sis (11-13). The primers used for amplification of the 16S coxon rank-sum test, as appropriate. p<0.05 was considered rRNA gene were B27F (5’-AGAGTTTGATCCTGGCTCAG- statistically