Nosocomial Liver Abscess Caused by Extended-Spectrum Beta-Lactamase ACCEPTED

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1 JCM Accepts, published online ahead of print on 8 November 2006 J. Clin. Microbiol. doi: /jcm Copyright 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved. Nosocomial Liver Abscess Caused by Extended-Spectrum Beta-Lactamase producing Klebsiella pneumoniae: A Case Report Jung-Chung Lin 1, L. K. Siu 2, Chang-Phone Fung 3, Kao-Ming Yeh 1, Feng-Yee Chang 1* 1 Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei; 2 Division of Clinical Research, National Health Research Institutes, Taipei; 3 National Yang-Ming University; Running Title: ESBL-producing K. pneumoniae liver abscess Key words: K. pneumoniae, Liver abscess, ESBL Corresponding author: Dr. Feng-Yee Chang Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan, ROC. Telephone: Facsimile: fychang@ndmctsgh.edu.tw 1

2 Abstract Nosocomial pyogenic liver abscess caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae presented in a man with adenocarcinoma of the stomach. K. pneumoniae strain isolated from blood and liver aspirate culture after antibiotic therapy for recurrent bacteremia, was resistant to all extended-spectrum beta-lactams except imipenem, and differed from K. pneumoniae strains causing community-acquired liver abscess. 2

3 Case report A 48-year-old man with adenocarcinoma of the stomach received radical gastrectomy in 2003 and then 11 courses of intensive chemotherapy with fluorouracil, calcium folinate, and oxaliplatin for tumor metastasis to liver and peritoneum. In July 2005, he was admitted to our hospital for treatment of oral candidiasis associated with shaking chills, spiking fever, and abdominal fullness. Initially, intravenous ampicillin/sulbactam and oral fluconazole were given. Escherichia coli, Bacteroides fragilis, and Fusobacterium varium were isolated from two sets of blood cultures. E. coli was susceptible to all cephalosporins, but resistant to ampicillin and trimethoprim/sulfamethoxazole. Cefpirome and metronidazole were administered 5 days later, but the patient s intermittent spiking fever persisted. A blood culture disclosed Enterococcus faecium and Bacteroides thetaiotaomicron. Gentamicin was added. On day 14, he developed spiking fever again with pain over the right upper quadrant of his abdomen. Computed tomography of the abdomen showed a 4-cm hypodense lesion over segment 6 of the liver (fig. 1). Percutaneous drainage was performed and pus was aspirated. The liver biopsy revealed a massive necrosis with inflammatory cells in liver tissue. Extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae detected by double disk screening and confirmatory tests based on CLSI recommendations was isolated from cultures of 3

4 blood and pus aspirated from the liver. K. pneumoniae was resistant to all cephalosporins and aminoglycosides, but it was sensitive to imipenem. The MICs of antimicrobial agents were determined by Etest using interpretive standards based on CLSI recommendations. The results of MICs of ceftazidime 256 μg/ml, ceftriaxone 256 μ g/ml, cefepime 128 μ g/ml, cefoxitin 128 μ g/ml, gentamicin 96 μ g/ml, ciprofloxacin 32μg/ml, and imipenem 0.75μg/ml were demonstrated (6). Detection of plasmid-mediated AmpC beta-lactamases with AmpC disk test was negative (figure was not shown) (1). The capsular serotype was non-k1/k2 by countercurrent immuno-electrophoresis and the phenotype was non-mucoid (9,10). PCR for maga gene was negative (7). In this case, the same antibiogram and Pulsed field gel electrophoresis (PFGE) demonstrated for isolates from blood and pus aspirated from the liver (data not shown). PFGE demonstrated completely different patterns for strains from community-acquired liver abscess and nosocomial ESBL-producing K. pneumoniae bacteremia (fig. 2A, 2B) (20). Though his clinical symptoms and signs improved after treatment with imipenem for 6 weeks, he died of progressive carcinomatosis with multiple organ failure 2 months later. 4

5 Discussion This is the first report on nosocomial liver abscess caused by ESBL-producing K. pneumoniae after intensive chemotherapy for carcinoma of the stomach and prolonged antibiotic treatment for recurrent bacteremia. K. pneumoniae has been emerging as the leading cause of community-acquired pyogenic liver abscess in Taiwan and the United States (2,3,8,11,14). Different clonal populations of K. pneumoniae cause community-acquired pyogenic liver abscess (4,5). Serotype K1/K2 accounts for 78% of isolates, and non-k1/k2 for 22% (9). ESBL-producing K. pneumoniae is one of the most frequent causes of nosocomial pneumonia, intra-abdominal infection, urinary tract infection, and primary bacteremia (13). The prevalence of ESBL-producing K. pneumoniae as a nosocomial pathogen is increasing worldwide (13,15,19). Information regarding K. pneumoniae associated infection is summarized in Table 1 (3,9,12-14,17). The newly emerged community-acquired K. pneumoniae strains causing liver abscess have been associated with more septic metastatic complications and low mortality rate, whereas nosocomial K. pneumoniae strains including non-esbl and ESBL-producing strains have been associated with less septic metastatic complications and high mortality. These community-acquired and nosocomial infections have very different presentations. 5

6 Extended-spectrum cephalosporins have facilitated treatment of severe infections caused by Gram-negative bacteria. However, increasing use of these agents has been associated with the emergence of resistant bacterial strains, such as those producing different SHV- or TEM-derived ESBLs (12,16). A well-known virulence factor of K. pneumoniae associated with liver abscess is the capsular polysaccharide serotype (such as K1 and K2) (9). However, the ESBL-producing K. pneumoniae strain in our case was maga - and non-k1/k2. The PFGE pattern of genomic DNA from the 8 K. pneumoniae strains isolated from community-acquired liver abscesses (serotype K1, n= 4), nosocomial bacteremias (K1 and non-k1/k2 [i.e., K54 and K55]), and the present case were different, and the genetic dendrogram showed low similarity. Further study is needed to determine whether other virulence factors such as the strain of ESBL-producing K pneumoniae are important. Intensive chemotherapy and prolonged use of antibiotics puts patients with intestinal tract tumors, hepato-biliary tract tumors, or intra-abdominal carcinomatosis at risk for infection by opportunistic pathogens and recurrent bacteremia (18). However, selective antibiotic pressure may play a role for the selection of ESBL-producing strains (13). In our case, nosocomial liver abscess caused by ESBL-producing K. pneumoniae was selected by prolonged broad-spectrum antibiotic treatment. 6

7 In conclusion, the strain of ESBL-producing K. pneumoniae causing nosocomial liver abscess in our case differed from strains causing community-acquired liver abscess with respect to capsular serotype, antibiogram pattern, and PFGE pattern. More judicious use of antibiotics is recommended to decrease resistance and slow the emergence of resistant bacteria. 7

8 Acknowledge This study was supported by grants from the Tri-Service General Hospital (TSGH-C95-50 & C95-51) and National Science Council (NSC B ). 8

9 Reference List 1. Black, J. A., E. S. Moland, and K. S. Thomson AmpC disk test for detection of plasmid-mediated AmpC β -lactamases in Enterobacteriaceae lacking chromosomal AmpC β-lactamases. J.Clin.Microbiol. 43: Chan, K. S., C. M. Chen, K. C. Cheng, C. C. Hou, H. J. Lin, and W. L. Yu Pyogenic liver abscess: a retrospective analysis of 107 patients during a 3-year period. Jpn.J.Infect.Dis. 58: Chang, F. Y. and M. Y. Chou Comparison of pyogenic liver abscesses caused by Klebsiella pneumoniae and non-k. pneumoniae pathogens. J.Formos.Med.Assoc. 94: Chang, S. C., C. T. Fang, P. R. Hsueh, Y. C. Chen, and K. T. Luh Klebsiella pneumoniae isolates causing liver abscess in Taiwan. Diagn.Microbiol.Infect.Dis. 37: Cheng, H. P., F. Y. Chang, C. P. Fung, and L. K. Siu Klebsiella pneumoniae liver abscess in Taiwan is not caused by a clonal spread strain. J.Microbiol.Immunol.Infect. 35:

10 6. Clinical and Laboratory Standards Institute/NCCLS. Performance Standards for Antimicrobial Susceptibility Testing: Fifiteenth Informational Supplement. CLSI/NCCLS document M100-S15,Wayne, Pa. 7. Fang, C. T., Y. P. Chuang, C. T. Shun, S. C. Chang, and J. T. Wang A novel virulence gene in Klebsiella pneumoniae strains causing primary liver abscess and septic metastatic complications. J.Exp.Med. 199: Fang, F. C., N. Sandler, and S. J. Libby Liver abscess caused by maga+ Klebsiella pneumoniae in North America. J.Clin.Microbiol. 43: Fung, C. P., F. Y. Chang, S. C. Lee, B. S. Hu, B. I. Kuo, C. Y. Liu, M. Ho, and L. K. Siu A global emerging disease of Klebsiella pneumoniae liver abscess: is serotype K1 an important factor for complicated endophthalmitis? Gut 50: Fung, C. P., B. S. Hu, F. Y. Chang, S. C. Lee, B. I. Kuo, M. Ho, L. K. Siu, and C. Y. Liu A 5-year study of the seroepidemiology of Klebsiella pneumoniae: high prevalence of capsular serotype K1 in Taiwan and implication for vaccine efficacy. J.Infect.Dis. 181:

11 11. Lederman, E. R. and N. F. Crum Pyogenic liver abscess with a focus on Klebsiella pneumoniae as a primary pathogen: an emerging disease with unique clinical characteristics. Am.J.Gastroenterol. 100: Paterson, D. L Extended-spectrum beta-lactamases: the European experience. Curr.Opin.Infect.Dis. 14: Paterson, D. L., W. C. Ko, G. A. Von, S. Mohapatra, J. M. Casellas, H. Goossens, L. Mulazimoglu, G. Trenholme, K. P. Klugman, R. A. Bonomo, L. B. Rice, M. M. Wagener, J. G. McCormack, and V. L. Yu International prospective study of Klebsiella pneumoniae bacteremia: implications of extended-spectrum beta-lactamase production in nosocomial Infections. Ann.Intern.Med. 140: Rahimian, J., T. Wilson, V. Oram, and R. S. Holzman Pyogenic liver abscess: recent trends in etiology and mortality. Clin.Infect.Dis. 39: Schiappa, D. A., M. K. Hayden, M. G. Matushek, F. N. Hashemi, J. Sullivan, K. Y. Smith, D. Miyashiro, J. P. Quinn, R. A. Weinstein, and G. M. Trenholme Ceftazidime-resistant Klebsiella pneumoniae and Escherichia coli bloodstream infection: a case-control and molecular epidemiologic investigation. J.Infect.Dis. 174:

12 16. Siu, L. K Antibiotics: action and resistance in gram-negative bacteria. J.Microbiol.Immunol.Infect. 35: Tsay, R. W., L. K. Siu, C. P. Fung, and F. Y. Chang Characteristics of bacteremia between community-acquired and nosocomial Klebsiella pneumoniae infection: risk factor for mortality and the impact of capsular serotypes as a herald for community-acquired infection. Arch.Intern.Med. 162: Weng, S. W., J. W. Liu, W. J. Chen, and P. W. Wang Recurrent Klebsiella pneumoniae liver abscess in a diabetic patient followed by Streptococcus bovis endocarditis--occult colon tumor plays an important role. Jpn.J.Infect.Dis. 58: Wiener, J., J. P. Quinn, P. A. Bradford, R. V. Goering, C. Nathan, K. Bush, and R. A. Weinstein Multiple antibiotic-resistant Klebsiella and Escherichia coli in nursing homes. JAMA 281: Wu, T. L., L. K. Siu, L. H. Su, T. L. Lauderdale, F. M. Lin, H. S. Leu, T. Y. Lin, and M. Ho Outer membrane protein change combined with co-existing TEM-1 and SHV-1 beta-lactamases lead to false identification of ESBL-producing Klebsiella pneumoniae. J.Antimicrob.Chemother. 47:

13 Table 1. Summary of Klebsiella pneumoniae infection Diagnosis Abbreviation: DM, diabetes mellitus; UTI, urinary tract infection; S/S, symptoms and signs; RUQ, right upper quadrant; GI tract, gastro-intestinal tract; and N/A, not assayed a Reference 17 b Reference 9 c Reference 14 d Reference 12,13 Mean age (SD or range) Community-acquired 61.2 K. pneumoniae bacteremia a (± 15.7) Community-acquired K. pneumoniae Liver abscess-taiwan b 56.4 (34-78) Community-acquired K. pneumoniae Liver abscess-usa c 56.4 (25-90) Nosocomial-acquired 59.2 K. pneumoniae bacteremia a (± 20.7) Nosocomial-acquired ESBL-K. pneumoniae bacteremia d 58 (17-90) Nosocomial-acquired ESBL-K. pneumoniae Liver abscess 48 S/S Fever Fever RUQ pain Fever RUQ pain Fever Jaundice Leukopenia Septic shock Pneumonia UTI Fever RUQ pain serotype K1: 30% K2: 6% Non-K1/K2: 64% K1: 64% K2: 14% Non-K1/K2: 22% Hepotobiliary- GI tract abnormal DM 13% 49% 8.2% 78.4% Metastatic complication Not found except combined with liver abscess Endophthalmitis: 10.4% Other site metastasis: 3% N/A 43% 15.2% Not found K1: 14% K2: 3% Non-K1/K2: 83% Mortality 14% 6% 2.5% 2% 12% Not found 36% ownloaded from on August 21, 2018 by guest N/A 13.1% 15.2% Not found 23.5% Non-K1/K2 Yes no Not found Expired 13

14 Figures Legends Fig. 1. Computed tomography of the abdomen showed a hypodense lesion about 4 cm in size over the right lobe of the liver. Fig. 2A. Dendrogram based on the PFGE results of 8 clinical isolates of K. pneumoniae. Strains were clustered by the unweighted-pair group method using arithmetic averages (Nos. 1, 3, 13, and 23: isolated from community-acquired liver abscess, serotype K1; Nos. 33, 37, and 38: isolated from nosocomial bloodstream infections of ESBL-producing non-k1/k2; I: the present strain). Fig. 2B. PFGE. Image shows the different molecular clones of K. pneumoniae strains isolated from community-acquired liver abscess and nosocomial bloodstream infection, and the presented strain. 14

15 Fig

16 Fig 2A 16

17 Fig. 2B. 17

18 d from on August 21, 2018 by guest