Infect Chemother.  2013 Sep;45(3):315-324. 10.3947/ic.2013.45.3.315.

Epidemiology and Clinical Features of Post-Transplant Bloodstream Infection: An Analysis of 222 Consecutive Liver Transplant Recipients

• Kim HK
• Park YK
• Wang HJ
• Kim BW
• Shin SY
• Lim SK
• Choi YH

• KMID: 2170431
• DOI: http://doi.org/10.3947/ic.2013.45.3.315

Abstract

BACKGROUND
Bloodstream infection (BSI) is a significant cause of morbidity and mortality in liver transplant (LT) recipients. This study aimed to investigate the epidemiology and clinical features of post-transplant BSI in LT recipients.
MATERIALS AND METHODS
The microbiology, frequency, and outcome of post-transplant BSI in the first year after LT were retrospectively analyzed in 222 consecutive patients who had received liver transplants at a single center between 2005 and 2011. The risk factors for post-transplant BSI and death were evaluated.
RESULTS
During a 1-year period after LT, 112 episodes of BSI occurred in 64 of the 222 patients (28.8%). A total of 135 microorganisms were isolated from 112 BSI episodes including 18 polymicrobial episodes. The median time to BSI onset ranged from 8 days for Klebsiella pneumoniae to 101 days for enterococci, and the overall median for all microorganisms was 28 days. The most frequent pathogens were Enterobacteriaceae members (32.5%), enterococci (17.8%), yeasts (14.0%), Staphylococcus aureus (10.3%), and Acinetobacter baumannii (10.3%); most of them showed resistance to major antibiotics. The major sources of BSI were biliary tract (36.2%), abdominal and/or wound (28.1%), and intravascular catheter (18.5%) infections. The independent risk factors for post-transplant BSI were biliary complications (odds ratio [OR]: 2.91, 95% confidence interval [CI]: 1.29 to 6.59, P = 0.010) and longer hospitalization in the intensive care unit (OR: 1.04, 95% CI: 1.00 to 1.08, P < 0.001) after LT. BSI was an independent risk factor for death (hazard ratio [HR]: 3.92, 95% CI: 2.22 to 6.91, P < 0.001), with a poorer survival rate observed in patients with BSI than in those without BSI (1-year survival rate: 60.0% versus 89.5%, respectively, P < 0.001) after LT. The strongest predictors for death in patients with BSI were hepatocellular carcinoma (HR: 3.82, 95% CI: 1.57 to 9.32, P = 0.003), candidemia (HR: 3.71, 95% CI: 1.58 to 8.71, P = 0.003), polymicrobial bacteremia (HR: 3.18, 95% CI: 1.39 to 7.28, P = 0.006), and post-transplant hemodialysis (HR: 2.44, 95% CI: 1.02 to 5.84, P = 0.044).
CONCLUSIONS
BSI was a frequent post-transplant complication, and most of the causative pathogens were multi-drug resistant. Biliary complications and BSIs resulting from biliary infection are major problems for LT recipients. The prevention of BSI and biliary complications is critical in improving prognosis in liver transplant recipients.

Keyword

Bacteremia; Bloodstream infection; Liver transplantation; Epidemiology

MeSH Terms

Acinetobacter baumannii
Anti-Bacterial Agents
Bacteremia
Biliary Tract
Candidemia
Carcinoma, Hepatocellular
Catheters
Enterobacteriaceae
Hospitalization
Humans
Intensive Care Units
Klebsiella pneumoniae
Liver
Liver Transplantation
Prognosis
Renal Dialysis
Retrospective Studies
Risk Factors
Staphylococcus aureus
Survival Rate
Transplants
Yeasts
Anti-Bacterial Agents

Figure

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  Figure 1 Time and frequency of causative organisms (n = 135) isolated in bloodstream infections after liver transplantation. GPC, gram-positive cocci; GNB, gram-negative bacilli.

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  Figure 2 Effect of bloodstream infection in the year after transplantation on Kaplan-Meier survival curves of liver transplant recipients. BSI, bloodstream infection.

Reference

1. Snydman DR. Infection in solid organ transplantation. Transpl Infect Dis. 1999; 1:21–28.

2. Kim SI, Kim YJ, Jun YH, Wie SH, Kim YR, Choi JY, Yoon SK, Moon IS, Kim DG, Lee MD, Kang MW. Epidemiology and risk factors for bacteremia in 144 consecutive living-donor liver transplant recipients. Yonsei Med J. 2009; 50:112–121.

3. Nah YW, Lee SG, Lee YJ, Park KM, Hwang S, Choi DL, Ahn CS, Park DE, Joo SH, Jeon JY, Min PC. Infection after adult-to-adult living donor liver transplantation. J Korean Soc Transplant. 2001; 15:93–105.

4. Wade JJ, Rolando N, Hayllar K, Philpott-Howard J, Casewell MW, Williams R. Bacterial and fungal infections after liver transplantation: an analysis of 284 patients. Hepatology. 1995; 21:1328–1336.

5. Singh N, Paterson DL, Gayowski T, Wagener MM, Marino IR. Predicting bacteremia and bacteremic mortality in liver transplant recipients. Liver Transpl. 2000; 6:54–61.

6. Iida T, Kaido T, Yagi S, Yoshizawa A, Hata K, Mizumoto M, Mori A, Ogura Y, Oike F, Uemoto S. Posttransplant bacteremia in adult living donor liver transplant recipients. Liver Transpl. 2010; 16:1379–1385.

7. Kawecki D, Chmura A, Pacholczyk M, Łagiewska B, Adadynski L, Wasiak D, Malkowski P, Rokosz A, Sawicka-Grzelak A, Szymanowska A, Swoboda-Kopec E, Wroblewska M, Rowinski W, Durlik M, Luczak M. Etiological agents of bacteremia in the early period after liver transplantation. Transplant Proc. 2007; 39:2816–2821.

8. Singh N, Wagener MM, Obman A, Cacciarelli TV, de Vera ME, Gayowski T. Bacteremias in liver transplant recipients: shift toward gram-negative bacteria as predominant pathogens. Liver Transpl. 2004; 10:844–849.

9. Shi SH, Kong HS, Xu J, Zhang WJ, Jia CK, Wang WL, Shen Y, Zhang M, Zheng SS. Multidrug resistant gram-negative bacilli as predominant bacteremic pathogens in liver transplant recipients. Transpl Infect Dis. 2009; 11:405–412.

10. Kim YJ, Kim SI, Ko SH, Jeon YH, Moon IS, Kim DG, Lee MD, Kang MW. Epidemiological data on antibiotic-resistant bacteria isolated in liver transplant recipients. J Korean Soc Transplant. 2008; 22:203–208.

11. Choe EK, Suh KS, Cho JY, Lee HW, Cho EH, Yi NJ, Lee KU. Clinical significance of vancomycin resistant enterococcus in liver transplantation. J Korean Soc Transplant. 2006; 20:241–247.

12. Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections, 1988. Am J Infect Control. 1988; 16:128–140.

13. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, Harbarth S, Hindler JF, Kahlmeter G, Olsson-Liljequist B, Paterson DL, Rice LB, Stelling J, Struelens MJ, Vatopoulos A, Weber JT, Monnet DL. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012; 18:268–281.

14. Hashimoto M, Sugawara Y, Tamura S, Kaneko J, Matsui Y, Togashi J, Makuuchi M. Bloodstream infection after living donor liver transplantation. Scand J Infect Dis. 2008; 40:509–516.

15. Bert F, Larroque B, Paugam-Burtz C, Janny S, Durand F, Dondero F, Valla DC, Belghiti J, Moreau R, Nicolas-Chanoine MH. Microbial epidemiology and outcome of bloodstream infections in liver transplant recipients: an analysis of 259 episodes. Liver Transpl. 2010; 16:393–401.

16. Li C, Mi K, Wen Tf, Yan Ln, Li B, Yang Jy, Xu Mq, Wang WT, Wei Yg. A learning curve for living donor liver transplantation. Dig Liver Dis. 2012; 44:597–602.

17. Kim BW, Bae BK, Lee JM, Won JH, Park YK, Xu WG, Wang HJ, Kim MW. Duct-to-duct biliary reconstructions and complications in 100 living donor liver transplantations. Transplant Proc. 2009; 41:1749–1755.

18. Hampe T, Dogan A, Encke J, Mehrabi A, Schemmer P, Schmidt J, Stiehl A, Sauer P. Biliary complications after liver transplantation. Clin Transplant. 2006; 20:Suppl 17. 93–96.

19. Linares L, García-Goez JF, Cervera C, Almela M, Sanclemente G, Cofán F, Ricart MJ, Navasa M, Moreno A. Early bacteremia after solid organ transplantation. Transplant Proc. 2009; 41:2262–2264.

20. Albrecht SJ, Fishman NO, Kitchen J, Nachamkin I, Bilker WB, Hoegg C, Samel C, Barbagallo S, Arentzen J, Lautenbach E. Reemergence of gram-negative health care-associated bloodstream infections. Arch Intern Med. 2006; 166:1289–1294.

21. Lee SO, Kang SH, Abdel-Massih RC, Brown RA, Razonable RR. Spectrum of early-onset and late-onset bacteremias after liver transplantation: implications for management. Liver Transpl. 2011; 17:733–741.

22. Kim YJ, Yoon JH, Kim SI, Hong KW, Kim JI, Choi JY, Yoon SK, You YK, Lee MD, Moon IS, Kim DG, Kang MW. High mortality associated with Acinetobacter species infection in liver transplant patients. Transplant Proc. 2011; 43:2397–2399.

23. Kim YJ, Kim SI, Hong KW, Kim YR, Park YJ, Kang MW. Risk factors for mortality in patients with carbapenem-resistant Acinetobacter baumannii bacteremia: impact of appropriate antimicrobial therapy. J Korean Med Sci. 2012; 27:471–475.

24. Faenza S, Santoro A, Mancini E, Pareschi S, Siniscalchi A, Zanzani C, Pinna AD. Acute renal failure requiring renal replacement therapy after orthotopic liver transplantation. Transplant Proc. 2006; 38:1141–1142.

25. Nieto-Rodriguez JA, Kusne S, Mañez R, Irish W, Linden P, Magnone M, Wing EJ, Fung JJ, Starzl TE. Factors associated with the development of candidemia and candidemia-related death among liver transplant recipients. Ann Surg. 1996; 223:70–76.

26. Klotz SA, Chasin BS, Powell B, Gaur NK, Lipke PN. Polymicrobial bloodstream infections involving Candida species: analysis of patients and review of the literature. Diagn Microbiol Infect Dis. 2007; 59:401–406.

27. Waki K, Sugawara Y, Tamura S, Mieno MN, Yamashiki N, Kadowaki T, Kokudo N. Outcome of liver transplantation for recipients with hepatitis B and hepatitis C virus coinfection: analysis of the UNOS data. Transplantation. 2011; 92:809–814.