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Intestinal colonization with resistant bacteria: a prognostic marker of mortality in decompensated cirrhosis

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Abstract

Infections due to drug-resistant (DR) bacteria are increasingly recognized as an emerging problem worldwide. Asymptomatically colonized patients may contribute to the reservoir in the hospital setting, causing both horizontal transmission and endogenous infections. We aimed to evaluate the prevalence of intestinal colonization with DR bacteria on subsequent clinical infection development and prognosis in patients with decompensated cirrhosis. One hundred seven patients without infection at baseline were screened and prospectively followed-up for 3 months. Among the patients screened, DR bacteria were isolated in 47 (43.9%), 14 colonized with multidrug- (MDR) and 33 with extensively drug (XDR)-resistant bacteria or a mixture of MDR/XDR bacteria. Severity of liver disease and demographic characteristics were similar among groups. The 20 (42.6%) with DR vs 14 (23.3%) without had hepatic encephalopathy and/or spontaneous bacterial peritonitis episodes over the past 6 months (p = 0.034). One third of both DR and non-DR groups developed infection during follow-up but in only 7 and 5, respectively, the infection was microbiologically documented. In a 3-month-follow-up period, mortality was higher in patients colonized with XDR compared to those without (log rank p = 0.027). In multivariate analysis, colonization with XDR bacteria [HR = 1.074, (CI:1.024–1.126), p = 0.003] and MELD score [HR = 2.579 (1.109–5.996), p = 0.028] were independently associated with low survival. Asymptomatic GI colonization with DR bacteria is a risk factor for increased mortality in decompensated cirrhosis. Frequent hospitalizations for complications of the underlying disease and selective pressure induced by the use of antimicrobials are probably the main determinants.

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References

  1. Fernández J, Navasa M, Gómez J, Colmenero J, Vila J, Arroyo V, Rodés J (2002) Bacterial infections in cirrhosis: epidemiological changes with invasive procedures and norfloxacin prophylaxis. Hepatology 35(1):140–148. https://doi.org/10.1053/jhep.2002.30082

    Article  PubMed  Google Scholar 

  2. Arvaniti V, D’Amico G, Fede G, Manousou P, Tsochatzis E, Pleguezuelo M, Burroughs AK (2010) Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis. Gastroenterology 139(4):1246–1256. https://doi.org/10.1053/j.gastro.2010.06.019

    Article  PubMed  Google Scholar 

  3. Salerno F, Borzio M, Pedicino C, Simonetti R, Rossini A, Boccia S, Cacciola I, Burroughs AK, Manini MA, La Mura V, Angeli P, Bernardi M, Dalla Gasperina D, Dionigi E, Dibenedetto C, Arghittu M, AISF Investigators (2017) The impact of infection by multidrug-resistant agents in patients with cirrhosis. A multicenter prospective study. Liver Int 37(1):71–79. https://doi.org/10.1111/liv.13195

    Article  CAS  PubMed  Google Scholar 

  4. Jalan R, Fernandez J, Wiest R, Schnabl B, Moreau R, Angeli P, Stadlbauer V, Gustot T, Bernardi M, Canton R, Albillos A, Lammert F, Wilmer A, Mookerjee R, Vila J, Garcia-Martinez R, Wendon J, Such J, Cordoba J, Sanyal A, Garcia-Tsao G, Arroyo V, Burroughs A, Ginès P (2014) Bacterial infections in cirrhosis: a position statement based on the EASL special conference 2013. J Hepatol 60(6):1310–1324. https://doi.org/10.1016/j.jhep.2014.01.024

    Article  PubMed  Google Scholar 

  5. Fernández J, Bert F, Nicolas-Chanoine MH (2016) The challenges of multi-drug-resistance in hepatology. J Hepatol 65(5):1043–1054. https://doi.org/10.1016/j.jhep.2016.08.006

    Article  PubMed  Google Scholar 

  6. Alexopoulou A, Papadopoulos N, Eliopoulos DG, Alexaki A, Tsiriga A, Toutouza M, Pectasides D (2013) Increasing frequency of gram-positive cocci and gram-negative multidrug-resistant bacteria in spontaneous bacterial peritonitis. Liver Int 33(7):975–981. https://doi.org/10.1111/liv.12152

    Article  CAS  PubMed  Google Scholar 

  7. Fernández J, Acevedo J, Castro M, Garcia O, de Lope CR, Roca D, Pavesi M, Sola E, Moreira L, Silva A, Seva-Pereira T, Corradi F, Mensa J, Ginès P, Arroyo V (2012) Prevalence and risk factors of infections by multiresistant bacteria in cirrhosis: a prospective study. Hepatology 55(5):1551–1561. https://doi.org/10.1002/hep.25532

    Article  PubMed  Google Scholar 

  8. Wiest R, Krag A, Gerbes A (2012) Spontaneous bacterial peritonitis: recentguidelines and beyond. Gut 61(2):297–310. https://doi.org/10.1136/gutjnl-2011-300779

    Article  CAS  PubMed  Google Scholar 

  9. Wiest R, Lawson M, Geuking M (2014) Pathological bacterial translocation in liver cirrhosis. J Hepatol 60(1):197–209. https://doi.org/10.1016/j.jhep.2013.07.044

    Article  PubMed  Google Scholar 

  10. Ford CD, Lopansri BK, Gazdik MA, Snow GL, Webb BJ, Konopa KL, Petersen FB (2015) The clinical impact of vancomycin-resistant Enterococcus colonization and bloodstream infection in patients undergoing autologous transplantation. Transpl Infect Dis 17(5):688–694. https://doi.org/10.1111/tid.12433

    Article  CAS  PubMed  Google Scholar 

  11. Kwon JH, Bommarito KM, Reske KA, Seiler SM, Hink T, Babcock HM, Kollef MH, Fraser VJ, Burnham CA, Dubberke ER, Centers for Disease Control and Prevention (CDC) Prevention Epicenters (2015) Randomized controlled trial to determine the impact of probiotic administration on colonization with multidrug-resistant organisms in critically ill patients. Infect Control Hosp Epidemiol 36(12):1451–1454. https://doi.org/10.1017/ice.2015.195

    Article  PubMed  PubMed Central  Google Scholar 

  12. Baron EJ, Miller JM, Weinstein MP, Richter SS, Gilligan PH, Thomson RB Jr, Bourbeau P, Carroll KC, Kehl SC, Dunne WM, Robinson-Dunn B, Schwartzman JD, Chapin KC, Snyder JW, Forbes BA, Patel R, Rosenblatt JE, Pritt BS (2013) A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2013 recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)(a). Clin Infect Dis 57(4):e22–e121. https://doi.org/10.1093/cid/cit278

    Article  PubMed  PubMed Central  Google Scholar 

  13. Friedman ND, Kaye KS, Stout JE et al (2002) Health care-associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections. Ann Intern Med 137:791–797

    Article  PubMed  Google Scholar 

  14. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L (1996) Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334(11):693–699. https://doi.org/10.1056/NEJM199603143341104

    Article  CAS  PubMed  Google Scholar 

  15. 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 (2012) Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18(3):268–281. https://doi.org/10.1111/j.1469-0691.2011.03570.x

    Article  CAS  PubMed  Google Scholar 

  16. Merli M, Lucidi C, Giannelli V, Giusto M, Riggio O, Falcone M, Ridola L, Attili AF, Venditti M (2010) Cirrhotic patients are at risk for health care-associated bacterial infections. Clin Gastroenterol Hepatol 8(11):979–985. https://doi.org/10.1016/j.cgh.2010.06.024

    Article  PubMed  Google Scholar 

  17. Merli M, Lucidi C, Di Gregorio V, Falcone M, Giannelli V, Lattanzi B, Giusto M, Ceccarelli G, Farcomeni A, Riggio O, Venditti M (2015) The spread of multi drug resistant infections is leading to an increase in the empirical antibiotic treatment failure in cirrhosis: a prospective survey. PLoS One 10(5):e0127448. https://doi.org/10.1371/journal.pone.0127448

    Article  PubMed  PubMed Central  Google Scholar 

  18. Ariza X, Castellote J, Lora-Tamayo J, Girbau A, Salord S, Rota R, Ariza J, Xiol X (2012) Risk factors for resistance to ceftriaxone and its impact on mortality in community, healthcare and nosocomial spontaneous bacterial peritonitis. J Hepatol 56(4):825–832. https://doi.org/10.1016/j.jhep.2011.11.010

    Article  CAS  PubMed  Google Scholar 

  19. Alexopoulou A, Vasilieva L, Agiasotelli D, Siranidi K, Pouriki S, Tsiriga A, Toutouza M, Dourakis SP (2016) Extensively drug-resistant bacteria are an independent predictive factor of mortality in 130 patients with spontaneous bacterial peritonitis or spontaneous bacteremia. World J Gastroenterol 22(15):4049–4056. https://doi.org/10.3748/wjg.v22.i15.4049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Merli M, Lucidi C, Gregorio D, Lattanzi B, Giannelli V, Giusto M, Farcomeni A, Ceccarelli G, Falcone M, Riggio O, Venditti M (2016) An empirical broad spectrum antibiotic therapy in health-care-associated infections improves survival in patients with cirrhosis: a randomized trial. Hepatology 63(5):1632–1639. https://doi.org/10.1002/hep.28332

    Article  CAS  PubMed  Google Scholar 

  21. Piano S, Fasolato S, Salinas F, Romano A, Tonon M, Morando F, Cavallin M, Gola E, Sticca A, Loregian A, Palù G, Zanus G, Senzolo M, Burra P, Cillo U, Angeli P (2016) The empirical antibiotic treatment of nosocomial spontaneous bacterial peritonitis: results of a randomized, controlled clinical trial. Hepatology 63(4):1299–1309. https://doi.org/10.1002/hep.27941

    Article  CAS  PubMed  Google Scholar 

  22. Papadimitriou-Olivgeris M, Spiliopoulou I, Christofidou M, Logothetis D, Manolopoulou P, Dodou V, Fligou F, Marangos M, Anastassiou ED (2015) Co-colonization by multidrug-resistant bacteria in two Greek intensive care units. Eur J Clin Microbiol Infect Dis 34(10):1947–1955. https://doi.org/10.1007/s10096-015-2436-2444

    Article  CAS  PubMed  Google Scholar 

  23. Gikas A, Christidou A, Scoulica E, Nikolaidis P, Skoutelis A, Levidiotou S, Kartali S, Maltezos E, Metalidis S, Kioumis J, Haliotis G, Dima S, Roumbelaki M, Papageorgiou N, Kritsotakis EI, Tselentis Y (2005) Epidemiology and molecular analysis of intestinal colonization by vancomycin-resistant enterococci in greek hospitals. J Clin Microbiol 43(11):5796–5799. https://doi.org/10.1128/JCM.43.11.5796-5799.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. European Association for the Study of the Liver (2010) EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol 53(3):397–417. https://doi.org/10.1016/j.jhep.2010.05.004

    Article  Google Scholar 

  25. Han JH, Nachamkin I, Zaoutis TE, Coffin SE, Linkin DR, Fishman NO, Weiner MG, Hu B, Tolomeo P, Lautenbach E (2012) Risk factors for gastrointestinal tract colonization with extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella species in hospitalized patients. Infect Control Hosp Epidemiol 33(12):1242–1245. https://doi.org/10.1086/668443

    Article  PubMed  PubMed Central  Google Scholar 

  26. Waidmann O, Kempf VA, Brandt C, Zeuzem S, Piiper A, Kronenberger B (2015) Colonisation with multidrug-resistant bacteria is associated with increased mortality in patients cirrhosis. Gut 64(7):1183–1184. https://doi.org/10.1136/gutjnl-2014-309104

    Article  PubMed  Google Scholar 

  27. Majumdar A, Tsochatzis E (2016) Biomarkers of bacterial translocation in advanced chronic liver disease: the key to individualizing prognosis. Ann Gastroenterol 29(1):1–2

    PubMed  PubMed Central  Google Scholar 

  28. Gonzalez VEP, Marco F, Arteaga M, Reverter E, Escorsell A, Carpio A, Mezzano G, Rodríguez S, Juanola A, Mensa J, Ginès P, Soriano A, Vila J, Fernandez J (2017) Prevalence and clinical impact of rectal colonization by multidrug-resistant bacteria in critically ill patients with and without cirrhosis. J Hepatol 66:S543. https://doi.org/10.1016/S0168-8278(17)31547-7

    Google Scholar 

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    Authors and Affiliations

    1. 2nd Department of Internal Medicine and Research Laboratory, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, 114 Vas Sophias St, Athens, Greece

      S. Pouriki, H. Sambatakou, A. Alexopoulou, L. Vasilieva, I. Mani & S. P. Dourakis

    2. Department of Microbiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece

      G. Vrioni & A. Tsakris

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    1. S. Pouriki
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    Correspondence to A. Alexopoulou.

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    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

    This article does not contain any studies with animals performed by any of the authors.

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    A. Tsakris and S. P. Dourakis contributed equally to this work.

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    Pouriki, S., Vrioni, G., Sambatakou, H. et al. Intestinal colonization with resistant bacteria: a prognostic marker of mortality in decompensated cirrhosis. Eur J Clin Microbiol Infect Dis 37, 127–134 (2018). https://doi.org/10.1007/s10096-017-3110-9

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