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Progress in Hepatology-rectal Colonization by Resistant Bacteria Increases the Risk of Infection by the Colonizing Strain in Critically Ill Patients with Cirrhosis

  • Akash Roy
    Correspondence
    Address for correspondence: Akash Roy, Assistant Professor, Department of Hepatology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh 226014, India. Tel: +91 9774056722.
    Affiliations
    Department of Hepatology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh 226014, India
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  • Madhumita Premkumar
    Affiliations
    Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
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      Abbreviations:

      ACLF (acute on chronic liver failure), ESBL (extended-spectrum beta-lactamase), MDROs (multidrug resistance organisms), VRE (vancomycin-resistant enterococci)
      Antimicrobial resistance has emerged as a global threat, and multidrug resistance organisms (MDROs) form one of the foremost challenges in the setting of decompensated cirrhosis. In this study, the authors examine two separate cohorts (Barcelona and Frankfurt cohorts) from two critical care units, one with prospective data and another with a retrospective analysis.
      • Prado V.
      • Hernández-Tejero M.
      • Mücke M.M.
      • Marco F.
      • Gu W.
      • Amoros A.
      • et al.
      Rectal colonization by resistant bacteria increases the risk of infection by the colonizing strain in critically ill patients with cirrhosis.
      The study’s primary objective was to ascertain the prevalence of rectal colonization by MDROs in critically ill patients, understand their epidemiological characteristics, and assess their prognostic impact. Rectal colonization was determined with cultures from rectal swabs at admission (within 48 h) and then weekly till discharge or death. The Barcelona cohort included patients both with (n = 174) and without liver disease (n = 312), while the Frankfurt cohort was composed of only patients with cirrhosis (n = 421).
      From the Barcelona cohort, the first key finding was the presence of significantly higher epidemiological risk factors (recent hospitalization, including ICU admission, antibiotic prophylaxis, and recent history of MDRO isolation). In this cohort, the prevalence of MDRO rectal colonization was significantly higher in patients with cirrhosis at admission. Interestingly, during the ICU stay, rates of rectal colonization were similar between those with cirrhosis and those without liver disease. Extended-spectrum beta-lactamase (ESBL) Enterobacterales were the most common isolated organisms, with MDR-Escherichia coli and Klebsiella pneumonia being more prevalent in patients with cirrhosis. The key factors that were associated with MDRO colonization in cirrhosis were antibiotic prophylaxis, overall disease severity, mechanical ventilation, and need for renal replacement therapy. Overall proven bacterial infections, infections with resistant organisms, and cumulative incident MDRO infections were more common in MDRO colonizers. The highlight of the cohort was a significantly higher rate of infection caused by corresponding resistant colonizers in patients with cirrhosis than those without as well as MDRO colonization as an independent predictor of infection by the corresponding resistant strain in cirrhotic (HR: 7.41; 95% CI: 2.58–21.30) and non-cirrhotic groups (HR: 5.65; 95% CI: 2.36–13.54). Lastly, colonization with MDROs was associated with increased mortality in patients with cirrhosis.
      The Frankfurt cohort only comprised patients with cirrhosis. Almost half (47%) of the cohort had MDRO colonization at admission, with vancomycin-resistant enterococci (VRE) being the commonest colonizer instead of ESBLs, as seen in the Barcelona cohort. In tune with the observations of the Barcelona cohort, infections due to resistant strains were more common in MDRO colonizers, with almost 90% of cases having the same MDR bacteria isolated in rectal swabs. However, the in-hospital mortality in this cohort was similar among MDRO colonizers and non-colonizers, although the development of incident VRE infection predicted worse survival.
      The intuitive concept of association of rectal carriage of MDROs and subsequent development of proven MDRO infections with a focus on Carbapenem-resistant Enterobacteriaceae and Pseudomonas infections has previously been demonstrated in intensive care as well as liver transplantation setting.
      • Schechner V.
      • Kotlovsky T.
      • Kazma M.
      • Mishali H.
      • Schwartz D.
      • Navon-Venezia S.
      • et al.
      Asymptomatic rectal carriage of blaKPC producing carbapenem-resistant Enterobacteriaceae: who is prone to become clinically infected?.
      • Gómez-Zorrilla S.
      • Camoez M.
      • Tubau F.
      • Cañizares R.
      • Periche E.
      • Dominguez M.A.
      • et al.
      Prospective observational study of prior rectal colonization status as a predictor for subsequent development of Pseudomonas aeruginosa clinical infections.
      • Giannella M.
      • Bartoletti M.
      • Morelli M.C.
      • Tedeschi S.
      • Cristini F.
      • Tumietto F.
      • et al.
      Risk factors for infection with carbapenem-resistant Klebsiella pneumoniae after liver transplantation: the importance of pre- and posttransplant colonization.
      However, the fundamental merits of this study lie in incorporating two large cohorts of patients with cirrhosis and meticulous follow-up for incident infections. MDRO infections in cirrhosis pose one of the most crucial challenges in clinical practice, and identifying the appropriate subset at risk for these infections for early directed therapy has remained a vexing predicament. Analysis of the study draws home two crucial points: a definitive risk of rectal colonization for incident infections and variance in the bacteriological profiles in different settings, which again re-enforces the need for individualized antimicrobial policy decisions rather than umbrella guidelines. The results of this study will generate evidence for future policymaking. However, certain key facts still need to be treated with caution. One of the cohorts has a relatively broad timespan of enrolment (2010–2018), which may influence the overall temporal trends of microbiological profiles. Additionally, although the cohorts included patients with cirrhosis primarily, some heterogeneity remained due to the incorporation of patients with acute liver failure and post-liver transplant patients who may behave differently. Lastly, as the choice and decision of empirical antibiotics in acute and chronic liver failure remain an elusive frontier, future studies focusing on Acute on Chronic Liver Failure (ACLF), a population with intrinsically high mortality, should stem out in the background of this crucial work.
      • Sundaram V.
      • Shah P.
      • Wong R.J.
      • Karvellas C.J.
      • Fortune B.E.
      • Mahmud N.
      • et al.
      Patients With Acute on Chronic Liver Failure Grade 3 Have Greater 14-Day Waitlist Mortality Than Status-1a Patients.

      Conflict of interest

      None.

      Acknowledgments

      None.

      Source of funding

      Nil.

      References

        • Prado V.
        • Hernández-Tejero M.
        • Mücke M.M.
        • Marco F.
        • Gu W.
        • Amoros A.
        • et al.
        Rectal colonization by resistant bacteria increases the risk of infection by the colonizing strain in critically ill patients with cirrhosis.
        J Hepatol. 2022; 76: 1079-1089
        • Schechner V.
        • Kotlovsky T.
        • Kazma M.
        • Mishali H.
        • Schwartz D.
        • Navon-Venezia S.
        • et al.
        Asymptomatic rectal carriage of blaKPC producing carbapenem-resistant Enterobacteriaceae: who is prone to become clinically infected?.
        Clin Microbiol Infect. 2013; 19: 451-456
        • Gómez-Zorrilla S.
        • Camoez M.
        • Tubau F.
        • Cañizares R.
        • Periche E.
        • Dominguez M.A.
        • et al.
        Prospective observational study of prior rectal colonization status as a predictor for subsequent development of Pseudomonas aeruginosa clinical infections.
        Antimicrob Agents Chemother. 2015; 59: 5213-5219
        • Giannella M.
        • Bartoletti M.
        • Morelli M.C.
        • Tedeschi S.
        • Cristini F.
        • Tumietto F.
        • et al.
        Risk factors for infection with carbapenem-resistant Klebsiella pneumoniae after liver transplantation: the importance of pre- and posttransplant colonization.
        Am J Transplant. 2015; 15: 1708-1715
        • Sundaram V.
        • Shah P.
        • Wong R.J.
        • Karvellas C.J.
        • Fortune B.E.
        • Mahmud N.
        • et al.
        Patients With Acute on Chronic Liver Failure Grade 3 Have Greater 14-Day Waitlist Mortality Than Status-1a Patients.
        Hepatology. 2019; 70: 334-345