Terlipressin therapy is associated with increased risk of colonisation with multidrug-resistant bacteria in patients with decompensated cirrhosis

Mücke, M.M.; Hernández-Tejero, M.; Gu, W.Y.; Kuhn, M.; Janz, M.; Keller, M.I.; Fullam, A.; Altepeter, L.; Mücke, V.T.; Finkelmeier, F.; Schwarzkopf, K.M.; Cremonese, C.; Hunyady, P.M.; Heilani, M.W.; Uschner, F.E.; Schierwagen, R.; Brol, M.J.; Fischer, J.; Klein, S.; Peiffer, K.H.; Hogardt, M.; Shoaie, S.; Coenraad, M.J.; Bojunga, J.; Arroyo, V.; Zeuzem, S.; Kempf, V.A.J.; Welsch, C.; Laleman, W.; Bork, P.; Fernandez, J.; Trebicka, J.; EASL-CLIF Consortium

doi:doi:10.1111/apt.17899

Aim: The aim of the study was to assess the influence of non-antibiotic medicationcontributing to MDRO colonisation.Methods: Three hundred twenty-four patients with AD and ACLF admitted to the ICUof Frankfurt University Hospital with MDRO screening were included. Regressionmodels were performed to identify drugs associated with MDRO colonisation.Another cohort (n = 129) from Barcelona was included to validate. A third multi-centre cohort (n = 203) with metagenomic sequencing data of stool was included todetect antibiotic resistance genes.Results: A total of 97 patients (30%) were identified to have MDRO colonisation and35 of them (11%) developed MDRO infection. Patients with MDRO colonisation hadsignificantly higher risk of MDRO infection than those without (p = 0.0098). Apartfrom antibiotic therapy (odds ratio (OR) 2.91, 95%-confidence interval (CI) 1.82–4.93,p < 0.0001), terlipressin therapy in the previous 14 days was the only independentcovariate associated with MDRO...Show moreAim: The aim of the study was to assess the influence of non-antibiotic medicationcontributing to MDRO colonisation.Methods: Three hundred twenty-four patients with AD and ACLF admitted to the ICUof Frankfurt University Hospital with MDRO screening were included. Regressionmodels were performed to identify drugs associated with MDRO colonisation.Another cohort (n = 129) from Barcelona was included to validate. A third multi-centre cohort (n = 203) with metagenomic sequencing data of stool was included todetect antibiotic resistance genes.Results: A total of 97 patients (30%) were identified to have MDRO colonisation and35 of them (11%) developed MDRO infection. Patients with MDRO colonisation hadsignificantly higher risk of MDRO infection than those without (p = 0.0098). Apartfrom antibiotic therapy (odds ratio (OR) 2.91, 95%-confidence interval (CI) 1.82–4.93,p < 0.0001), terlipressin therapy in the previous 14 days was the only independentcovariate associated with MDRO colonisation in both cohorts, the overall (OR 9.47,95%-CI 2.96–30.23, p < 0.0001) and after propensity score matching (OR 5.30, 95%-CI 1.22–23.03, p = 0.011). In the second cohort, prior terlipressin therapy was a riskfactor for MDRO colonisation (OR 2.49, 95% CI 0.911–6.823, p = 0.075) and associ-ated with risk of MDRO infection during follow-up (p = 0.017). The validation cohortdemonstrated that antibiotic inactivation genes were significantly associated withterlipressin administration (p = 0.001).Conclusions: Our study reports an increased risk of MDRO colonisation in patientswith AD or ACLF, who recently received terlipressin therapy, while other commonlyprescribed non-antibiotic co-medications had negligible influence. Future prospec-tive trials are needed to confirm these results.
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Terlipressin therapy is associated with increased risk of colonisation with multidrug-resistant bacteria in patients with decompensated cirrhosis