Terlipressin therapy is associated with increased risk of colonisation with multidrug-resistant bacteria in patients with decompensated cirrhosis.
Journal
Alimentary pharmacology & therapeutics
ISSN: 1365-2036
Titre abrégé: Aliment Pharmacol Ther
Pays: England
ID NLM: 8707234
Informations de publication
Date de publication:
27 Feb 2024
27 Feb 2024
Historique:
revised:
20
12
2023
received:
23
11
2023
accepted:
28
01
2024
medline:
28
2
2024
pubmed:
28
2
2024
entrez:
28
2
2024
Statut:
aheadofprint
Résumé
Patients with cirrhosis are susceptible to develop bacterial infections that trigger acute decompensation (AD) and acute-on-chronic liver failure (ACLF). Infections with multidrug-resistant organisms (MDRO) are associated with deleterious outcome. MDRO colonisation frequently proceeds MDRO infections and antibiotic therapy has been associated with MDRO colonisation. The aim of the study was to assess the influence of non-antibiotic medication contributing to MDRO colonisation. Three hundred twenty-four patients with AD and ACLF admitted to the ICU of Frankfurt University Hospital with MDRO screening were included. Regression models 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 to detect antibiotic resistance genes. A total of 97 patients (30%) were identified to have MDRO colonisation and 35 of them (11%) developed MDRO infection. Patients with MDRO colonisation had significantly higher risk of MDRO infection than those without (p = 0.0098). Apart from 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 independent covariate 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 risk factor for MDRO colonisation (OR 2.49, 95% CI 0.911-6.823, p = 0.075) and associated with risk of MDRO infection during follow-up (p = 0.017). The validation cohort demonstrated that antibiotic inactivation genes were significantly associated with terlipressin administration (p = 0.001). Our study reports an increased risk of MDRO colonisation in patients with AD or ACLF, who recently received terlipressin therapy, while other commonly prescribed non-antibiotic co-medications had negligible influence. Future prospective trials are needed to confirm these results.
Sections du résumé
BACKGROUND
BACKGROUND
Patients with cirrhosis are susceptible to develop bacterial infections that trigger acute decompensation (AD) and acute-on-chronic liver failure (ACLF). Infections with multidrug-resistant organisms (MDRO) are associated with deleterious outcome. MDRO colonisation frequently proceeds MDRO infections and antibiotic therapy has been associated with MDRO colonisation.
AIM
OBJECTIVE
The aim of the study was to assess the influence of non-antibiotic medication contributing to MDRO colonisation.
METHODS
METHODS
Three hundred twenty-four patients with AD and ACLF admitted to the ICU of Frankfurt University Hospital with MDRO screening were included. Regression models 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 to detect antibiotic resistance genes.
RESULTS
RESULTS
A total of 97 patients (30%) were identified to have MDRO colonisation and 35 of them (11%) developed MDRO infection. Patients with MDRO colonisation had significantly higher risk of MDRO infection than those without (p = 0.0098). Apart from 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 independent covariate 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 risk factor for MDRO colonisation (OR 2.49, 95% CI 0.911-6.823, p = 0.075) and associated with risk of MDRO infection during follow-up (p = 0.017). The validation cohort demonstrated that antibiotic inactivation genes were significantly associated with terlipressin administration (p = 0.001).
CONCLUSIONS
CONCLUSIONS
Our study reports an increased risk of MDRO colonisation in patients with AD or ACLF, who recently received terlipressin therapy, while other commonly prescribed non-antibiotic co-medications had negligible influence. Future prospective trials are needed to confirm these results.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : the European Union's Horizon 2020 research and innovation program
ID : DECISION (project ID 847949)
Organisme : the European Union's Horizon 2020 research and innovation program
ID : GALAXY (project ID 668031)
Organisme : the European Union's Horizon 2020 research and innovation program
ID : IHMCSA (project ID 964590)
Organisme : the European Union's Horizon 2020 research and innovation program
ID : LIVERHOPE (project ID 731875)
Organisme : the European Union's Horizon 2020 research and innovation program
ID : MICROB-PREDICT (project ID 825694)
Organisme : Hessian Ministry of Higher Education, Research and the Arts (HMWK)
ID : ACLF-I cluster
Organisme : German Federal Ministry of Education and Research (BMBF)
ID : DEEP-HCC
Organisme : Deutsche Forschungsgemeinschaft
ID : 403224013-SFB 1382 (A09)
Informations de copyright
© 2024 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
Références
Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology. 2013;144(7):1426-1437, e1421-1429.
Mücke MM, Rumyantseva T, Mücke VT, Schwarzkopf K, Joshi S, Kempf VAJ, et al. Bacterial infection-triggered acute-on-chronic liver failure is associated with increased mortality. Liver Int. 2018;38(4):645-653.
Trebicka J, Fernandez J, Papp M, Caraceni P, Laleman W, Gambino C, et al. The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology. J Hepatol. 2020;73(4):842-854.
Fernandez J, Acevedo J, Wiest R, Gustot T, Amorós A, Deulofeu C, et al. Bacterial and fungal infections in acute-on-chronic liver failure: prevalence, characteristics and impact on prognosis. Gut. 2018;67(10):1870-1880.
Fernandez J, Prado V, Trebicka J, Amoros A, Gustot T, Wiest R, et al. Multidrug-resistant bacterial infections in patients with decompensated cirrhosis and with acute-on-chronic liver failure in Europe. J Hepatol. 2019;70(3):398-411.
Wong F, Piano S, Singh V, Bartoletti M, Maiwall R, Alessandria C, et al. Clinical features and evolution of bacterial infection-related acute-on-chronic liver failure. J Hepatol. 2021;74(2):330-339.
Piano S, Singh V, Caraceni P, Maiwall R, Alessandria C, Fernandez J, et al. Epidemiology and effects of bacterial infections in patients with cirrhosis worldwide. Gastroenterology. 2019;156(5):1368-1380.e10.
Trebicka J, Fernandez J, Papp M, Caraceni P, Laleman W, Gambino C, et al. PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis. J Hepatol. 2021;74(5):1097-1108.
European Association for the Study of the L. EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69(2):406-460.
Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-1377.
Teerawattanapong N, Kengkla K, Dilokthornsakul P, Saokaew S, Apisarnthanarak A, Chaiyakunapruk N. Prevention and control of multidrug-resistant gram-negative bacteria in adult intensive care units: a systematic review and network meta-analysis. Clin Infect Dis. 2017;64(suppl_2):S51-S60.
Mücke MM, Mayer A, Kessel J, Mücke VT, Bon D, Schwarzkopf K, et al. Quinolone- and multidrug-resistance predict failure of antibiotic prophylaxis of spontaneous bacterial peritonitis. Clin Infect Dis. 2019;70:1916-1924.
Waidmann O, Kempf VA, Brandt C, Zeuzem S, Piiper A, Kronenberger B. Colonisation with multidrug-resistant bacteria is associated with increased mortality in patients with cirrhosis. Gut. 2015;64(7):1183-1184.
Hernandez-Tejero M, Reverte FM, Aziz F, Pitart C, Campo I, Carpio A, et al. SAT-046-clinical impact of rectal colonization by multidrug-resistant bacteria in patients with deceompensated cirrhosis. J Hepatol. 2019;70(1):E647.
Maier L, Pruteanu M, Kuhn M, Zeller G, Telzerow A, Anderson EE, et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018;555(7698):623-628.
Prado V, Hernández-Tejero M, Mücke MM, 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(5):1079-1089.
Mücke MM, Mücke VM, Graf C, Schwarzkopf KM, Ferstl PG, Fernandez J, et al. Efficacy of norfloxacin prophylaxis to prevent spontaneous bacterial peritonitis: a systematic review and meta-analysis. Clin Transl Gastroenterol. 2020;11(8):e00223.
Vich Vila A, Collij V, Sanna S, Sinha T, Imhann F, Bourgonje AR, et al. Impact of commonly used drugs on the composition and metabolic function of the gut microbiota. Nat Commun. 2020;11(1):362.