title: The impact of carbapenem resistance on clinical deterioration and mortality in patients with liver disease.
abstract: Infections with multidrug-resistant gram-negative bacteria are significantly impairing the prognosis of patients with liver disease. In particular, carbapenem resistance further narrows therapeutic options. This study investigates the impact of carbapenem-resistant gram-negative bacteria on the outcome of patients with liver disease and cirrhosis.
  
  
  
  Between January 2011 and July 2015, 132 patients treated at the tertiary liver transplant centre at University Hospital Frankfurt, Germany, were tested positive for carbapenem-resistant gram-negative bacteria and retrospectively analysed in this study. Risk factors for fatal outcome were evaluated using multivariate regression analysis. Competing-risk analysis was performed on patients tested positive for Enterobacteriaceae or non-fermenting species, for example, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia. Subgroup analysis of cirrhotic patients was performed on a matched cohort of cirrhotic patients, comparable model for end-stage liver disease and tested negative for carbapenem-resistant gram-negative bacteria.
  
  
  
  97 (73.5%) and 35 (26.5%) patients were infected or colonised with carbapenem-resistant gram-negative bacteria respectively. Within the observation period, 61/132 (46.2%) patients died, with sepsis being the leading cause (38/61, 62.3%). Decompensated liver disease, sepsis and admission to intensive care unit were independent risk factors for fatal outcome. Lethal sepsis in patients positive for non-fermenting bacteria was significantly more frequent than in those positive for Enterobacteriaceae, independently from liver function. Subgroup analysis of cirrhotic patients showed that sepsis (54.9% vs 13%) and lethal sepsis were significantly more frequent after detection of carbapenem-resistant gram-negative bacteria, independently from localisation of pathogen detection.
  
  
  
  Patients with advanced liver disease are prone to fatal infections caused by carbapenem-resistant gram-negative bacteria.
authors.affiliation: Department for Internal Medicine I/Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt am Main, Germany.|University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Philip G
authors.identifier: 0000-0002-0836-6643
authors.initials: PG
authors.lastname: Ferstl
authors.affiliation: Institute of Biostatistics and Mathematical Modeling, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Filmann
authors.affiliation: University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany.|Institute for Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Brandt
authors.affiliation: Department for Internal Medicine I/Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt am Main, Germany.|University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany.|Institute for Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hogardt
authors.affiliation: University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany.|Institute for Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Volkhard A J
authors.initials: VAJ
authors.lastname: Kempf
authors.affiliation: Department for Internal Medicine I/Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Mona
authors.initials: M
authors.lastname: Müller
authors.affiliation: Department for Internal Medicine I/Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt am Main, Germany.|University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Waidmann
authors.affiliation: University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Frankfurt am Main, Germany.|Institute for Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Reinheimer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015780:Carbapenems / Q000627:therapeutic use; D016009:Chi-Square Distribution; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D005858:Germany; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000472:pathogenicity; D016905:Gram-Negative Bacterial Infections / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology* / Q000401:mortality*; D006785:Hospitals, University; D006801:Humans; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000382:microbiology* / Q000401:mortality* / Q000601:surgery; D016031:Liver Transplantation / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D018805:Sepsis / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology* / Q000401:mortality*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015780:Carbapenems
keywords: carbapenem resistance; cirrhosis; liver disease; multidrug-resistant organisms; sepsis