Abstract
Background: Carbapenem-resistant Gram-negative bacteria (CRGN) cause life-threatening infections due to limited antimicrobial treatment options. The occurrence of CRGN is often linked to hospitalization and antimicrobial treatment but remains incompletely understood. CRGN are common in patients with severe illness (e.g., liver transplantation patients). Using whole-genome sequencing (WGS), we aimed to elucidate the evolution of CRGN in this vulnerable cohort and to reconstruct potential transmission routes.Methods: From 351 patients evaluated for liver transplantation, 18 CRGN isolates (from 17 patients) were analyzed. Using WGS and bioinformatic analysis, genotypes and phylogenetic relationships were explored. Potential epidemiological links were assessed by analysis of patient charts.Results: Carbapenem-resistant (CR) Klebsiella pneumoniae (n=9) and CR Pseudomonas aeruginosa (n=7) were the predominating pathogens. In silico analysis revealed that 14/18 CRGN did not harbor carbapenemase-coding genes, whereas in 4/18 CRGN, carbapenemases (VIM-1, VIM-2, OXA-232, and OXA-72) were detected. Among all isolates, there was no evidence of plasmid transfer-mediated carbapenem resistance. A close phylogenetic relatedness was found for three K. pneumoniae isolates. Although no epidemiological context was comprehensible for the CRGN isolates, evidence was found that the isolates resulted of a transmission of a carbapenem-susceptible ancestor before individual radiation into CRGN.Conclusion: The integrative epidemiological study reveals a high diversity of CRGN in liver cirrhosis patients. Mutation of carbapenem-susceptible ancestors appears to be the dominant way of CR acquisition rather than in-hospital transmission of CRGN or carbapenemase-encoding genetic elements. This study underlines the need to avoid transmission of carbapenem-susceptible ancestors in vulnerable patient cohorts.
Highlights
Liver transplantation (LT) is the only curative treatment for liver cirrhosis, but donor organs are scarce and allocated at a late stage of the disease (Tacke et al, 2016; Adam et al, 2018)
From 2008 to 2018, 351 patients evaluated and listed for LT had undergone multidrug-resistant organisms (MDRO) screening according to the in-house hygiene plan (Ferstl et al, 2021)
Among these 351 patients, 24 carbapenem-resistant Gram-negative bacteria (CRGN) were identified in 23 patients, including one patient with the detection of two CRGN (K. pneumoniae and P. aeruginosa)
Summary
Liver transplantation (LT) is the only curative treatment for liver cirrhosis, but donor organs are scarce and allocated at a late stage of the disease (Tacke et al, 2016; Adam et al, 2018). Therapeutic options are further limited in case of infection with carbapenem-resistant Gram-negative bacteria (CRGN), often leading to clinical deterioration and death (Ferstl et al, 2017, 2018; Fernández et al, 2019). Implementation of infection control measures and an active surveillance of CRGN strains in transplantation centers are crucial (Geladari et al, 2017). Since patients evaluated for LT are regularly screened for CRGN at our center, we reasoned that this vulnerable population might be well-suited for the study of mechanisms leading to carbapenem resistance (CR). Carbapenem-resistant Gram-negative bacteria (CRGN) cause lifethreatening infections due to limited antimicrobial treatment options. The occurrence of CRGN is often linked to hospitalization and antimicrobial treatment but remains incompletely understood. CRGN are common in patients with severe illness (e.g., liver transplantation patients). Using whole-genome sequencing (WGS), we aimed to elucidate the evolution of CRGN in this vulnerable cohort and to reconstruct potential transmission routes
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