Emergence of OXA-48-like producing Citrobacter species, Germany, 2011 to 2022

Abstract

BackgroundCarbapenemase-producing Enterobacterales are a public health threat worldwide and OXA-48 is the most prevalent carbapenemase in Germany and western Europe. However, the molecular epidemiology of OXA-48 in species other than <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> remains poorly understood.AimTo analyse the molecular epidemiology of OXA-48 and OXA-48-like carbapenemases in <i>Citrobacter</i> species (spp.) in Germany between 2011 and 2022.MethodsData of 26,822 Enterobacterales isolates sent to the National Reference Centre (NRC) for Gram-negative bacteria were evaluated. Ninety-one <i>Citrobacter</i> isolates from 40 German hospitals harbouring <i>bla</i> _{OXA-48/OXA-48‑like} were analysed by whole genome sequencing and conjugation experiments.ResultsThe frequency of OXA-48 in <i>Citrobacter freundii</i> (CF) has increased steadily since 2011 and is now the most prevalent carbapenemase in this species in Germany. Among 91 in-depth analysed <i>Citrobacter</i> spp. isolates, CF (n = 73) and <i>C. koseri</i> (n = 8) were the most common species and OXA-48 was the most common variant (n = 77), followed by OXA-162 (n = 11) and OXA‑181 (n = 3). Forty percent of the isolates belonged to only two sequence types (ST19 and ST22), while most other STs were singletons. The plasmids harbouring <i>bla</i> _OXA‑48 and <i>bla</i> _OXA-162 belonged to the plasmid types IncL (n = 85) or IncF (n = 3), and plasmids harbouring <i>bla</i> _OXA‑181 to IncX3 (n = 3). Three IncL plasmid clusters (57/85 IncL plasmids) were identified, which were highly transferable in contrast to sporadic plasmids.ConclusionIn CF in Germany, OXA-48 is the predominant carbapenemase. Dissemination is likely due to distinct highly transmissible plasmids harbouring <i>bla</i> _OXA‑48 or <i>bla</i> _OXA-48-like and the spread of the high-risk clonal lineages ST19 and ST22.