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 Escherichia coli and Klebsiella pneumoniae remains poorly understood.AimTo analyse the molecular epidemiology of OXA-48 and OXA-48-like carbapenemases in Citrobacter 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 Citrobacter isolates from 40 German hospitals harbouring bla _{OXA-48/OXA-48‑like} were analysed by whole genome sequencing and conjugation experiments.ResultsThe frequency of OXA-48 in Citrobacter freundii (CF) has increased steadily since 2011 and is now the most prevalent carbapenemase in this species in Germany. Among 91 in-depth analysed Citrobacter spp. isolates, CF (n = 73) and C. koseri (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 bla _OXA‑48 and bla _OXA-162 belonged to the plasmid types IncL (n = 85) or IncF (n = 3), and plasmids harbouring bla _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 bla _OXA‑48 or bla _OXA-48-like and the spread of the high-risk clonal lineages ST19 and ST22.

Keywords: Antimicrobial susceptibility, Carbapenemases, OXA-48, Citrobacter, Germany; Enterobacterales.

Figure 1

Carbapenemase production in Enterobacterales isolates (n = 26,822) and carbapenemase types in Citrobacter freundii isolates (n = 91) sent to the German National Reference Centre for Multidrug-resistant Gram-negative Bacteria, Germany, 2011–2022

Figure 2

Emergence of OXA-48 and OXA-48-like producing isolates of Citrobacter species, Germany, 2011–2022 (n = 91)

Figure 3

Antimicrobial susceptibility of OXA-48 and OXA-48-like producing Citrobacter species isolates, Germany, 2011–2022 (n = 91)

Figure 4

Phylogeny of OXA-48 and OXA-48-like harbouring Citrobacter freundii, Germany, 2011–2022 (n = 73)

Figure 5

Phylogeny of IncL OXA-48 and OXA-48-like plasmids from isolates of Citrobacter species, Germany, 2011-2022 (n = 85)

Figure 6

Multilocus sequence typing-based phylogeny of isolates of Citrobacter species available from public sequence databases with and without carbapenemase genes, 2003-2022^a (n = 1,946)