Dissemination of extensively drug-resistant NDM-producing Providencia stuartii in Europe linked to patients transferred from Ukraine, March 2022 to March 2023

Abstract

BackgroundThe war in Ukraine led to migration of Ukrainian people. Early 2022, several European national surveillance systems detected multidrug-resistant (MDR) bacteria related to Ukrainian patients.AimTo investigate the genomic epidemiology of New Delhi metallo-β-lactamase (NDM)-producing Providencia stuartii from Ukrainian patients among European countries.MethodsWhole-genome sequencing of 66 isolates sampled in 2022-2023 in 10 European countries enabled whole-genome multilocus sequence typing (wgMLST), identification of resistance genes, replicons, and plasmid reconstructions. Five bla _NDM-1-carrying-P. stuartii isolates underwent antimicrobial susceptibility testing (AST). Transferability to Escherichia coli of a bla _NDM-1-carrying plasmid from a patient strain was assessed. Epidemiological characteristics of patients with NDM-producing P. stuartii were gathered by questionnaire.ResultswgMLST of the 66 isolates revealed two genetic clusters unrelated to Ukraine and three linked to Ukrainian patients. Of these three, two comprised bla _NDM-1-carrying-P. stuartii and the third bla _NDM-5-carrying-P. stuartii. The bla _NDM-1 clusters (PstCluster-001, n = 22 isolates; PstCluster-002, n = 8 isolates) comprised strains from seven and four countries, respectively. The bla _NDM-5 cluster (PstCluster-003) included 13 isolates from six countries. PstCluster-001 and PstCluster-002 isolates carried an MDR plasmid harbouring bla _NDM-1, bla _OXA-10, bla _CMY-16, rmtC and armA, which was transferrable in vitro and, for some Ukrainian patients, shared by other Enterobacterales. AST revealed PstCluster-001 isolates to be extensively drug-resistant (XDR), but susceptible to cefiderocol and aztreonam-avibactam. Patients with data on age (n = 41) were 19-74 years old; of 49 with information on sex, 38 were male.ConclusionXDR P. stuartii were introduced into European countries, requiring increased awareness and precautions when treating patients from conflict-affected areas.

Keywords: New Delhi metallo-β-lactamase; Providencia stuartii; Ukrainian patients; dissemination; war.

Figure 1

(A) Minimum spanning tree with Providencia stuartii RefSeq isolates (n = 68), as well as isolates (n = 66) collected in 10 European countries including from patients linked to Ukraine, and (B–D) focus on individual clusters within the tree, March 2022–March 2023 (n = 134 total isolates)

Figure 2

Resistomes of Providencia stuartii strains isolated in 10 European countries, which belonged to a cluster according to the study^a, March 2022–March 2023 (n = 47 total isolates)

Figure 3

Comparing sequences of Providencia stuartii bla _NDM-1-carrying IncC plasmids obtained in the study with those of other reported NDM-1-IncC-plasmids, March 2022–March 2023 (n = 48 isolates)^a

Figure 4

Distribution of antimicrobial resistance genes on plasmids versus chromosomes of Providencia stuartii strains, March 2022–March 2023 (n = 7 isolates)

Figure 5

Results of an in vitro trans conjugation experiment at (A) genetic and (B) phenotypic level (n = 3 isolates)