The ongiong conflict in Ukraine has placed extraordinary pressure on medical infrastructure and health delivery services in the region (1). Previous reports from Eastern Ukraine have noted the emergence of multidrug-resistant (MDR) Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacterales infections during hospitalization (2). Those strains encompassed a variety of clonal lineages, with many carrying carbapenemases, extended-spectrum β-lactamases (ESBLs), and 16S methyltransferases (2,3). We describe the isolation of 6 extensively drug-resistant (XDR) organisms from a single soldier from Ukraine.

A man in his mid-50s suffered multiple traumatic injuries after a vehicle fire, including full-thickness burns covering 60% of his total body surface. He was initially treated in a medical facility near Dnipro, Ukraine, before being transferred to a hospital in Kyiv, Ukraine, where healthcare practitioners performed burn wound debridement and escharotomies. Thereafter, the patient was transported to a US military hospital in Germany, where doctors obtained blood, urine, respiratory, and peri-rectal surveillance cultures. Surveillance cultures grew A. baumannii, Enterococcus faecium, Klebsiella pneumoniae, and 2 distinct morphologies of P. aeruginosa. Blood cultures grew a third P. aeruginosa (Table). By using the Vitek 2 automated system (bioMérieux, https://www.biomerieux.com), the gram-negative organisms were found to be nonsusceptible to almost every antibiotic tested (Appendix Table 1), with the exception of A. baumannii, which was susceptible to tetracycline (MIC 2 µg/mL). The E. faecium was nonsusceptible to vancomycin. Researchers used a customized Sensititer panel (Thermo Scientific, https://www.thermofisher.com) to test the gram-negative organisms against colistin, eravacycline, imipenem/relebactam, meropenem/vaborbactam, omadacycline, and plazomicin; they used disk diffusion (Hardy Diagnostics, https://hardydiagnostics.com) to test against cefiderocol (Appendix Table 1). Researchers performed whole-genome sequencing of all isolates by using an Illumina Miseq and the MiSeq Reagent Kit version 3 (600 cycles, 2 × 300 bp) (Illumina, https://www.illumina.com).

The K. pneumoniae isolate, designated MRSN 110821, was nonsusceptible to every antibiotic tested (Appendix Table 1). Testing identified 24 antimicrobial resistance genes, including the carbapenemases bla_NDM-1 and bla_OXA-48, the RMTase armA, and the ESBL bla_CTX-M-15 (Table). Five plasmid replicons were identified (Appendix Table 2), but long-read sequencing is underway to better understand the plasmid structure (data not shown). Colistin resistance likely resulted from a previously characterized E82K mutation in the 2-component transcriptional regulator PhoP (4). Cefiderocol resistance could be linked to mutations in the outer membrane protein OmpK36 combined with NDM (5). The isolate also carried several hypervirulence genetic markers, including ybt16 (yersiniabactin siderophore), iuc1 (aerobactin), and rmpADC/rmpA2 (mucoviscosity and capsule).

Figure

Figure. Core genome, SNP-based phylogenetic tree for Klebsiella pneumoniae from an injured service member from Ukraine (MRSN 110821) and 17 closely related sequence type 395 K. pneumoniae....

The isolate belonged to clade B1 of the clonal lineage sequence type (ST) 395 (6) and was K-antigen capsular biosynthesis loci, K39, and O-antigen type O2 variant 1 (O2v1). ST395 was first described in France in 2010, and carbapenemase-producing strains are increasingly being reported across Europe (6). We downloaded all clade B1 ST395 isolates from Pathogenwatch (https://pathogen.watch) and constructed a phylogenetic tree (Figure). We included 3 ST395 genomes identified by Sandfort et al, which they cultured from patients from Ukraine who were hospitalized in Germany (7). Of note, MRSN 110821 was separated by just 20 single nucleotide polymorphisms from NRZ-78043a from the Sandfort study and by just 19 from NRZ-78056b from that same study (Figure). Those 3 isolates clustered more broadly with isolates from Russia and Finland (Figure), but have since acquired armA, bla_NDM-1, and the mucoviscosity and capsule loci rmpADC, further increasing their antibiotic resistance profile and virulence potential.

We found A. baumannii MRSN 110819 to be resistant to all antibiotics except cefiderocol, colistin, eravacycline, and omadacycline (Appendix Table 1). The isolate carried 18 AMR genes, including the RMTase armA, the ESBL bla_CTX-M-115, and 2 carbapenemases, bla_OXA-23 and bla_OXA-72 (Table). The isolate was assigned to ST78, a clonal group known as the Italian clone because it emerged in Italy in the mid-2000s (8). This clonal group has also been identified in war wounds of service members from Ukraine during the earlier conflict in Eastern Ukraine (2).

The 3 P. aeruginosa isolates belonged to 3 distinct strains (Table). All 3 isolates had high MICs to 20 of the 23 antibiotics tested (Appendix Table 1). Only colistin and cefiderocol appeared effective in vitro, although MRSN 110818 was susceptible to imipenem/relebactam using US Food and Drug Administration breakpoints (MIC 2 mg/L). All 3 carried carbapenemases, ESBLs, and 16S methyltransferases (Table). MRSN 110818 and 110817 belonged to well-known (ST357) and emerging (ST773) epidemic, high-risk clones that are increasingly associated with horizontally acquired β-lactamases (9). The single blood isolate was assigned to ST1047.

E. faecium MRSN 110820 carried 8 AMR genes, including the vanA operon (Table). The strain was assigned to ST117, a member of clonal complex 78.

Gaps in such services as infection control, caused by limited resources and personnel, are exacerbating the transmission of MDR organisms in Ukraine. As a result, healthcare networks in Europe now consider prior hospitalization in Ukraine to be a critical risk factor for colonization of MDR organisms (7,10). Healthcare practitioners treating citizens of Ukraine need to be cognizant of the increased risk for MDR organism transmission and infection imposed by the conflict in Ukraine and implement appropriate infection control measures to mitigate their spread.

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