Pandrug-resistant Klebsiella pneumoniae isolated from Ukrainian war victims are hypervirulent

Abstract

Objectives: Carbapenem- and colistin-resistant Klebsiella pneumoniae were isolated from war victims treated in hospitals in Ukraine. The question was whether these pandrug-resistant K. pneumoniae are pathogenic and capable of causing disease in a broader context.

Methods: Klebsiella pneumoniae clinical isolates (n = 37) were tested for antibiotic resistance and subjected to whole-genome sequencing (WGS). In addition, their pathogenicity was tested by serum resistance and two separate animal models.

Results: Isolates belonging to the sequence types (ST) 23, 147, 307, 395, and 512 were found to harbor resistance genes against carbapenems and cephalosporins. Nine isolates carried point mutations in pmrB and phoP genes associated with colistin resistance. All bacteria were equipped with multiple virulence genes, and the colistin-resistant isolates each carried 10 different genes. Colistin-resistant K. pneumoniae were more serum-resistant, more virulent against G. mellonella larvae, and displayed an increased survival in mice compared to colistin-susceptible bacteria. The iucA, peg-344, rmpA, rmpC, and rmpD genes were associated with increased virulence in animals.

Conclusions: Pandrug-resistant K. pneumoniae in Ukraine are hypervirulent and retain their pathogenicity, highlighting the need to prevent disseminated spread.

Keywords: AMR; Antimicrobial resistance; Carbapenemase; Colistin; Extensively drug-resistant; Healthcare-associated infection; MDR; Multi-drug resistant; PDR; Pandrug-resistant.