Antimicrobial Resistance and Genomic Characterization of OXA-48- and CTX-M-15-Co-Producing Hypervirulent Klebsiella pneumoniae ST23 Recovered from Nosocomial Outbreak

Abstract

Multidrug resistance (MDR) and hypervirulence (hv) have been long considered distinct evolutionary traits for Klebsiella pneumoniae (Kp), a versatile human pathogen. The recent emergence of Kp strains combining these traits poses a serious global threat. In this article, we describe the phenotypic and genomic characteristics of an MDR hvKp isolate, MAR14-456, representative of a nosocomial outbreak in Moscow, Russia, that was recovered from a postoperative wound in a patient who later developed multiple abscesses, fatal sepsis, and septic shock. Broth microdilution testing revealed decreased susceptibility of MAR14-456 to carbapenems (MICs 0.5–2 mg/L) and a high-level resistance to most β-lactams, β-lactam-β-lactamase-inhibitor combinations, and non-β-lactam antibiotics, except ceftazidime-avibactam, amikacin, tigecycline, and colistin. Whole-genome sequencing using Illumina MiSeq and ONT MinION systems allowed to identify and completely assemble two conjugative resistance plasmids, a typical ‘European’ epidemic IncL/M plasmid that carries the gene of OXA-48 carbapenemase, and an IncFIIK plasmid that carries the gene of CTX-M-15 ESBL and other resistance genes. MLST profile, capsular, lipopolysaccharide, virulence genes encoded on chromosome and IncHI1B/FIB plasmid, and the presence of apparently functional type I-E* CRISPR-Cas system were all characteristic of hvKp ST23, serotype K1-O1v2. Phylogenetic analysis showed the closest relatedness of MAR14-456 to ST23 isolates from China. This report highlights the threat of multiple resistance acquisition by hvKp strain and its spread as a nosocomial pathogen.

Emergence of Hybrid Resistance and Virulence Plasmids Harboring New Delhi Metallo-β-Lactamase in Klebsiella pneumoniae in Russia

“…Shaidulina et al used Illumina MiSeq and ONT MinION systems and succeeded in localizing the virulence genes and bla OXA-48 on different plasmids. To the best of our knowledge, no reports of CR-hvKp isolates with confirmed hybrid plasmids coharboring genes of carbapenemases and virulence genes have been published in Russia so far [11]. In the present study, we aimed to describe the emergence of Kpn isolates of different STs (ST15, ST147, ST395, and ST874) with hybrid plasmids co-harboring virulence genes and bla NDM in the hospitals in St. Petersburg.…”

OXA-48 Carbapenemase-Producing Enterobacterales in Spanish Hospitals: An Updated Comprehensive Review on a Rising Antimicrobial Resistance

“…However, varying rates of resistance to all of them have been reported, thus different antibiotics are continuously being tested. Treatment of OXA-48 CRE with ceftazidime-avibactam could be effective according to a study conducted in Italy [ 105 ], which is consistent with the resistance profile of an OXA-48 CRE outbreak in Russia [ 106 ]. A study performed in Australia also reported effectiveness of other avibactam combinations (imipenem-avibactam or aztreonam-avibactam), suggesting that avibactam may be the most potent β-lactamase inhibitor [ 107 ].…”

“…Although the authors stated that combined therapy is more effective, successful outcomes were observed in 70% of the patients treated with ceftazidime-avibactam in monotherapy. Carbapenem in combination with amikacin or colistin may be useful in certain cases, but recent reports of resistance are concerning [ 106 ].…”

A Study in a Regional Hospital of a Mid-Sized Spanish City Indicates a Major Increase in Infection/Colonization by Carbapenem-Resistant Bacteria, Coinciding with the COVID-19 Pandemic

“…Although not as notorious as K. pneumoniae , the other CPB described in this study form part of a group of multidrug-resistant microorganisms that pose a major public health threat [ 34 ] and show increased diversity over time, as reported in a Portuguese study [ 4 ]. The frequency of their detection is rising among colonized and infected hospital patients, despite the implementation of infection prevention and control measures and routine colonization screenings [ 4 ].…”