In vivo selection of carbapenem resistance during persistent Klebsiella pneumoniae sequence type 395 bloodstream infection due to OmpK36 deletion

• Published in: Antimicrobial agents and chemotherapy Vol. 68; no. 8; p. e0066324
• Main Authors: Strahilevitz, Jacob, Motro, Yair, Temper, Violeta, Merezhko, Diana, Ayalon, Oshrat, Bar Moshe, Yehonatan, Lam, Margaret M. C., Holt, Kathryn E., Moran-Gilad, Jacob
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 07.08.2024
• Subjects: Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Bacteremia - drug therapy; Bacteremia - microbiology; Bacterial Proteins - genetics; beta-Lactamases - genetics; Carbapenems - pharmacology; Carbapenems - therapeutic use; Clinical Microbiology; Genome, Bacterial - genetics; Humans; Klebsiella Infections - drug therapy; Klebsiella Infections - microbiology; Klebsiella pneumoniae - drug effects; Klebsiella pneumoniae - genetics; Klebsiella pneumoniae - isolation & purification; Male; Mechanisms of Resistance; Microbial Sensitivity Tests; Phylogeny; Plasmids - genetics; Porins - genetics; Klebsiella; in vivo; carbapenem; selection; resistance; porin loss
• ISSN: 0066-4804; 1098-6596; 1098-6596
• DOI: 10.1128/aac.00663-24

Non-carbapenemase-producing carbapenem-resistant (non-CP CRE) may be associated with a grave outcome. The common underlying mechanism is beta-lactamases and mutations in outer membrane porins. We report a case of a deep-seated infection caused by ST395 not amenable to source control, involving recurrent bloodstream infection, resulting in selection of carbapenem resistance under therapy. Three consecutive blood isolates were studied using short- and long-read sequencing. The genomes were subject to resistome and virulome, phylogenetic, and plasmid analyses. porins were analyzed at the nucleotide and amino acid levels. Genomes were compared to 297 public ST395 genomes using cgMLST, resistome, and porin analyses and the EuSCAPE project. Relevant and sequences were extracted and analyzed as above. The three sequential blood isolates belonged to the same clone. Subsequent CR isolates revealed a new large deletion of the gene also involving the upstream region (deletion of ). Comparison with public ST395 genomes revealed the study isolates belonged to clade B, representing a separate clone. N-terminal large truncations were uncommon in both public data sets. selection of non-CP CRE could have substantial clinical implications. Such selection should be scrutinized through repeated cultures and frequent susceptibility testing during antimicrobial treatment, especially in the context of persistent or recurrent bloodstream infections and when adequate source control cannot be achieved. The occurrence of an unusually large deletion involving the locus and upstream should be further studied.