Colistin-resistant Klebsiella pneumoniae bloodstream infection: old drug, bad bug

• Published in: Archives of microbiology 2021-08, Vol.203 (6), p.2999-3006
• Main Authors: Ben-Chetrit, Eli, Mc Gann, Patrick, Maybank, Rosslyn, Stam, Jason, Assous, Marc V., Katz, David E.
• Format: Article
• Language: English
• Subjects: Ablation; Antibiotics; Biochemistry; Biomedical and Life Sciences; Biotechnology; Carbapenemase; Carbapenems; Cell Biology; Colistin; Drug resistance; Ecology; Gene sequencing; Genomes; Klebsiella; Klebsiella pneumoniae; Life Sciences; Microbial Ecology; Microbiology; Mutation; Original Paper; Patients; Plasmids; Whole genome sequencing
• ISSN: 0302-8933; 1432-072X
• DOI: 10.1007/s00203-021-02289-4

Multi-drug-resistant (MDR)  Enterobacteriaceae  pose a global threat to hospitalized patients. We report a series of colistin-resistant  Klebsiella pneumoniae  blood isolates from Israel and explore their resistance mechanisms using whole genome sequencing (WGS). Patients with colistin-resistant  K. pneumoniae  bloodstream infection (BSI) were identified during the period between 2006 and 2018. Demographic and clinical data were collected, and antibiotic susceptibility testing (AST) was performed using three commercial platforms. Long and short read sequencing were performed on a PacBio RS II (Pacific Biosciences) and an Illumina Miseq (Illumina), respectively. Thirteen patients with colistin-resistant  K. pneumoniae  BSI were identified, and seven isolates from seven different patients were successfully revived. Patient records indicated that five of the patients were previously treated with colistin. AST indicated that six of the seven isolates were colistin resistant and four of these isolates were resistant to carbapenems. WGS assigned the isolates to four distinct clusters that corresponded to in silico-derived multi-locus sequence types (MLST). Three isolates carried  bla KPC-3  on two different plasmids and one carried  bla OXA-48  on a novel IncL/M plasmid. All colistin-resistant isolates carried a variety of different mutations that inactivated the  mgrB  gene. We report the first comprehensive analysis of a series of colistin-resistant  K. pneumoniae  from Israel. A diverse set of isolates were obtained and colistin resistance was found to be attributed to different mechanisms that ablated the  mgrB  gene. Notably, carbapenemase genes were identified in four isolates and were carried on novel plasmids.