Characterization of Extensively Drug-Resistant or Pandrug-Resistant Sequence Type 147 and 101 OXA-48-Producing Klebsiella pneumoniae Causing Bloodstream Infections in Patients in an Intensive Care Unit

Abstract

Carbapenem-resistant causes important health care-associated infections worldwide. An outbreak of sequence type 11 (ST11) OXA-48-producing (OXA-48-Kp) isolates occurred in Tzaneio Hospital in 2012 and was contained until 2014, when OXA-48-Kp reemerged. The present study involved 19 bloodstream infection (BSI) OXA-48-Kp isolates recovered from 19 intensive care unit (ICU) patients hospitalized between August 2014 and July 2016. MICs were determined by broth microdilution. Beta-lactamase genes were detected by PCR. All isolates were typed by pulsed-field gel electrophoresis/multilocus sequence typing (PFGE/MLST), and 10 representative isolates were typed by next-generation sequencing (NGS). Of the 19 study patients, 9 had previous hospitalizations, and 10 carried OXA-48-Kp prior to BSI isolation; median time from ICU admission to BSI was 29 days. Four OXA-48-Kp isolates belonged to PFGE profile A (ST147) and were pandrug resistant (PDR), while 15 isolates exhibited PFGE profile B (ST101) and were extensively drug resistant. Genes detected via NGS resistome analysis accounted for most of the resistance phenotypes, except for tigecycline and fosfomycin. Insertional inactivation of (distinct per clone) conferred colistin resistance in all 19 isolates. NGS single nucleotide polymorphism (SNP) analysis validated the clonal relatedness of the ST147 and ST101 strains and revealed the possible presence of two index ST147 strains and the microevolution of ST101 strains. Distinct, but highly related, IncL OXA-48-encoding plasmid lineages were identified; plasmids of the ST147 strains were identical with the plasmid of ST11 OXA-48-Kp which caused the 2012 outbreak. In conclusion, biclonal circulation of OXA-48-Kp and, alarmingly, emergence of a PDR clone are reported. These observations, along with the challenging phenotypic detection of OXA-48 producers and the high reported transmissibility of, necessitate intensive efforts to prevent their further spread.

Genomic Epidemiology of Carbapenem- and Colistin-Resistant Klebsiella pneumoniae Isolates From Serbia: Predominance of ST101 Strains Carrying a Novel OXA-48 Plasmid

“…ST101/OXA-48 has been frequently reported, and in an 11-year epidemiology study of OXA-48 producers among European and north-African countries, a quarter of the OXA-48 K. pneumoniae isolates belonged to ST101 (Potron et al, 2013). Outbreaks of ST101/OXA-48 were also described, with reports from Spain (Pitart et al, 2011;Cubero et al, 2015), Algeria (Loucif et al, 2016), Czech Republic (Skálová et al, 2016) and Greece (Avgoulea et al, 2018). The challenging phenotypic detection of OXA-48 carbapenemases and the rapid horizontal transfer of OXA-48-encoding plasmids favor hospital outbreaks linked to patient transfer (Skálová et al, 2016) and draw attention to the need for continuous and meticulous surveillance, as well as timely investigation.…”

Prolonged outbreak of New Delhi metallo-beta-lactamase-producing carbapenem-resistant Enterobacterales (NDM-CRE), Tuscany, Italy, 2018 to 2019

“…The presence and nature of carbapenemase determinants was determined by molecular testing of bacterial isolates using either PCR-based platforms (Xpert-CarbaR, Cepheid, Toulouse, France; Allplex, Seegene Inc, Seoul, Korea) or lateral flow immunochromatography systems (Resist-5 OOKNV, CorisBio, Gembloux, Belgium ). Whole genome sequencing (WGS) was performed on BSI isolates as described previously [3]. BSI: bloodstream infection; NDM-CRE: New Delhi metallo-beta-lactamase-producing carbapenem-resistant Enterobacterales.…”

The role of iron uptake systems in the pathogenesis of colistin-resistant hypervirulent K.pneumoniae infections

“…K.pneumoniae ST101 is known as hypervirulent clone mostly responsible for pneumonia and bacteremia in intensive care units. (30, 31). In our study, ColR-HvKP ST101 isolates were found to be associated with VAP infections (p=0.009).…”