Polyclonal Dissemination of OXA-232 Carbapenemase–Producing Klebsiella pneumoniae, France, 2013–2021

During 2013–2021, increased prevalence of oxacillinase 232–producing Enterobacterales was observed in France, mostly driven by its emergence in Klebsiella pneumoniae. Whole-genome sequencing identified that oxacillinase 232–producing K. pneumoniae belonged to 14 sequence types (STs), among which 2 polyclonal high-risk clones, ST-231 and ST-2096, were overrepresented.

dissemination. In this study, we used wholegenome sequencing to decipher the epidemiology of OXA-232-producing K. pneumoniae in France during 2013-2021.
Among the 95 patients colonized or infected with OXA-232-producing K. pneumoniae, 19 had recently returned from Asia (including 15 from India) and 12 from the Middle East. Among K. pneumoniae isolates, we identified 14 different STs, 5 of which were  We observed a diversification in OXA-232-producing K. pneumoniae STs over the last 2 years of the study period. In addition, the number of K. pneumoniae ST-231 isolates decreased, whereas the number of K. pneumoniae ST-2096 isolates increased (Figure 1,  panel B). We built single nucleotide polymorphism (SNP) matrices and phylogenetic trees for the 2 main STs (ST-231 and ST-2096) and compared them to epidemiologic data. We considered 2 isolates to be clonally related (probably by cross-transmission) if they differed by <21 SNPs, as previously reported for K. pneumoniae clonal complex 258 (15). For both STs, we identified many subclones (20 for ST-231 and 21 for ST-2096) (Figure 2), suggesting polyclonal dissemination including within these 2 high-risk clones.  Figure). Furthermore, 3 non-clonally related isolates coproduced the acquired C. freundii intrinsic cephalosporinase 6 (ST-231, ST-11, and ST-15) (Appendix Figure). Analysis of the genetic environment revealed that the bla OXA-232 was carried by the 6-kb in size ColE-type plasmid as previously described (5)

Conclusions
Recent data suggested that the dissemination of OXA-232-producing K. pneumoniae is increasing rapidly, especially in Asia and the Middle East (7,11). In our study, about a third of patients had recently visited 1 of these regions. Furthermore, we observed an increasing number of OXA-232 and NDM coproducers. These isolates are of high concern because of their lack of susceptibility to all antimicrobials, including last-resort combinations such as ceftazidime/avibactam, meropenem/vaborbactam, and imipenem/relebactam. The OXA-232-producing K. pneumoniae isolates that are reported to be responsible for outbreaks usually belonged to ST-231, ST-15, ST-16 and ST-147 (4,9). In our study, a wide diversity of STs was found, but the 2 main types were ST-231 and ST-2096. ST-231 was widely reported with OXA-232-producing K. pneumoniae, but ST-2096 was first reported only recently in India in 2019 (7,9). ST-2096 in India was also reported to be hypervirulent because it produced characteristic virulence genes such as rmpA2, iutA, and iuc operon (9). Our results suggest that the ST-2096 appeared very recently in France (2017). SNPs analysis demonstrated that the emergence and rapid dissemination of ST-2096 OXA-232-producing K. pneumoniae is not linked to a single or a few outbreaks. In our collection, 29 of the 30 ST-2096 K. pneumoniae isolates produced OXA-232, whereas the remaining isolate did not produce any carbapenemase, suggesting a recent acquisition of bla OXA-232 in this clone.
A recent publication reported an association between ST-2096 and a higher risk for bacteriemia and death (7). In our study, the unique isolate responsible for bacteriemia belonged to ST-231. In contrast, 25 of the 29 ST-2096 isolates were cultured from rectal swabs.
As expected, bla OXA-232 was located on a ColE plasmid in all isolates. The close genetic environment of bla OXA-232 involved ISEcp1 upstream of the bla OXA-232 gene as previously described (5).