bEnzymes of the OXA-48 family have become some of the most important beta-lactamases in the world. A new OXA-48 variant (OXA-370) was first described for an Enterobacter hormaechei strain isolated in Rio Grande do Sul (southern region of Brazil) in 2013. Here we report detection of the bla OXA-370 gene in 24 isolates belonging to three Enterobacteriaceae species (22 Klebsiella pneumoniae isolates, 1 Enterobacter cloacae isolate, and 1 Enterobacter aerogenes isolate) collected from five hospitals in Rio de Janeiro, Brazil, in 2013 and 2014. The isolates showed a multidrug resistance profile, and 12.5% were resistant to polymyxin B. Besides bla OXA-370 , no other carbapenemase genes were observed by PCR, whereas bla OXA-1 was found in all isolates and 22 isolates (91.6%) possessed bla CTX-M-15 . Molecular typing of the K. pneumoniae isolates by pulsed-field gel electrophoresis (PFGE) showed the presence of two clonal groups, i.e., KpA (21 isolates) and KpB (1 isolate). KpA was characterized as sequence type 16 (ST16) and KpB as ST1041 by multilocus sequence typing (MLST). ST16 has been observed for KPC-producing K. pneumoniae in Rio de Janeiro. Plasmid analysis performed with six representative OXA-370-producing isolates showed plasmids harboring the bla OXA-370 gene in all strains, ranging from 25 kb to 150 kb. This study suggests that there is an urgent need to investigate the presence of OXA-370 and dissemination of the K. pneumoniae ST16 clone carrying this gene in Brazil.

Significance and Impact of the Study: This study shows, for the first time, the promising antimicrobial activity of phenanthroline derivatives against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae clinical strains. It is interesting to highlight that, in addition to a significant antimicrobial effect, studied compounds also showed a strong ability in reduce meropenem minimal inhibitory concentration values of some strains to therapeutic levels (re-sensitization). We believe that we are facing to a group of compounds that should be explored from a therapeutic perspective since they have demonstrated, in previous studies from our research group, low toxicity in vivo and effectiveness against several other microbial species.

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