Association of blaNDM-1 with blaKPC-2 and aminoglycoside-modifying enzyme genes among Klebsiella pneumoniae, Proteus mirabilis and Serratia marcescens clinical isolates in Brazil.

ABSTRACT

OBJECTIVES: Carbapenemase-producing Enterobacterales are frequently involved in healthcare-associated infections worldwide. The objectives of this study were to investigate (i) the frequency of the main genes encoding carbapenemases, 16S rRNA methylases and aminoglycoside-modifying enzymes (AMEs) as well as the mcr gene and (ii) the clonal relationship of enterobacteria isolates resistant to carbapenems and aminoglycosides from colonisation and infection in patients from hospitals in northeastern Brazil. METHODS: Antimicrobial susceptibility was determined using an automated VITEK®2 system. Presence of carbapenemase, AME and 16S rRNA methylase genes as well as the mcr gene was determined by PCR and amplicon sequencing. Genetic variability was determined by ERIC-PCR. RESULTS: A total of 35 isolates resistant to carbapenems and aminoglycosides were selected for this study. Klebsiella pneumoniae was most common (45.7%), followed by Proteus mirabilis (28.6%) and Serratia marcescens (25.7%). AME genes were found in 97.1% of isolates, most commonly aph(3')-VI and aac(6')-Ib. The blaNDM-1 and blaKPC-2 genes were detected in 25.7% and 88.6% of isolates, respectively; five isolates harboured these genes concomitantly. According to the literature, this is the first report of the association of blaNDM-1 and blaKPC-2 in P. mirabilis and S. marcescens in Brazil. The isolates showed a multiclonal profile by ERIC-PCR. CONCLUSION: The emergence of blaNDM-1 associated with blaKPC-2 and AME genes in K. pneumoniae, P. mirabilis and S. marcescens isolates with a multiclonal profile is of concern as this limits therapeutic options. These results should alert medical authorities to establish rigorous detection methods to reduce the spread of these antimicrobial resistance genes.