NDM OUTBREAK IN A PORTUGUESE HOSPITAL: MOLECULAR EPIDEMIOLOGY, RESISTOME AND VIRULOME

Abstract

Intro: The emergence and spread of antibiotic-resistant bacteria is a global public health problem. blaNDM gene encodes the New Delhi metallo-beta-lactamase (NDM). NMD hydrolyses beta-lactam antibiotics, mainly carbapenems and, so far, has no effective inhibitors. blaNDM is frequently associated with other antibiotic resistance genes (ARGs) and mobile genetic elements, which increases the pathogenicity risk of its bacterial recipients. Hospitals need to manage efficiently blaNDM-positive patients to minimize risks of nosocomial infections normally associated with high mortality and morbidity. Additionally, databases of blaNDM positive strains are needed in healthcare facilities that will support the outline of management plans over the time. We focused on the sudden increase of NDM-producing Klebsiella pneumoniae (NDM- p-KP) strains causing urinary tract infections at a Portuguese hospital (CHBV). Our aim was to the outbreak's origin and to characterize, at genetic level, the NDM-p-KP strains. Methods: We determined the resistance phenotype and epidemiological relationship by BOX-PCR and PFGE of eight NDM-p-KP, which was followed by genome sequencing and bioinformatic analysis to determine sequence type (ST) group, resistome and virulome. Findings: BOX-PCR and PFGE showed a high-level of similarity between strains (> 90%), supporting their clonal relationship. However, patient's admission historical do not support the nosocomial nature of the outbreak. NDM- p-KP belong to the ST11 group and harbour several virulence factors that may potentiate their pathogenicity. Apart from blaNDM-1, other ARGs were detected, including quinolone and aminoglycoside, confirming the strain's resistance profile. Conclusion: NDM-p-KP clonal relationship suggests a common origin and results point towards a dissemination route external to CHBV facility. The molecular epidemiology, resistome and virulome of the outbreak strains was determined that will be used to implement a database for surveillance of blaNDM associated infections. Furthermore, the contribution of virulence factors identified to the infection process will be investigated in more detail.