The spread and acquisition of NDM-1: a multifactorial problem

Abstract

bla _NDM is a major mechanism of resistance of Gram-negative bacteria to β-lactam antibiotics including the carbapenems. bla _NDM has been acquired by a large range of Gram-negative bacilli, especially by the Enterobacteriaceae and Acinetobacter spp. The combination of human factors (suboptimal antibiotic stewardship and infection control, movement of people between countries) plus bacterial factors (hospital adapted clones, environmental persistence and prolific horizontal gene transfer) have led to global spread of bla _NDM at a rapid pace. Treatment options for New Delhi metallo-β-lactamase (NDM) producers are very limited. For serious infections, combination therapy including a polymyxin is preferred. However, resistance to polymyxins is emerging. Clearly, substantial international efforts must be made to control the spread of NDM producers or else many of the advances of modern medicine may be undermined by untreatable infections.

Keywords::

• community
• genetic mobilization
• medical tourism
• NDM-1
• nosocomial
• plasmid
• polymyxins
• transmission routes
• transposition
• Tn125

Financial & competing interests disclosure

DL Paterson is on the advisory board for Merck, Astrazenica and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Reservoir countries of bla _NDM have expanded from the Indian subcontinent, China and the Balkan states to south-western Europe, the Greater Middle East and southeast Asia.

• Medical tourism and personal travel are major factors that have allowed the globalization of the carbapenem resistance provided by NDM-1.

• The three routes of human NDM acquisition are: nosocomial; personal travel and community acquired.

• Predominant bacterial hosts producing NDM are K. pneumoniae, E. coli and A. baumannii.

• bla _NDM is encoded on various plasmid backbones capable of horizontal gene transfer, most predominant being IncA/C.

• Genetic mobilization through transposons and IS elements, initially via Tn125 and ISAba125, has allowed bla _NDM to traverse among various plasmid backbones.

• The more genetic tiers a resistance gene is incorporated within the broader the range of potential bacterial hosts, which in turn determines the routes of acquisition by a human host.

• Infection control intervention to prevent spread of NDM producers include compliance with hand hygiene, use of contact isolation precautions, vigorous hospital cleaning and good antibiotic stewardship.

• The key antibiotic for serious infections with NDM producers is colistin.