From the Research
The emergence of plasmid-mediated colistin resistance genes, such as MCR-1 to MCR-10, poses a significant threat to public health, and combination therapy approaches, including the use of colistin with other antimicrobials like carbapenems or novel agents, are being investigated to overcome colistin resistance. These genes encode phosphoethanolamine transferases that modify bacterial lipopolysaccharides by adding phosphoethanolamine to lipid A, which reduces the binding affinity of colistin and polymyxin antibiotics 1. MCR-1 was first identified in China in 2015 in Escherichia coli isolates from food animals, and since then, additional variants (MCR-2 through MCR-10) have been discovered worldwide 1. The prevalence of MCR genes varies geographically, with higher rates in areas where colistin has been extensively used in agriculture. To address this growing problem, many countries have restricted colistin use in veterinary medicine, implemented enhanced surveillance programs, and developed rapid diagnostic tests to detect MCR-positive isolates.
Some key points to consider when addressing MCR-1 to MCR-10 include:
- The use of combination therapy approaches, such as the combination of polymyxin B, aztreonam, and amikacin, which has been shown to provide complete eradication of MCR-1- and NDM-5-producing E. coli 2
- The development of novel beta-lactam/beta-lactamase inhibitor combinations, such as ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam, which have been shown to be effective against carbapenemase-producing Enterobacterales 3
- The potential for structure-based design of inhibitors to tackle polymyxin resistance, targeting the MCR-1 protein 4
- The importance of restricting colistin use in veterinary medicine and implementing enhanced surveillance programs to detect MCR-positive isolates 1
Overall, the emergence of MCR-1 to MCR-10 highlights the need for continued vigilance and research into the development of effective treatment strategies for infections caused by multidrug-resistant Gram-negative bacteria. The use of combination therapy approaches and the development of novel antimicrobial agents are critical to addressing this growing public health threat.