Novel combination of antibiotics promising against multidrug-resistant E. coli

Escherichia coli strains carrying the mcr-1 and ndm-5 genes have been established to be resistant to carbapenem treatment and an infection with this superbug can be deadly as optimal treatment strategies are undefined. However, a recent study published in mBio, a journal for the American Society of Microbiology, has demonstrated the first novel combination of antibiotics capable of lysing the bacterium and preventing re-growth.

Researchers at the University of Buffalo (NY, USA) distinguished that a unique 3-drug combination including polymyxin B – a last-resort antibiotic – provided complete eradication within 24 hours and prevention of a non-replicating persister phenotype.

“The threat of Gram-negative bacteria, including E. coli carrying mcr-1, is worrisome,” explained first author of the paper Zackery Bulman (University of Illinois, IL, USA). “We believe that the appearance of mcr-1 and ndm-5 in patients may be a harbinger for what is to come. The golden era of antibiotics isn’t over yet, but we wanted to help clinicians prepare therapeutically for the occurrence of these strains”.

It is noteworthy to mention that traditional combinations of this ‘super team’ team of antibiotics have been unsuccessful against E. coli MCR1_NJ. This is due to the strain co-harboring antibiotic resistance genes: mobile colistin resistance (mcr1) and the New Delhi metallo-β-lactamase (ndm-5).

Fewer than a dozen cases of mcr-1 carrying E.coli infections have been reported in the US, however, with incidence on the rise around the world, the bacterium’s immunity to all known antibiotic regimens could lead the medical community vulnerable to an unstoppable outbreak.

“That is why the mcr-1 and ndm-5 strains represent an urgent threat, because of the high-degree of resistance combined with the potential for rapid spread in the community setting. We had to work quickly and think outside of the box, beyond traditional antibiotic combinations” stated corresponding author Brian Tsuji (University of Buffalo).

“This is the first study to propose therapeutic solutions with three drugs against superbugs harboring mcr-1 and ndm-5. The results will help prepare clinicians for future occurrences of these pathogens,” he continued.

Polymaxins are deployed as a last resort antibiotic due to their ability to combat multi-drug resistant bacteria but with a damaging effect on the kidneys.

The research team assessed the bacterial killing of 15 antibiotics alone and in combination with polymyxin B against E. coli MCR1_NJ. Each pair of antibiotics displayed differing bactericidal levels, but all allowed re-growth to initial levels after 96 hours.

“We knew that polymyxins alone couldn’t work. Only the three drugs combined were able to work synergistically to suppress and kill the bacteria,” commented Bulman. “We overcame the bacteria by pushing it as far as possible with an agent that it was resistant to while simultaneously administering two other antibiotics.”

The promising 3-drug therapeutic solution offers a feasible treatment against mcr-1 and ndm-5 harboring E. coli strains.

Sources: Bulman ZP, Chen L, Walsh TJ, et al. Polymyxin combinations combat Escherichia coli harboring mcr-1 and blaNDM-5: preparation for a postantibiotic eramBio 8(4) e00540-17 (2017);


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