A potentially devastating strand of bacteria that could have made antibiotics futile in the fight against disease has finally been quashed by a team of scientists.
The strand of E.coli – which US health officials dubbed a ‘nightmare’ bacteria – posed an ‘urgent threat’ to global health as it had a very high-degree of resistance and could spread rapidly.
Researchers led by the University of Buffalo have now created three antibiotics that together could eradicate E.coli genes mcr-1 and ndm-5 that previously made the bacterium immune.
Health officials were worried the mcr-1 gene, which is carried by a highly mobile piece of DNA called a plasmid could potentially make infections untreatable.
The scientists found a novel combination of aztreonam, amikacin and polymyxin B – a last-resort antibiotic – was able to kill the mcr-1 and ndm-5 genes within 24 hours while also preventing regrowth.
A novel combination of aztreonam, amikacin and polymyxin B was able to kill E. coli carrying mcr-1 and ndm-5 – genes that make the bacterium immune to last-resort antibiotics
Golden era of antibiotics isn’t over yet
Eighteen months ago, the E.coli gene variant mcr-1 emerged in bacteria from pigs in China.
Since then has been identified in farm animals and people in about 20 countries, including China, Germany and Italy since 2016 and spread around the world at an alarming rate.
The bacteria can be transmitted by fecal contact and poor hygiene, which suggests a far wider likely presence than the documented cases so far, according to leading infectious disease experts.
‘The threat of gram-negative bacteria, including E. coli carrying mcr-1, is worrisome,’ said lead author Zackery Bulman, assistant professor at the University of Illinois at Chicago College of Pharmacy.
‘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’, he said.
Fewer than two dozen cases of E. coli carrying mcr-1 have been reported in the U.S.
However, with additional cases reported worldwide, the bacteria’s immunity to available antibiotics has left the medical community vulnerable to a massive outbreak of infections.
We had to work quickly
‘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’, siad Brian Tsuji associate professor in the School of Pharmacy and Pharmaceutical Sciences.
‘We had to work quickly and think outside of the box, beyond traditional antibiotic combinations’, he said.
Although the two genes were found on separate plasmids it’s common for one plasmid to carry resistance genes for multiple drugs.
Fewer than two dozen cases of E. coli carrying mcr-1 have been reported in the US, however, the bacteria’s immunity to available antibiotics has left the medical community vulnerable to a massive outbreak of infections
‘This is the first study to propose therapeutic solutions with three drugs against superbugs harboring mcr-1 and ndm-5’, he said.
Researchers say the results will help prepare clinicians for future occurrences of these pathogens.
Only the triple combination worked
The rapid increase in antibiotic-resistant bacteria has resurrected the importance of polymyxins, a class of antibiotics that are effective but employed as a last resort because of the damage they can cause to the kidneys.
To avoid prescribing high dosages of polymyxins and to make up for the antibiotic’s weaknesses, the researchers decided to turn to new dosing strategies and multiple antibiotic combinations.
After conducting studies on dozens of combinations of more than 15 antibiotics paired with polymyxin B, the researchers discovered two effective treatments.
Combinations of polymyxin B with either aztreonam or amikacin resulted in undetectable bacterial counts after 24 hours.
Only the triple combination of of aztreonam, amikacin and polymyxin B eliminated the E. coli strain and prevented regrowth.
‘We knew that polymyxins alone couldn’t work. Only the three drugs combined were able to work synergistically to suppress and kill the bacteria,’ said Dr 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 finding may provide a viable treatment against mcr-1 and ndm-5 strains.