Technique battles antimicrobial resistance
8 Apr 2015
Researchers at the University of Exeter have shown that the use of sequential antibiotic treatments could offer effective treatment against bacterial infection.
The technique also reduces the risk of bacteria becoming resistant to antibiotics - thereby maintain the long-term effectiveness of the drugs, the researchers said.
Led by Professor Robert Beardmore, the research indicates that drug treatments with two antibiotics can be designed to kill bacteria at dosages that would ordinarily cause rapid development of drug resistance and sustained bacterial growth, when administered alone or in combination.
“Our study finds a complex relationship between dose, bacterial population densities and drug resistance
Lead researcher Robert Beardmore
“Our study finds a complex relationship between dose, bacterial population densities and drug resistance,” Beardmore said.
“As we demonstrate, it is possible to reduce bacterial load to zero at dosages that are usually said to be sub lethal and, therefore, are assumed to select for increased drug resistance,” he said.
To conduct its research, the Exeter-based team used a test-tube model of a bacterial infection to show that, even in bacteria that already harbour drug resistance genes, sequential treatments could deal with the bacteria, even when much higher doses of single drugs or mixtures of two drugs failed to do so.
The study also revealed that, although sequential treatments were not shown to suppress the rise of all drug resistance mutations in the bacteria, one drug would sensitise the bacteria to the second drug, and therefore reduce the risk of resistance occurring.
“Research has concentrated for decades on synergistic drug cocktails,” said Ayari Fuentes-Hernandez, study co-author.
“We believe ’sequential synergies’ might be just as potent if we look for them, this research will therefore be of interest to the pharma and dwindling antibiotic discovery communities.”
Engineering and Physical Sciences Research Council-funded researcher Jessica Plucain suggests the study demonstrates how effective sequential treatments could be when using drug doses below their maximal potency.
“One outcome of this highly surprising result will be to set in motion a series of studies to determine ways of using antibiotics not only in combination, but sequentially and with the potential for lower dosages than is currently thought possible,” Plucain said.
