Researchers from the University of Exeter, UK, have shown that the use of ‘sequential treatments' - using alternating doses of antibiotics - might offer effective treatment against bacterial infection.
Crucially, the findings also demonstrate this technique for administering treatment also reduces the risk of the bacteria becoming resistant to antibiotics, and so maintaining the long-term effectiveness of the drugs.
The collaborative international study, led by professor Robert Beardmore, PhD, University of Exeter, is published in the scientific journal PLOS Biology.
The findings show 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. The researchers used a test-tube model of a bacterial infection to show that, even in bacteria that already harbor 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.
"Our study finds a complex relationship between dose, bacterial population densities, and drug resistance," says Beardmore, the lead author. "As we demonstrate, it is possible to reduce bacterial load to zero at dosages that are usually said to be sublethal and, therefore, are assumed to select for increased drug resistance."
The researchers also discovered that, although sequential treatments didn't suppress the rise of all drug resistance mutations in the bacteria, one drug would ‘sensitize' the bacteria to the second drug, and therefore reduce the risk of resistance occurring.
"Research has concentrated for decades on synergistic drug cocktails," says study co-author Ayari Fuentes-Hernandez, PhD. "We believe ‘sequential synergies' might be just as potent if we look for them."
While bacteria are masters at adapting to antibiotic challenge, this research suggests that there is a way to use this adaptation against them. The fluctuating environments created by well-designed sequential treatments can sensitize bacteria and render them susceptible to concentrations of antibiotics that would normally induce drug resistance and continued existence.
Researcher Jessica Plucain, PhD, says that although extensive further work will be needed before sequential treatments make it into the clinic, the research demonstrates they can be effective even 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," she says.
[Source: University of Exeter]