survival when used alone or combined.
Writing in the journal PLOS Biology, the international team -led by Robert Beardmore, a biosciences professor at the
University of Exeter in the UK - describes how carefully devised "sequential treatments" using antibiotics may help combat the rise of resistant bacteria.
Prof. Beardmore says they found a complex relationship between dose, density of bacteria population and drug resistance, and: "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."
Another crucial finding of the study is that the technique may
also reduce the risk of bacteria developing resistance to
antibiotics, thereby extending their useful lifetime.
The researchers decided to carry out the study because for decades research has focused on using drugs as "cocktails"
where the drugs help each other as a "synergistic combination." But what if there is also an effect from "sequential synergy?"
Sequential treatment worked with antibiotic doses that singly or combined had no effect
For their investigation, the team used a simple test-tube model of an Escherichia coli bacterial infection where the bacteria had some antibiotic resistance genes.
They tested the effect of two commonly prescribed antibiotics - erythromycin and doxycycline - on the bacteria in three ways:
given singly, given as a combination cocktail and given as a sequential treatment.
The results showed that antibiotics given in certain sequential treatments cleared the infection - even when those same drugs given at higher doses singly or combined failed to have any effect.
Further tests showed that while sequential treatments did not stop drug resistance mutations in the bacteria altogether, the first drug made the bacteria sensitive to the second drug and thereby reduced the risk of resistance developing.
The researchers suggest that the fluctuating environment created by a well-designed sequence of alternating precise doses is what sensitizes the bacteria to concentrations that, in a steady environment, would normally induce drug resistance and extend survival.
They note that these findings are still at the experimental stage, and there is still a lot of work to do before any sequential treatments are ready for clinical use.
The team expects the findings will trigger a series of studies
looking at sequential ways to use antibiotics at doses lower
than previously thought possible.
The study was funded by the Engineering and Physical
Sciences Research Council (EPSRC) - the main body for
funding research in engineering and the physical sciences in the
UK. Prof. Beardmore is an EPSRC Leadership Fellow in
Mathematical Biosciences.
Meanwhile, Medical News Today recently learned that a
multi-drug resistant intestinal bug is spreading in the US. The authorities say the Shigella bacteria are entering the country in infected travelers and causing a series of outbreaks.
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