Aggressive treatment may not kill resistant pathogens

A study has questioned the accepted wisdom that aggressive treatment with high-drug dosages over long duration is the best way to stem the emergence and spread of resistant pathogens.

The logic behind aggressive treatment is to kill off as many microbes as you can, so that few will be around to evolve into resistant forms.

However, the new study reveals the lack of evidence behind the practice of aggressive treatment in many cases.

Microbes like bacteria and parasites can evade powerful drugs by undergoing genetic mutations, which enable them to avoid being killed by the drug, said the researchers.

"We found that while there are many studies that test for resistance emergence between different drug regimes, surprisingly few have looked at the topic of how varying drug dosage might affect the emergence and spread of resistance," said Ruthie Birger, from the Princeton University in the US, who works with C. Jessica Metcalf, an assistant professor of ecology and evolutionary biology at Princeton's Woodrow Wilson school.

"We are a long way from having the evidence for the best treatment decisions with respect to resistance for a range of diseases," Birger said.

From a study on a mice, scientists found that the high-dose drug treatment killed off the non-resistant malarial parasites, leaving the resistant strains to multiply and make the mice even sicker.

Taking a cue from the experiment on mice, the authors of the current study examined whether the same may be true for other types of microbes such as bacteria.

Finding the ideal dose and duration of treatment, one that cures the patient without aiding the spread of resistance, will likely be done on a disease by disease basis, the authors found.

Aggressive treatment might be best for pathogens that develop resistance slowly, over the course of several mutations. High-doses early in the process could be effective at heading off the development of resistance, concluded the researchers.

The study was published in the journal Proceedings of the Royal Society B