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Imperfect drug delivery can increase pathogens' resistance

May 28, 2015

Healthcare workers are often aware of the dangers of bloodborne pathogens, and how needlestick injuries can increase their risk of being exposed to them and contracting a life-changing illness.

Following sharps safety practices can significantly help to minimise this risk, alongside proper training and risk assessment, but a new study has suggested that there could be more involved in safeguarding against pathogens.

Research published in the Proceedings of the National Academy of Sciences (PNAS) journal, has found that prescribing patients two or more drugs that do not target the same part of the body could increase a pathogen's resistance to all of the drugs being used in treatment.

Known as "imperfect drug penetration," not all drugs can reach all parts of the body, but the researchers found that when there is a "pocket" of the body where only one drug is present a pathogen can quickly develop resistance to one drug at a time.

"If there is a space where there is only one drug, that's the place where the pathogen can start its escape," says Pleuni Pennings, an assistant professor of biology at San Francisco State University and co-author of the study. "Once it no longer has the first drug to deal with, it's very easy for it to quickly become resistant to a second drug."

The findings could have major implications for how healthcare workers treat patients, especially when there are cases of HIV, malaria and tuberculosis. As pathogens can quickly evolve to become resistant, patients are often prescribed more than one to boost their effectiveness.

However, the new study suggests that this could be detrimental in some cases, and that healthcare workers should carefully consider which parts of the body each drug will reach.

"It may be better in some cases to leave a pocket of the body without any drugs instead of leaving a pocket with just one drug," Dr Pennings says.

It is the first study to look at the relationship between drug penetration and multidrug resistance. 

Dr Pennings and her colleagues used computer simulations to look at the behaviour of pathogens in response to changes in the drugs used in treatment and their levels of penetration. 

The team found that, when even small parts of the body could only be reached by one drug, the pathogen's ability to build resistance to either drug was increased, compared to cases where there were no pockets.

"This requires a new way of thinking about drug combinations that is a bit counterintuitive," Dr Pennings said. "Suppose that drug A does not reach the brain, but drug B does. You'll see the pathogen evolving resistance to drug B and assume that's where the problem lies. But in fact it is drug A that is not doing its job because it's not reaching the brain, and that's the drug you may have to actually fix."

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