SAN FRANCISCO, May 19 (UPI) — Not all drugs reach all parts of the body, leaving places for a pathogen to hide and develop resistance to them, according to new research.

The issue, called “imperfect penetration,” is significant for patients with HIV, malaria, tuberculosis, and other diseases which require combinations of multiple drugs in treatment. The combination is meant to overpower the pathogens in a patient’s system, but with only one drug present in some parts of the body, pathogens can begin to adapt and survive, eventually rendering the entire drug cocktail moot.

“This requires a new way of thinking about drug combinations that is a bit counterintuitive,” said Pleuni Pennings, an assistant professor of biology at San Francisco State University, in a press release. “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.”

This research is the first to look at how drugs spread through the system, often leaving “pockets” of the body unreached. Even when only small parts of the body haven’t been reached by drugs, viruses’ and bacteria’s resistance to the drugs begins to speed up.

Pennings said that doctors need to consider what parts of the body drugs reach when designing treatment plans to better slow the development of resistance.

Future research, she said, should focus on the most effective combinations of drugs that reach the reach the most areas of the body together.

The study is published in Proceedings of the National Academy of Sciences.