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When treating patients with malaria and other infectious diseases, doctors should consider using drug combinations that reach similar parts of the body, according to researchers.
The group found that imperfect drug penetration—when drugs don’t reach all parts of the body—accelerates treatment resistance.
When there is a “pocket” of the body where only one drug is present, such as the brain or the digestive system, 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,” said Pleuni Pennings, PhD, of San Francisco State University in California.
“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.”
Dr Pennings and her colleagues reported these findings in PNAS.
The team believes this research could have major implications for how treatment plans are designed and prescribed to patients with malaria, HIV, tuberculosis, and other ailments.
Because pathogens can quickly develop resistance to a single drug, providers often prescribe multiple drugs to increase their effectiveness.
The results of the study suggest that, when doing so, doctors should carefully consider which parts of the body each drug will reach and whether selecting medications with imperfect but similar penetrations might be the best treatment option.
“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 said.
The study is the first to look at the connection between drug penetration and multidrug resistance. Dr Pennings and her colleagues ran computer simulations to observe the behavior of pathogens in response to changes in drugs and their levels of penetration.
The team found that, in instances where even small parts of the body could only be reached by one drug, the pathogen’s ability to build resistance to both drugs was accelerated compared to situations where no such pockets existed.
“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.”
With future research, Dr Pennings and her colleagues hope to outline the most effective drug combinations by exploring which parts of the body cannot be reached by specific drugs and where and how quickly specific pathogens are able to develop resistance. 
Photo courtesy of the CDC
When treating patients with malaria and other infectious diseases, doctors should consider using drug combinations that reach similar parts of the body, according to researchers.
The group found that imperfect drug penetration—when drugs don’t reach all parts of the body—accelerates treatment resistance.
When there is a “pocket” of the body where only one drug is present, such as the brain or the digestive system, 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,” said Pleuni Pennings, PhD, of San Francisco State University in California.
“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.”
Dr Pennings and her colleagues reported these findings in PNAS.
The team believes this research could have major implications for how treatment plans are designed and prescribed to patients with malaria, HIV, tuberculosis, and other ailments.
Because pathogens can quickly develop resistance to a single drug, providers often prescribe multiple drugs to increase their effectiveness.
The results of the study suggest that, when doing so, doctors should carefully consider which parts of the body each drug will reach and whether selecting medications with imperfect but similar penetrations might be the best treatment option.
“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 said.
The study is the first to look at the connection between drug penetration and multidrug resistance. Dr Pennings and her colleagues ran computer simulations to observe the behavior of pathogens in response to changes in drugs and their levels of penetration.
The team found that, in instances where even small parts of the body could only be reached by one drug, the pathogen’s ability to build resistance to both drugs was accelerated compared to situations where no such pockets existed.
“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.”
With future research, Dr Pennings and her colleagues hope to outline the most effective drug combinations by exploring which parts of the body cannot be reached by specific drugs and where and how quickly specific pathogens are able to develop resistance.
Photo courtesy of the CDC
When treating patients with malaria and other infectious diseases, doctors should consider using drug combinations that reach similar parts of the body, according to researchers.
The group found that imperfect drug penetration—when drugs don’t reach all parts of the body—accelerates treatment resistance.
When there is a “pocket” of the body where only one drug is present, such as the brain or the digestive system, 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,” said Pleuni Pennings, PhD, of San Francisco State University in California.
“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.”
Dr Pennings and her colleagues reported these findings in PNAS.
The team believes this research could have major implications for how treatment plans are designed and prescribed to patients with malaria, HIV, tuberculosis, and other ailments.
Because pathogens can quickly develop resistance to a single drug, providers often prescribe multiple drugs to increase their effectiveness.
The results of the study suggest that, when doing so, doctors should carefully consider which parts of the body each drug will reach and whether selecting medications with imperfect but similar penetrations might be the best treatment option.
“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 said.
The study is the first to look at the connection between drug penetration and multidrug resistance. Dr Pennings and her colleagues ran computer simulations to observe the behavior of pathogens in response to changes in drugs and their levels of penetration.
The team found that, in instances where even small parts of the body could only be reached by one drug, the pathogen’s ability to build resistance to both drugs was accelerated compared to situations where no such pockets existed.
“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.”
With future research, Dr Pennings and her colleagues hope to outline the most effective drug combinations by exploring which parts of the body cannot be reached by specific drugs and where and how quickly specific pathogens are able to develop resistance.