Overcoming Antibiotic Resistance is Not an Easy Feat

PITTSBURGH – In a paper published today in The Lancet Microbe, researchers from the University of Pittsburgh School of Medicine found that when bacteria become resistant to one antimicrobial drug, they are likely to become resistant to most others. That is, resistance begets more resistance, suggesting that the popular approach of switching between different antimicrobials to avoid resistance may be a losing battle.

But there is good news: In rare cases, certain antibiotics can make bacteria sensitive to other antibiotics, and the scientists found that switching between these drugs might be useful to circumvent antimicrobial resistance in clinical trials.

“Unfortunately, switching between different drugs at random is not a panacea,” said senior author Erik Wright, Ph.D., assistant professor of biomedical informatics at Pitt. “But our data show that it might still be possible to implement that idea in practice. It will just take extra effort.”

Overcoming antimicrobial resistance is no small feat. It’s difficult to come up with more powerful antimicrobials, and history shows most attempts to overcome resistance are destined to fail.

In their quest for antibiotic pairs that could be considered for treatment strategies, the researchers scanned hundreds of thousands of health records containing results of antimicrobial susceptibility tests of patients at UPMC hospitals. 

Remarkably, researchers found that more than half of tested antibiotic combinations were ineffective at avoiding bacteria’s resistance mechanisms. Conversely, less than 1% of the antibiotic pairs displayed the property of mutually exclusive resistance, which would, in principle, allow for alternating between two drugs without fanning the flames of antimicrobial resistance.

With careful planning, researchers say, certain drug pairs hold potential for treating specific pathogens and these strategies deserve to be explored in clinical trials. But as a whole, the researchers discourage clinicians from relying on antibiotic cycling as a cure for antibiotic resistance. 

“Ruling out a failing strategy is just as important as ruling in a successful one,” said Wright. “Even though developing strategies based on alternating between drugs might be promising in some ways, this won’t cure antibiotic resistance across the board. The task at hand is much more complex, and we need to pursue alternative strategies to find realistic ways to fight bacterial infections.”

Andrew Beckley, M.S., of Pitt, was a lead author of the manuscript.

This research was supported by National Institutes of Health grants T15LM007059-33 and 1DP2AI145058-01.

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