It’s World Antibiotic Awareness Week, and the World Health Organization (WHO) is urging global healthcare providers to exercise caution when prescribing antibiotics to prevent the spread of antibiotic-resistant bacteria. To help identify drugs which may be effective against bacterial infections which are impervious to traditional antibiotics, researchers at the National Institutes of Health’s (NIH) National Center for Advancing Translational Sciences (NCATS) Clinical Center, and the National Institute of Allergy and Infectious Diseases (NIAID), have developed a new drug-screening assay.
The assay is capable of screening thousands of drug candidates and assessing their effectiveness against a number of different strains of resistant bacteria. This method could help researchers repurpose already-approved drugs to deal with hospital-acquired infections as they emerge.
The researchers used the assay to screen around 4,000 approved drugs, and identified 25 compounds which were able to suppress the growth of two antibiotic-resistant strains of Klebsiella pneumoniae. This type of pathogen has been implicated in the deaths of many patients in hospitals across the US.
Of the 25 drugs identified, 11 have already received US Food and Drug Administration (FDA) approval, while 14 are still under review. The compounds belong to a wide range of drug classes, including antibiotics, antifungals, antimalarials and anticancer drugs.
Using this assay, the researchers also identified three drug combinations which were effective against 10 strains of antibiotic-resistant bacteria. The results of this study were published in the journal, Emerging Microbes and Infections.
“The results are very promising, and we think that the test can eventually help repurpose approved drugs and other compounds and find clinically relevant drug combinations that can be approved for to use in different ways that we have never used before,” said Dr. Wei Zheng, a scientist at NCATS. “We’re hoping this approach will lead to approvable, effective ways to combat dangerous infections by drug-resistant bacteria.”
According to Zheng, antibiotic-resistant bacterial strains are becoming more common in the hospital setting, however these facilities often aren’t able to rapidly test large numbers of drug combinations to determine which might be effective against a particular infection. To help solve this problem, Zheng and his colleagues combined the newly-identified drugs with the standard-of-care antibiotics that were no longer effective.
The found that when the drugs were used in combination, they were able to restore the antibiotic activity of the standard-of-care compound. In other words, in the presence of the second drug, previously ineffective drugs were able to inhibit growth of Klebsiella pneumoniae.
“We wanted to see which three-drug combinations made sense,” said Zheng. “We screened hundreds of drugs against Klebsiella pneumoniae, and tested 15 combinations against the 10 strains. We found three sets of three-drug combinations had the most activity, and think these three combinations eventually may be useful to clinicians.”