Pharmacology

Novel Screening Test Sparks New Ideas About Old Drugs

Through a new screen test, researchers find ways to repurpose drugs and create combinations to combat drug-resistant bacteria.


 

Repurposing standard drugs and rethinking drug combinations may lead to more effective ways to combat drug-resistant bacteria, according to findings from an NIH study.

Researchers developed an assay to screen for effectiveness and used it on 5,170 drugs and other biologically active compounds. They identified 25 that suppress the growth of 2 strains of Klebsiella pneumonia (K pneumonia ) that are resistant to most antibiotics: 11 FDA-approved drugs and 14 drugs still under investigation, including antibiotics, antifungals, and antiseptics, and an antiviral, antimalarial and anticancer drug/compound.

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They also looked for combinations of drugs and paired newly identified drugs from the repurposing screen with a standard-of-care antibiotic that did not work by itself. They found four 2-drug combinations that work against K pneumoniae , meaning the ineffective antibiotics became active again in the presence of the second drug. Combining colistin with doxycycline, for instance, reversed the drug resistance.

They also tested 3-drug combinations against 10 common strains of multidrug-resistant bacteria and found 3 different combinations of broad-acting antibiotics that were effective. For instance, colistin-auranofin-ceftazidime and colistin-auranofin-rifabutin suppressed more than 80% growth of all 10 strains. Rifabutin-colistin-imipenem inhibited more than 75% of the strains, except 2 Acinetobacter baumannii isolates.

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Their results demonstrate that their assay has potential as a real-time clinical tool, the researchers say. “The results are very promising,” said one of the investigators. “We think the test can eventually help repurpose approved drugs and other compounds and find clinically relevant drug combinations that can be approved for use in different ways that we have never used before.”

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