In an effort to fight ever-more-present antibiotic-resistant superbugs, University at Buffalo (UB) researchers are turning to an old class of antibiotics.
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Developed half a century ago, polymyxins are effective at fighting gram-negative bacteria which produces superbugs, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumonia. However, the class of antibiotics was not subject to modern drug development standards and has been found to be toxic to kidneys and the nervous system.
Through the project, funded by a $4.4 million NIH grant, researchers will evaluate new dosing regimens for polymyxin combinations to minimize the drugs' toxicity and maximize its antibacterial quality, says Brian Tsuji, lead researcher and director of clinical research at UB's Department of Pharmacy Practice. The team will use their findings to propose new, optimal polymyxin regimens.
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"This is a massive public health problem because the emergence of these new highly resistant strains has been coupled with a dwindling pipeline of development and approval for new drugs," Tsuji says, adding that even resistance to polymyxins is growing in the meantime.
"Therefore we needed to think innovatively and differently about how to attack this problem," Tsuji says. Researchers will test the effectiveness of different polymyxin combinations by using a Hollow Fiber Model System, which mimics the concentrations of antibiotic-resistant bacteria against bacteria in critically ill patients.
"In the lab, we can study these combination regimens very intensely over the same time frame that we would treat a patient with bacterial pneumonia (14 days) to understand the fundamental basis for drug resistance," Tsuji says, adding that the experiments "will allow us to address the public health disaster of antimicrobial resistance and to fight these deadly infections in severely ill patients where no traditional treatments exist" (Infection Control Today, 6/23; Saldi, University at Buffalo Reporter, 6/18).
Antibiotic resistance grows
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