Killing Resistant Superbugs with Antibiotic Triumvirate

저자：   업로드：2017-08-24  조회수：

    The exponential rise in antibiotic-resistant microbes is a major public health threat worldwide. Moreover, with approval times for new antibiotics taking more than a decade in most cases, finding a viable treatment among previously approved compounds is imperative to stem the drug-resistant tide.

    Now, researchers at the University at Buffalo (UB) have assembled of three antibiotics that when used in concert together, are capable of eradicating deadly Escherichia coli carrying the mcr-1 and ndm-5 genes, making the bacterium immune to last-resort antibiotics.      

 

    Findings from the new study were published recently in mBio in an article entitled “Polymyxin Combinations Combat Escherichia coli Harboring mcr-1 and blaNDM-5: Preparation for a Postantibiotic Era.”

    "The threat of Gram-negative bacteria, including E. coli carrying mcr-1, is worrisome," remarked lead study investigator Zackery Bulman, Pharm.D., who is currently an assistant professor at the University of Illinois at Chicago College of Pharmacy. "We believe that the appearance of mcr-1 and ndm-5 in patients may be a harbinger for what is to come. The golden era of antibiotics isn't over yet, but we wanted to help clinicians prepare therapeutically for the occurrence of these strains."

    In the current study, the researchers found that a novel combination of aztreonam, amikacin, and polymyxin B—a last-resort antibiotic—was able to kill E. coli carrying mcr-1 and ndm-5 genes within 24 hours while also preventing regrowth. Traditional combinations of these antibiotics were unable to kill the E. coli and resulted in rapid resistance.

    “We assessed the bacterial killing of 15 different FDA-approved antibiotics alone, and in combination with polymyxin B in time-killing experiments against Escherichia coli MCR1_NJ, the first reported isolate in the United States to coharbor mcr-1 and a New Delhi metallo-β-lactamase gene (bla_NDM-5),” the authors wrote. “The most promising regimens were advanced to the hollow-fiber infection model (HFIM), where human pharmacokinetics for polymyxin B, aztreonam, and amikacin were simulated over 240 h. Exposure to polymyxin B monotherapy was accompanied by MCR1_NJ regrowth but not resistance amplification (polymyxin B MIC from

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