An experimental drug for neurodegenerative diseases can also reverse resistance to "last-resort" polymyxin antibiotics among bacteria that cause sepsis, a life-threatening complication from infections. The findings in mice suggest that repurposing the compound, named PBT2, could help clinicians cope with the issue of polymyxin resistance, which poses a grave threat to patients with bacterial infections. Sepsis can occur in patients with infections caused by various species of bacteria, including the gram-negative species Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. The spread of antibiotic resistance has made sepsis even more dangerous, as many of these bacteria have become resistant to both first-line antibiotics and to polymyxin antibiotics, which are only used when all other options have failed. One potential solution involves studying and repurposing drugs intended for other diseases, to try to target bacteria that have acquired antibiotic resistance. David De Oliveira and colleagues applied this approach to PBT2, an experimental compound being tested in phase 2 trials to treat Huntington's disease and Alzheimer's disease. The scientists found that PBT2 disrupted metals such as iron and zinc in polymyxin-resistant K. pneumoniae and P. aeruginosa, which resensitized the bacteria to polymyxin treatment. Combining PBT2 with polymyxin also substantially boosted survival rates and lowered bacterial loads in mice with sepsis caused by a highly invasive, polymyxin-resistant strain of K. pneumoniae. The authors call for further work to establish the safety and clinical potential of combining PBT2 with polymyxin antibiotics in humans.
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Science Translational Medicine