Study Shows Promising Therapy for Drug-Resistant Klebsiella Pneumoniae
A promising strategy to tame troublesome drug-resistant bacteria is bacteriophage, or phage therapy, which uses viruses instead of antibiotics. NIH scientists have used two different bacteriophage viruses individually and then together to successfully treat research mice infected with multidrug-resistant Klebsiella pneumoniae sequence type 258 (ST258).
The bacterium K. pneumoniae ST258 is included on a CDC list of biggest antibiotic resistance threats in the U.S. High rates of morbidity and mortality are associated with untreated K. pneumoniae infections.
Phage therapy has been pursued for about a century, though clinical research has provided mixed results. In a new paper published in the journal mBio, NIH scientists noted the significance of this research given the lack of alternative treatment options for drug-resistant infections. Bacterial resistance has emerged against even the newest drug combinations, leaving some patients with few or no effective treatment options.
In research conducted at NIAID’s Rocky Mountain Laboratories in collaboration with NCI, scientists treated mice with phage P1, P2 or a combination of the two, all injected at different times following ST258 infection. Each of the three experimental treatment regimens helped the mice recover from ST258 infection.
The scientists noted that recovery was more dependent on timing than dosage. Mice treated one hour after infection showed the strongest recovery, followed by those treated 8 or more hours after infection. Control mice treated with saline all quickly developed severe disease and died.
The scientists also checked the blood and tissue of phage-treated mice and found there were significantly fewer ST258 bacteria at all time points compared to control mice. Unfortunately, there also were signs that the ST258 bacteria had begun developing phage resistance, a finding the scientists are continuing to investigate.
This study represents a first step in evaluating phage therapy for treating severe K. pneumoniae ST258 infection in humans.