Developing an Alternative Approach for Treating MDR Klebsiella pneumoniae

Scientists from the NIH and Rutgers New Jersey Medical School are in the process of developing a promising alternative to antibiotic treatments for multidrug-resistant Klebsiella pneumoniae bacteria.

Scientists from the National Institute of Allergy and Infectious Diseases’ Rocky Mountain Laboratories have teamed up with Rutgers New Jersey Medical School to develop an alternative approach for treating Klebsiella pneumoniae bacteria that have developed resistance against carbapenem antibiotics.

The research is still in its early stages, but it uses antibodies to target the bacteria’s protective capsule polysaccharide, which allows neutrophils to attack and kill the bacteria.

Carbapenem-resistant Klebsiella pneumoniae is a problem worldwide,” the authors stress in their paper. “A carbapenem-resistant K. pneumoniae lineage classified as multilocus sequence type 258 (ST258) is prominent in the health care setting in many regions of the world, including the United States.” As these strains have the potential to be resistant to all available antibiotics effective against infection, treatment is very difficult, and thus, mortality rates are high, especially among those with bloodstream infections.

Recent genome analyses have found that there are 2 major clades of ST258 that are known to encode capsule polysaccharide types by gene clusters: cps-1 and cps-2. Previous to this study, the scientists had demonstrated that these 2 ST258 isolates were “largely resistant to phagocytosis by human neutrophils but that any ingested bacteria are killed readily.” They also found that “optimal killing of ST258 by serum complement” happens when naturally occurring immunoglobulin is present. This supports the idea that an immunotherapy approach could potentially be considered for the prevention and treatment of carbapenem-resistant K. pneumoniae infections.

For this study, the scientists took the first step in validating this hypothesis by generating antibodies in rabbits specific for the 2 ST258 isolates and testing how capable they were of enhancing “serum bactericidal activity and promote phagocytosis and killing by human neutrophils,” according to study authors.

Their findings? Cell culture experiments showed that 1 of the antibodies generated worked to boost neutrophils’ ability to ingest and kill the bacteria.

“A vaccine that targets the most prominent strains of carbapenem-resistant K. pneumoniae need be effective only against cps-1 and cps-2 strains,” the authors write. “The number of cps types to be included in a potential vaccine could then be expanded based on clinical and molecular epidemiology.”

The next steps for the scientists is to test the approach in mice. In this research, the scientists will look at immunization with purified capsule polysaccharide (active immunization) and compare it with capsule-specific antibodies as a therapy (passive immunization). The underlying goal is to improve care for those with hard-to-treat K. pneumoniae infections—whether it’s through antibody treatment alone or in combination with antibiotics.