Researchers
are developing a promising alternative to antibiotic treatment for infections
caused by Klebsiella pneumoniae bacteria resistant to carbapenem antibiotics.
The approach uses antibodies to target the K. pneumoniae protective capsule
polysaccharide, allowing immune system cells called neutrophils to attack and
kill the bacteria.
Klebsiella
bacteria cause about 10 percent of all hospital-acquired infections in the
United States. A carbapenem-resistant K. pneumoniae strain known as multilocus
sequence type 258 (ST258) is one of the antibiotic-resistant organisms labeled
an urgent threat by the Centers for Disease Control and Prevention. ST258 is
particularly concerning because it is resistant to most antibiotics. It is a
significant cause of mortality among people with bloodstream infections.
The
researchers first determined that the bacterial capsule prevents immune system
neutrophils from ingesting and killing ST258. They then extracted capsule from
the two most abundant capsule types of ST258 and used them to generate
antibodies in rabbits. In cell culture experiments they found that one of the
antibodies enhanced the ability of neutrophils to ingest and kill bacteria.
These results are a "proof of concept" for a potential immunotherapy
approach for treatment of multidrug-resistant K. pneumoniae infections, the
authors write.
Next
up, the researchers will test the therapeutic concept in mice. They also will
compare immunization with purified capsule polysaccharide as a preventive
approach (active immunization) versus using capsule-specific antibodies as a
therapy (passive immunization). Ultimately, they hope either antibody treatment
alone or in combination with antibiotics could greatly improve care for people
with multidrug-resistant K. pneumoniae infections.
See:
Posted by Dr. Tim Sandle
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Pharmaceutical Microbiology