Background
Antimicrobial resistance is an emerging problem and multi-drug resistant (MDR) Klebsiella pneumoniae represents an enormous risk of failing therapy in nosocomial pneumonia. 

Aim of the study
To determine the immunomodulatory effect of topical flagellin in addition to antibiotic treatment during pneumosepsis evoked by hypervirulent Klebsiella pneumoniae in mice.

Methods
C57BL6 mice were inoculated intranasally with hypervirulent Klebsiella pneumoniae (K2:O1) which were either antibiotic susceptible (Kpneu) or MDR (MDR-Kpneu). Subsequently, mice were treated with antibiotics intraperitoneally and flagellin or vehicle intranasally 6 hours after infection. Mice were sacrificed 24 hours after infection. Samples were analysed for bacterial loads and inflammatory markers.

Results
Flagellin therapy induced neutrophil influx in the lung during antibiotic-treated pneumonia evoked by either Kpneu or MDR-Kpneu. The pulmonary neutrophil response was accompanied by elevated levels of myeloperoxidase, elastase, and neutrophil-attracting chemokines. The combined therapy of effective antibiotics (ceftriaxone for Kpneu; colistin for MDR-Kpneu) and flagellin reduced Klebsiella loads in distant organs, but did not impact bacterial counts in the lung. This flagellin-mediated effect was diminished when neutrophils were depleted during infection.

Conclusions
Topical flagellin administration as an adjunctive to antibiotic treatment induced neutrophil recruitment and activation during (MDR-)Klebsiella pneumonia, thereby reducing bacterial dissemination to distant organs.