Inhalative use of the endolysin Cpl-1 rescues mice with fatal pneumococcal pneumonia

Community-acquired pneumonia (CAP) is associated with considerable morbidity and mortality. S. pneumoniae remains the most common cause in pneumonia and pneumococcal resistance to multiple antibiotics is increasing. The purified bacteriophage endolysin Cpl-1 rapidly and specifically kills pneumococci on contact. We have recently shown that repetitive intraperitoneal injections with Cpl-1 rescued mice with fatal pneumococcal pneumonia (Witzenrath et al., Crit Care Med 2009). The aim of the current study was to determine the therapeutic potential of aerosolized Cpl-1 in pneumococcal pneumonia.

Mice were transnasally infected with pneumococci. When serious pneumonia had established 24 hours after infection, Cpl-1 (25µl) was aerosolized once by means of a microsprayer. Cpl-1 dramatically reduced pulmonary bacterial counts and almost abolished bacteremia. All mice treated with Cpl-1 survived otherwise fatal pneumonia. In the Cpl-1 treatment group, inflammation was reduced as determined by multiplex cytokine analysis, and mice recovered rapidly as shown by increasing body weight.

Inhalative administration of Cpl-1 may offer a therapeutic perspective in the treatment of pneumococcal lung infection, particularly when being caused by antibiotic resistant pneumococci.