OBJECTIVES: Pneumonia is associated with a high morbidity and mortality worldwide. Streptococcus pneumoniae remains the most common cause of pneumonia, and pneumococcal antibiotic resistance is increasing. The purified bacteriophage endolysin Cpl-1 rapidly and specifically kills pneumococci. We tested the hypothesis that a single dose of recombinant aerosolized Cpl-1 would rescue mice with severe pneumococcal pneumonia. METHODS: Female C57Bl/6 mice (aged 8-12 weeks) were transnasally infected with pneumococci. When severe pneumonia was established 24 h after infection, mice were treated with 25 μL of aerosolized Cpl-1. Survival was monitored for 10 days and the pulmonary and systemic bacterial burdens were assessed. Furthermore, cytokines were quantified in bronchoalveolar lavage fluid, and lung morphology was analysed histologically. RESULTS: The endolysin efficiently reduced pulmonary bacterial counts and averted bacteraemia. Although concentrations of inflammatory cytokines were increased shortly after Cpl-1 inhalation, mice recovered rapidly, as shown by increasing body weight, and inflammatory infiltrates resolved in the lungs, leading to a reduction in mortality of 80%. CONCLUSIONS: Administration of Cpl-1 by inhalation may offer a new therapeutic perspective for the treatment of pneumococcal lung infection.
OBJECTIVES:Pneumonia is associated with a high morbidity and mortality worldwide. Streptococcus pneumoniae remains the most common cause of pneumonia, and pneumococcal antibiotic resistance is increasing. The purified bacteriophage endolysin Cpl-1 rapidly and specifically kills pneumococci. We tested the hypothesis that a single dose of recombinant aerosolized Cpl-1 would rescue mice with severe pneumococcal pneumonia. METHODS: Female C57Bl/6 mice (aged 8-12 weeks) were transnasally infected with pneumococci. When severe pneumonia was established 24 h after infection, mice were treated with 25 μL of aerosolized Cpl-1. Survival was monitored for 10 days and the pulmonary and systemic bacterial burdens were assessed. Furthermore, cytokines were quantified in bronchoalveolar lavage fluid, and lung morphology was analysed histologically. RESULTS: The endolysin efficiently reduced pulmonary bacterial counts and averted bacteraemia. Although concentrations of inflammatory cytokines were increased shortly after Cpl-1 inhalation, mice recovered rapidly, as shown by increasing body weight, and inflammatory infiltrates resolved in the lungs, leading to a reduction in mortality of 80%. CONCLUSIONS: Administration of Cpl-1 by inhalation may offer a new therapeutic perspective for the treatment of pneumococcal lung infection.
Authors: Ji Yun Bae; Kang Il Jun; Chang Kyung Kang; Kyoung-Ho Song; Pyoeng Gyun Choe; Ji-Hwan Bang; Eu Suk Kim; Sang Won Park; Hong Bin Kim; Nam-Joong Kim; Wan Beom Park; Myoung-Don Oh Journal: Antimicrob Agents Chemother Date: 2019-03-27 Impact factor: 5.191