Bactericidal synergism between antibiotics and phage endolysin Cpl-711 to kill multidrug-resistant pneumococcus

Aim: To test the synergistic effect of Cpl-711 endolysin and antibiotics for antipneumococcal activity. Materials & methods: A combination of Cpl-711 and different antibiotics (amoxicillin, cefotaxime, levofloxacin and vancomycin) was tested in a checkerboard assay against several multidrug-resistant Streptococcus pneumoniae strains. Mouse and zebrafish models of pneumococcal sepsis were used to confirm the in vitro data. Results: The activity of Cpl-711 combined with amoxicillin or cefotaxime was synergistic in the bactericidal effect against a serotype 23F multiresistant clinical isolate of S. pneumoniae. Synergy between Cpl-711 and cefotaxime was validated using both mouse and zebrafish models. Conclusion: Combination of Cpl-711 and cefotaxime may help in the treatment of diseases caused by multiresistant pneumococcal strains. Graphical abstract [GRAPHICS] .