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

Future Microbiol. 2018 Sep;13(11):1215-1223. doi: 10.2217/fmb-2018-0077. Epub 2018 Sep 21.

Abstract

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.

Keywords: Streptococcus pneumoniae; antibiotic multidrug-resistant; endolysin; mouse model; synergy; zebrafish model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Cefotaxime / pharmacology
  • Cefotaxime / therapeutic use
  • Disease Models, Animal
  • Drug Resistance, Multiple, Bacterial*
  • Drug Synergism
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Muramidase / pharmacology*
  • Muramidase / therapeutic use
  • Pneumococcal Infections / drug therapy
  • Pneumococcal Infections / microbiology*
  • Recombinant Fusion Proteins / pharmacology*
  • Recombinant Fusion Proteins / therapeutic use
  • Sepsis / drug therapy
  • Sepsis / microbiology*
  • Streptococcus Phages / enzymology
  • Streptococcus pneumoniae / drug effects*
  • Zebrafish

Substances

  • Anti-Bacterial Agents
  • Recombinant Fusion Proteins
  • CPL7 lysozyme
  • Muramidase
  • Cefotaxime