@article{10.1371/journal.pone.0004944, doi = {10.1371/journal.pone.0004944}, author = {Merabishvili, Maya AND Pirnay, Jean-Paul AND Verbeken, Gilbert AND Chanishvili, Nina AND Tediashvili, Marina AND Lashkhi, Nino AND Glonti, Thea AND Krylov, Victor AND Mast, Jan AND Van Parys, Luc AND Lavigne, Rob AND Volckaert, Guido AND Mattheus, Wesley AND Verween, Gunther AND De Corte, Peter AND Rose, Thomas AND Jennes, Serge AND Zizi, Martin AND De Vos, Daniel AND Vaneechoutte, Mario}, journal = {PLOS ONE}, publisher = {Public Library of Science}, title = {Quality-Controlled Small-Scale Production of a Well-Defined Bacteriophage Cocktail for Use in Human Clinical Trials}, year = {2009}, month = {03}, volume = {4}, url = {https://doi.org/10.1371/journal.pone.0004944}, pages = {1-10}, abstract = {We describe the small-scale, laboratory-based, production and quality control of a cocktail, consisting of exclusively lytic bacteriophages, designed for the treatment of Pseudomonas aeruginosa and Staphylococcus aureus infections in burn wound patients. Based on succesive selection rounds three bacteriophages were retained from an initial pool of 82 P. aeruginosa and 8 S. aureus bacteriophages, specific for prevalent P. aeruginosa and S. aureus strains in the Burn Centre of the Queen Astrid Military Hospital in Brussels, Belgium. This cocktail, consisting of P. aeruginosa phages 14/1 (Myoviridae) and PNM (Podoviridae) and S. aureus phage ISP (Myoviridae) was produced and purified of endotoxin. Quality control included Stability (shelf life), determination of pyrogenicity, sterility and cytotoxicity, confirmation of the absence of temperate bacteriophages and transmission electron microscopy-based confirmation of the presence of the expected virion morphologic particles as well as of their specific interaction with the target bacteria. Bacteriophage genome and proteome analysis confirmed the lytic nature of the bacteriophages, the absence of toxin-coding genes and showed that the selected phages 14/1, PNM and ISP are close relatives of respectively F8, φKMV and phage G1. The bacteriophage cocktail is currently being evaluated in a pilot clinical study cleared by a leading Medical Ethical Committee.}, number = {3}, }