title: A window of opportunity to control the bacterial pathogen Pseudomonas aeruginosa combining antibiotics and phages.
abstract: The evolution of antibiotic resistance in bacteria is a global concern and the use of bacteriophages alone or in combined therapies is attracting increasing attention as an alternative. Evolutionary theory predicts that the probability of bacterial resistance to both phages and antibiotics will be lower than to either separately, due for example to fitness costs or to trade-offs between phage resistance mechanisms and bacterial growth. In this study, we assess the population impacts of either individual or combined treatments of a bacteriophage and streptomycin on the nosocomial pathogen Pseudomonas aeruginosa. We show that combining phage and antibiotics substantially increases bacterial control compared to either separately, and that there is a specific time delay in antibiotic introduction independent of antibiotic dose, that minimizes both bacterial density and resistance to either antibiotics or phage. These results have implications for optimal combined therapeutic approaches.
authors.affiliation: Institut des Sciences de l'Evolution, CNRS-Université Montpellier 2, Montpellier, France.
authors.forename: Clara
authors.initials: C
authors.lastname: Torres-Barceló
authors.affiliation: Institut des Sciences de l'Evolution, CNRS-Université Montpellier 2, Montpellier, France.
authors.forename: Flor I
authors.initials: FI
authors.lastname: Arias-Sánchez
authors.affiliation: Institut des Sciences de l'Evolution, CNRS-Université Montpellier 2, Montpellier, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Vasse
authors.affiliation: Institut des Sciences de l'Evolution, CNRS-Université Montpellier 2, Montpellier, France.
authors.forename: Johan
authors.initials: J
authors.lastname: Ramsayer
authors.affiliation: Institut des Sciences de l'Evolution, CNRS-Université Montpellier 2, Montpellier, France.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kaltz
authors.affiliation: Institut des Sciences de l'Evolution, CNRS-Université Montpellier 2, Montpellier, France; Santa Fe Institute, Santa Fe, New Mexico, United States of America; Wissenshaftskolleg zu Berlin, Berlin, Germany.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Hochberg
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001435:Bacteriophages / Q000502:physiology*; D024881:Drug Resistance, Bacterial; D006801:Humans; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000517:prevention & control; D017105:Pseudomonas Phages; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development / Q000821:virology*
chemical_list: D000900:Anti-Bacterial Agents