BACKGROUND: There is a need for new antibiotics or combination of antibiotics that possess activity against increasingly resistant cystic fibrosis (CF) respiratory pathogens such as Pseudomonas aeruginosa and MRSA. METHODS: The antimicrobial activity of a novel 4:1 (w/w) fosfomycin:tobramycin (F:T) combination against CF respiratory pathogens under both aerobic and anaerobic conditions was determined by MIC, time-kill and biofilm studies, and compared with activity of fosfomycin and tobramycin, individually. RESULTS: F:T and fosfomycin had excellent activity against P. aeruginosa and were more active than tobramycin against P. aeruginosa under anaerobic conditions with lower MIC(50), MIC(90) and geometric mean values. F:T (p<0.001) and fosfomycin (p<0.001) MICs for P. aeruginosa were significantly lower under anaerobic conditions with tobramycin MICs significantly higher (p<0.001). F:T and fosfomycin also had high activity against MRSA with both being more active than tobramycin. In time-kill studies, F:T was rapidly bactericidal against all 15 P. aeruginosa and 3/5 MRSA isolates tested. F:T also demonstrated bactericidal activity against P. aeruginosa grown in biofilm under both aerobic and anaerobic conditions. CONCLUSIONS: F:T has promising in vitro antimicrobial activity against MRSA and P. aeruginosa with greater activity under anaerobic conditions similar to those found in the CF lung.
BACKGROUND: There is a need for new antibiotics or combination of antibiotics that possess activity against increasingly resistant cystic fibrosis (CF) respiratory pathogens such as Pseudomonas aeruginosa and MRSA. METHODS: The antimicrobial activity of a novel 4:1 (w/w) fosfomycin:tobramycin (F:T) combination against CF respiratory pathogens under both aerobic and anaerobic conditions was determined by MIC, time-kill and biofilm studies, and compared with activity of fosfomycin and tobramycin, individually. RESULTS: F:T and fosfomycin had excellent activity against P. aeruginosa and were more active than tobramycin against P. aeruginosa under anaerobic conditions with lower MIC(50), MIC(90) and geometric mean values. F:T (p<0.001) and fosfomycin (p<0.001) MICs for P. aeruginosa were significantly lower under anaerobic conditions with tobramycin MICs significantly higher (p<0.001). F:T and fosfomycin also had high activity against MRSA with both being more active than tobramycin. In time-kill studies, F:T was rapidly bactericidal against all 15 P. aeruginosa and 3/5 MRSA isolates tested. F:T also demonstrated bactericidal activity against P. aeruginosa grown in biofilm under both aerobic and anaerobic conditions. CONCLUSIONS: F:T has promising in vitro antimicrobial activity against MRSA and P. aeruginosa with greater activity under anaerobic conditions similar to those found in the CF lung.
Authors: Miquel B Ekkelenkamp; Rafael Cantón; María Díez-Aguilar; Michael M Tunney; Deirdre F Gilpin; Francesca Bernardini; Glenn E Dale; J Stuart Elborn; Jumamurat R Bayjanov; Ad Fluit Journal: Antimicrob Agents Chemother Date: 2020-01-27 Impact factor: 5.191
Authors: Gerard McCaughey; Deirdre F Gilpin; Thamarai Schneiders; Lucas R Hoffman; Matt McKevitt; J Stuart Elborn; Michael M Tunney Journal: Antimicrob Agents Chemother Date: 2013-08-19 Impact factor: 5.191
Authors: Susan Hoe; James W Ivey; Mohammed A Boraey; Abouzar Shamsaddini-Shahrbabak; Emadeddin Javaheri; Sadaf Matinkhoo; Warren H Finlay; Reinhard Vehring Journal: Pharm Res Date: 2013-08-23 Impact factor: 4.200
Authors: Ad C Fluit; Jumamurat R Bayjanov; María Díez Aguilar; Rafael Cantón; Stuart Elborn; Michael M Tunney; Jelle Scharringa; Barry J Benaissa-Trouw; Miquel B Ekkelenkamp Journal: BMC Microbiol Date: 2022-05-12 Impact factor: 4.465
Authors: Pedrina G Vidigal; Mathias Müsken; Katrin A Becker; Susanne Häussler; Jost Wingender; Eike Steinmann; Jan Kehrmann; Erich Gulbins; Jan Buer; Peter Michael Rath; Jörg Steinmann Journal: PLoS One Date: 2014-04-01 Impact factor: 3.240