LAUSR

The increasing prevalence of antibiotic resistance in Pseudomonas aeruginosa has created an urgent need for suitable therapy. Here we systematically explored the pairing of doxycycline with other antipseudomonal antibiotic partners and found a synergistic combination of polymyxin B - doxycycline against clinical strains of P. aeruginosa. This synergistic combination was studied by checkerboard assays and time-kill curve analysis. Further, in vitro biofilm disruption, pyoverdine inhibition assays were performed. Finally, the efficacy of this combination was evaluated on the acute mice pneumonia model by inhalation. Polymyxin B and doxycycline combination displayed synergistic action in both in vitro and in vivo studies. The combination decreased the biofilms of P. aeruginosa and also reduced pyoverdine levels, an important siderophore of P. aeruginosa. This combination decreased the P. aeruginosa population by 3 Log10 (P < 0.01) in mice acute pneumonia model and showed improvement in lung function by inhalation. To the best of our knowledge, this is the first in vivo study that evaluates the combination efficacy of polymyxin B and doxycycline against P. aeruginosa, showing a possible promising option for acute pneumonia due to MDR P. aeruginosa.