Efficacy of aerosolized rifaximin versus tobramycin for the treatment of Pseudomonas aeruginosa pneumonia in mice.

Efficacy of aerosolized rifaximin versus tobramycin for the treatment of Pseudomonas aeruginosa pneumonia in mice. Antimicrob Agents Chemother. 2019 Apr 22;: Authors: Kirby BD, Al Ahmar R, Withers TR, Valentine ME, Valentovic M, Long TE, Gaskins JR, Yu HD Abstract Pseudomonas aeruginosa is a Gram-negative opportunistic bacterial pathogen that can cause chronic lung infections in patients with cystic fibrosis (CF). The current preferred treatment for CF lung infections includes inhaled tobramycin (TOB); however, studies suggest TOB cannot effectively inhibit biofilm formation. Using a NIH small compounds drug library approved for safe use in humans, we identified rifaximin (RFX), a semisynthetic, rifamycin family, non-systemic antibiotic that inhibits alginate production and growth in P. aeruginosa Inhibition of alginate production was further analyzed using the uronic acid carbazole assay and a promoter reporter assay that measures the transcription of the alginate biosynthetic operon. Compared to TOB, RFX significantly reduced alginate production in laboratory and CF sputum isolates of P. aeruginosa In addition, RFX showed a narrow range of minimum inhibitory concentrations when measured with multidrug-resistant bacterial species of clinical relevance, synergistic activities with TOB or amikacin against clinical isolates, as well as reduction towards in vitro pre-formed biofilms. In C57BL/6 mice, penetration of nebulized TOB into th...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research