Anti-biofilm and resistance suppression activities of CXA-101 against chronic respiratory infection phenotypes of Pseudomonas aeruginosa strain PAO1

Objectives Biofilm growth, mucoid phenotype and proficient resistance development by hypermutable strains dramatically limit the efficacy of current therapies for Pseudomonas aeruginosa chronic respiratory infection (CRI) in cystic fibrosis (CF) patients. We evaluated the activity of the new cephalosporin CXA-101, ceftazidime, meropenem and ciprofloxacin against biofilms of wild-type PAO1 and its mucoid (mucA), hypermutable (mutS) and mucoid-hypermutable derivatives, and analysed the capacity of these strains to develop resistance during planktonic and biofilm growth. Methods MICs and MBCs were determined by microdilution, and mutant frequencies were determined at 4× and 16× the MICs. Biofilms were formed using a modified Calgary device and were incubated for 24 h with 0×, 1×, 4× or 16× the MIC of each antibiotic. Biofilms were plated, and total cells and resistant mutants enumerated. Results CXA-101 showed concentration-independent biofilm bactericidal activity, being the most potent agent tested at 1× the MIC for wild-type, mucoid and hypermutable strains. The spontaneous mutant frequencies for CXA-101 were extremely low (