Trends of antimicrobial resistance and combination susceptibility testing of cystic fibrosis multidrug-resistant Pseudomonas aeruginosa: A ten-year update.

Background: Antimicrobial combination therapy is a time/resource- intensive procedure commonly employed in the treatment of cystic fibrosis (CF) pulmonary exacerbations caused by P. aeruginosa Ten years ago the most promising antimicrobial combinations were proposed, but there has since been the introduction of new β-lactam+β-lactamase inhibitor antimicrobial combinations. The aims of this study were i) to compare in vitro activity of these new antimicrobials with other anti-pseudomonals agents and suggest their most synergistic antimicrobial combinations. ii) to determine antimicrobial resistance rates and study inherent trends of antimicrobials over ten years.Methods: A total of 721 multidrug-resistant P. aeruginosa isolates from 183 patients were collated over the study period. Antimicrobial susceptibility and combination testing were carried out using the Etest method. The results were further assessed using the fractional inhibitory concentration index (FICI) and the susceptible breakpoint index (SBPI).Results: Resistance to almost all antimicrobial agents maintained a similar level during the studied period. Colistin (p<0.001) and tobramycin (p=0.001) were the only antimicrobials with significant increasing isolate susceptibility while an increasing resistance trend was observed for levofloxacin. The most active antimicrobials were colistin, ceftolozane/tazobactam, ceftazidime/avibactam, and gentamicin. All combinations with β-lactam+β-lactamase inhibitors produced some synergistic results. Ciprofloxacin+ceftolozane/tazobactam (40%) and amikacin+ceftazidime (36.7%) were the most synergistic combinations while colistin combinations gave the best median SPBI (50.11).Conclusions: This study suggests that effective fluoroquinolone stewardship should be employed for CF patients. It also presents in vitro data to support the efficacy of novel combinations for use in the treatment of chronic P. aeruginosa infections.