Activity of newest generation β-lactam/β-lactamase inhibitor combination therapies against biofilm-forming multidrug resistant Pseudomonas aeruginosa.
Mr Robbie Haines1, Dr Papanin Putsathit2, Dr Anna Tai3,4,5, Dr Katherine Hammer1
1School of Biomedical Sciences, University Of Western Australia, NEDLANDS, Australia
2School of Medical and Health Sciences, Edith Cowan University, JOONDALUP, Australia
3Department of Respiratory Medicine, Sir Charles Gairdner Hospital, NEDLANDS, Australia
4Institute for Respiratory Health, NEDLANDS, Australia
5Medical School, The University of Western Australia, CRAWLEY, Australia
Background: Multi-drug resistant organisms are a significant source of secondary morbidity and mortality in already critically or chronically ill patients. In particular, Pseudomonas aeruginosa has a propensity to develop clinically concerning carbapenemase mediated resistance to β-lactam antimicrobials. Ceftolozane/tazobactam (Zerbaxa®), ceftazidime/avibactam (Zavicefta®), and imipenem/relebactam/cilastatin (Recarbiro®) are currently available β-lactam/β-lactamase inhibitor combination therapies that do not have a well-defined role. In our study we determined the antimicrobial activity of imipenem/relebactam, ceftazidime/avibactam, and ceftolozane/tazobactam against multi-drug resistant P. aeruginosa isolated from the airways of cystic fibrosis patients.
Methods: The inhibitory concentrations of imipenem, imipenem/relebactam, ceftazidime, ceftazidime/avibactam, and ceftolozane/tazobactam were obtained for cystic fibrosis associated multi-drug resistant P. aeruginosa (n=20) using a broth microdilution assay according to Clinical Laboratory Standards Institute protocols and breakpoints.
Results: The addition of avibactam (4µg · mL-1) to ceftazidime converted 69% of isolates from ceftazidime resistant to ceftazidime sensitive. Similarly, the addition of relebactam (4µg · mL-1) to imipenem converted 20% of imipenem resistant isolates to imipenem sensitive. Additionally, 71% of isolates that were cefepime resistant were sensitive to ceftolozane/tazobactam.
Conclusions: Ceftazidime/avibactam and ceftolozane/tazobactam are two currently available newer generation β-lactam/β-lactamase inhibitor combination therapies which show promise in vitro for MDR P. aeruginosa associated with cystic fibrosis where other antimicrobials have failed. These results can be applied to other highly resistant P. aeruginosa airway infections, such as ventilator associated pneumonia.
Biography:
Former critical care nurse and recent Master of Infectious Diseases graduate with research interests in AMR, bacterial HAIs, and with a particular focus on biofilm forming organisms.