Susceptibility of Pseudomonas aeruginosa recovered from cystic fibrosis patients to murepavadin and thirteen comparator antibiotics

Objectives: To determine the in vitro antimicrobial susceptibility of Pseudomonas aeruginosa isolates cultured from cystic fibrosis (CF) patients and explore associations between strain sequence type and susceptibility.Patients and Methods: Fourteen antibiotics and antibiotic combinations, including the novel antibacterial peptide murepavadin, were tested for activity against 414 Pseudomonas aeruginosa isolates cultured from respiratory samples of CF patients. The complete genomes of the isolates were sequenced and minimum spanning trees were constructed based on the sequence types (STs).Results: Percentage resistance (R) according to CLSI-2019 breakpoints were as follows: cefepime 14%, ceftazidime 11%, ceftazidime-avibactam 7%, ceftolozane-tazobactam 3%, piperacillin-tazobactam 12%, meropenem 18%, imipenem 32%, aztreonam 23%, ciprofloxacin 30%, gentamicin 30%, tobramycin 12%, amikacin 18%, and colistin 4%. Murepavadin MIC50 and MIC90 were 0.12 mg/L and 2 mg/L, respectively. There were no apparent clonal clusters associated with resistance, but higher MICs did appear to occur more often in STs with multiple isolates than in single ST isolates. In general the CF isolates showed a wide genetic distribution.Conclusions: P. aeruginosa CF isolates exhibited the lowest resistance rates against ceftolozane-tazobactam, ceftazidime-avibactam and colistin. Murepavadin demonstrated the highest activity on a per weight basis and may therefore become a valuable addition to the currently available antibiotics for treatment of respiratory infection in people with CF.