In vitro evidence of the synergistic interaction of ceftopibrole and other antibiotics against multidrug-resistant Gram-negative isolates

The purpose of the present study was to investigate the in vitro activity of ceftobiprole in combination with other antimicrobials against 27 selected Gram-negative isolates, including ESBL-producing E. coli and KPC-OXA-48-producing K. pneumoniae. Ceftobiprole activity in combination with amikacin, colistin, levofloxacin, piperacillin/tazobactam and rifampin was evaluated by time-kill curves and gradient-cross method (except colistin). Among the 27 strains tested with gradient strips most were resistant to ceftobiprole. Synergy was observed in some cases with piperacillin/tazobactam. There was at least one synergistic combination towards 9 isolates belonging to different species. No antagonism was observed with any of the antibiotic tested. In time-kill curves, performed for 12 selected isolates, synergistic interaction was more frequent, occurring with 32/60 combinations. The most interesting results of our study are the bactericidal effects of ceftobiprole in combination with colistin or piperacillin/tazobactam tested against Gram-negative isolates, including KPC and OXA-48-producing K. pneumoniae.