Antimicrobial activities of LCB10-0200, a novel siderophore cephalosporin, against the clinical isolates of Pseudomonas aeruginosa and other pathogens

Infections caused by multidrug-resistant bacteria, including Pseudomonas aeruginosa, are threatening public health worldwide. Therefore, a novel antibacterial agent is needed to treat these infections. Here, we investigated the in vitro and in vivo activities of a novel siderophore-conjugated cephalosporin, LCB10-0200, against the clinical isolates of Gram-negative bacteria, including multidrug-resistant P. aeruginosa. In vitro susceptibility to LCB10-0200 was assessed by performing a two-fold agar dilution method, as described by the Clinical and Laboratory Standards Institute. LCB10-0200 showed the most potent antibacterial activity against P. aeruginosa clinical isolates, including β-lactamase-producing strains. Moreover, LCB10-0200 showed better antibacterial activity against recently isolated clinical isolates than its comparators, except colistin. The in vivo activity of LCB10-0200 was examined using four mouse models of systemic, thigh, respiratory tract, and urinary tract infections. LCB10-0200 was more effective than ceftazidime in treating systemic, thigh, respiratory tract, and urinary tract infections caused by drug-susceptible and drug-resistant P. aeruginosa strains in these mouse models. Thus, the potent in vitro and in vivo activities of LCB10–0200 observed in the present study indicate that it has the potential for treating infections caused by Gram-negative bacteria, including P. aeruginosa.