(Chemical Equation Presented) CXA-101 is a novel broad-spectrum cephalosporin active against highly resistant clinical isolates and laboratory strains of Pseudomonas aeruginosa, including isolates resistant to ceftazidime, multidrug-resistant isolates, AmpC-hyperproducing clones and highly resistant cystic fibrosis isolates. Activity appears not to be affected by efflux mechanisms, porin deficiency or altered penicillin-binding proteins (PBPs). CXA-101 is very stable and not substantially affected by mutation-mediated mechanisms of resistance. It conserves activity against some extended-spectrum β-lactamase (ESBL)-expressing isolates, but not against metallo-β-lactamases. The activity profile for non-pseudomonal isolates is comparable to that of third-generation cephalosporins. CXA-101 is administered i.v. and more than 90% of the unmodified drug is secreted via the kidneys. The plasma half-life is approximately 2 h. No drug accumulation occurred in subjects receiving multiple doses of the drug. Phase I and II safety analysis showed that CXA-101 is well tolerated. A randomized phase II trial in patients affected by complicated urinary tract infections has been recently completed. Current available data on CXA-101 are promising and endorse further clinical development of this agent. The drug is foreseen to be further investigated and developed in combination with the β-lactamase inhibitor tazobactam (CXA-201).