Ceftolozane Sulfate

Ceftolozane Sulfate is a broad-spectrum, fifth-generation cephalosporin with bactericidal activity belonging to the β-lactam group of antibiotics. It can be used for impurity profiling and chemical stability testing. It can also be used for penicillin binding protein (PBP) studies using infection models. It was approved by the FDA in 2014 (Cubist Pharmaceuticals) in combination with tazobactam, a β-lactamase inhibitor. This combination has activity similar to ceftazidime.
Ceftolozane Sulfate is soluble in DMSO.

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Background

Ceftolozane Sulfate is a 3'-aminopyrazolium cephalosporin. Cephalosporins interfere with PBP (penicillin binding protein) activity involved in the final phase of peptidoglycan synthesis. Ceftolozane is a potent PBP3 inhibitor and has a higher affinity for PBP1b compared with other β-lactam agents. PBP’s catalyze a pentaglycine crosslink between alanine and lysine residues providing additional strength to the cell wall. Without a pentaglycine crosslink, the integrity of the cell wall is severely compromised and ultimately leads to cell lysis and death. PBPs of P. aeruginiosa include PBP1b, PBP1c and PBP3. PBP's of E. coli include PBP3. Resistance to cephalosporins is commonly due to cells containing plasmid-encoded β-lactamases such as AmpC β-lactamase. Resistance may also include modification of PBPs by gene acquisition or target alteration, up-regulation of efflux pumps, and loss of outer membrane porin.