title: Profile of ceftolozane/tazobactam and its potential in the treatment of complicated intra-abdominal infections.
abstract: Drug-resistant pathogens have gained a foothold especially in the most vulnerable patient populations, hospitalized and immunocompromised individuals. Furthermore, extended-spectrum β-lactamase and carbapenemase-producing organisms are finding their way even into the community, with patients presenting to the hospital with established colonization and infection with resistant Enterobacteriaceae in particular. Recently, a novel antipseudomonal cephalosporin in combination with an established Class A β-lactamase inhibitor, ceftolozane/tazobactam has been approved by the FDA for use in the treatment of complicated urinary tract infections and complicated intra-abdominal infections. Ceftolozane is a uniquely potent antipseudomonal cephalosporin because of its high affinity for the penicillin-binding proteins of Pseudomonas aeruginosa, its low affinity for the intrinsic Class C β-lactamases of P. aeruginosa, its ability to enter P. aeruginosa through the outer membrane without the utilization of OprD protein, and the fact that it is not a substrate of the often upregulated MexAB/OprM efflux system of P. aeruginosa. The biological chemistry, pharmacokinetics/pharmacodynamics, microbiologic spectrum, and clinical trials that led to the approval of ceftolozane is reviewed. A discussion regarding its potential role in the treatment of complicated intra-abdominal infections and other infectious disease syndromes associated with drug-resistant pathogens follows.
authors.affiliation: Department of Medicine, Louis Stokes Cleveland Department of Veterans Affairs and Case Western Reserve University School of Medicine, Cleveland, OH, USA ; Department of Biochemistry, Louis Stokes Cleveland Department of Veterans Affairs and Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Marion J
authors.initials: MJ
authors.lastname: Skalweit
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002511:Cephalosporins / Q000627:therapeutic use*; D017277:Drug Approval; D024881:Drug Resistance, Bacterial; D006801:Humans; D059413:Intraabdominal Infections / Q000188:drug therapy* / Q000382:microbiology; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000078142:Tazobactam; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C000594038:ceftolozane, tazobactam drug combination; D010397:Penicillanic Acid; D000078142:Tazobactam
keywords: Pseudomonas aeruginosa; ceftolozane/tazobactam; complicated intra-abdominal infections