title: Ceftolozane/Tazobactam: A New Cephalosporin and β-Lactamase Inhibitor Combination.
abstract: OBJECTIVE
  To review the chemistry, pharmacology, microbiology, pharmacokinetics, pharmacodynamics, clinical efficacy, tolerability, dosage, and administration of ceftolozane/tazobactam, a new antipseudomonal cephalosporin combined with a well-established β-lactamase inhibitor.
  
  
  METHODS
  A literature search through clinicaltrials.gov and PubMed was conducted (January 2007-May 2015) using the search terms ceftolozane, ceftolozane/tazobactam, FR264205, CXA-101/tazobactam, and CXA-201. References from retrieved articles and abstracts presented at recent meetings were reviewed to identify additional material. The prescribing information was also reviewed.
  
  
  METHODS
  Preclinical data as well as phase 1, 2, and 3 studies published in English were evaluated.
  
  
  RESULTS
  Ceftolozane/tazobactam displays enhanced potency against Pseudomonas aeruginosa in vitro. Clinical trials have shown that ceftolozane/tazobactam is noninferior to levofloxacin for the treatment of complicated urinary tract infections (76.9% vs 68.4%, 95% CI = 2.3-14.6) and when used in combination with metronidazole is noninferior to meropenem for the treatment of complicated intra-abdominal infections (83% vs 87.3%, 95% CI = -8.91 to 0.54). An alternate antibiotic should be considered in patients who have a severe β-lactam allergy or an estimated creatinine clearance between 30 and 50 mL/min. Ceftolozane/tazobactam is well tolerated, with few drug interactions and no effects on the cytochrome P450 system.
  
  
  CONCLUSIONS
  In an era of increasing resistance to antimicrobials, ceftolozane/tazobactam provides clinicians with an additional treatment option for infections caused by multidrug-resistant Gram-negative organisms, including extended-spectrum β-lactamase-producing bacteria and Pseudomonas aeruginosa.
authors.affiliation: Regis University School of Pharmacy, Denver, CO, USA asucher@regis.edu.
authors.forename: Allana J
authors.initials: AJ
authors.lastname: Sucher
authors.affiliation: Palm Beach Atlantic University School of Pharmacy, West Palm Beach, FL, USA.
authors.forename: Elias B
authors.initials: EB
authors.lastname: Chahine
authors.affiliation: Regis University School of Pharmacy, Denver, CO, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Cogan
authors.affiliation: Regis University School of Pharmacy, Denver, CO, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Fete
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004338:Drug Combinations; D004347:Drug Interactions; D024881:Drug Resistance, Bacterial; D006801:Humans; D059413:Intraabdominal Infections / Q000188:drug therapy / Q000382:microbiology; D051379:Mice; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D011552:Pseudomonas Infections / Q000188:drug therapy; D000078142:Tazobactam; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000382:microbiology; D065093:beta-Lactamase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D004338:Drug Combinations; D065093:beta-Lactamase Inhibitors; C000594038:ceftolozane, tazobactam drug combination; D010397:Penicillanic Acid; D000078142:Tazobactam
keywords: antibiotic resistance; antibiotics; cephalosporins; infectious disease; β-lactams