Ceftolozane/Tazobactam: A New Cephalosporin and β-Lactamase Inhibitor Combination

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. Data Sources: 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. Study Selection and Data Extraction: Preclinical data as well as phase 1, 2, and 3 studies published in English were evaluated. Data Synthesis: 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.