Ceftolozane-tazobactam is a novel antipseudomonal cephalosporin with a -lactamase inhibitor. We investigated the pharmacokinetics (PK) and safety of ceftolozane-tazobactam in subjects with various degrees of renal function. In two phase I, openlabel studies, a single dose of ceftolozane-tazobactam was administered as a 1-h intravenous infusion to 24 subjects with normal, mild, or moderate renal impairment (1,000/500 mg) and six subjects with severe renal impairment (500/250 mg). Six subjects with end-stage renal disease (ESRD) received two doses of ceftolozane-tazobactam (500/250 mg each), pre-and posthemodialysis (post-HD). PK parameters were determined by noncompartmental methods. Plasma exposure to ceftolozane-tazobactam increased as renal function declined with only slightly increased exposures in subjects with mild renal impairment; the median area under the concentration-time curve from time zero to infinity (AUC 0-ؕ ) for ceftolozane and tazobactam increased 1.4-and 1.2-fold, respectively. In subjects with moderate renal impairment, the AUC 0-ؕ increased 2.5-and 2.2-fold for ceftolozane and tazobactam, respectively. In subjects with severe renal impairment, the dose-normalized median AUC 0-ؕ for ceftolozane and tazobactam increased 4.4-and 3.8-fold, respectively. In ESRD subjects, ceftolozane and tazobactam concentrations declined rapidly following the start of HD, with approximately 66 and 56% reductions in overall exposure based on the AUC 0-ؕ before and after dialysis. Slight increases in exposure with mild renal impairment do not warrant a dose adjustment; however, subjects with moderate or severe renal impairment and those on HD require a decrease in the dose, a change in the frequency of administration, or both to achieve exposures within the established safety and efficacy margins of ceftolozane-tazobactam. Ceftolozane-tazobactam was well tolerated by all renal impairment groups. C eftolozane-tazobactam is a novel antibacterial with activity against Pseudomonas aeruginosa, including drug-resistant strains, and other common Gram-negative pathogens, including most extended-spectrum -lactamase (ESBL)-producing Enterobacteriaceae (1, 2). Ceftolozane exerts its bactericidal activity by inhibiting essential penicillin-binding proteins, resulting in inhibition of cell wall synthesis and subsequent cell death (Cubist Pharmaceuticals, data on file, 2009). Tazobactam, an inhibitor of most class A -lactamases and some class C -lactamases, protects ceftolozane from hydrolysis and broadens its coverage to include most ESBL-producing members of the family Enterobacteriaceae (Cubist Pharmaceuticals, data on file, 2006, 2013).The pharmacokinetics (PK) of ceftolozane-tazobactam in patients with normal renal function are linear across a wide range of doses (up to 3,000 mg/1,500 mg as a single dose). The terminal elimination half-life (t 1/2 ) is approximately 2.5 h for ceftolozane and 1 h for tazobactam. Both compounds exhibit low protein binding (approximately 20% for ceftolozane and 30% for tazobactam) and are...