Journal Article

Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI)

Darouiche, Rabih O, Steenbergen, Judith, Umeh, Obiamiwe, Yuan, Guojun, Wagenlehner, Florian M

2015

Overview

Treatment of complicated urinary-tract infections is challenging due to rising antimicrobial resistance. We assessed the efficacy and safety of ceftolozane-tazobactam, a novel antibacterial with Gram-negative activity, in the treatment of patients with complicated lower-urinary-tract infections or pyelonephritis. ASPECT-cUTI was a randomised, double-blind, double-dummy, non-inferiority trial done in 209 centres in 25 countries. Between July, 2011, and September, 2013, hospital inpatients aged 18 years or older who had pyuria and a diagnosis of a complicated lower-urinary-tract infection or pyelonephritis were randomly assigned in a 1:1 ratio to receive intravenous 1·5 g ceftolozane-tazobactam every 8 h or intravenous high-dose (750 mg) levofloxacin once daily for 7 days. The randomisation schedule was computer generated in blocks of four and stratified by study site. The next allocation was obtained by the study site pharmacist via an interactive voice-response system. The primary endpoint was a composite of microbiological eradication and clinical cure 5–9 days after treatment in the microbiological modified intention-to-treat (MITT) population, with a non-inferiority margin of 10%. This study is registered with ClinicalTrials.gov, numbers NCT01345929 and NCT01345955. Of 1083 patients enrolled, 800 (73·9%), of whom 656 (82·0%) had pyelonephritis, were included in the microbiological MITT population. Ceftolozane-tazobactam was non-inferior to levofloxacin for composite cure (306 [76·9%] of 398 vs 275 [68·4%] of 402, 95% CI 2·3–14·6) and, as the lower bound of the two-sided 95% CI around the treatment difference was positive and greater than zero, superiority was indicated. Adverse event profiles were similar in the two treatment groups and were mainly non-serious. Treatment with ceftolozane-tazobactam led to better responses than high-dose levofloxacin in patients with complicated lower-urinary-tract infections or pyelonephritis. Cubist Pharmaceuticals.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adult / Aged / Anti-Infective Agents, Urinary - administration & dosage / Anti-Infective Agents, Urinary - adverse effects / Antibiotics / Antimicrobial agents / Cephalosporins - administration & dosage / Cephalosporins - adverse effects / Double-Blind Method / Drug Administration Schedule / Drug dosages / Drug resistance / Drug therapy / Female / Gram-Negative Bacterial Infections - drug therapy / Gram-Positive Bacterial Infections - drug therapy / Humans / Infections / Infusions, Intravenous / Internal Medicine / Levofloxacin - administration & dosage / Levofloxacin - adverse effects / Male / Middle Aged / Penicillanic Acid - administration & dosage / Penicillanic Acid - adverse effects / Penicillanic Acid - analogs & derivatives / Pyelonephritis - drug therapy / Treatment Outcome / Urinary Tract Infections - drug therapy / Urine / Urogenital system / Young Adult