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

作者：Wagenlehner, Florian M.^*; Umeh, Obiamiwe; Steenbergen, Judith; Yuan, Guojun; Darouiche, Rabih O.

来源：Lancet, 2015, 385(9981): 1949-1956.

DOI：10.1016/S0140-6736(14)62220-0

• GRAM-NEGATIVE BACILLI
• UNITED-STATES
• TRIMETHOPRIM-SULFAMETHOXAZOLE
• INTRAVENOUS DORIPENEM
• RESISTANCE PATTERNS
• ESCHERICHIA-COLI
• CIPROFLOXACIN
• MULTICENTER
• PREVALENCE
• PREVENTION

Background 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. @@@ Methods 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. Findings 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. @@@ Interpretation Treatment with ceftolozane-tazobactam led to better responses than high-dose levofloxacin in patients with complicated lower-urinary-tract infections or pyelonephritis.

• 出版日期2015-5-16