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Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI).
Lancet. 2015 May 16; 385(9981):1949-56.Lct

Abstract

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.

FUNDING

Cubist Pharmaceuticals.

Authors+Show Affiliations

Clinic for Urology, Paediatric Urology and Andrology, Justus-Liebig University, Giessen, Germany. Electronic address: florian.wagenlehner@chiru.med.uni-giessen.de.Cubist Pharmaceuticals, Lexington, MA, USA.Cubist Pharmaceuticals, Lexington, MA, USA.Cubist Pharmaceuticals, Lexington, MA, USA.Michael E DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA.

Pub Type(s)

Clinical Trial, Phase III
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25931244

Citation

Wagenlehner, Florian M., et al. "Ceftolozane-tazobactam Compared With Levofloxacin in the Treatment of Complicated Urinary-tract Infections, Including Pyelonephritis: a Randomised, Double-blind, Phase 3 Trial (ASPECT-cUTI)." Lancet (London, England), vol. 385, no. 9981, 2015, pp. 1949-56.
Wagenlehner FM, Umeh O, Steenbergen J, et al. Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI). Lancet. 2015;385(9981):1949-56.
Wagenlehner, F. M., Umeh, O., Steenbergen, J., Yuan, G., & Darouiche, R. O. (2015). Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI). Lancet (London, England), 385(9981), 1949-56. https://doi.org/10.1016/S0140-6736(14)62220-0
Wagenlehner FM, et al. Ceftolozane-tazobactam Compared With Levofloxacin in the Treatment of Complicated Urinary-tract Infections, Including Pyelonephritis: a Randomised, Double-blind, Phase 3 Trial (ASPECT-cUTI). Lancet. 2015 May 16;385(9981):1949-56. PubMed PMID: 25931244.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI). AU - Wagenlehner,Florian M, AU - Umeh,Obiamiwe, AU - Steenbergen,Judith, AU - Yuan,Guojun, AU - Darouiche,Rabih O, Y1 - 2015/04/27/ PY - 2015/5/2/entrez PY - 2015/5/2/pubmed PY - 2015/6/30/medline SP - 1949 EP - 56 JF - Lancet (London, England) JO - Lancet VL - 385 IS - 9981 N2 - 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. FUNDING: Cubist Pharmaceuticals. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/25931244/Ceftolozane_tazobactam_compared_with_levofloxacin_in_the_treatment_of_complicated_urinary_tract_infections_including_pyelonephritis:_a_randomised_double_blind_phase_3_trial__ASPECT_cUTI__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(14)62220-0 DB - PRIME DP - Unbound Medicine ER -