Efficacy and safety of ceftazidime–avibactam versus imipenem–cilastatin in the treatment of complicated urinary tract infections, including acute pyelonephritis, in hospitalized adults: results of a prospective, investigator-blinded, randomized study

Objectives:The aim of this prospective phase II, randomized, investigator-blinded study (NCT00690378) was to compare the efficacy and safety of ceftazidime–avibactam and imipenem–cilastatin in hospitalized adults with serious complicated urinary tract infection (cUTI) due to Gram-negative pathogens.Patients and methods:Patients aged between 18 and 90 years with cUTI were enrolled and stratified by infection type (acute pyelonephritis or other cUTI) and randomized 1:1 to receive intravenous ceftazidime 500 mg plus avibactam 125 mg every 8 hours or imipenem–cilastatin 500 mg every 6 hours. Patients meeting pre-specified improvement criteria after 4 days could be switched to oral ciprofloxacin. Patients were treated for a total of 7–14 days. The primary efficacy objective was a favorable microbiological response at the test-of-cure (TOC) visit 5–9 days post-therapy in microbiologically evaluable (ME) patients.Results:Overall, 135 patients received study therapy (safety population); 62 were included in the ME population (ceftazidime–avibactam, n = 27; imipenem–cilastatin, n = 35). The predominant uropathogen was Escherichia coli. Favorable microbiological response was achieved in 70.4% of ME patients receiving ceftazidime–avibactam and 71.4% receiving imipenem–cilastatin at the TOC visit (observed difference −1.1% [95% CI: −27.2%, 25.0%]). Among ME patients with ceftazidime-resistant uropathogens, response was observed in 6/7 (85.7%) receiving ceftazidime–avibactam. Adverse events were observed in 67.6% and 76.1% of patients receiving ceftazidime–avibactam and imipenem–cilastatin, respectively. Limitations of the study include the small number of patients in the ME population.Conclusion:The results suggest that the efficacy and safety of ceftazidime–avibactam may be similar to that of imipenem–cilastatin.Trial registration: ClinicalTrials.gov identifier: NCT00690378.