A prospective, multicenter,investigator-blinded, randomized, comparative study to estimate safety,tolerability & efficasy of NXL104/Ceftazidime vs. Imipenem cilastatin followed by appropriate oral therapy in the treatment of complicated urinary tract infections in hospitalized adults

This is a prospective, multicenter, investigator-blinded, randomized, two arm, parallel group (1:1) study to estimate the efficacy, safety, and tolerability of study drug vs. imipenem cilastatin in the treatment of adults with cUTI. The recruitment of patients is under progress in USA, Jordan and Lebanon. As of 1st December, 2009, total of 78 subjects have been randomized in the study and have received the assigned trial medicines. The patient recruitment is expected to start in India and Guatemala is expected to start around 12th December 2009. The recruitment is competitive and anticipated enrollment from India is around 40 subjects in the period of 3 months. Each patient is expected to complete the study, including follow up, within approximately 8 weeks. The total duration of antibiotic therapy (IV plus oral) should be 7 to 14 days. Complicated urinary tract infections include acute pyelonephritis, UTI in men, or UTI associated with obstruction, foreign bodies, or urologic abnormalities. Eligible patients include adults (>18 years and <65 years of age) suspected of having cUTIs due to gram-negative pathogens and judged by the investigator to require parenteral therapy and to be treatable with 7 to 14 days of therapy. Patients will be stratified based on the type of infection (pyelonephritis or other cUTI without pyelonephritis). If a patient has a urinary catheter in place at entry, it should be removed or replaced before initiating study therapy.Study medication will be given intravenously every 8 hours and 500 mg imipenem cilastatin will be given IV every 6 hours. Patients will be evaluated daily while on IV therapy. If after at least 4 full days of IV therapy, a patient meets protocol-specified criteria for clinical improvement, they are allowed to switch to oral ciprofloxacin 500 mg every 12 hours to complete the treatment course. If the patient cannot tolerate ciprofloxacin or if in vitro susceptibility shows that ciprofloxacin would not be effective, an alternative therapy may be chosen after discussion with the medical monitor. Patients are to receive a minimum of 7 days and a maximum of 14 days of total antibiotic therapy.An overall clinical assessment, detailed description and evaluation of the infectious process, urinalysis, and quantitative urine cultures are to be performed at baseline (within 48 hours of entry), during parenteral study antibiotic therapy (Day 3, 4, or 5), at the discontinuation of parenteral therapy, at the Test of Cure visit 5 to 9 days post-antibiotic therapy, and at 4 to 6 weeks post-antibiotic therapy (Late Follow-up). A blinded investigator should be identified who will be responsible for determining if the patient should be switched to oral therapy, assessing the patient?s response to therapy, determining the appropriate duration of IV therapy (and subsequent oral therapy), and assessing the relationship of adverse events to study therapy.