Durlobactam (DUR; ETX2514) is a novel β-lactamase inhibitor with broad-spectrum activity against Ambler class A, C, and D β-lactamases. Durlobactam restores the in vitro activity of sulbactam (SUL) against members of the Acinetobacter baumannii-A. calcoaceticus complex (ABC). Sulbactam (SUL)-durlobactam (SUL-DUR) is under development for the treatment of ABC infections. Eighty patients with complicated urinary tract infection (cUTI), including acute pyelonephritis (AP), were randomized 2:1 to receive SUL-DUR at 1 g/1 g intravenously (i.v.) or placebo every 6 h (q6h) for 7 days and background therapy with imipenem-cilastatin (IMI) at 500 mg i.v. q6h to evaluate the tolerability of SUL-DUR in hospitalized patients. Patients with bacteremia could receive up to 14 days of therapy. SUL-DUR tolerability and the values of various pharmacokinetic (PK) parameters were determined. Efficacy was recorded at the test-of-cure (TOC) visit. SUL-DUR was well tolerated, with no serious adverse events (AEs) being reported. Headache (5.7%), nausea (3.8%), diarrhea (3.8%), and vascular pain (3.8%) were the most common drug-related AEs with SUL-DUR and were mostly of mild or moderate severity. The PK profile of DUR and SUL in hospitalized patients was consistent with observations in healthy volunteers. Overall success in the microbiological modified intent-to-treat (m-MITT) population was similar between the groups, as would be expected with IMI background therapy in all patients (overall success at the TOC visit, 76.6% [n = 36] with SUL-DUR and 81.0% [n = 17] with placebo). SUL-DUR in combination with IMI was well tolerated in patients with cUTIs. The pharmacokinetics of SUL-DUR observed in hospitalized patients was similar to that observed in healthy volunteers. (This study has been registered at ClinicalTrials.gov under identifier NCT03445195.)

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IntroductionThe aim of the present study was to evaluate the influence of clinicopathological factors including age, gender, tumor grade, tumor stage, lymphovascular invasion (LVI), tumor necrosis and previous history of non-muscle invasive bladder cancer on outcomes of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU).Material and methodsA total of 60 patients who underwent radical nephroureterectomy for upper tract urothelial carcinoma at our institute between 2005 to 2012 were included in our study. Univariate and multivariate analysis was performed using the Kaplan-Meier method, log rank statistics, the chi-square test and Cox regression models.ResultsThe mean length of follow-up time was 33.3 months. There were 27 (45%) patients alive with the disease, whereas 33 (55%) were dead. In 19 cases (31.7%) the tumor grade was low, while in 41 cases (68.3%) it was high. Lymphovascular invasion was observed in 28 (46.7%) cases. Tumor necrosis was registered in 14 patients (23.3%). From the patients with LVI, 3 (9.6%) were alive, whereas from the patients negative for LVI, 75% were alive. Significant relationship was found between gender and grading and between positive LVI and low grading.ConclusionsDay case Variables such as gender, grading, tumor stage, LVI and tumor necrosis were all demonstrated to be significant independent prognostic factors for the overall survival. On the multivariate analysis only LVI remained statistically significant, which may explain the different clinical course in patients and could be considered as a part of pathological reporting and treatment planning for the future.