clinicaltrials.gov Identifier: NCT02166476.

BackgroundZTI-01 (fosfomycin for injection) is an epoxide antibiotic with a differentiated mechanism of action (MOA) inhibiting an early step in bacterial cell wall synthesis. ZTI-01 has broad in vitro spectrum of activity, including multidrug-resistant Gram-negative pathogens, and is being developed for treatment of complicated urinary tract infection (cUTI) and acute pyelonephritis (AP) in the United States.MethodsHospitalized adults with suspected or microbiologically confirmed cUTI/AP were randomized 1:1 to 6 g ZTI-01 q8h or 4.5 g intravenous (IV) piperacillin-tazobactam (PIP-TAZ) q8h for a fixed 7-day course (no oral switch); patients with concomitant bacteremia could receive up to 14 days.ResultsOf 465 randomized patients, 233 and 231 were treated with ZTI-01 and PIP-TAZ, respectively. In the microbiologic modified intent-to-treat (m-MITT) population, ZTI-01 met the primary objective of noninferiority compared with PIP-TAZ with overall success rates of 64.7% (119/184 patients) vs 54.5% (97/178 patients), respectively; treatment difference was 10.2% (95% confidence interval [CI]: −0.4, 20.8). Clinical cure rates at test of cure (TOC, day 19–21) were high and similar between treatments (90.8% [167/184] vs 91.6% [163/178], respectively). In post hoc analysis using unique pathogens typed by pulsed-field gel electrophoresis, overall success rates at TOC in m-MITT were 69.0% (127/184) for ZTI-01 versus 57.3% (102/178) for PIP-TAZ (difference 11.7% 95% CI: 1.3, 22.1). ZTI-01 was well tolerated. Most treatment-emergent adverse events, including hypokalemia and elevated serum aminotransferases, were mild and transient.ConclusionsZTI-01 was effective for treatment of cUTI including AP and offers a new IV therapeutic option with a differentiated MOA for patients with serious Gram-negative infections.Clinical Trial RegistrationNCT02753946

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.)

Purpose of the study. Clarification of absolute and relative criteria for the surgical treatment of pelvic pelvic prolapse (PMT) and stress urinary incontinence (SNA). Materials and methods. A survey was conducted on 85 patients in whom OST and SNA were detected. The women were divided into groups according to the stage of POMT and SNM: 2nd group – 32 patients with PIDs of stages I and II and SNM 2a, 2b types of lung and moderate severity; Group 3 (main) - 53 patients with MIDI III and IV stages and MSM type 3 moderate and severe severity. This group of patients subsequently undergone operative treatment according to the patent for utility model No. 109201. The main group (3rd group) included: 3a group – 28 women from the OMT III and IV stages and SNM 3rd type of medium and severe severity without delay in urination; 3b group – 25 women with STI III and IV stages and SNM of type 3 of moderate and severe degree of severity with delay of urination (chronic or acute). 15 women were examined without complaints, who entered the control group (1st group). Results. According to the results of the study, it was recorded that, regardless of the stage of the PMS and SNM, even their minimal manifestations significantly reduced the quality of life of patients (by 64%) due to the impact on the physical, but to a greater extent, on the psychological components of health. Conclusion. The absolute criterion for operative treatment is a set of prolapse of the pelvic organs (PMTCT), urinary incontinence, vesicularization of the bladder type 2a and above, an increase in the posterior urethro-vascular angle of more than 114 °. Treatment of stress urinary incontinence on the background of OST should necessarily include fixation of the uterine ligation apparatus and surgery on the Berch in connection with significant deformation of the bladder neck. Keywords: pelvic organ prolapse, urinary incontinence, methods of diagnostics.