scholarly journals 1367. Clinical Cure in Secondary Efficacy Populations in Patients With Complicated Urinary Tract Infection Treated With ZTI-01 (Fosfomycin for Injection): Findings From the ZEUS Trial

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S418-S419 ◽  
Author(s):  
Keith Kaye ◽  
Louis B Rice ◽  
Viktor Stus ◽  
Olexsiy Sagan ◽  
Elena Fedosiuk ◽  
...  
Keyword(s):  
United States ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Clinical Cure ◽  
Complicated Urinary Tract Infection ◽  
The United States ◽  
Research Support ◽  
Gram Negative ◽  
Cure Rates

Abstract Background ZTI-01 (fosfomycin for injection) is an investigational epoxide antibiotic with a differentiated mechanism of action (MOA) inhibiting an early step in bacterial cell wall synthesis. ZTI-01 has a broad spectrum of in vitro activity, including multidrug-resistant Gram-negative pathogens, and is being developed for the treatment of patients with complicated urinary tract infection (cUTI) and acute pyelonephritis (AP) in the United States. Methods ZEUS was a multicenter, double-blind, Phase 2/3 trial in hospitalized adults with cUTI and AP to evaluate safety and efficacy. Randomized patients received 6 g ZTI-01 q8h or 4.5 g IV piperacillin/tazobactam (PIP-TAZ) q8h for 7 days; patients with baseline bacteremia could receive up to 14 days; study continued to late follow-up (LFU, 26 ± 2 days). Oral step-down therapy was prohibited. ZTI-01 met the primary endpoint of noninferiority to PIP-TAZ. Secondary objectives included comparing clinical cure rates (assessed by investigator) in the modified intent-to-treat (MITT), microbiologic MITT (m-MITT), clinical evaluable (CE), and microbiologic evaluable (ME) populations at test-of-cure (TOC, Day 19 ± 2 days). Results There were 464 patients randomized who received study drug. In all populations, clinical cure rates at TOC were high and similar between treatment groups (>90%) (table). Conclusion These results demonstrate consistent efficacy in multiple secondary efficacy populations for patients with cUTI and AP who were treated with either ZTI-01 or PIP-TAZ. If approved by FDA, ZTI-01 may provide a new IV option with a differentiated MOA for patients in the United States with serious Gram-negative infections. 95% confidence intervals (CIs, two-sided) were computed using a continuity-corrected Zstatistic. Disclosures K. Kaye, Zavante Therapeutics, Inc.: Scientific Advisor, Consulting fee. L. B. Rice, Zavante Therapeutics, Inc.: Scientific Advisor, Consulting fee. V. Stus, Zavante Therapeutics, Inc.: Investigator, Research support. O. Sagan, Zavante Therapeutics, Inc.: Investigator, Research support. E. Fedosiuk, Zavante Therapeutics, Inc.: Investigator, Research support. A. Das, Zavante Therapeutics, Inc.: Consultant, Consulting fee. D. Skarinksy, Zavante Therapeutics, Inc.: Employee and Shareholder, Salary. P. B. Eckburg, Zavante Therapeutics, Inc.: Consultant and Shareholder, Consulting fee. K. Manvelian, Zavante Therapeutics, Inc.: Employee and Shareholder, Salary. E. J. Ellis-Grosse, Zavante Therapeutics, Inc.: Employee and Shareholder, Salary.

scholarly journals Fosfomycin for Injection (ZTI-01) Versus Piperacillin-tazobactam for the Treatment of Complicated Urinary Tract Infection Including Acute Pyelonephritis: ZEUS, A Phase 2/3 Randomized Trial

2019 ◽  
Vol 69 (12) ◽  
pp. 2045-2056 ◽  
Author(s):  
Keith S Kaye ◽  
Louis B Rice ◽  
Aaron L Dane ◽  
Viktor Stus ◽  
Olexiy Sagan ◽  
...  
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Acute Pyelonephritis ◽  
Therapeutic Option ◽  
Elevated Serum ◽  
Complicated Urinary Tract Infection ◽  
The United States ◽  
Success Rates ◽  
Gram Negative

Abstract Background ZTI-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. Methods Hospitalized 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. Results Of 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. Conclusions ZTI-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 Registration NCT02753946

scholarly journals Intravenous Doripenem at 500 Milligrams versus Levofloxacin at 250 Milligrams, with an Option To Switch to Oral Therapy, for Treatment of Complicated Lower Urinary Tract Infection and Pyelonephritis

2009 ◽  
Vol 53 (9) ◽  
pp. 3782-3792 ◽  
Author(s):  
K. G. Naber ◽  
L. Llorens ◽  
K. Kaniga ◽  
P. Kotey ◽  
D. Hedrich ◽  
...  
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Complicated Urinary Tract Infection ◽  
The United States ◽  
Double Blind Study ◽  
Cure Rate ◽  
The Difference ◽  
Cure Rates ◽  
Microbiological Cure

ABSTRACT The prospective, multicenter, double-blind study presented in this report evaluated whether or not intravenous (IV) administration of doripenem, a carbapenem with bactericidal activity against gram-negative and gram-positive uropathogens, is inferior to IV administration of levofloxacin in the treatment of complicated urinary tract infection (cUTI). Patients (n = 753) with complicated lower UTI or pyelonephritis were randomly assigned to receive IV doripenem at 500 mg every 8 h (q8h) or IV levofloxacin at 250 mg q24h. Patients in both treatment arms were eligible to switch to oral levofloxacin after 3 days of IV therapy to complete a 10-day treatment course if they demonstrated significant clinical and microbiological improvements. The microbiological cure rate (primary end point) was determined at the test-of-cure (TOC) visit occurring 5 to 11 days after the last dose of antibiotic. For the microbiologically evaluable patients (n = 545), the microbiological cure rates were 82.1% and 83.4% for doripenem and levofloxacin, respectively (95% confidence interval [CI] for the difference, −8.0 to 5.5%); in the microbiological modified intent-to-treat cohort (n = 648), the cure rates were 79.2% and 78.2%, respectively. Clinical cure rates at the TOC visit were 95.1% in the doripenem arm and 90.2% in the levofloxacin arm (95% CI around the difference in cure rates [doripenem cure rate minus levofloxacin cure rate], 0.2% to 9.6%). Both treatment regimens were generally well tolerated. Doripenem was found not to be inferior to levofloxacin in terms of therapeutics and is now approved for use in the United States and Europe for the treatment of adults with cUTI, including pyelonephritis. As fluoroquinolone resistance increases, doripenem may become a more important option for successful treatment of cUTIs, including treatment of pyelonephritis.

scholarly journals Heterogeneity of Recent Phase 3 Complicated Urinary Tract Infection Clinical Trials

2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Simon Portsmouth ◽  
Almasa Bass ◽  
Roger Echols ◽  
Glenn Tillotson
Keyword(s):  
Clinical Trials ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Study Design ◽  
Patient Population ◽  
Complicated Urinary Tract Infection ◽  
Gram Negative ◽  
Regulatory Guidelines ◽  
New Antibiotics

Abstract Background For new antibiotics developed to treat antibiotic-resistant Gram-negative infections, the US Food and Drug Administration (FDA) regulatory pathway includes complicated urinary tract infection (cUTI) clinical trials in which the clinical isolates are susceptible to the active control. This allows for inferential testing in a noninferiority study design. Although complying with regulatory guidelines, individual clinical trials may differ substantially in design and patient population. To determine variables that impacted patient selection and outcome parameters, 6 recent cUTI trials that were pivotal to an new drug application (NDA) submission were reviewed. Methods This selective descriptive analysis utilized cUTI trial data, obtained from publicly disclosed information including FDA documents and peer-reviewed publications, from 6 new antibiotics developed to treat multidrug-resistant Gram-negative infections: ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, cefiderocol, plazomicin, and fosfomycin. Eravacycline was not approved for cUTI and is not included. Results Microbiologic modified intent-to-treat sample size, age, proportions of female patients, acute pyelonephritis (AP), Escherichia coli and other pathogens at baseline, protocol-specified switch to oral antibiotic, and the noninferiority margin were compared. Outcome data included clinical response, microbiologic eradication, and composite outcomes, including a subset of patients with AP. Conclusions A study design can follow regulatory guidelines but still have variable populations. The proportion of AP within a study varied greatly and influenced population demographics (age, gender) and baseline microbiology. A smaller proportion of AP resulted in an older patient population, fewer females, less E coli, and lower proportions of patients achieving success. Fluoroquinolones and piperacillin/tazobactam should be reconsidered as active comparators given the high rates of resistance to these antibiotics.

scholarly journals Preventing Hospital-Acquired Urinary Tract Infection in the United States: A National Study

2008 ◽  
Vol 46 (2) ◽  
pp. 243-250 ◽  
Author(s):  
S. Saint ◽  
C. P. Kowalski ◽  
S. R. Kaufman ◽  
T. P. Hofer ◽  
C. A. Kauffman ◽  
...  
Keyword(s):  
United States ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
The United States ◽  
National Study ◽  
Hospital Acquired

Evaluation of Serum Metalloprotinase-9 (MMP-9) in Iraqi Men with urinary tract infection

2017 ◽  
Vol 6 (12) ◽  
pp. 5558
Author(s):  
Hanan D. Abbas
Keyword(s):  
United States ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
United States Of America ◽  
Prognostic Biomarker ◽  
The United States ◽  
Control Group ◽  
Strong Relation ◽  
Tract Infections

Objective: The inflammation of the urinary tract and its various causes is one of the important diseases, which neglect and non-treatment lead to many amplifications, therefore, many countries including the United States of America has given urinary tract infection ″UTI″ a great interest. Since the disease is sometimes without obvious symptoms and because of research lacking that are using MMP-9. The aim of this work is to study the alterations in the Metalloprotinase-9 (MMP-9), and its role in pathogenicity of urinary tract infections ″UTI″ in serum of men who are initially diagnosed with this disease.Methods: This study was applied in educational Alsader hospital in Najaf city by using Enzyme Linked Immuno Sorbent Assay (ELISA) on serum taken from 42 men infected with UTI, and other 38 healthy considered as a control group to detect MMP-9.Data analysis: SPSS computerizing system has been used for statistically analysis of data. Results: The results revealed a highly significant (P<0. 05) level of ″MMP-9″in serum of patients in comparison with the control group. The result also demonstrated the strong relation between MMP-9 and other parameters such as age and smoking.Conclusion: It was concluded from the results of the present study thatMetalloprotinase-9″MMP-9″ was good prognostic biomarker for ″UTI″ in men, and these results significantly correlate with the early stages of disease.Recommendation: 1-It may be recommended that using MMP-9 to predict and diagnosis the urinary tract infection. 2-It may be also recommended to measure MMP-9 in women to establish its role in this disease 

scholarly journals 500. Prevalence of Extended-Spectrum β-lactamase and Carbapenem-Resistant Gram-Negative Bacteria in Patients with Urinary Tract Infection and Urosepsis Admitted through Emergency Departments in the United States

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S243-S243
Author(s):  
Sukhjit Takhar ◽  
Anusha Krishnadasan ◽  
Gregory J Moran ◽  
William Mower ◽  
Kavitha Pathmarajah ◽  
...  
Keyword(s):  
Risk Factors ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Susceptibility Testing ◽  
The United States ◽  
Gram Negative ◽  
Resistance Risk ◽  
Carbapenem Resistant ◽  
Extended Spectrum

Abstract Background Gram-negative infections due to extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, and carbapenem-resistant Enterobacteriaceae (CRE) and non-fermenting (CR-NF) strains, are increasingly encountered. Study objectives were to determine prevalence and associated risk factors and outcomes for these strains among emergency department patients hospitalized for urinary tract infection (UTI) at 11 US hospitals. Methods This was a prospective observational study of patients ≥18 years hospitalized for UTI. Clinical data were collected at the index visit. Urine was obtained for culture and susceptibility testing. Electronic medical record and telephone follow-up were conducted after 30 days for site laboratory results, treatment, and clinical outcomes. Positive culture was defined as 1 uropathogen with growth at ≥104 cfu/mL, or 2 with 1 or both at ≥105 cfu/mL, or ≥3 with 1 or 2 at ≥105 cfu/mL. Isolates with ceftriaxone (CRO) or meropenem MIC >1 μg/mL will undergo reference laboratory (IHMA, Inc., Schaumburg, IL) susceptibility testing, including against newer antibiotics and cefiderocol. Results We enrolled 774 participants between 2018 and 2019; 289 (37.3%) excluded due to urine culture not done, no growth, or contamination. Of 485 culture-positive participants (median age 56 years, 62.0% female), 432 (89.1%) grew 1 uropathogen, 48 (9.9%) 2, and 5 (1.0%) ≥3. Prevalences of CRO-resistant Enterobacteriaceae, CRE, and CR-NF were 19.9%, 2.1%, and 10.7%, respectively. At sites, 95.7% of CRO-resistant Enterobacteriaceae isolates were ESBL. Among participants with any or no antibiotic resistance risk factors, i.e., antibiotics, hospitalization, long-term care, or travel within 90 days, prevalence of CRO-resistant Enterobacteriaceae was 68/228 (29.8%) and 10/155 (6.5%), respectively. Among those with CRO-resistant vs. susceptible Enterobacteriaceae infections, ICU admission and death occurred in 9.9% vs. 6.6% and 3.7% vs. 1.0%, with median time home over 30 days, 24 vs. 27 days, respectively. Conclusion Among US hospitalized patients with UTI, infections due to CRE remain uncommon; however, ESBL and CR-NF now account for a substantial proportion of cases and are associated with resistance risk factors and worse outcomes. Disclosures All authors: No reported disclosures.

Sign in / Sign up

Export Citation Format

Share Document