scholarly journals 1473. Structured Patient Interview in Complicated Urinary Tract Infections to Assess Clinical Outcomes vs. Investigator’s Evaluation in the APEKS-cUTI Study

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S537-S537
Author(s):  
Simon Portsmouth ◽  
Kiichiro Toyoizumi ◽  
Tsutae Den Nagata ◽  
Glenn S Tillotson ◽  
Roger Echols
Keyword(s):  
Urinary Tract ◽  
Clinical Outcomes ◽  
Clinical Cure ◽  
Response To Therapy ◽  
Alternative Measure ◽  
Double Blind Study ◽  
Treatment Difference ◽  
Patient Interview ◽  
Patient Reported ◽  
Tract Infections

Abstract Background Based on the 2009 US FDA guidance, patient-reported outcome (PRO) measures are recommended in clinical study designs for certain indications to evaluate response to therapy from the patient’s perspective, and a PRO was recommended in the final complicated urinary tract infection (cUTI) guidance in 2014. Several PRO tools have been rigorously validated, but currently, no tool exists for evaluating cUTI. We included a “structured patient interview (SPI)“ while conducting a randomized, double-blind, study (NCT02321800) investigating cefiderocol (CFDC) vs. imipenem–cilastatin (IPM/CS) in cUTI patients to support the physician’s assessment of clinical response. Methods Patients, who were fully alert and oriented, were interviewed at randomization, end of treatment, test of cure (TOC), and follow-up (FUP) by the same interviewer. The questionnaire identified the presence or absence of relevant symptoms pertinent to cUTI. Responses were graded as none, or if present, mild, moderate, or severe. Investigator assessment included objective measures of clinical outcome(s) and was performed independently from the patient-reported symptoms collected in the SPI. Changes in the patient’s responses were compared with the investigator’s assessment at randomization and at each study visit. A kappa correlation coefficient comparing the SPI and physician’s clinical assessment was calculated at each evaluation time point. Results Based on investigator assessment, 89.7% (226 out of 252 patients) in the CFDC arm and 87.4% (104 out of 119 patients) in the IPM/CS arm achieved clinical cure (adjusted treatment difference: 2.39%; 95% CI: –4.66; 9.44) at TOC. Based on the SPI responses, 89.7% (226 out of 252 patients) in the CFDC arm and 84.9% (101 out of 119 patients) in the IPM/CS arm achieved clinical cure (adjusted treatment difference: 4.96%; 95% CI: –2.48; 12.39) in favor of CFDC. The correlation between SPI evaluation and physician’s assessment of clinical outcomes was very high at TOC and FUP visits (Kappa coefficients: 0.820 and 0.766, respectively). Conclusion The strong correlation between patients’ reported symptoms collected in the SPI and investigator assessment showed that SPI responses could be a useful alternative measure of clinical outcomes in cUTI studies. Disclosures All authors: No reported disclosures.

scholarly journals Structured patient interview to assess clinical outcomes in complicated urinary tract infections in the APEKS-cUTI study: pilot investigation

2021 ◽  
Vol 8 ◽  
pp. 204993612110582
Author(s):  
Simon Portsmouth ◽  
Roger Echols ◽  
Kiichiro Toyoizumi ◽  
Glenn Tillotson ◽  
Tsutae Den Nagata
Keyword(s):  
Urinary Tract ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Urinary Tract Infections ◽  
Early Assessment ◽  
Double Blind ◽  
Patient Interview ◽  
Patient Reported ◽  
Tract Infections ◽  
Time Point

Background: The APEKS-cUTI study demonstrated the non-inferiority of cefiderocol to imipenem−cilastatin in the primary endpoint of the composite of clinical and microbiological outcome in patients with complicated urinary tract infections (cUTIs). We piloted a structured patient interview (SPI) to evaluate clinical outcomes based on patient-reported symptoms while conducting this pivotal randomized, double-blind, phase-2 study. The objectives were to assess the value of the SPI, using its performance relative to physician assessment, and also to strengthen the value of patient-reported measures in conducting clinical trials for cUTI treatment. Methods: In addition to the protocol-defined clinical and microbiological outcomes, patients randomized in the APEKS-cUTI study were interviewed by the investigator or qualified study personnel at screening/baseline, early assessment (EA), end of treatment (EOT), test of cure (TOC), and follow-up (FUP). The 14-element questionnaire graded cUTI symptoms as absent or present, and if present, as mild, moderate, or severe. Changes in post-baseline symptoms based on patients’ responses were rated by the interviewer. The overall clinical outcome was evaluated based on the responses provided by patients at each time point. Results: Among the 371 patients in the modified intention-to-treat population, the rate of SPI completion in each treatment arm exceeded 90% at each time point. SPI-assessed clinical cure rates were 89.7% in the cefiderocol arm and 84.9% in the imipenem–cilastatin arm. There was substantial agreement between SPI evaluation and investigator global assessment of clinical outcome at TOC and FUP, with lower agreement at EA and EOT. Conclusion: This analysis suggests that patient-reported symptoms can be effectively captured in hospitalized patients with cUTI in a clinical trial setting. Development of a validated patient-reported outcome for use in such a setting is warranted. Registration: NCT02321800 (registered on 22 December 2014).

scholarly journals 1143. Safety and Efficacy of Ceftolozane/Tazobactam Versus Meropenem in Neonatal and Pediatric Participants With Complicated Urinary Tract Infection, Including Pyelonephritis: A Phase 2, Randomized, Clinical Trial

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S663-S664
Author(s):  
Emmanuel Roilides ◽  
Negar Ashouri ◽  
John S Bradley ◽  
Matthew G Johnson ◽  
Julia Lonchar ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Safety Profile ◽  
Clinical Cure ◽  
Treatment Duration ◽  
Double Blind Study ◽  
Phase 2 ◽  
Research Support ◽  
Safety And Efficacy ◽  
Step Down ◽  
Tract Infections

Abstract Background Ceftolozane/tazobactam (C/T) is a cephalosporin–β-lactamase inhibitor combination approved to treat complicated urinary tract infections (cUTI), complicated intra-abdominal infections, and nosocomial pneumonia in adults. Safety and efficacy of C/T in neonatal and pediatric participants with cUTI was assessed. Methods This phase 2, randomized, double-blind study (NCT03230838) compared C/T with meropenem (MEM) for treatment of cUTI, including pyelonephritis in participants from birth to 18 years of age. Treatment duration was 7-14 days. After 3 days of intravenous therapy, optional oral step-down therapy was allowed. Participants were stratified and dosed by age group (Table 1). The primary objective was to evaluate the safety and tolerability of C/T compared with MEM, and key secondary end points included clinical response and per-participant microbiologic response at end of treatment (EOT) and test of cure (TOC). Results Participants were randomized 3:1 and treated with C/T (n=100) or MEM (n=33). The microbiologic modified intent-to-treat population (mMITT) included 95 participants in the C/T (n=71) and MEM (n=24) arms; the most common reason for mMITT exclusion was lack of a qualifying baseline uropathogen (28.4%). Pyelonephritis was the most common baseline diagnosis (83.2%), and Escherichia coli was the most common qualifying baseline uropathogen (77.9%). Overall mean treatment duration was comparable in both arms (C/T, 10.2 days; MEM, 10.7); a total of 50 (70.4%) and 20 (83.3%) participants switched to optional oral step-down therapy in the C/T and MEM arms, respectively, both for a mean of approximately 6 days. The overall incidence of adverse events (AE; all and drug related), serious AE (SAE), and AE leading to discontinuation was comparable between C/T and MEM arms. There were no AE leading to death, drug-related SAE, or discontinuations due to drug-related AE or SAE (Table 2). For C/T and MEM, rates of clinical cure and microbiologic eradication at EOT and TOC were high (Figure). Conclusion In this study, C/T was well tolerated with a safety profile comparable to MEM and to the previously reported safety profile for C/T in adults with cUTI. C/T achieved high clinical cure and microbiologic eradication rates and is a potential new treatment option for children with cUTI. Disclosures Emmanuel Roilides, MD, PhD, FIDSA, FAAM, FESCMID, Merck Sharp & Dohme Corp. (Consultant, Grant/Research Support) Negar Ashouri, MD, Merck Sharp & Dohme Corp. (Grant/Research Support) Matthew G. Johnson, MD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Julia Lonchar, MSc, Merck Sharp & Dohme Corp. (Employee, Shareholder) Feng-Hsiu Su, MPH, MBA, Merck Sharp & Dohme Corp. (Employee, Shareholder) Jennifer A. Huntington, PharmD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Myra W. Popejoy, PharmD, Merck Sharp & Dohme Corp. (Employee) Mekki Bensaci, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Carisa S. De Anda, PharmD, Merck Sharp & Dohme Corp. (Employee, Shareholder) Elizabeth G. Rhee, MD, Merck Sharp & Dohme Corp (Employee, Shareholder) Christopher Bruno, MD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee)

Clinical Study of Gud-Amalaka Yoga in Garbhini Mutrakrichra w.s.r to Urinary Tract Infections during Pregnancy

2017 ◽  
Vol 2 (2) ◽  
Author(s):  
Sandeep Kumar Rajan ◽  
Rajnish Gautam ◽  
Pankaj Mishra
Keyword(s):  
Pregnant Woman ◽  
Urinary Tract ◽  
The Body ◽  
Premature Delivery ◽  
Healthy Baby ◽  
Patient Reported ◽  
Long Term Result ◽  
Tract Infections ◽  
Prompt Attention

Healthy mother and healthy baby are foremost aim of antenatal care. Progressive anatomical and physiological changes during pregnancy are not only confined to the genital organs however within other systems of the body too, some may be felt as discomfort by a pregnant woman. A pregnant woman having pain or burning micturition, fever with chills, nausea, vomiting and cloudy urine having bad smell can be diagnosed as having Urinary Tract Infection (UTI). UTI is most common bacterial infection encountered during Pregnancy and troublesome to the woman suffering from it. Pyelonephritis, premature delivery and other risk such as PROM, IUGR etc. can be the long term result of UTI hence prompt attention is requisite. In the present study Gud-Amalaka Yoga has been tried in 15 patients for evaluation of its clinical efficacy and adverse / side effects if any. It was observed that Gud-Amalaka Yoga showed better results (25% patients were moderately improved, 75% patients were mildly improved). None of the patient reported any adverse effect during or after the treatment.

scholarly journals Clinical Impact of Revised Ciprofloxacin Breakpoint in Patients with Urinary Tract Infections by Enterobacteriaceae

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 469
Author(s):  
Ga-Eun Park ◽  
Jae-Hoon Ko ◽  
Sun-Young Cho ◽  
Hee-Jae Huh ◽  
Jin-Yang Baek ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Clinical Outcomes ◽  
Urinary Tract Infections ◽  
Inhibitory Concentration ◽  
Clinical Impact ◽  
Definitive Treatment ◽  
Primary Endpoints ◽  
Tract Infections ◽  
Susceptible Group ◽  
Selection Of

In 2018, the Clinical and Laboratory Standards Institute (CLSI) revised ciprofloxacin (CIP)-susceptible breakpoint for Enterobacteriaceae from ≤1 μg/mL to ≤0.25 μg/mL, based on pharmacokinetic-pharmacodynamic (PK-PD) analysis. However, clinical data supporting the lowered CIP breakpoint are insufficient. This retrospective cohort study evaluated the clinical outcomes of patients with bacteremic urinary tract infections (UTIs) caused by Enterobacteriaceae, which were previously CIP-susceptible and changed to non-susceptible. Bacteremic UTIs caused by Enterobacteriaceae with CIP minimal inhibitory concentration (MIC) ≤ 1 μg/mL were screened, and then patients treated with CIP as a definitive treatment were finally included. Patients in CIP-non-susceptible group (MIC = 0.5 or 1 μg/mL) were compared with patients in CIP-susceptible group (MIC ≤ 0.25 μg/mL). Primary endpoints were recurrence of UTIs within 4 weeks and 90 days. A total of 334 patients were evaluated, including 282 of CIP-susceptible and 52 of CIP-non-susceptible. There were no significant differences in clinical outcomes between two groups. In multivariate analysis, CIP non-susceptibility was not associated with recurrence of UTIs. CIP non-susceptibility based on a revised CIP breakpoint, which was formerly susceptible, was not associated with poor clinical outcomes in bacteremic UTI patients were treated with CIP, similar to those of the susceptible group. Further evaluation is needed to guide the selection of definitive antibiotics for UTIs.

Urinary Tract Infections Caused by Multi-Drug Resistant Proteus mirabilis: Risk Factors and Clinical Outcomes

Infection ◽  
2009 ◽  
Vol 38 (1) ◽  
pp. 41-46 ◽  
Author(s):  
K. Cohen-Nahum ◽  
L. Saidel-Odes ◽  
K. Riesenberg ◽  
F. Schlaeffer ◽  
A. Borer
Keyword(s):  
Risk Factors ◽  
Urinary Tract ◽  
Clinical Outcomes ◽  
Urinary Tract Infections ◽  
Proteus Mirabilis ◽  
Drug Resistant ◽  
Tract Infections

scholarly journals P1062EXPANDED DIALYSIS (HDX): IS THERE AN IMPACT ON PATIENT REPORTED SYMPTOM?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Jarrin Penny ◽  
Fabio R Salerno ◽  
Lisa Hur ◽  
Christopher McIntyre
Keyword(s):  
Quality Of Life ◽  
Clinical Outcomes ◽  
Symptom Burden ◽  
Well Being ◽  
Response To Therapy ◽  
High Flux ◽  
Patient Reported ◽  
Dialysis Membranes ◽  
The Impact

Abstract Background and Aims High flux dialysis membranes sufficiently remove smaller sized uremic toxins however, the accumulation and retention of larger middle molecular weight toxins, which are associated with chronic inflammation, cardiovascular disease and suboptimal outcomes are poorly cleared. The recent advent of medium-cut-off dialysis membranes, labelled “expanded dialysis” (HDx) are permeable to molecules of larger size responsible for poor clinical outcomes. However, it remains unclear if HDx can directly impact the symptoms associated with hemodialysis (HD). Symptom burden plays a significant role in quality of life (QOL) and mortality rates in the HD population. The London Evaluation of Illness (LEVIL), an application-based platform has been developed to measure patient reported outcomes (PROM). In comparison to cross-sectional PROM’s, LEVIL more accurately represents the fluctuations in daily symptoms and the impact of intervention. LEVIL evaluates general well-being, energy, sleep, appetite, pain and breathing, all of which are outcomes of interest on symptom burden in chronic kidney disease. Our aim was to determine if HDx therapy had any effect on symtoms/QOL domains using LEVIL. Method 28 patients from two dialysis centers in London Ontario were consented to participate. Patients were required to be over 18 years of age and on conventional thrice weekly maintenance HD for at least three months. 23 participants completed study and analyzed (five lost for various reasons). Baseline (BL) symptom characteristics were obtained while using high flux membrane for two weeks. Symptoms continued to be measured throughout the 12 weeks of HDx therapy two-three times weekly using LEVIL. Laboratory biomarkers including beta-2 microglobulin and free-light chains were collected at baseline and after 12 weeks of HDx therapy. Results Patients were stratified into tertiles (high/middle/low) using mean values of BL symptoms scores in each domain (wellbeing, energy, sleep, appetite, pain, breathing). Those in the high BL group were labeled as “control”. Low and middle BL measures were further stratified into responders vs. non-responders (responders were considered to have a 50% increase in any symptom domain by ≥50%). Of those domains which responded to HDx, 76% also had low BL scores with 27% having middle BL scores. General wellbeing, energy and sleep were domains with the greatest response reaching statistical significance after eight weeks of therapy. HDx had limited effect on appetite, pain and breathing. Although stratification was per domain, overall, 74% of the population studied did respond in at least one domain, with some responding in as many as five. Conclusion HDx using Theranova (Baxter) shows the most benefit in domains with low BL measures. Additionally, not everyone who had low BL scores responded after 12 weeks of therapy, leaving us to question whether HDx may have a latent effect in some individuals/populations. Those who had no response to therapy in certain domains also had greater baseline quality of life respectively. This information may assist in decision making/rationale for the utilization and implementation of such therapy. Although more work is required to further stratify symptoms in relation to demographic/biochemical finding and clinical outcomes. It is evident that HDx improves patient reported symptoms and QOL.

scholarly journals Oral beta-lactam step down in bacteremic E. coli urinary tract infections

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Stephan Saad ◽  
Neil Mina ◽  
Colin Lee ◽  
Kevin Afra
Keyword(s):  
Urinary Tract ◽  
Propensity Score ◽  
Urinary Tract Infections ◽  
Clinical Cure ◽  
Beta Lactam ◽  
Beta Lactams ◽  
E Coli ◽  
Secondary Outcomes ◽  
Step Down ◽  
Tract Infections

Abstract Background Literature is scarce regarding oral step down to beta-lactams in bacteremic urinary tract infections. Oral fluoroquinolones are an accepted and common step down for bacteremic urinary tract infections; however, their use is associated with mounting safety concerns. We compared clinical cure in patients with E. coli bacteremic urinary tract infections who were stepped down to oral beta-lactams compared to oral fluoroquinolones. Methods This multicentre retrospective cohort study included patients with first positive concurrent urine and blood cultures from January 2016 to December 2016. Patients were included if they received empiric intravenous beta-lactam therapy with step down to either oral beta-lactam or fluoroquinolone for treatment completion. The primary outcome was clinical cure. Secondary outcomes were length of hospitalization, all-cause mortality and C. difficile infection. Multivariate analysis and propensity score were used to control for confounding. Results A total of 207 patients were identified with bacteremic E.coli urinary tract infections. Clinical cure was achieved in 72/77 (94%) in the oral beta-lactam group versus 127/130 (98%) in the oral fluoroquinolone group (absolute difference − 4.2, 95% confidence interval [CI] -10.3 to 1.9%, p = 0.13). The adjusted odds ratio (OR) for clinical cure with oral beta-lactams was 0.31 (95% CI 0.05–1.90, p = 0.21); propensity score adjusted analysis showed a similar result. There was no statistically significant difference in secondary outcomes. Conclusions Oral beta-lactams appear to be a safe and effective step down option in bacteremic E. coli urinary tract infections compared to oral fluoroquinolones.

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