scholarly journals Microbiome recovery in adult females with uncomplicated urinary tract infections in a randomised phase 2A trial of the novel antibiotic gepotidacin (GSK140944)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Andrea Nuzzo ◽  
Stephanie Van Horn ◽  
Christopher Traini ◽  
Caroline R. Perry ◽  
Etienne F. Dumont ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Human Microbiome ◽  
Time Points ◽  
Pharyngeal Cavity ◽  
Adult Females ◽  
Microbiome Diversity ◽  
Antibiotic Drug ◽  
Tract Infections

Abstract Background With increasing concerns about the impact of frequent antibiotic usage on the human microbiome, it is important to characterize the potential for such effects in early antibiotic drug development clinical trials. In a randomised Phase 2a clinical trial study that evaluated the pharmacokinetics of repeated oral doses of gepotidacin, a first-in-chemical-class triazaacenaphthylene antibiotic with a distinct mechanism of action, in adult females with uncomplicated urinary tract infections for gepotidacin (GSK2140944) we evaluated the potential changes in microbiome composition across multiple time points and body-sites (ClinicalTrials.gov: NCT03568942). Results Samples of gastrointestinal tract (GIT), pharyngeal cavity and vaginal microbiota were collected with consent from 22 patients at three time points relative to the gepotidacin dosing regimen; Day 1 (pre-dose), Day 5 (end of dosing) and Follow-up (Day 28 ± 3 days). Microbiota composition was determined by DNA sequencing of 16S rRNA gene variable region 4 amplicons. By Day 5, significant changes were observed in the microbiome diversity relative to pre-dose across the tested body-sites. However, by the Follow-up visit, microbiome diversity changes were reverted to compositions comparable to Day 1. The greatest range of microbiome changes by body-site were GIT followed by the pharyngeal cavity then vagina. In Follow-up visit samples we found no statistically significant occurrences of pathogenic taxa. Conclusion Our findings suggest that gepotidacin alteration of the human microbiome after 5 days of dosing is temporary and rebound to pre-dosing states is evident within the first month post-treatment. We recommend that future antibiotic drug trials include similar exploratory investigations into the duration and context of microbiome modification and recovery. Trial registration NCT03568942. Registered 26 June 2018.

scholarly journals Infeções do Trato Urinário numa Coorte de Transplantados Renais

2014 ◽  
Vol 27 (3) ◽  
pp. 364 ◽  
Author(s):  
Ana Bispo ◽  
Milene Fernandes ◽  
Cristina Toscano ◽  
Teresa Marques ◽  
Domingos Machado ◽  
...  
Keyword(s):  
Risk Factors ◽  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Urinary Tract Infections ◽  
Hospital Admissions ◽  
Female Gender ◽  
Tract Infections

<strong>Introduction:</strong> Urinary tract infection is the most common infectious complication following renal transplantation and its frequency is insufficiently studied in Portugal. The aim of this study was to characterize the incidence of urinary tract infections and recurrent urinary tract infections in renal transplant recipients.<br /><strong>Material and Methods:</strong> This was a retrospective cohort observational study, obtained from clinical files of all patients who received a renal transplant at the Hospital of Santa Cruz, from January 2004 to December 2005, with a mean follow-up period of five years or until date of graft loss, death or loss of follow-up. After a descriptive analysis of the population, we used bivariate tests to identify risk factors for urinary tract infections.<br /><strong>Results:</strong> A total of 127 patients were included, with a 593 patients.year follow-up. We detected 53 patients (41.7%) presenting with at least one episode of urinary tract infection; 21 patients (16.5%) had recurrent urinary tract infection. Female gender was the only risk factor associated with the occurrence of urinary tract infections (p &lt; 0.001, OR = 7.08, RR = 2.95) and recurrent urinary tract infections (p &lt; 0.001, OR = 4.66, RR = 2.83). Escherichia coli (51.6%), Klebsiella pneumoniae (15.5%) and Enterobacter spp (9.9%) were the<br />most frequently identified pathogens. Patients did not reveal an increased mortality or allograft loss. However, urinary tract infections were the most important cause of hospital admissions.<br /><strong>Discussion:</strong> Female gender was the only risk factor for urinary tract infections in this population. Escherichia coli was the most frequent agent isolated.<br /><strong>Conclusion:</strong> Despite preventive measures, urinary tract infections remain an important cause of morbidity and hospital admissions.<br /><strong>Keywords:</strong> Urinary Tract Infections; Postoperative Complications; Risk Factors; Kidney Transplantation; Portugal.

Fifteen-minute consultation: Why and how do children get urinary tract infections?

2019 ◽  
Vol 104 (5) ◽  
pp. 244-247 ◽  
Author(s):  
Kjell Tullus
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Bacterial Virulence ◽  
Host Defence ◽  
Tract Infections

This paper describes urinary tract infections (UTI) from the perspective of a disturbed balance between bacterial virulence and host defence. In some children, a UTI is caused by a virulent Escherichia coli, while in other cases children with abnormal renal tracts can get infected by almost any bacteria. Such knowledge can help in guiding treatment, investigations and follow-up of a child with a UTI.

Extended Therapy with a Trimethoprim-Sulphonamide for the Treatment of Established Urinary Tract Infection

1971 ◽  
Vol 16 (12) ◽  
pp. 506-508 ◽  
Author(s):  
H. Gavras ◽  
D. H. Lawson ◽  
A. L. Linton
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Success Rate ◽  
Urinary Tract Infections ◽  
Allergic Reactions ◽  
Extended Treatment ◽  
Recurrent Urinary Tract Infections ◽  
Tract Infections

Thirty patients with recurrent urinary tract infections who had failed to respond to previous extended treatment with Sulphadimidine and/or Ampicillin were treated with a Trimethoprim-sulphamethoxazole combination ‘Septrin’. Twenty six per cent developed allergic reactions. In those who completed a 3-months' course there was a 59 per cent success rate in eradicating bacteriuria at a 6-months follow-up.

Vesicular Cystitis: A Chronic Cystitis Variant Often Unresponsive to Antibiotics and Electrofulguration

2020 ◽  
pp. 1-6
Author(s):  
Joseph J. Crivelli ◽  
Philippe E. Zimmern
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Urine Culture ◽  
Anterior Wall ◽  
Chronic Cystitis ◽  
Positive Urine Culture ◽  
Institutional Review ◽  
Tract Infections ◽  
Cystitis Cystica

<b><i>Objective:</i></b> The aim of the study was to report on the presentation and outcomes of vesicular cystitis (VC), a chronic cystitis exhibiting translucent bladder mucosal vesicles, among women with antibiotic-refractory recurrent urinary tract infections (RUTIs). <b><i>Methods:</i></b> An analysis of our Institutional Review Board-approved series on antibiotic-refractory RUTIs was performed, selecting for documented VC lesions on cystoscopy. All patients had RUTIs defined as ≥3 urinary tract infections/year with positive urine culture. All patients were extensively treated with antibiotics with no resolution of RUTIs and were offered electrofulguration (EF) of VC lesions under anesthesia as a last resort. All patients had a 6-month post-EF office cystoscopy documenting persistence or resolution of the lesions, and a clinical outcome assessment based on RUTI frequency. <b><i>Results:</i></b> Of 482 patients, 18 (3.7%) treated during 2011–2017 met the study criteria. VC was most commonly found over the dome/anterior wall (7/18, 38%) and as pancystitis (7/18, 38%). There was often concomitant cystitis cystica of the trigone (8/18, 44%). At post-EF cystoscopy, persistence of VC was noted in 10/18 (56%) patients; 6/18 (33%) underwent repeat EF and an additional 3/18 (17%) were retreated due to new lesions after initial resolution. Two (11%) patients required simple cystectomy and urinary diversion due to RUTIs refractory to all interventions. Within a median follow-up of 2.8 years after EF, clinical cure was observed in 5/18 (28%), improvement in 10/18 (56%), and failure in 3/18 (17%) patients. <b><i>Conclusions:</i></b> Among women with antibiotic-refractory RUTIs, VC is an infrequent and persistent form of cystitis with a predilection for non-trigonal bladder surfaces, whose management is challenging.

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