A multi-centric randomized trial of daily nitrofurantoin versus bladder fulguration plus daily nitrofurantoin for the long-term management of cystitis in women with recurrent urinary tract infections

Ut Southwestern Medical Center, Dallas TX

Investigators

Abstract

ABSTRACT Urinary tract infections (UTIs) result in considerable morbidity and healthcare expenditures, especially for those who suffer from recurrent UTIs (rUTIs), defined as 3 or more symptomatic UTIs in a 12-month period or 2 or more in a 6-month period. Recent research has determined the considerable physical and psychological toll of UTIs and our work has demonstrated the frequency and impacts of antibiotic resistance and allergy in patients with rUTIs. Low-dose long-term antibiotic prophylaxis is one of the strategies typically considered for individuals who have frequent UTIs and have not durably responded to several 5-7-day courses of antibiotics. To investigate the source of reinfection in rUTI sufferers, our group examined the bladder wall during office cystoscopy and observed evidence of chronic inflammatory changes over the trigone and bladder base. Using a simple outpatient cystoscopic procedure, electrofulguration (EF), or cauterization of these areas of chronic inflammation within the bladder, we have shown symptomatic relief, endoscopic resolution of cystitis lesions, and clinical reduction in rUTIs. We recently reported long-term outcomes after EF (median follow-up 11 years) in women with stage 1 and 2 cystitis and a history of uncomplicated rUTI; 72% of women were cured, 22% were improved, and 6% did not benefit from the procedure. Work with collaborators using 16S rRNA fluorescence in situ hybridization (FISH) revealed resident intracellular/intratissue bacteria in inflamed regions of the bladder wallputative sources of reinfection. Despite our promising results, large gaps in knowledge on the management of women with rUTI indicate the need for definitive Level I evidence comparing the benefits of guideline-driven management relying on long-term (6 months) daily antibiotic prophylaxis versus EF of areas of chronic cystitis combined with long- term (6 months) daily antibiotic prophylaxis. Our central hypothesis is that those treated with EF will experience superior reduction in UTI episodes compared to those undergoing the standard antibiotic therapy alone. Here, we will perform a multicenter, randomized trial to determine whether EF with 6-month antibiotic prophylaxis will reduce UTI episodes in the 1-year (Aim 1) and 2-year (Aim 3) follow-up compared to 6-month antibiotic prophylaxis alone in women with a well-documented history of uncomplicated rUTI (Aim 1). We will determine changes in the urinary microbiomes due to EF with 6-month antibiotic prophylaxis compared to 6-month antibiotic prophylaxis alone (Aim 2). The multicenter, randomized clinical trial will enroll 104 women, aged 18 – 85, and consistent with current guidelines, use nitrofurantoin for antibiotic prophylaxis, a preferred antibiotic for rUTI treatment and prevention due to its concentration in the urine, low rates of resistance and allergy, and favorable safety profile to treat cystitis alone.