Julia Shinnick, MD
Awards
Advance RI-CTR Pilot Projects Program (Cycle 9)
“Intravesical Instillation of Gentamicin for Prevention of Recurrent UTI”
Urinary tract infections (UTls) are the second most common cause for hospital admission in patients ~65 years old, and are associated with secondary morbidity, including increased likelihood of acute ischemic stroke.
Repeated treatment of these infections is associated with antimicrobial resistance, antibiotic side-effects, and adverse downstream health effects. There is a need to minimize systemic antibiotic exposure in the treatment and prevention of UTI, and the current project proposes an innovative pilot trial to reduce systemic antibiotic exposure in a high-risk postmenopausal recurrent UTI cohort.
Dr. Shinnick proposes a feasibility pilot trial evaluating local administration of gentamicin into the bladder (intravesical gentamicin) compared to the current standard of care of oral nitrofurantoin prophylaxis in a postmenopausal recurrent urinary tract infection (UTI) population. The hypothesis is that intravesical gentamicin will be equally as effective as the standard of care in decreasing the number of UTls experienced by patients. In addition, the hypothesis that intravesical gentamicin will also improve patient-reported outcomes and favorably shift the urinary microbiome will be tested. Prior to starting the pilot trial, community engagement studios will be completed to garner patient expertise related to study design. Then, patient recommendations will be incorporated into the feasibility pilot trial.
The number of symptomatic, culture-proven, breakthrough UTls experienced by patients receiving prophylaxis for 3 months will be compared between the intravesical gentamicin and oral nitrofurantoin groups. Patients will be followed for an additional 3 months after their prophylactic treatment ends (total study period of 6 months) to evaluate post-treatment effect. Patient-reported outcome measures between groups at baseline will also be compared, upon completion of treatment (3 months), and end of follow-up (6 months). At baseline, 3- and 6-months the urinary microbiome composition of those exposed to intravesical gentamicin to those exposed to oral nitrofurantoin will additionally be compared. Shotgun metagenomics will be performed to provide species level data and examine microbial biomarkers associated with breakthrough UTls and patient-reported outcomes. An exploratory analysis of the impact of the two proposed therapies on antimicrobial gene (ARG) and virulence gene abundance will be conducted.
This trial has the potential to positively impact public health through creation of a patient-informed approach to UTI prevention while contributing valuable information to the emerging urobiome field.