Unmet Needs in Complicated Urinary Tract Infections: Challenges, Recommendations, and Emerging Treatment Pathways

Abstract

While urinary tract infections (UTIs) are one of the most common types of infections globally, the wide variety of presentations and of severity of disease can make it difficult to manage. The definition for uncomplicated UTIs (uUTIs) is generally regarded as UTIs in healthy, non-pregnant women whereas all other UTIs are considered complicated. There is, however, a lack of consensus definition of complicated UTIs (cUTIs), leading to global differences in management. In addition, the patients who develop complicated UTIs generally have other comorbidities that warrant more urgent intervention. One of the biggest challenges in treating cUTIs is the rise of antimicrobial resistance (AMR). While there have been recent drug approvals for new antibiotic to treat these resistant organisms, a multidisciplinary approach, including regulatory frameworks, provider education and public awareness campaigns, is crucial to limiting unnecessary treatments for asymptomatic bacteriuria (ASB) and uUTIs that can ultimately lead to more severe infections.

Interpretable machine learning-based decision support for prediction of antibiotic resistance for complicated urinary tract infections

“…It is also essential to emphasize that the AMR-UTI dataset lacks information to ascertain whether patients had other conditions, such as asymptomatic bacteriuria (ASB), which often leads to positive urine cultures. However, ASB is typically not an appropriate indication for antibiotic therapy 13 , 40 . Consequently, there is a possibility that these patients might inadvertently be included in the training and validation cohorts without explicit identification.…”

“…We chose to focus on potentially complicated UTIs, as these infections typically carry a higher risk of treatment failure due to prior antibiotic therapy, and are associated with more adverse outcomes with ineffective treatment. These infections may also require longer courses of treatment, different antibiotics, and varying degrees of intervention 12,13 , emphasizing the necessity for novel intervention methods. We specifically opted for interpretable machine learning algorithms, based on the unique importance of interpreting and elucidating model predictions in clinical settings.…”

Phages prevent biofilm formation on catheters under flow

“…These biofilms can form under different nutrient conditions and flow levels, and once formed are hard to remove (Melo and Vieira, 1999). The increasing prevalence of AMR and biofilm formation in CAUTIs makes the need for alternative or complementary treatments to existing antibiotics critical (Gul et al, 2021;Marantidis and Sussman, 2023). Bacteriophages (phages for short) represent an alternative approach with the potential to treat or prevent AMR bacterial infections, including CAUTIs (Chegini et al, 2021;Lehman and Donlan, 2015;Milo et al, 2017;Townsend et al, 2020).…”