Chronic lower urinary tract symptoms (LUTS) are a prevalent and detrimental issue that affects the quality of life of women. Due to the heterogeneity of LUTS, various factors have been implicated in their development. Recently, the infectious/inflammatory category has garnered attention for its potential use of long-term antibiotics in treatment. Despite the potential for adverse effects, specific types of antibiotics have shown to be effective with minimal long-term side effects in treating this category. Our study aimed to conduct a systematic review of the literature on long-term antibiotic regimens for the treatment of chronic LUTS caused by recurrent urinary tract infections (rUTI), chronic recalcitrant cystitis (CRC), or interstitial cystitis (IC). In addition, we sought to identify novel antibiotic delivery mechanisms that may improve the treatment of chronic LUTS.

A comprehensive search using a validated search strategy was performed on electronic databases including MEDLINE, EMBASE, Web of Science, and Clinicaltrials.gov, from their inception until March 22nd, 2022. The inclusion criteria for the retrieved studies involved the use of long-term (>28 days) antibiotic treatment for the management of LUTS secondary to rUTI, CRC, or IC, or the use of novel delivery mechanisms/drugs in treating LUTS. The screening was performed by two independent reviewers and data extraction, which encompassed key findings and quality assessment, was carried out in duplicate and independently.

The systematic electronic search yielded 19,499 studies, of which only nine studies met the predetermined eligibility criteria and were included in this review. Of the included studies, six were randomized controlled trials, one was a single-arm observational study, and two were basic science studies. Our assessment of study quality indicates that studies investigating the use of antibiotics for the management of chronic LUTS have a low-quality rating, with two out of five studies exhibiting a high risk of bias and the remaining three studies exhibiting some concerns for bias. Three theoretical studies exploring novel antibiotic delivery mechanisms were not subject to quality assessment due to their study design.
The available evidence from the included studies suggests that long-term, low-dose, daily antibiotic use may reduce the incidence of LUTS due to rUTI and CRC. However, the continuous use of antibiotics was associated with a significantly higher incidence of gastrointestinal adverse events. However, the use of first-generation cephalosporin and intermittent antimicrobial susceptibility testing may mitigate these risks.
Multiple antibiotics regimens, as well as single antibiotic regimens, have been shown to be effective in the management of LUTS due to rUTI and CRC. Long-term fluoroquinolones were shown to be well-tolerated and effective option for chronic LUTS secondary to rUTI, and Nitrofurantoin showed to be very effective in acute settings, although it may confer a higher-risk of adverse events with long-term use. Evidence supporting the use of long-term antibiotics for IC was not as robust. Our review also identified two promising novel approaches for managing LUTS: one that employed a novel delivery mechanism for Nitrofurantoin, and another that used a novel strategy to inhibit E. coli fimbriae adhesion.

The present study found clinical evidence on the use of antibiotics for the management of chronic LUTS caused by rUTI, CRC, and IC. Multiple barriers hinder the implementation of high-quality studies on the use of long-term antibiotics for chronic LUTS. Firstly, the heterogeneous definition of rUTI, CRC, or IC impedes research standardization. Secondly, prescribing long-term antibiotics for the treatment of chronic LUTS is often met with fear of retaliation from the medical community. Despite the aforementioned barriers, the included studies in this systematic review have shown promising results on the use of antibiotics for the management of chronic LUTS. However, our data demonstrate that there is still insufficient evidence supporting the use of long-term antibiotics for the management of chronic LUTS secondary to IC, and more investigation is warranted. As a relatively new approach in the management of chronic LUTS, further evidence is required to establish a robust conclusion on the benefits and drawbacks of this modality of treatment. Regarding novel antibiotic delivery mechanisms, theoretical studies were unable to be quality assessed due to study design. Nevertheless, available low-quality evidence suggests that innovative approaches such as small nanoparticles carrying Nitrofurantoin may have the potential to mitigate the symptoms of chronic LUTS while avoiding the adverse effects of long-term antibiotic therapy.

The evidence supporting the long-term use of antibiotics for managing chronic LUTS is currently limited and of low quality. Although some studies have shown the potential effectiveness of certain antibiotics in reducing chronic LUTS, high-quality research is necessary to determine the optimal antibiotic regimen for these conditions. Additionally, there is a need for the development of novel therapies that can alleviate the negative effects of chronic LUTS without the potential side effects of long-term antibiotic use.