Hypothesis / aims of study
Overactive bladder (OAB) is a symptom syndrome characterised by “urgency with or without urinary incontinence, usually with increased daytime frequency and nocturia”, and is a diagnosis of exclusion [1]. Urine infection has long been implicated in the pathophysiology of OAB, with proponents suggesting that the infection-associated inflammatory response exaggerates bladder sensory signaling. In addition, it is also possible that bacteria can directly and indirectly sensitise the sensory neurons with locally acting toxins and metabolites, as well as promote urothelial shedding, leading to increased bladder permeability, which allows urine to directly affect nerves, elicit pain and lead to the origin of storage symptoms [2].
Antibiotic therapy leads to a decrease in the pro-inflammatory cytokines in urine which in some studies correlates with decreased severity of the OAB symptoms [2]. However, there is still considerable debate about the role of infection and antibiotic therapy in the treatment of these conditions. The aim of this study was to review the existing evidence for use of antibiotic therapy in female overactive bladder patients.
Study design, materials and methods
This systematic review was undertaken to identify the studies exploring the effects of antibiotic treatment in accordance with the JBI methodology for systematic reviews [3].
A systematic search of PubMed, Ovid Embase, and Cochrane Library was implemented using combinations of medical subject headings and keywords based on the following two significant terms: “overactive bladder” and “antibiotics”, and the abstracts were screened for primary published research studies on the long-term or full-dose antibiotic effect on female adult patients with OAB. In addition to that, a grey literature search was performed on Google, using general and targeted internet searches for the electronic formats of conference abstracts, editorial letters, websites and guidelines.
Results
We identified a total of eight studies covering the research question: five published papers and four conference proceedings, which are described in detail in Table 1. Studies varied in inclusion criteria, design, duration, and nature of antibiotic therapy. There was one double-blinded randomised non-comparative placebo-controlled trial and eight cohort studies.
Some of the studies focused on long-term antibiotic treatment only of those OAB patients who had microscopic pyuria on the basis of the argument that the presence of microscopic pyuria might represent urinary tract infection which is undetectable using standard culture techniques. The largest case study included a mixed group of female patients with LUTS, had no formal study design, and therefore lacked any formally defined study outcomes.
The pre-existing treatment for OAB was variably stopped or continued, with one of the studies excluding patients on antimuscarinics. The follow-up period varied from four weeks to six months. Patients in several studies were treated until the resolution of their symptoms with a mean treatment length of up to 383 days.
The reviewed studies used different outcome measures; analysis and reporting also varied. The only RCT measured the change in urgency incontinence, and the rest of the studies measured improvement in storage symptoms as a primary or, more commonly, as a secondary outcome. Changes in symptoms were assessed using a variety of questionnaires, which did not allow a direct comparison between the studies.
Whilst the only RCT demonstrated a reduction in urgency incontinence in the group of patients treated with antibiotics, not seen in the placebo group, it failed to demonstrate any difference in PPIUS (patient perception of the intensity of urgency) scores.
Reporting of adverse events and safety was poor, with only three studies addressing adverse events related to antibiotic use and antibiotic resistance.
No study compared antibiotic therapy to conventional treatment for OAB (pharmacotherapy, intravesical botulinum toxin, sacral nerve stimulation) and none included patients who had previously trialed beta-3-agonists or undergone intravesical botulinum toxin injections before being started on antibiotic therapy. The only randomised controlled trial reviewed here also reported difficulties with recruiting patients, as the intravesical onabotulinumtoxinA injections became funded for refractory OAB at the time of the study.
Interpretation of results
The published evidence regarding antibiotic treatment in female overactive bladder patients is limited, largely comprising of small-scale cohort studies with short follow-up periods. The only randomised placebo-controlled trial had a small number of participants and failed to demonstrate an improvement in urinary urgency despite improving urge incontinence symptoms.
Gaps identified in this review include a lack of placebo or conventionally treated comparators, the adequate study design of a standardized duration, and a standard characterization of patients for inclusion. Safety reporting also needs standardization according to agreed datasets.