Dear colleagues—urologists, gynaecologists, general practitioners, and all healthcare professionals involved in the management of urinary tract infections (UTIs) - The management and prevention of urinary tract infections (UTIs) constitute a routine component of clinical practice for many healthcare providers. This Newsletter aims to review the most recent recommendations concerning the management and prevention of urinary tract infections. 

Our principal objectives are to reduce the incidence of infection, to avoid inappropriate antibiotic prescribing in order to limit the development of antimicrobial resistance, and to evaluate the available evidence regarding non-antibiotic preventive strategies. Robust scientific evidence and current guideline recommendations underpin the information presented herein.

The first article examines the impact of urinary pH on the antimicrobial susceptibility of nitrofurantoin, a commonly prescribed first-line antibiotic for the treatment of uncomplicated UTIs, and highlights the beneficial effect of an acidic urinary pH on its activity.

The second article reviews the utility of the Acute Cystitis Symptom Score (ACSS) in the evaluation of patients with acute cystitis. Threshold cut-off points are established to identify patients with a higher probability of clinical response and cure.

The third article explores the relationship between overactive bladder and urinary tract infections. It presents a study in which patients with overactive bladder who were refractory to anticholinergic therapy and were treated with prolonged courses of antibiotics, evaluating the potential association between infection and refractory symptoms.

2'

The study evaluated the effect of nitrofurantoin across different urinary pH cut-off values on antimicrobial susceptibility in uropathogenic Escherichia coli (UPEC). E. coli is the predominant causative organism in sporadic urinary tract infections, and nitrofurantoin is regarded as one of the first-line oral antimicrobial agents for the treatment of uncomplicated infection.

The investigation was conducted on 100 culture-confirmed UPEC isolates. Nitrofurantoin susceptibility was assessed at urinary pH levels of 5.5 and 7.2, with estimation of minimum inhibitory concentrations (MICs). The study population comprised 54 female and 46 male patients, with an age range of 1–85 years (mean age 60 years).

At a urinary pH of 7.2, the susceptibility rate was 85%. An acidic urinary pH (5.5) significantly enhanced the antimicrobial activity of nitrofurantoin, as demonstrated by lower minimum bactericidal concentration (MBC) and estimated MIC values compared with neutral conditions. Validation in selected isolates confirmed a four- to sixteen-fold reduction in MIC under acidic conditions. The estimated susceptibility at pH 5.5, at a drug concentration <32 mg/L, was 87%, compared with 75% at pH 7.2. The resistance rate at the same cut-off concentration was 2% at pH 5.5 and 7% at pH 7.2. Urinary pH also influenced the MIC values, favouring increased antimicrobial efficacy in acidic conditions.

These findings are consistent with previous pharmacodynamic studies demonstrating that nitrofurantoin’s bactericidal activity is potentiated in acidic environments. Overall, the study confirms that nitrofurantoin exhibits pH-dependent antimicrobial activity, with acidic conditions enhancing its bactericidal efficacy against UPEC. Modulation of urinary pH towards a more acidic range (for exemple, through the use of agents such as Metiofitina^®) may therefore represent a potential adjunctive strategy to optimise antibiotic efficacy in the management of urinary tract infections. 

Furthermore, it should be noted that certain members of the Enterobacteriaceae family demonstrate reduced growth capacity in acidic urinary environments, which may further contribute to the observed effect.

2'

Urinary tract infections (UTIs) are a common reason for seeking medical attention and represent one of the principal indications for antibiotic prescribing. However, sporadic UTIs in patients without identifiable risk factors may, in selected cases, be managed using non-antibiotic strategies. Non-antibacterial agents may act by reducing bacterial virulence properties or by modulating the host inflammatory response.

It should also be borne in mind that antibiotic therapy is frequently initiated empirically, prior to the availability of microbiological results. In this context, the article evaluates symptom assessment using the Acute Cystitis Symptom Score (ACSS) questionnaire in adult females (285 patients with UTI and 232 controls).

The ACSS includes the typical symptoms of acute cystitis: increased urinary frequency, urgency, dysuria, sensation of incomplete bladder emptying, suprapubic pain, and haematuria. The study assessed different cut-off values for the principal symptoms associated with UTI in order to establish clinically relevant parameters for treatment indication and outcome assessment.

The ACSS questionnaire was shown to be a useful instrument for predicting the likelihood of clinical cure, with a summary score of the “typical” domain of ≥6 indicating a higher probability of treatment success. Furthermore, changes in symptom severity 2–4 days after the initiation of treatment represent the most reliable parameter for evaluating therapeutic efficacy. This may be particularly valuable when assessing response to non-antibiotic treatment strategies and determining whether modification of management is required.

A summary score of the five typical ACSS symptoms >6, or the presence of any typical symptom with a severity score of at least 2, should be considered indicative of clinical failure. In addition, persistent visible haematuria should also be regarded as a potential sign of treatment failure, and alternative causes of haematuria must be investigated as part of the differential diagnosis of urinary tract infection.

2'

Patients with overactive bladder (OAB) have a higher reported likelihood of urinary tract infection (UTI), with prevalence estimates ranging from 27% to 56%. Inflammatory changes and dysregulation of the urothelium have been described as potential pathophysiological mechanisms in both OAB and recurrent UTI. OAB is a chronic condition with a substantial proportion of patients demonstrating refractoriness to anticholinergic agents or β3-adrenergic agonists.

The aim of this multicentre, randomised study was to compare the efficacy of a six-week course of rotating antibiotics versus placebo, administered in conjunction with anticholinergic therapy, on changes in OAB symptoms, including urinary incontinence. All included patients had detrusor overactivity confirmed by urodynamic assessment.

Participants were randomised in a 2:1 ratio to receive antibiotics or placebo for six weeks, in addition to darifenacin 15 mg once daily for six months in both groups. The antibiotic regimen consisted of sequential two-week courses of norfloxacin (400 mg twice daily), amoxicillin 500 mg/clavulanic acid 125 mg twice daily, and nitrofurantoin (100 mg four times daily).

Although 278 women were screened, only 36 were randomised, and 33 (91.7%) completed the trial. The principal reasons for exclusion included absence of refractory detrusor overactivity and patient refusal (116 cases). At the time of randomisation, the proportion of patients with a positive urine culture was 16.7% overall (33.3% in the placebo group and 8.3% in the antibiotic group).

At six months, leakage as measured by the 24-hour pad test decreased by 75 g in the antibiotic group compared with 35 g in the placebo group. Urge urinary incontinence improved in 10/21 (48%) patients receiving antibiotics versus 2/12 (17%) receiving placebo. The proportion of patients developing a UTI requiring antibiotic treatment during follow-up was 41.6% in the placebo group and 16.7% in the antibiotic group.

The authors concluded that, in patients with urge urinary incontinence refractory to oral pharmacotherapy, infection may play a role in the pathogenesis and warrants further investigation. However, it should be noted that the role of prolonged antibiotic therapy in OAB has recently been critically appraised in the article “Pereca, Jelizaveta et al. “Antibiotic therapy for treating overactive bladder is not supported by clinical evidence.” Nature reviews. Urology vol. 22,6 (2025): 366-374”. 

The revision stated that the available evidence is based on seven published studies and four conference proceedings, which are heterogeneous in study design, inclusion and exclusion criteria, treatment regimens, concomitant use of antimuscarinic therapy, follow-up protocols, and outcome measures. The existing studies are subject to methodological limitations and potential bias. Furthermore, the risks associated with prolonged antibiotic therapy—including antimicrobial resistance and adverse events—must be carefully considered.

Therefore, in the absence of an acute UTI, management of the non-specific syndrome of OAB should adhere to established evidence-based investigative and therapeutic guidelines. These include optimisation of fluid intake, anticholinergic or β3-adrenergic agonist therapy, and progression to intravesical onabotulinumtoxinA injections or neuromodulation in patients who do not respond to oral pharmacological treatment.