Secondary Analysis of Interstitial Cystitis/Bladder Pain Syndrome Patients Enrolled in a Recurrent Urinary Tract Infection Prevention Study Provides a Novel Paradigm for Etio-Pathogenesis and Practical Management of This Infection Phenotype.

INTRODUCTION: A subset of interstitial cystitis/bladder pain syndrome (IC/BPS) patients experience recurrent urinary tract infection (rUTI) associated with symptom flares. Recurrent UTI subjects with associated IC/BPS were enrolled in the first North American early clinical experience trial evaluating a new sublingual UTI preventative vaccine, MV140. It has been shown that women with rUTI develop an imbalance in the T helper 1 and 2 (Th2 over-expression) in the bladder mucosa. Our hypothesis-generating secondary analysis will suggest that this infection subcategory of IC/BPS patients develop a similar imbalance of Th1-Th2 response type to bacteria present in their urinary microbiome, leading to a bladder hypersensitivity that responds to mucosal immune modulation. METHODS: Female participants with ≥3 documented UTI/year underwent a 3-month vaccination treatment period with a 9-month efficacy period after completion of vaccine treatment (total 12 months). There were no exclusion criteria for subjects in relation to baseline urinary symptoms and/or discomfort/pain. Primary outcome was no UTI following vaccination. Secondary outcomes included change in UTI incidence, overall patient-reported subjective global assessment (SGA responder defined as moderately or markedly improved on 7-point scale), and safety. RESULTS: Sixteen subjects with IC/BPS-related symptoms and rUTI (mean age 47; range 23-74 years; mean number of UTI episodes in previous year 6.1 +/- 4.2) were eligible to be included in the Health Canada-approved MV140 vaccine study for prevention of rUTI. All subjects completed the 3-month vaccination period. One subject was lost to follow-up after their 6-month visit. Six subjects were UTI-free, while all 16 subjects had a reduction in UTI episodes compared to the year pre-vaccination. The total post-vaccination reduction in UTI episodes compared to pre-vaccination was 80% (0.1 UTI/subject/month from 0.5 UTI/subject/month, respectively). At 12 months, 13 subjects (81%) were SGA responders (moderately or markedly improved), and the responders reported a reduction in IC/BPS symptoms, with 8 subjects reporting significant or almost complete resolution of their specific long-term bladder discomfort/pain and bothersome urinary frequency or urgency. Four subjects reported mild and self-limited adverse events during vaccination period, but none were related to MV140 vaccine. CONCLUSION: Sublingual MV140 vaccine in IC/BPS patients with rUTI not only achieved UTI-free or reduced UTI incidence status but also, after approximately 9 months post vaccination, resolution of patients' long-term treatment-refractory IC/BPS symptoms. This suggests some cases of IC/BPS may be etiologically based on Th2-driven hypersensitivity to bacteria within or entering the urinary microbiome that responds to a vaccine whose mechanism of action is to normalize or balance the bladder Th1/Th2 mucosal immune system.

Reducing Recurrent Urinary Tract Infections in Women with MV140 Impacts Personal Burden of Disease: Secondary Analyses of a Randomized Placebo-controlled Efficacy Study.

Background: Recurrent urinary tract infection (rUTI) remains a major health burden for women. A randomized, double-blind, placebo-controlled trial (RCT; NCT02543827) reported that female patients with rUTI receiving a sublingual vaccine, MV140, had a reduction in rUTI and increase in UTI-free rate compared with placebo. Objective: To determine the impact of MV140 on the personal burden of disease in women with rUTI using secondary endpoint data from the pivotal RCT evaluating MV140. Design setting and participants: In the primary RCT, female patients with rUTI enrolled in Spain and UK (from October 2015 to April 2019) were randomized to placebo (6 mo) or MV140 (3 or 6 mo), and followed for 12 mo. Individuals analyzed in this secondary analysis included those in the placebo and 3-mo (recommended dose) groups. Intervention: A polybacterial sublingual vaccine, MV140 (four inactivated whole-cell bacteria-Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, and Enterococcus faecalis), or placebo. Outcome measurements and statistical analysis: Symptom severity scoring, antibiotic use, safety, and multiple aspects of quality of life (QoL; Short-Form Questionnaire [SF-36]) were assessed. Results and limitations: Compared with the placebo group (n = 76), the 3-mo vaccinated group (n = 74) experienced fewer overall UTI symptoms (mean symptom score 102.2 ± 222.9 vs 194.2 ± 178.8; p = 0.0002), fewer days on antibiotics (12.4 ± 17.7 vs 28.7 ± 25.2; p = 0.0001), and improved total, general, and physical SF-36 QoL improvement (differences in means for total SF-36 score 15.7; 95% confidence interval [CI] 8.80, 22.64; p < 0.0001), with only social function QoL showing no impact (4.07; 95% CI -4.93, 13.08; p = 0.3744). Conclusions: Three months of MV140 is associated with a reduction of the personal burden of UTI by reducing overall UTI symptoms and antibiotic use, improving QoL in women with rUTI. Patient summary: Three months of MV140 vaccine, which has previously been shown to reduce the risk of urinary tract infection safely, is associated with a reduction in the personal burden of disease.

Understanding the sleep-pain relationship in patients with interstitial cystitis/bladder pain syndrome.

INTRODUCTION: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pelvic pain condition with critical symptoms of urinary urgency and frequency, persistent bladder-related pain, and reduced quality of life. Poor-quality sleep can lead to significant disturbances in daily life and increased pain in IC/BPS patients. Resilience, depressive symptoms, and pain catastrophizing have univariate associations with sleep and pain in IC/BPS, suggesting they may be mechanisms in this sleep and pain relationship. METHODS: This online study recruited patients self-reporting a diagnosis of IC/BPS through support groups, social media posts (Facebook, Reddit, and Instagram), and urology clinic advertisements. Participants completed questionnaires on demographics, urologic symptoms, pain, pain catastrophizing, depressive symptoms, and resilience. Only those participants who met the RAND Interstitial Cystitis Epidemiology (RICE) criteria for IC/BPS diagnosis were included. A multiple mediation model was first examined, followed by a serial mediation model. RESULTS: Seventy-four participants (Mage= 47.0, standard deviation [SD ] 16.7, range 18-83 years) met inclusion criteria. A multiple mediation model showed greater sleep disturbance was associated with greater pain severity through depressive symptoms and pain catastrophizing, but not resilience (b=0.79, bootSE =0.26, bootCI [0.33, 1.35]). A serial mediation showed that the sleep-to-pain relationship had a significant indirect effect through pain catastrophizing and depressive symptoms (b=0.78, bootSE =0.26, bootCI [0.35, 1.32]). CONCLUSIONS: Findings suggest depressive symptoms and pain catastrophizing may be important psychosocial mechanisms in the sleep-to-pain relationship. These results help guide future sleep and pain research in IC/BPS and aid in developing and refining treatments.

MV140 sublingual vaccine reduces recurrent urinary tract infection in women Results from the first North American clinical experience study.

INTRODUCTION: This is the first North American clinical evidence for MV140, a novel bacterial sublingual vaccine, developed for prevention of recurrent urinary tract infection (UTI) in women. METHODS: Female subjects with ≥3 documented UTIs/year underwent three-month vaccination treatment, nine-month efficacy period, and optional three-month followup (total 15 months). Primary outcome was no clinically diagnosed UTI following vaccination (UTI-free rate). Secondary outcomes included absolute, mean, and median overall reduction in UTI compared to pre-vaccination, quality of life, global response assessment, patient satisfaction, microbiology, and safety. RESULTS: Sixty-seven subjects (mean age 56 years, range 18-80) were enrolled; 64 completed the vaccination period and at least one post-vaccination assessment. Prior to vaccination, subjects reported a mean 6.8 UTIs/year. The UTI-free rate for the nine-month efficacy period was 40.6%. Compared to the infection rate in the year prior to vaccination, the reduction was 75.3% for the nine-month efficacy period post-vaccination. At 12-month followup, 80.3% reported that they were moderately/markedly improved; 58.1% were mostly satisfied, pleased, or delighted, while mean quality of life score improved by 1.5 points. Fourteen of the adverse events in nine subjects were potentially related to the vaccine - all mild and resolved by three months. None of the 13 serious adverse events were related to vaccine. CONCLUSIONS: This first-in-North-America, prospective case series with the sublingual vaccine, MV140, adds further clinical evidence to its safety and effectiveness in reducing recurrent UTIs in women.

A phase 1 study of an injectable lidocaine paste for spermatic cord block in men with chronic scrotal content pain.

INTRODUCTION: Patients with chronic scrotal content pain (CSCP) lack effective, non-invasive treatment options. We aimed to determine the local and systemic safety, tolerability, pharmacokinetics (PK), and efficacy of a long-lasting local anesthetic in patients with CSCP. METHODS: This was a prospective, single-center, open-label, single-arm, phase 1, dose-escalating trial completed between October 2019 and March 2021. Twelve patients ≥19 years old with unilateral scrotal pain lasting ≥3 months reporting an average maximum pain score over seven days of ≥4 on a 0-10 numerical rating scale (NRS) were included. Patients underwent a test spermatic cord block and those reporting a decrease of ≥2 points were included. The investigational drug, ST-01 (sustained-release lidocaine polymer solution), is a long-acting injection of lidocaine around the spermatic cord. Subjects were provided a NRS dairy and recorded their NRS score until day 28. The Chronic Epididymitis Symptom Index (CESI) was completed on days 0, 7, 14, and 28. All patients underwent an examination and assessment for adverse events (AE) on days 0, 1, 7, 14, and 28. Exploratory statistical hypothesis testing was planned for this study due to its investigative nature. RESULTS: There were no serious adverse events (SAEs) reported. All subjects reported at least one treatment-emergent adverse event (TEAE); 83% of related AEs were injection-site reactions consisting of swelling and bruising. NRS was reduced across all cohorts between baseline and end of study. CONCLUSIONS: This study provides evidence that the novel ST-01 treatment is safe and well-tolerated.

An Effective Sublingual Vaccine, MV140, Safely Reduces Risk of Recurrent Urinary Tract Infection in Women.

Uncomplicated recurrent urinary tract infections (rUTIs) in women are associated with episodic bothersome symptoms and have a significant impact on the mental and physical quality of life. Treatment with antibiotics (short- and long-term dosing) results in acute and chronic side effects and costs and promotes general antibiotic resistance. Improved nonantibiotic management of rUTI in women represents a true, unmet medical need. MV140 is a novel sublingual mucosal-based bacterial vaccine developed for the prevention of rUTI in women. Based on observational, prospective, and randomized placebo-controlled studies, MV140 has been shown to safely prevent (or reduce the risk of) UTIs, reduce antibiotic use, overall management costs, and patient burden while improving the overall quality of life in women suffering from rUTIs.

Molecular Diagnostic Methods Versus Conventional Urine Culture for Diagnosis and Treatment of Urinary Tract Infection: A Systematic Review and Meta-analysis.

Context: Urine culture has low sensitivity in the diagnosis of urinary tract infection (UTI). Next-generation sequencing (NGS) and polymerase chain reaction (PCR) are culture-independent molecular methods available for commercial use to diagnose UTI. Objective: To systematically evaluate the evidence comparing the diagnostic and therapeutic values of molecular diagnostic methods to urine culture in the management of UTI in adults. Evidence acquisition: We performed a critical review of Embase, Ovid, and PubMed in February 2022 according to the Preferred Reporting Items for Systematic Review and Meta-analyses statement. Studies involving pregnant women, ureteral stones, ureteral stents, and percutaneous nephrostomy tubes were excluded. Risk of bias and methodological quality were assessed using the Cochrane risk of bias tool and Newcastle Ottawa Scale. Fifteen publications were selected for inclusion. Evidence synthesis: Included reports compared NGS (nine studies) and PCR (six studies) to urine culture. A meta-analysis of seven similar studies utilizing NGS demonstrates that NGS is more sensitive in the identification of urinary bacteria and detects greater species diversity per urine sample than culture. PCR protocols designed to detect a diverse range of microbes had increased sensitivity and species diversity compared with culture. Phenotypic and genotypic resistomes are concordant in approximately 85% of cases. There is insufficient evidence to compare patient symptomatic responses to antibiotic therapy guided by molecular testing versus standard susceptibility testing. Conclusions: Moderately strong evidence exists that molecular diagnostics demonstrate increased sensitivity in detecting urinary bacteria at the expense of poor specificity in controls. Additional data comparing patient symptoms and cure rates following antibiotic selection directed by molecular methods compared with culture are needed to elucidate their place in UTI care. Patient summary: We compare culture-independent molecular methods with urine culture in the management of urinary tract infection. We found good evidence that molecular methods detect more bacteria than culture; however, the clinical implications to support their routine use are unclear.

Oral pharmacological treatments for chronic prostatitis/chronic pelvic pain syndrome: A systematic review and network meta-analysis of randomised controlled trials.

Background: Pharmacological treatments for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are empirically used. However, the quantitative comparative effectiveness and safety of multiple pharmacological treatments is lacking. Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched from inception to March 22, 2022. Randomised controlled trials comparing two or more oral pharmacological treatments for patients with CP/CPPS were included. Title, abstract, and full-text screening were independently screened by four reviewers. Primary outcomes were efficacy (the National Institutes of Health Chronic Prostatitis Symptom Index [NIH-CPSI] total score, pain score, urinary score, and quality of life score [QoL]) and safety (adverse events). This study was registered with PROSPERO, CRD42020184106. Findings: 25 studies (3514 patients) assessed 26 treatments. Low to very low quality evidence indicated that doxazosin (Mean difference [MD], -11.4, 95% Credible interval [CrI], -17.5 to -5.1) and the doxazosin, ibuprofen, and thiocolchicoside combination (MD, -11.6, CrI, -18.1 to -5.3) were significantly more effective than placebo in the NIH-CPSI total score. Other NIH-CPSI relative outcomes (pain, urinary, and QoL scores) showed a similar pattern. Low and very low quality evidence suggested that combination treatment including doxazosin, ibuprofen, and thiocolchicoside (odds ratios [OR], 3.2, CrI, 0.5 to 19.3) and the tamsulosin and dapoxetine combination (OR, 6.0, CrI, 0.7 to 67.3) caused more adverse events. In half of all comparisons regarding NIH-CPSI pain scores and quality of life scores, heterogeneity was minimal or low. Heterogeneity was high in both NIH-CPSI total symptom scores (I2  = 78.0%) and pain scores (I2  = 87. 0%) for tamsulosin versus placebo. There was also high heterogeneity in NIH-CPSI urine scores for the combination of tamsulosin and ciprofloxacin versus tamsulosin (I2  = 66.8%), tamsulosin and levofloxacin versus tamsulosin (I2  = 93.3%), and tamsulosin versus placebo (I2  = 83%). Interpretation: Pharmacological treatments have little evidence supporting efficacy in CP/CPPS. Future studies could personalise therapy for individuals according to specific symptoms and identify non-pharmacological targets for CP/CPPS. Funding: Dr Jiani Wu received funding for this project from the China Association for Science and Technology (2017QNRC001), the China Academy of Chinese Medical Sciences (ZZ13-YQ-027), and the National Natural Science Foundation of China (82105037).

Chronic Pain-Related Jaw Muscle Motor Load and Sensory Processing.

Chronic pain associated with temporomandibular disorders (TMDs) may reflect muscle mechanoreceptor afferent barrage and dysregulated sensory processing. This observational study tested for associations between Characteristic Pain Intensity (CPI), physical symptoms (Patient Health Questionnaire-15 [PHQ-15]), and cumulative jaw muscle motor load (mV*s). In accordance with institutional review board oversight and Strengthening the Reporting of Observational Studies in Epidemiology guidelines, adult subjects gave informed consent and were identified via Diagnostic Criteria for TMD (DC-TMD) examination and research protocols. Subjects were assigned to ±Pain groups using DC-TMD criteria for myalgia. CPI scores characterized pain intensity. PHQ-15 scores were surrogate measures of dysregulated sensory processing. Laboratory tests were performed to quantify masseter and temporalis muscle activities (mV) per bite force (N) for each subject. In their natural environments, subjects recorded day- and nighttime electromyography from which cumulative jaw muscle motor loads (mV*s) were determined for activities consistent with bite forces of >1 to ≤2 and >2 to ≤5 N. Data were assessed using univariate analysis of variance, simple effects tests, K-means cluster classification, and 3-dimensional regression analyses. Of 242 individuals screened, 144 enrolled, and 125 with complete data from study protocols, there were 35 females and 15 males for +Pain and 35 females and 40 males for -Pain. Subjects produced 324 daytime and 341 nighttime recordings of average duration 6.9 ± 1.7 and 7.6 ± 1.7 h, respectively. Overall, +Pain compared to -Pain subjects had significantly higher (all P ≤ 0.002) CPI and PHQ-15 scores. Cumulative jaw muscle motor loads showed significant between-subject effects for time, diagnostic group, and sex (all P < 0.003), where motor loads tended to be higher for daytime versus nighttime, +Pain versus -Pain groups, and males versus females. Two clusters were identified, and regression relations showed associations of low-magnitude daytime masseter motor load, PHQ-15, and CPI scores for cluster 1 (n = 105, R2 = 0.44) and cluster 2 (n = 18, R2 = 0.80). Furthermore, these regression relations showed thresholds of motor load and PHQ-15 scores, above which there were nonlinear increases in reported pain.

The healthy urinary microbiome in asymptomatic participants in the MAPP Network Study: Relation to gender, age, and menopausal status.

INTRODUCTION: To understand the role of the urinary microbiome in disease states and interpret non-culture-based diagnostic urine testing of midstream urine specimens, we must have a better understanding of the urinary microbiome in asymptomatic, healthy individuals. We examined the impact of gender, age, and menopausal status on the healthy human urinary microbiome in asymptomatic control subjects enrolled in the multi-institution National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Multidisciplinary Approach to the Study of Chronic Pelvic Pain Network (MAPP) study. METHODS: Asymptomatic, healthy controls, recruited to be ageand sex-matched to patients in the Trans-MAPP Epidemiology and Phenotyping Study, provided midstream urine collection for polymerase chain reaction (PCR)-electrospray ionization mass spectrometry identification of urinary microbiota. The microbiomes of male and female participants were described and analyzed for differences in composition and diversity at the species and genus level by sex, age, and, in females, by menopausal status. RESULTS: Sixty-six total species were detected with a mean of 1.2 species (standard deviation [SD] 1.1) per male (n=97; mean age=43) and 2.3 (SD 1.3) per female (n=110, mean age=38) in asymptomatic, healthy controls. Species and genera diversity analyses showed significantly greater richness and diversity in females. With regard to species, Bifidobacterium subtile, Lactobacillus crispatus, and Lactobacillus johnsonii were more predominant in females. The genera Bifidobacterium, Staphylococcus, Lactobacillus, and Corynebacterium were more predominant in females, while for males the most prevalent organisms included Staphylococcus and Propionibacterium; only Propionibacterium approached a significant difference between genders. No significant difference in the presence and/or diversity of micro-organisms with menopausal status could be observed. Sex-specific age trends, particularly diversity, were larger for females than males. CONCLUSIONS: These results suggest the urinary microbiome of healthy, asymptomatic subjects differed between genders and age in females, but not menopausal status. Gender differences may be attributable to the detection of urethral/vaginal organisms in females and prostate organisms in males. These findings will better allow us to interpret the results of microbiome reports in the midstream urine specimens of patients with urinary symptoms.

Chronic prostatitis/chronic pelvic pain syndrome-related pain symptoms and their impact on sexual functioning.

INTRODUCTION: The present study sought to examine a new model to evaluate the mechanistic pathways between pain and sexual dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), incorporating cognitive and emotional factors. METHODS: Men with a self-reported diagnosis of CP/CPPS (n=94, 24-69 years, Mage=44.22, standard deviation 11.25) were recruited through social media, support groups, and urology clinics and completed an online questionnaire of demographic, pain, cognitive, psychological, and sexual variables. Descriptive statistics, correlation analysis, and serial mediation analyses assessed variable associations. RESULTS: Almost half of participants reported mild to severe erectile dysfunction (47.4%). Sexual dysfunction was associated with greater pain symptom severity and pain catastrophizing, as well as depressive symptoms (p<0.01 for all). While pain did not independently predict levels of sexual dysfunction, the addition of pain catastrophizing and depressive symptoms into the pathway explained the association between increased pain symptoms and decreased sexual functioning (p<0.01). CONCLUSIONS: Beyond generally poor sexual functioning in the current sample, it appears as if cognitive and emotional factors play a role in the association between pain symptoms and sexual functioning in these men with CP/CPPS. The findings of how pain catastrophizing and depression impact the association of pain severity and decreased sexual functioning is important for improving patient care.

Overview of seminal fluid biomarkers for the evaluation of chronic prostatitis: a scoping review.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a very common and difficult condition to evaluate, as it is a clinical diagnosis, without a measurable diagnostic "gold standard". The aim of this scoping review is to synthesize all the available data for seminal fluid biomarkers used to assess patients with CP/CPPS. METHODS: A systematic search to identify all relevant publications was conducted on October 22, 2020 across five databases: Ovid Medline, Ovid EMBASE, PubMed, CCRT, and the CINAHL. Two independent authors screened all articles and extracted relevant data. RESULTS: A total of 27 articles met the eligibility criteria. A majority of studies were case-control (15), with 6 observational cohorts and 6 comparative interventional studies. The total number of pooled patients included 585 patients with CP/CPPS (unspecified subtype), 371 patients with inflammatory CP/CPPS, 387 patients with non-inflammatory CP/CPPS, 354 patients with chronic bacterial prostatitis, and 432 healthy controls. Inflammatory seminal biomarkers were the most frequently studied, with IL6, IL8, TNFα and IL1ß being the most promising candidates. CONCLUSIONS: There are a number of very promising seminal biomarkers to help categorize and monitor therapies in CP/CPPS. Large multicentre studies using a shared protocol for measuring seminal biomarkers with the primary intention of biomarker validation are needed prior to clinical implementation. Identification of biomarker(s) will facilitate the etiological categorization of patients with chronic prostatitis and provide an objective framework to tailor specific therapies according to the biomarker family.

The bacterial microbiota of Hunner lesion interstitial cystitis/bladder pain syndrome.

OBJECTIVE: To undertake the first comprehensive evaluation of the urinary microbiota associated with Hunner lesion (HL) interstitial cystitis/bladder pain syndrome (IC/BPS). Despite no previous identification of a distinct IC/BPS microbial urotype, HL IC/BPS, an inflammatory subtype of IC/BPS, was hypothesized most likely to be associated with a specific bacterial species or microbial pattern. PARTICIPANTS AND METHODS: The bacterial microbiota of midstream urine specimens from HL IC/BPS and age- and gender-matched IC/BPS patients without HL (non-HL IC/BPS) were examined using the pan-bacterial domain clinical-level molecular diagnostic Pacific Biosciences full-length 16S gene sequencing protocol, informatics pipeline and database. We characterized the differential presence, abundances, and diversity of species, as well as gender-specific differences between and among HL and non-HL IC/BPS patients. RESULTS: A total of 59 patients with IC/BPS were enrolled (29 HL, 30 non-HL; 43 women, 16 men) from a single centre and the microbiota in midstream urine specimens was available for comparison. The species abundance differentiation between the HL and non-HL groups (12 species) was not significantly different after Bonferroni adjustments for multiple comparisons. Similarly, the nine differentiating species noted between female HL and non-HL patients were not significantly different after similar statistical correction. However, four species abundances (out of the 10 species differences identified prior to correction) remained significantly different between male HL and non-HL subjects: Negativicoccus succinivorans, Porphyromonas somerae, Mobiluncus curtisii and Corynebacterium renale. Shannon diversity metrics showed significantly higher diversity among HL male patients than HL female patients (P = 0.045), but no significant diversity differences between HL and non-HL patients overall. CONCLUSIONS: We were not able to identify a unique pathogenic urinary microbiota that differentiates all HL from all non-HL IC/BPS. It is likely that the male-specific differences resulted from colonization/contamination remote from the bladder. We were not able to show that bacteria play an important role in patients with HL IC/BPS.

Fosfomycin Trometamol for the Prevention of Infectious Complications After Prostate Biopsy: A Consensus Statement by an International Multidisciplinary Group.

CONTEXT: Transrectal ultrasound-guided prostate biopsy (TRPB) has been a standard of care for diagnosing prostate cancer but is associated with a high incidence of infectious complications. OBJECTIVE: To achieve an expert consensus on whether fosfomycin trometamol provides adequate prophylaxis in TRPB and discuss its role as prophylaxis in transperineal prostate biopsy (TPPB). EVIDENCE ACQUISITION: An international multidisciplinary group of experts convened remotely to discuss how to best use fosfomycin in various clinical settings and patient situations. Six statements related to prostate biopsy and the role of fosfomycin were developed, based on literature searches and relevant clinical experience. EVIDENCE SYNTHESIS: Consensus was reached for all six statements. The group of experts was unanimous regarding fosfomycin as a preferred candidate for antimicrobial prophylaxis in TRPB. Fosfomycin potentially also meets the requirements for empiric prophylaxis in TPPB, although further clinical studies are needed to confirm or refute its utility in this setting. There is a risk of bias due to sponsorship by a pharmaceutical company. CONCLUSIONS: Antimicrobial prophylaxis is mandatory in TRPB, and fosfomycin trometamol is an appropriate candidate due to low rates of resistance, a good safety profile, sufficient prostate concentrations, and demonstrated efficacy in reducing the risk of infectious complications following TRPB. PATIENT SUMMARY: Patients undergoing transrectal ultrasound-guided prostate biopsy (TRPB) have a high risk of infectious complications, and antimicrobial prophylaxis is mandatory. However, increasing antimicrobial resistance, as well as safety concerns with fluoroquinolones, has restricted the number of antimicrobial options. Fosfomycin trometamol meets the requirements for a preferred antimicrobial in the prophylaxis of TRPB.