Non-Antibiotic Prophylaxis for Recurrent UTIs in Neurogenic Lower Urinary Tract Dysfunction (NAPRUN): Study Protocol for a Prospective, Longitudinal Multi-Arm Observational Study.

INTRODUCTION: Patients with neurogenic lower urinary tract dysfunction (NLUTD) reliant on intermittent self-catheterization for bladder emptying are at an increased risk of recurrent urinary tract infections (rUTI). So far, the most common practice in the prevention of rUTIs is long-term low-dose antibiotic prophylaxis, phytotherapy, and immunomodulation, whereby antibiotic prophylaxis inevitably leads to the emergence of drug-resistant pathogens and difficulty in treating infections. Therefore, non-antibiotic alternatives in the prevention of rUTIs are urgently required. We aim to identify the comparative clinical effectiveness of a non-antibiotic prophylaxis regimen in the prevention of recurrent urinary tract infections in patients with neurogenic bladder dysfunction who practice intermittent self-catheterization. METHODS AND ANALYSIS: In this multi-centre, prospective longitudinal multi-arm observational study, a total of 785 patients practising intermittent self-catheterisation due to NLUTD will be included. After inclusion, non-antibiotic prophylaxis regimens will be instilled with either UroVaxom® (OM-89) standard regimen, StroVac® (bacterial lysate vaccine) standard regimen, Angocin®, D-mannose (oral dose 2 g), bladder irrigation with saline (once per day). The management protocols will be pre-defined, but the selection of the protocol will be at the clinicians' discretion. Patients will be followed for 12 months from the onset of the prophylaxis protocol. The primary outcome is to identify the incidence of breakthrough infections. The secondary outcomes are adverse events associated with the prophylaxis regimens and the severity of breakthrough infections. Other outcomes include the exploration of change in susceptibility pattern via the optional rectal and perineal swab, as well as health-related quality of life over time (HRQoL), which will be measured in a random subgroup of 30 patients. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the ethical review board of the University Medical Centre Rostock (A 2021-0238 from 28 October 2021). The results will be published in a peer-reviewed journal and presented at relevant meetings. STUDY REGISTRATION NUMBER: German Clinical Trials Register: Number DRKS00029142.

Nonantibiotic Strategies for the Prevention of Infectious Complications following Prostate Biopsy: A Systematic Review and Meta-Analysis.

PURPOSE: We identify which nonantibiotic strategies could reduce the risk of infectious complications following prostate biopsy. MATERIALS AND METHODS: We performed a literature search on MEDLINE®, Embase® and the Cochrane Database for randomized controlled trials (inception to May 2020) assessing nonantibiotic interventions in prostate biopsy. Primary outcome was pooled infectious complications (fever, sepsis and symptomatic urinary tract infection) and secondary outcome was hospitalization. Cochrane risk of bias tool and GRADE approach were used to assess the bias and the certainty of evidence. The study protocol was registered with PROSPERO (CRD42015026354). RESULTS: A total of 90 randomized controlled trials (16,941 participants) were included in the analysis, with 83 trials being categorized into one of 10 different interventions. Transperineal biopsy was associated with significantly reduced infectious complications as compared to transrectal biopsy (RR 0.55, 95% CI 0.33-0.92, p=0.02, I2=0%, 1,330 participants, 7 studies). Rectal preparation with povidone-iodine was also shown to reduce infectious complications (RR 0.50, 95% CI 0.38-0.65, p <0.000001, I2=27%, 1,686 participants, 8 studies) as well as hospitalization (RR 0.38, 95% CI 0.21-0.69, p=0.002, I2=0%, 620 participants, 4 studies). We found no difference in infectious complications/hospitalization for 6 other interventions, ie number of biopsy cores, periprostatic nerve block, number of injections for periprostatic nerve block, needle guide type, needle type and rectal preparation with enema. In 2 interventions (needle diameter, rectal preparation with chlorhexidine) meta-analysis was not possible. Finally, 7 studies had unique interventions. The certainty of evidence was rated as low/very low for all interventions. CONCLUSIONS: Transperineal biopsy significantly reduces infectious complications compared to transrectal biopsy and should therefore be preferred. If transrectal biopsy is performed, rectal preparation with povidone-iodine is highly recommended. The other investigated nonantibiotic strategies did not significantly influence infection and hospitalization after prostate biopsy.

Antibiotic resistance, hospitalizations, and mortality related to prostate biopsy: first report from the Norwegian Patient Registry.

BACKGROUND: A 68-year-old man died of cerebral arterial embolism 6 days after transrectal prostate biopsy with a single p.o. dose of trimethoprim sulfamethoxazole (TMP-SMX) as prophylaxis. The case precipitated analysis of local antibiotic resistance and complication rates. MATERIALS AND METHODS: Data on E. coli resistance from Oslo University Hospital and national data on hospitalizations and mortality after biopsy were retrieved from local microbiology files and the Norwegian Patient Registry (NPR) 2011-2017. RESULTS: Urine E. coli resistance against TMP-SMX increased from 35% in 2013 to more than 60% in 2015. For ciprofloxacin, the resistance increased from 15% in 2013 to about 45% in 2016. The highest annual E. coli resistance in blood cultures for TMP-SMX and ciprofloxacin was 37% and 28%, respectively. 10% of patients were hospitalized with a diagnosis of infection within the first 60 days after biopsy and there was a relative increase in mortality rate of 261% within the first 30 days. Due to the severity of the figures, the story and the NPR data were published in Norway's leading newspaper and were succeeded by a series of chronicles and commentaries. CONCLUSIONS: Several critical points of the biopsy procedure were not performed according to current standards. We believe that the patient might have died of septic embolism after biopsy. As a result of the findings and the debate, local practice was changed from transrectal to transperineal prostate biopsies.

Transurethral Resection of the Prostate: are We Following the Guidelines? - Outcomes from the Global Prevalence of Infections in Urology (GPIU) Study.

Transurethral resection of the prostate (TURP) is one of the most common urological procedures. With the increasing rate of multiresistant infections including urosepsis, it is essential for all surgeons to adhere to the relevant international guidelines to prevent infectious complications. The aim of this prospective, multinational, multicentre study was to evaluate compliance with recommended infection control measures regarding TURP procedures. The study was performed as a side questionnaire to the annual Global Prevalence Study of Infections in Urology (GPIU) between 2006 and 2009. Patients that had undergone TURP were eligible. Baseline data about hospitals and patients were collected. The questionnaire contained questions regarding preoperative microbiological investigations, catheter care and performance of perioperative antibiotic prophylaxis. A total of 825 men were included from 138 participating centres from Africa, Asia, Europe and South America. Only 50.1% of the patients received perioperative antibiotic prophylaxis with a median duration of 3 days (interquartile range [IQR] = 1-7 days). Preoperative urine culture was taken in 59.2%. The catheter was replaced in 1 week prior to the surgery only in 38.3% of cases. Compliance with the recommended infection control measures regarding TURP were only moderate, despite high grade recommendations in relevant international Guidelines. Stronger guideline adherence is necessary to improve patient care decrease antibiotic consumption in line with antibiotic stewardship in surgical practices.

Update on Strategies to Reduce Infectious Complications After Prostate Biopsy.

CONTEXT: Prostate biopsy is one of the most performed procedures in urology. As a diagnostic procedure it should be of low risk. However, morbidity following prostate biopsy is common due to infectious complications. OBJECTIVE: To describe how to reduce infectious complications following prostate biopsy. We report on antibiotic and technical interventions to reduce infectious complications. EVIDENCE ACQUISITION: The data presented are based on a narrative review. Search in PubMed and Medline was performed until May 2018 with a focus on randomised controlled trials and meta-analyses. Articles were reviewed for data on symptomatic infections, hospitalisation, and adverse events. EVIDENCE SYNTHESIS: Antibiotic prophylaxis is the standard of care. However, the duration of antibiotic preemptive treatment is still under debate. The use of augmented antibiotic prophylaxis as well as targeted antibiotic prophylaxis might be of potential value, but evidence is currently limited. Moreover, no antibiotic class was shown to be clearly superior to another. The evaluation of the technical aspects during prostate biopsy reveals that rectal preparation with povidone-iodine is clearly effective to reduce infectious complications. Transperineal biopsy has a potential benefit to reduce infectious complications, but powerful randomised controlled studies are missing. Finally, the number of biopsy cores, the application of periprostatic nerve block, or the use of a cleansing enema has no impact on prostate biopsy in terms of infectious complications. CONCLUSIONS: The available data only suggest that rectal preparation with povidone-iodine as well as antibiotic prophylaxis is of significant advantage to reduce infectious complications following prostate biopsy. The augmented and targeted antibiotic prophylaxis shows some potential, but need further validation. PATIENT SUMMARY: In this review we evaluate the best management strategy to prevent infectious complications following prostate biopsy. We show that antibiotic prophylaxis is essential for prostate biopsy and that rectal preparation with povidone-iodine is mandatory.

The role of nutraceuticals and phytotherapy in the management of urinary tract infections: What we need to know?

Urinary Tract Infections (UTIs) are amongst the most common infectious diseases and carry a significant impact on patient quality of life and health care costs. Despite that, there is no well-established recommendation for a "standard" prophylactic antibiotic management to prevent UTI recurrences. The majority of patients undergoes long-term antibiotic treatment that severely impairs the normal microbiota and increases the risk of development of multidrugresistant microorganisms. In this scenario, the use of phytotherapy to both alleviate symptoms related to UTI and decrease the rate of symptomatic recurrences is an attractive alternative. Several recently published papers report conflicting findings and cannot give confident recommendations for the everyday clinical practice. A new approach to the management of patients with recurrent UTI might be to use nutraceuticals or phytotherapy after an accurate assessment of the patient`s risk factors. No single compound or mixture has been identified so far as the best preventive approach in patients with recurrent UTI. We reviewed our non-antibiotic approach to the management of recurrent UTI patients in order to clarify the evidence-base for the commonly used substances, understand their pharmacokinetics and pharmacodynamics in order to tailor the best way to improve patient's quality of life and reduce the rate of antibiotic resistance. Lack of a gold-standard recommendation and the risk of increasing antibiotic resistance is the reason why we need alternatives to antibiotics in the management of urinary tract infections (UTIs). A tailored approach according to bacterial characteristics and the patient risk factors profile is a promising option.