Prophylaxis Of Urinary Tract Infections Research Articles

Safety and Efficacy of D-mannose as Prophylaxis of Urinary Tract Infection: A Systematic Review and Meta-Analysis

Safety and Efficacy of D-mannose as Prophylaxis of Urinary Tract Infection: A Systematic Review and Meta-Analysis

Fosfomycin-induced liver injury: A case report and literature review

Background: Fosfomycin is an antibiotic often used to treat urinary tract infections (UTIs) with only rare transient hepatotoxicity. We present a case of fosfomycin-induced liver injury and describe the histopathologic findings on biopsy. Methods: A 64-year-old female patient with no prior liver disease or risk factors was started on fosfomycin as prophylaxis for recurrent UTIs. Within a week of her first dose, she presented with fatigue, jaundice, and mixed liver enzyme elevation. Clinical workup for acute liver injury was unremarkable, and biopsy showed panacinar and portal necroinflammation with predominantly lymphocytic infiltrate and cholestasis, with no evidence of cirrhosis. This was thought to be likely related to fosfomycin exposure. Although liver enzymes trended down, bilirubin initially remained elevated. However, within 3 months the patient achieved clinical and biochemical recovery. Results: Only two other reports of fosfomycin-induced liver injury requiring biopsy were found. Both developed acute cholestatic hepatitis within days of exposure, and subsequent biopsy similarly showed lymphocytic necroinflammation. Although one patient initially developed acute liver failure, both recovered fully within a few months. Conclusion: Overall, these cases suggest potentially an idiosyncratic or immune-mediated liver toxicity of Fosfomycin, which is typically self-limited but may take months to fully resolve. Liver biopsy may be useful in confirming the diagnosis.

Nonantibiotic prophylaxis for urinary tract infections: a network meta-analysis of randomized controlled trials.

Recent guidelines indicated that, in addition to antibiotics, nonantibiotic interventions serve as available preventive options for urinary tract infections (UTIs). This study aimed to compare the efficacy and safety of various nonantibiotic interventions in preventing UTIs. The authors systematically searched databases for eligible studies. The inclusion criteria encompassed randomized controlled trials (RCTs) focusing on one or more nonantibiotic interventions for UTI prevention, with the incidence of UTIs being a key outcome measure. Subgroup analyses were performed according to age, sex, and follow-up. 50 RCTs comprising 10,495 subjects and investigating 14 interventions, were included. Nearly 80% of the RCTs utilized double-blind or triple-blind designs. In the whole group, D-mannose (risk ratio [RR] 0.34, 0.21 to 0.56), vaccine (RR 0.65, 0.52 to 0.82), probiotics (RR 0.69, 0.50 to 0.94), cranberry (RR 0.72, 0.60 to 0.87), and triple therapy (cranberry plus probiotics plus vitamin A) (RR 0.27, 0.09 to 0.87), exhibited a significant reduction in UTI incidence compared to the placebo. Probiotics (RR 0.50, 0.28 to 0.89) were the most effective in the nonadult group, while vitamin D (RR 0.46, 0.27 to 0.81) showed the highest efficacy in the long follow-up group (≥ 1 year). There was no significant difference in the incidence of adverse events between the interventions and the placebo group. D-mannose, triple therapy, vaccine, probiotics, and cranberry serve as potential nonantibiotic intervention options for clinical UTI prevention.

Anti-Microbial Effects of Vaccinium Macrocarpon (Cranberry) Extract on Serotypes 26 and 45 of Escherichia Coli as a Prophylaxis of Recurrent Urinary Tract Infection (UTI)

Background: Urinary tract infection (UTI) is the second most common type of bacterial infection globally, affecting people of different age groups. Cranberry is renowned for its antibacterial properties and has been used to treat UTIs in recent years. Objective: This study aimed to assess the antimicrobial effects of cranberry extract on the prophylaxis of recurrent UTI caused by different serotypes of Escherichia coli (E. coli). Methods: This quasi-experimental study recruited 60 recurrent UTI patients from the Urology department of King Edward Medical University, Lahore, Pakistan. Patients with a history of recurrent UTIs caused by E. coli were included. Urine microscopy and culture tests were performed, and only E. coli-positive cases were serotyped. Patients received Vaccinium macrocarpon (cranberry) extract at a dose of 500 mg/day for four weeks along with their standard treatment. Follow-up evaluations were conducted after one and three months to assess UTI symptoms and the presence of E. coli in urine samples. Statistical analysis was performed using SPSS version 25, with quantitative variables expressed as mean ± standard deviation and qualitative variables as frequencies and percentages. Results: Of the 60 patients, 15 (25%) were positive for E. coli. Serotyping revealed 8 patients (53%) with serotype 26 and 7 patients (47%) with serotype 45. After three months of treatment, cranberry extract eradicated E. coli in 12 patients (80%); specifically, it eradicated 100% of serotype 45 and 62% of serotype 26 cases. Conclusion: Cranberry extract (500 mg/day) for three months demonstrated significant antimicrobial effects on E. coli serotypes 26 and 45, with greater efficacy observed in serotype 45. These findings suggest cranberry extract as a potential prophylactic treatment for recurrent UTIs. Keywords: Cranberry extract, recurrent UTI, E. coli serotypes, antimicrobial effects, prophylactic treatment, Vaccinium macrocarpon, urinary tract infection, Escherichia coli

Patient-reported signs and symptoms of urinary tract infections after video-urodynamic studies in individuals with neurogenic lower urinary tract dysfunction-A single-center observational study.

Video-urodynamic studies (VUDS) are the recommended standard of diagnostic care to objectively assess neurogenic lower urinary tract dysfunction (NLUTD) in individuals with spinal cord injury/disease (SCI/D). This examination requires the insertion of a catheter into the bladder, which increases the risk of a urinary tract infection (UTI). Data on symptomatic UTIs after VUDS are limited. A single-center, observational study was conducted to evaluate the incidence of patient-reported UTI signs and symptoms 7 days after VUDS. No peri-interventional antibiotics were administered. The effect of sex, age, SCI/D duration, bladder evacuation method, bacteriuria, UTI prophylaxis, UTI history, or unfavorable VUDS results on the occurrence of patient-reported UTI signs or symptoms after VUDS was examined using binary logistic regression analysis. A total of 140 individuals with a mean age of 59.1 ± 14.0 years and a median SCI/D duration of 15.0 years (6/29 years) were evaluated. Seven days (mean 7 ± 1 days) after VUDS, 42 (30%) individuals reported at least one UTI sign or symptom. In the majority, signs and symptoms resolved without the need for antibiotic treatment, which was required in seven participants (5%). Male sex significantly (p = 0.04) increased the odds (odds ratio 3.74) of experiencing UTI signs and symptoms after VUDS. In individuals with NLUTD, 30% experienced UTI signs and symptoms 1 week after VUDS. However, these signs and symptoms were transient and only 5% required antibiotic treatment. Thus, antibiotic prophylaxis does not seem necessary in all individuals with SCI/D undergoing VUDS.

Effect of Probiotics on Urinary Tract Infections in Children: A Systematic Review and Meta-Analysis.

Urinary tract infections (UTIs) are the most prevalent bacterial infections that occur in children worldwide. This meta-analysis aims to investigate the utility of probiotics as preventive therapy in children with a UTI. The Web of Science, PubMed, and Scopus were searched for articles that investigated the relationship between probiotic consumption and the risk of UTIs. The quality of the articles was evaluated using the Jadad scale. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model. Subgroup analyses and sensitivity analyses were also conducted. The Cochran Q test and the statistic I2 were used to evaluate heterogeneity. To determine any potential publication bias, the Egger's and Begg's tests were used. In total, eleven studies were selected for the systematic review and meta-analysis. Compared to children who did not receive probiotics, the OR of developing or having a recurring urinary tract infection in those who received probiotics was 0.94 (95% CI; 0.88-0.999; p-value=0.046). The Begg's and Egger's tests showed no evidence of publication bias between probiotics and the risk of developing new or recurring urinary tract infections. Based on this systematic review and meta-analysis, probiotics could be an alternative therapy for children who are at risk of developing a UTI. They are non-pharmaceutical options and could be used as natural prophylaxis for UTIs. However, the currently published evidence does not irrefutably confirm that probiotics provide a protective effect against urinary bacterial infections. Therefore, there need to be large-scale randomized clinical trials undertaken to investigate the possible prophylaxis of probiotics.

Gram negative bacteria related urinary tract infections: spectrum of antimicrobial resistance over 9 years in a University tertiary referral Hospital.

Overuse of antibiotics has led to an increase in antimicrobial resistance (AMR) worldwide, with a negative impact on the healthcare system and the patients. In this context, our study aims to assess the current AMR patterns of urinary tract infections (UTIs) associated to Gram-negative bacteria. Thus, we provide useful information for doctors dealing with prophylactic and therapeutic empiric therapies. We retrospectively analysed more than 650,000 urine cultures collected in the Microbiology Department of a referral University Hospital of Southern England from January 2014 to December 2022. AMR spectra for 164,059 Gram-negative associated (UTIs) were analysed. The lowest percentage of resistance was found for Amikacin (2.30%), Gentamicin (5.89%) and Co-Amoxiclav (10.49%). Over a 9-year time, there was no significant change in resistance to Amikacin (2.04% in 2014 compared to 2.18% in 2022; p = 0.602) and to Fosfomycin (11.50% in 2014 versus 16.65% in 2022; p = 0.577). Overall, the trend of AMR significantly rose for Cefalexin (17.96-18.42%; p < 0.0001), Co-amoxiclav (9.46-12.69%; p < 0.0001), Nitrofurantoin (10.20-14.18%; p < 0.0001) and Piperacillin/Tazobactam (14.52-18.96%; p < 0.0001). Gram-negative resistance spectrum towards Ciprofloxacin (11.83-9.01%; p < 0.0001), Gentamicin (6.29-5.26%; p < 0.0001), Pivmecillinam (26.88-11.02%; p < 0.0001), Trimethoprim (36.72-29.23%; p < 0.0001) and Ampicillin/Amoxicillin (65.20-57.99%; p < 0.0001) significantly decreased. Despite the application of national and international guidelines for prophylaxis and treatment of UTIs, the spectrum of resistance for the most common antibiotics is still changing. Clinicians in primary and secondary care must keep that in mind when prescribing antibiotics for suspected UTI and sepsis associated with Gram-negative infections Up-to-date therapeutic strategies can help implement treatment of UTI, reducing selection of multi-resistant pathogens and providing more accurate care for patients. Future studies will be required to help clinicians and keep the guidelines updated.

Cranberry Supplements for Urinary Tract Infection Prophylaxis in Pregnant Women: A Systematic Review of Clinical Trials and Observational Studies on Efficacy, Acceptability, Outcomes Measurement Methods, and Studies' Feasibility.

Cranberry supplements are commonly used to prevent urinary tract infections (UTIs).However, their usefulness is uncertain in pregnant women.We aimed to comprehensively summarize the current knowledge on cranberry supplements' efficacy and acceptability during pregnancy in addition to the outcomes measurementmethods and studies' feasibility. To achieve it, wesearched PubMed, PMC, and Europe PMC databases plus screened citations followed bycritical appraisal of included eligible English-written primary studies that(1) focused on pregnant women supplemented with any cranberry supplements; (2) provided data on cranberry supplements' efficacy, acceptability, outcomes measurementmethods, and studies' feasibility;(3) included human subjects; and (4) published worldwide.Two randomized clinical trials (RCTs) and one nested cohort study, including 1156 pregnant women in total, contributed to our analysis.A tendency toward UTI reduction was demonstrated, although the results' validity was impacted by significantjuice-induced gastrointestinal intolerance(23%; 44 of 188 subjects).Changing the form of supplementation from cranberry juice to capsules reduced the issue,causing side effects inone of 49subjects (2%). Nevertheless, both RCTs still experienced significant recruitment andretention problems, which wereat 33% and59% onaverage, respectively.Newly acquired safety data on 919 more subjects suggests no increased risks of all malformations, vaginal bleeding, and neonatal complications. Investigating cranberry capsules' efficacy as a non-antibacterial option for UTI prevention in pregnant women has become a feasible and important direction with the current advancement in understanding cranberry supplements' actions, recommended doses plus regimens, and their safety in the population. We reviewed the challenges and discovered knowledge gaps and the implementation strategies for future studies.

P06 Stewardship potential—the hidden burden of antibiotic prophylaxis in primary care

Abstract Background This study aimed to decrease unnecessary long-term antimicrobial use in primary care by identifying and highlighting patients with long-term or repeated exposure to antibiotics to GP teams for review. The broad spectrum antimicrobial co-amoxiclav was targeted following data showing rising DDD per prescription in our Health Board. Methods Community antibiotic prescribing from the national Prescribing Information System (PIS) was searched for NHS Lothian (126 GP practices) using DDD to identify patients. Long courses of co-amoxiclav were defined as ≥63 DDD. Ninety-eight patients were identified with high antimicrobial usage and a data collection form was sent to the Primary Care Pharmacy teams to voluntarily collate data for each patient. Results The data collection form had a 97% response rate. Of the 94 patients with full data 62 (66%) patients had co-amoxiclav initiated due to secondary care specialist advice and 26 (28%) had been initiated by primary care. Forty-four patients (47%) were aged 65 or over, putting them at high risk of Clostridioides difficile. Forty-one patients had multiple courses of co-amoxiclav and 39 patients were prescribed co-amoxiclav as prophylaxis; of these 59% were for urinary tract infection (UTI). Thirty-four of 94 patients (36%) had been on prophylaxis for over 5 years with 9 patients on co-amoxiclav for over 20 years. Of note in 39 of 94 patients no microbiology samples were available and where samples were available (n=55), narrower spectrum options were available in 38 patients (69%) and 17 patients (31%) had samples showing resistance to co-amoxiclav. Following this intervention to highlight use, the number of patients on long-term courses or prophylaxis with co-amoxiclav reduced by 70% in the following year. Conclusions Patients on long-term antibiotics are priorities for antimicrobial stewardship interventions. This work demonstrated that ongoing appropriateness and efficacy of long-term antibiotic courses were not routinely reviewed. Using pharmacy data proved an effective method to highlight patients and ultimately reduce patient antibiotic exposure. UTI prophylaxis was the majority patient group in this study and interventions to review and decrease long-term UTI prophylaxis in our Board using this method are underway.

Literature Review of Ascorbic Acid, Cranberry, and D-mannose for Urinary Tract Infection Prophylaxis in Older People.

Background Urinary tract infections (UTIs) are the most prevalent infections in older patients with the potential for morbidity and mortality. Antibiotics are not generally recommended for UTI prophylaxis in this population. There is interest among the public and health providers to try over-the-counter products, such as cranberry, D-mannose, and vitamin C. The objective of this analysis was to review the literature for the efficacy and tolerability of these supplements in older individuals. Methods A literature review was conducted on PubMed using the search terms urinary tract infection or UTI, prevention/prophylaxis, cranberry, D-mannose, vitamin C/ascorbic acid. Few studies were conducted among older people; therefore, the authors included studies of all adults who had recurrent UTIs or were at increased risk of UTIs. Level (quality) of evidence were determined using the ACC/AHA Clinical Practice Guideline Recommendation Classification System. Results A total of 24 studies were included. This review captured all studies in previous reviews as well as recent publications. The authors determined that there were limited data for D-mannose and vitamin C, and randomized data for cranberry as defined by the classification system. Conclusions The three supplements reviewed appear not to be strongly supported by clinical data. For those who are interested in trying these products despite the lack of robust evidence for clinical efficacy, it may be helpful to know that the studies included in this review did not identify any clinically important signs of harm, to the extent that safety data were documented and reported.

Effect of Mannan Oligosaccharides Extracts in Uropathogenic Escherichia coli Adhesion in Human Bladder Cells.

Urinary tract infections (UTIs) are a common public health problem, mainly caused by uropathogenic Escherichia coli (UPEC). Patients with chronic UTIs are usually treated with long-acting prophylactic antibiotics, which promotes the development of antibiotic-resistant UPEC strains and may complicate their long-term management. D-mannose and extracts rich in D-mannose such as mannan oligosaccharides (MOS; D-mannose oligomers) are promising alternatives to antibiotic prophylaxis due to their ability to inhibit bacterial adhesion to urothelial cells and, therefore, infection. This highlights the therapeutic potential and commercial value of using them as health supplements. Studies on the effect of MOS in UTIs are, however, scarce. Aiming to evaluate the potential benefits of using MOS extracts in UTIs prophylaxis, their ability to inhibit the adhesion of UPEC to urothelial cells and its mechanism of action were assessed. Additionally, the expression levels of the pro-inflammatory marker interleukin 6 (IL-6) were also evaluated. After characterizing their cytotoxic profiles, the preliminary results indicated that MOS extracts have potential to be used for the handling of UTIs and demonstrated that the mechanism through which they inhibit bacterial adhesion is through the competitive inhibition of FimH adhesins through the action of mannose, validated by a bacterial growth impact assessment.

P39 A qualitative study investigating the views of nurses and doctors on the management of urinary tract infections in long-term care facilities

Abstract Background The most commonly reported infections in older persons’ long-term care facilities (LTCFs) are urinary tract infections (UTIs). UTIs contribute to high rates of antimicrobial prescribing, for the treatment and prophylaxis of UTI. Antimicrobials are often inappropriately prescribed and can increase the risk of antimicrobial resistance and other negative outcomes in LTCF populations.1 Objectives To explore the views and experiences of nurses and doctors working in LTCF on the management of UTIs. Methods Qualitative, semi-structured interviews were conducted with nurses and GPs who work in or provide medical service in LTCFs in November 2022. Interviews were conducted online or by telephone, and recordings transcribed. Thematic analysis was conducted, and the themes were mapped to the Theoretical Domains Framework (TDF)1.2 Results Seven nurses and eight GPs were interviewed. Key domains such as knowledge, memory, attention and decision making and beliefs about consequences had an influential role on UTI management as reported by participants. Contextual factors such as the time taken to obtain urine culture results, and social factors such as the key role of the LTCF nurse, were reported as key issues. Variability in practice and inconsistent knowledge of urine dipstick and UTI management guidelines were acknowledged in the management of UTIs and urine dipstick practices between participants. Conclusions This study identified social factors, contextual LTCF factors and variability in the management of UTI and urine dipstick practices across the participants. LTCFs require improved access to urine culture results, improved communication between all healthcare professionals involved and increased implementation of dipstick and UTI management guidelines.

Fosfomycin for Antibiotic Prophylaxis in Men Undergoing a Transrectal Prostate Biopsy: A Systematic Review and Meta-Analysis.

Background and Objectives: To assess the effects of fosfomycin compared with other antibiotics as a prophylaxis for urinary tract infections (UTIs) in men undergoing transrectal prostate biopsies. Materials and Methods: We searched multiple databases and trial registries without publication language or status restrictions until 4 January 2022. Parallel-group randomized controlled trials (RCTs) and non-randomized studies (NRS) were included. The primary outcomes were febrile UTI, afebrile UTI, and overall UTI. We used GRADE guidance to rate the certainty of evidence of RCTs and NRSs. The protocol was registered with PROSPERO (CRD42022302743). Results: We found data on five comparisons; however, this abstract focuses on the primary outcomes of the two most clinically relevant comparisons. Regarding fosfomycin versus fluoroquinolone, five RCTs and four NRSs with a one-month follow-up were included. Based on the RCT evidence, fosfomycin likely resulted in little to no difference in febrile UTIs compared with fluoroquinolone. This difference corresponded to four fewer febrile UTIs per 1000 patients. Fosfomycin likely resulted in little to no difference in afebrile UTIs compared with fluoroquinolone. This difference corresponded to 29 fewer afebrile UTIs per 1000 patients. Fosfomycin likely resulted in little to no difference in overall UTIs compared with fluoroquinolone. This difference corresponded to 35 fewer overall UTIs per 1000 patients. Regarding fosfomycin and fluoroquinolone combined versus fluoroquinolone, two NRSs with a one- to three-month follow-up were included. Based on the NRS evidence, fosfomycin and fluoroquinolone combined may result in little to no difference in febrile UTIs compared with fluoroquinolone. This difference corresponded to 16 fewer febrile UTIs per 1000 patients. Conclusions: Compared with fluoroquinolone, fosfomycin or fosfomycin and fluoroquinolone combined may have a similar prophylactic effect on UTIs after a transrectal prostate biopsy. Given the increasing fluoroquinolone resistance and its ease to use, fosfomycin may be a good option for antibiotic prophylaxis.

Evaluation of risk factors, causative pathogens, and treatment in recurrent percutaneous nephrostomy catheter-related urinary tract infections in cancer patients

In cancer patients, percutaneous nephrostomy (PN) catheters can be used to relieve obstruction from chemotherapy, radiation therapy, or surgery, thereby improving kidney function and preventing further kidney damage. One of the complications of PN catheters is infections. Recurrent infections may delay chemotherapy, increase antimicrobial resistance with frequent antibiotic use, deteriorate the quality of life of patients, and increase costs. In this study, it was aimed to evaluate risk factors, causative pathogens, and treatment in recurrent PN catheter-related urinary tract infections in cancer patients. Cancer patients with PN catheter-associated urinary tract infection who were followed-up in the Infectious Diseases and Clinical Microbiology Clinic between January 1, 2012 and December 31, 2021 were included in the study. The total catheterization time, and occurrence of preinfection catheter replacement, active chemotherapy, and kidney stones were significantly higher in patients with recurrent infection when compared to the other group (P = .000, P = .000, P = .007, and P = .018, respectively). ESBL-positive Escherichia coli and ESBL-positive Klebsiella pneumoniae were most commonly isolated from the PN catheter urine cultures of patients with recurrent infections. Long-term use of the PN catheter increases the risk of urinary tract infection and sepsis. In this study, the total catheterization time, and occurrence of preinfection catheter replacement, active chemotherapy, and kidney stones were found to be risk factors for the development of recurrent PN catheter-related urinary tract infection in cancer patients. It is important to know the risk factors in recurrent PN catheter-related urinary tract infections in cancer patients, take maximum protective measures, and follow-up. Knowing both the causative profile and the resistance rates will increase the chance of success in the treatment when empirical treatment is required. It should also be noted that these patients should be included in the group of patients who need prophylaxis for urinary tract infection.

Natural Polyphenols for Prevention and Treatment of Urinary Tract Infections

Urinary tract infections (UTIs) are the second most common type of bacterial infection worldwide. UTIs are gender-specific diseases, with a higher incidence in women. This type of infection could occur in the upper part of the urogenital tract, leading to pyelonephritis and kidney infections, or in the lower part of the urinary tract, leading to less serious pathologies, mainly cystitis and urethritis. The most common etiological agent is uropathogenic E. coli (UPEC), followed by Pseudomonas aeruginosa and Proteus mirabilis. Conventional therapeutic treatment involves the use of antimicrobial agents, but due to the dramatic increase in antimicrobial resistance (AMR), this strategy has partially lost its therapeutic efficacy. For this reason, the search for natural alternatives for UTI treatment represents a current research topic. Therefore, this review summarized the results of in vitro and animal- or human-based in vivo studies aimed to assess the potential therapeutic anti-UTI effects of natural polyphenol-based nutraceuticals and foods. In particular, the main in vitro studies were reported, describing the principal molecular therapeutic targets and the mechanism of action of the different polyphenols studied. Furthermore, the results of the most relevant clinical trials for the treatment of urinary tract health were described. Future research is needed to confirm and validate the potential of polyphenols in the clinical prophylaxis of UTIs.

Antibiotic prophylaxis for urinary tract infection

What is the efficacy of antibiotic prophylaxis for recurrent urinary tract infections (UTIs) in nonpregnant women? Antibiotic prophylaxis lowers the risk of recurrent UTIs (12% vs 66% placebo) over 6 to 12 months. Yet, more women have adverse events with antibiotics (15% vs 8% placebo). Long-term

Bacterial Urinary Tract Infection and Early Asymptomatic Bacteriuria in Kidney Transplantation Still Negatively Affect Kidney Transplant Outcomes in the Era of Modern Immunosuppression and Cotrimoxazole Prophylaxis.

Risk factors and consequences of urinary tract infection (UTI) post-kidney transplant have been variously reported by studies that were heterogenous in immunosuppressants and prophylactic protocols. We aimed to clarify the risks and consequences of UTI in kidney transplant recipients with post-transplantation cotrimoxazole prophylaxis in the context of modern immunosuppression. This retrospective cohort included kidney transplant recipients receiving tacrolimus, mycophenolate, prednisolone, and cotrimoxazole for bacterial UTI prophylaxis. Recipients were categorized into non-UTI and UTI groups. Asymptomatic bacteriuria (ASB) was screened in the first 3 months and was evaluated for association with UTI. Of 348 kidney transplant recipients, 129 were in the UTI group and 219 in the non-UTI group. UTI risk factors were female sex, body mass index ≥ 25 kg/m2, human leukocyte antigen mismatch, and panel reactive antibody ≥ 50%. Recipients with recurrent UTI had inferior allograft function compared with non-UTI recipients. Patient survival was significantly lower in recipients with UTI in the first post-transplant month. Higher degree of immunosuppressions was associated with recurrent UTI and drug-resistant organisms. In conclusion, UTI continues to negatively affect graft function and survival of kidney transplant recipients. Treating ASB in the first 3 months did not reduce the UTI incidence in the first transplantation year.

326 USE OF A PHARMACY PRIORITISATION TOOLKIT IN FRAIL OLDER ADULTS PRESENTING TO THE EMERGENCY DEPARTMENT

Abstract Background A Pharmacy Prioritisation Toolkit (PPT) was adapted for use by a front door frailty multidisciplinary team to direct pharmacist review. Methods Over a 4-week period pharmacist referrals based on a toolkit used by the team were reviewed. Data was recorded in Excel including age, reason for referral and outcome of Medicines Optimisation Review (MOR). Pharmacy-identified patients were also analysed. Results Forty-Five patients were referred by the team using the PPT and 25 were pharmacist-identified for review. Reason for referral were use of high-risk medication (20/45), suspected medication related admission (9/45), chronic kidney disease or acute kidney injury (7/45), specific pharmaceutical concerns (5/45) &amp;gt;10 regular medications (4/45). Of those reviewed, 29 MORs were made. Of patients who were pharmacist identified, 10 MORs were made (53% of patients). The toolkit was retrospectively applied to these patients and would have selected all but 3. Conclusion The PPT was successfully used by the team to generate 45 referrals for pharmacist review over a 4-week period. As a result of analysis of these recommendations, antimicrobial prophylaxis for urinary tract infections will be added to the high-risk medicines list on the PPT. Development of the toolkit is ongoing using a plan, do, study, act model with input from all members of the team to further improve both its efficacy and utility.

Cranberry Ingestion Modulated Drug Transporters and Metabolizing Enzymes: Gefitinib Used as a Probe Substrate in Rats.

Cranberry, a polyphenol-rich functional food, is commonly used for the prophylaxis of urinary tract infections. Gefitinib, an anticancer agent clinically prescribed to treat non-small-cell lung cancer, is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), and metabolized mainly by cytochrome P450 (CYP) 3A4 and CYP2D6. This study used gefitinib as a probe substrate to investigate the modulation of cranberry on P-gp, BCRP, CYP3A4 and CYP2D6. Rats were administered gefitinib with and without 5.0 g/kg of cranberry as juice (CJ). The concentration of gefitinib in serum was determined by LC-MS/MS. The results showed that CJ significantly increased the Cmax and AUC0-t of gefitinib by 28% and 55%, respectively. Mechanism studies indicated that CJ activated P-gp, and cranberry metabolites (CM) inhibited CYP2D6. Moreover, the protein level of P-gp in rat enterocytes was decreased, whereas that in hepatocytes was increased. In addition, the protein levels of BCRP, CYP3A4 and CYP2D6 in enterocytes and hepatocytes were decreased. In conclusion, CJ ingestion affected the activities and protein levels of P-gp, BCRP, CYP3A4 and CYP2D6.

Alternative therapies for recurrent cystitis in menopausal women

Worldwide, urinary tract infections (UTIs) are reported in 150-250 million people per year. Annual direct and indirect costs of UTIs for overall patients are estimated to be from $2.4 billion to $3.5 billion Uropathogenic Escherichia coli is the most common cause of UTIs. These bacteria have the ability to colonize urothelium, persist in epithelial cells, and form quiescent biofilms. This bacterial reservoir may provide a source for bacterial persistence and UTIs recurrence. Besides, recurrent UTIs may be caused by the translocation of other bacteria which originate from the gastrointestinal tract or reinfections due to external sources. Menopause and pregnancy are considered as complicating factors that predispose to UTIs. Oral vaccine OM-89 and D-mannose are specified in the European Urological Association guidelines among non-pharmacological methods for the prevention of recurrent UTIs in postmenopausal women. The rationale to the use of D-mannose in UTI prophylaxis is based on its competitive inhibition of bacterial adherence to urothelial cells due to binding of type 1 fimbriae expressed on the bacteria. Exogenous D-mannose is absorbed, but not metabolized by the human body and it is excreted intact in urine. In vivo and in vitro studies showed the ability of mannose-like molecules to provide a 2-fold reduction of bacterial load in the urinary tract after 4 intravesical instillations. Clinical studies also demonstrated a high efficacy of the six months course of oral mannose in the prevention of UTIs.