Empiric versus culture-based antibiotic therapy for UTIs in menopausal women.

PURPOSE: To assess the benefits and risks associated with empiric prescription of antibiotic therapy for treatment of a urinary tract infection (UTI). METHODS: Following IRB approval menopausal women presenting with a symptomatic UTI to a single urology clinic were prospectively assigned to one of the two treatment groups based on day of presentation: culture-based treatment (CB) (Monday, Tuesday, Wednesday) or empiric treatment (ET) (Thursday, Friday) and started on nitrofurantoin (NF) pending culture results. Both groups were contacted at 7 and 14 days following treatment. Side effects and answers to a standardized questionnaire (UTISA) were recorded. Success was defined as a total UTISA score < 3. Any NF retreatment, use of another antibiotic therapy, or extension of the original antibiotic course was considered treatment failures. RESULTS: From July 2020 to March 2022, 65 women with 80 UTI events were included in the study, with CB treatment used for 60 UTIs and ET used for 23 UTIs. At 7 days after start of treatment, questionnaire failure rate was 44% (20/45) for the CB group and 16% (3/19) for the ET group (P = 0.076). At 14 days following start of treatment, questionnaire failure rate was 31% (13/42) for the CB group and 17% (3/18) for the ET group (P = 0.3). In the ET group, 11% of cultures were found to be resistant to NF. CONCLUSION: Outcomes for the empiric treatment of uncomplicated UTI with NF at both 7 and 14 days are not significantly different than outcomes with culture-based treatment.

d-mannosuria levels measured 1 h after d-mannose intake can select out favorable responders: A pilot study.

BACKGROUND: d-mannose is used as preventive measure against recurrent urinary tract infections (RUTIs). We studied d-mannosuria after a challenge test to identify favorable responders that could be targeted for long-term preventive therapy. MATERIAL AND METHODS: Following institutional review board approval, women attending a specialized tertiary care center urology clinic with a history of RUTIs were invited to participate by providing a urine sample (baseline), followed by the intake of home-dose d-mannose, and a second urine sample 1 h later (post). Urine samples were processed according to a d-mannosuria assay technique reported previously by our group. d-mannose concentrations were normalized to urinary creatinine. RESULTS: From July 2020 to March 2021, 26 patients met study criteria. Thirteen had a lower or unchanged ratio of baseline to post d-mannose, whereas 13 were responders. Among 19 taking 2 g, 12 had a lower or unchanged trend and 7 were responders with >20% increase in the d-mannose/creatinine ratio. Comparison of urinary baseline d-mannose/creatinine ratios was significantly different between the responder (mean = 0.337 ± 0.158) and nonresponder (mean = 0.692 ± 0.444; p = 0.016) groups. Urinary post d-mannose/creatinine ratios did not significantly differ between the two groups (p = 0.46). d-mannose-naïve patients had few responders, and age and urinary creatinine did not affect the findings. CONCLUSION: This preliminary study on d-mannose challenge tests indicates a urine response if urinary d-mannose/creatinine ratio is low, which it was in some women with a history of RUTIs.

Bacterial Growth of Uropathogenic Escherichia coli in Pooled Urine Is Much Higher than Predicted from the Average Growth in Individual Urine Samples.

Urinary tract infections (UTIs), mostly caused by uropathogenic E. coli (UPEC), affect most women, and often recur. Genomic and transcriptomic analyses have not identified a common set of virulence genes, which has suggested complex host-pathogen interactions and multiple virulence mechanisms. One aspect of the host-pathogen interaction is rapid UPEC growth in urine in vivo. When bacterial growth in urine is studied in vitro, urine is pooled, which is assumed to diminish individual variation. We grew one nonpathogenic and two pathogenic E. coli strains in urine from individuals who never had a UTI, had a UTI history but no current infection, and had a UTI history with a current infection. Bacterial growth showed large variations in individual urine samples, and pooled urine often supported significantly more growth than the average growth from individual urine samples. Total nutrient content tended to be higher in current group urine samples than the never and history grouped samples urine. We propose that pooling optimizes a nutrient mixture in the never and history group urine samples, which are often studied, whereas urine from current group individuals may have a more optimal nutrient mixture because of additional nutrient sources. We conclude that a pooled urine is not "an average urine sample," and that the best comparisons of results between labs using pooled urine would also include results with a standardized synthetic urine. IMPORTANCE Urinary tract infections (UTIs) will affect most women, can recur especially in postmenopausal women, and can become antibiotic recalcitrant. Escherichia coli causes most community-acquired UTIs and recurrent UTIs. Current theories of virulence, based on studies of UTI-associated E. coli, propose multiple virulence mechanisms and complex host-pathogen interactions. Studies of bacterial growth in urine samples-one aspect of the host-pathogen interaction-invariably involve pooled urine that are assumed to eliminate variations between individuals. Our results show that a pooled urine is not necessarily an average urine sample, and we suggest that quantitative and qualitative variations in nutrient content are the basis for this discrepancy. Knowledge of growth-promoting urinary components is important for understanding host-pathogen interactions during UTIs and could contribute to developing nonantibiotic-based therapies.

Challenges of Managing Lower Urinary Tract Symptoms in Women with Tamoxifen Use.

Objective: Tamoxifen complicates management of conditions such as urinary tract infections (UTIs), urinary incontinence (UI), and/or pelvic organ prolapse (POP) that traditionally benefit from hormonal intake; thus, we reviewed our experience in managing these hormonally deprived women. Materials and Methods: After IRB approval, electronic medical records from women with current use or history of tamoxifen use and referred to a tertiary care center with female pelvic medicine and reconstructive surgery expertise for UTI, UI, and/or POP were reviewed. Results: From 2015 to 2020, 32 women treated with tamoxifen 10-40 mg for a median of 4 years were referred for UTIs (9), UI (10), symptomatic POP (8), or for a combination of these (5). Participants with UTI treated with antibiotics, prophylactic supplements, and/or electrofulguration had satisfactory response at median follow-up of 1 year (interquartile range [IQR]: 0.5-1). Ten of 15 women with UI chose intervention, with no self-reported UI recurrence at median follow-up of 2.5 years (IQR: 1-3). All but one participant with POP underwent vaginal or open/robotic mesh repairs, with satisfactory outcomes at median follow-up of 3 years (IQR: 2-7). Conclusions: The management of UTIs, UI, and POP in women on tamoxifen or unable to benefit from hormonal intake is challenging, but traditional interventions can be considered with satisfactory results.

Does Urinary pH and Diet Influence the Rate of Urinary Tract Infection Recurrence After Electrofulguration in Women With Antibiotic-Recalcitrant Recurrent Urinary Tract Infections?

OBJECTIVES: To assess if urine acidity may be preventative against urinary tract infection (UTIs) and affected by diet. Our goal was to evaluate the effect of urine pH on the rate of recurrent UTIs (RUTIs) after electrofulguration (EF) in 3 groups of women with different urine pH ranges as well as the relation between their diet composition and urine pH. METHODS: In a prior IRB-approved prospective study, women recorded urinary pH 4 times a day and diet for a week. Three urinary pH groups were identified: never below 6, never above 6, and above and below 6. In this study, a 3-day diet analysis involved categorizing different foods by acidity based on pH food charts and calculating amounts consumed using a nutritional analysis database. Rate of UTIs after EF and urine pH after consumption of acidic foods was compared between urine pH groups. Our hypothesis was that low urinary pH protects against RUTIs. RESULTS: Of 37/69 patients who underwent EF with long median follow-up duration (4-6 years), no difference was found among the groups for UTI frequency, rate, and culture characteristics. There was a no significant difference in the mean amount of acidic foods eaten and the urine pH after each meal as well as in total. CONCLUSIONS: During long-term follow-up, no association was found between urine pH groups and acidic food intake, and rates of UTIs after EF, possibly because of no link between urine pH and UTIs or EF already provokes an important reduction in rates of UTIs.

The effects of ER morphology on synaptic structure and function in Drosophila melanogaster.

Hereditary spastic paraplegia (HSP) is a set of genetic diseases caused by mutations in one of 72 genes that results in age-dependent corticospinal axon degeneration accompanied by spasticity and paralysis. Two genes implicated in HSPs encode proteins that regulate endoplasmic reticulum (ER) morphology. Atlastin 1 (ATL1, also known as SPG3A) encodes an ER membrane fusion GTPase and reticulon 2 (RTN2, also known as SPG12) helps shape ER tube formation. Here, we use a new fluorescent ER marker to show that the ER within wild-type Drosophila motor nerve terminals forms a network of tubules that is fragmented and made diffuse upon loss of the atlastin 1 ortholog atl. atl or Rtnl1 loss decreases evoked transmitter release and increases arborization. Similar to other HSP proteins, Atl inhibits bone morphogenetic protein (BMP) signaling, and loss of atl causes age-dependent locomotor deficits in adults. These results demonstrate a crucial role for ER in neuronal function, and identify mechanistic links between ER morphology, neuronal function, BMP signaling and adult behavior.