Browsing by Subject "Urinary Tract Infections"
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Item Changing the culture of culturing: diagnostic stewardship for healthcare-associated infections(2023-11-10) Kang, MinjiItem Genus-Level Identification of Bladder-Resident Bacteria Associated with Recurrent Urinary Tract Infection in Post-Menopausal Women by Fluorescence In-Situ Hybridization(2022-02-01) Kenee, Parker R.M.; Gadhvi, Jashkaran G.; Khan, Fatima; Christie, Alana; De Nisco, Nicole; Zimmern, Philippe E.INTRODUCTION/BACKGROUND: Antibiotic-recalcitrant recurrent urinary tract infection (rUTI) is common in postmenopausal women. Many women elect to undergo electrofulguration (EF) of areas of chronic cystitis when standard antibiotic therapies fail. One potential benefit of this procedure is the removal of tissue-resident bacterial communities.1 Although tissue-resident bacteria have been observed in the bladder walls of postmenopausal women with rUTI by fluorescence in situ hybridization (FISH), genus and species level identification of these bacteria by FISH has not yet been reported.2 Here, we use genus-specific probes to quantify Escherichia spp. present in the bladder biopsies taken from postmenopausal women with rUTI undergoing EF and investigate the relationship between detected bacterial community sizes and stage of cystitis. METHODS: Following IRB approval, bladder biopsies were obtained from consenting postmenopausal women who elected EF for the advanced management of rUTI. Biopsies were immediately fixed in paraformaldehyde and then paraffin-embedded and sectioned (5 μm). FISH was performed as described previously2 using the following probe sets: 1. Scramble-AlexaFluor488/647 (control), 2. Universal 16s rRNA-AlexaFluor647 (all bacteria), and 3. Escherichia 16s rRNA-AlexaFluor488. Slides were imaged using a Zeiss LSM880 with a 63x objective. 10 randomly sampled images were collected for each biopsy section. Images analysis was performed blinded to quantify bacterial community sizes. Patients were classified by cystitis stage (Stage 1 (trigone alone) to 4 (pancystitis)) determined by cystoscopy at time of the biopsy. Least mean squares statistical analysis was used to generate an average number of bacterial organisms per 10x1 μm2 for each cystitis stage. RESULTS: Genera-specific FISH was performed on bladder biopsies from 23 women. The universal 16s rRNA probe detected tissue-resident bacteria in the biopsies of 95.7% (22/23) women. Tissue-resident Escherichia spp. were detected in the bladder biopsies of 52.1% (12/23) women. The highest average bacterial community sizes were observed in Stage 1 cystitis bladder biopsies (8.4 per 10x1 μm2, 95% C.I. 6.6 - 10.1). CONCLUSION: For the first time, 16s rRNA FISH was used to detect Escherichia spp. in the bladders of postmenopausal women electing to undergo EF for the advanced management of rUTI. Interestingly, bladder-resident bacterial community sizes were highest in bladder biopsies from women with Stage 1 cystitis.Item Hospital-acquired urinary tract infections(1963-10-03) Sanford, Jay P.Item Identification of Acyloxyacyl Hydrolase, a Lipopolysaccharide Detoxifying Enzyme, in the Murine Urinary Tract(2003-10-8) Feulner, J. Amelia; Munford, Robert S.Acyloxyacyl hydrolase (AOAH) is a lipase that removes the secondary fatty acyl chains that are substituted to the hydroxyl groups of glucosamine-linked 3-hydroxyacyl residues in lipid A, the bioactive center of Gram-negative bacterial lipopolysaccharides (LPS). Such limited deacylation has been shown to attenuate cytokine and chemokine responses to LPS, suggesting a role for AOAH in modulating (downregulating) inflammatory responses to invading Gramnegative bacteria. Prior to the experiments described in this report, AOAH had only been found in myeloid lineage cells (monocyte-macrophages, neutrophils and dendritic cells). In the work presented here, AOAH was found in murine renal proximal tubule cells and in human renal v cortex. Proximal tubule cells are known targets for invading Gram-negative uropathogens and we hypothesize that possessing AOAH may help them degrade the LPS contained within these bacteria. I further found that AOAH is secreted from proximal tubules in vitro and that it can be detected in murine urine, where it is able to deacylate purified LPS. AOAH may also associate with downstream bladder epithelial cells (which do not express AOAH) and be processed by them to its more enzymatically active, mature form. Bladder cells that have taken up AOAH in vitro are able to deacylate LPS. To determine the in vivo role of AOAH, I induced ascending urinary tract infections (UTIs) in wild type and AOAH null mice. To my surprise, AOAH null mice were able to clear bacteria from their urine faster than did wild type mice. An analysis of the immune response by histological analysis of bladder tissue and enumeration of neutrophils in the urine did not show a significant difference between wild type and AOAH null mice at any of the time points examined. Although I do not yet understand the mechanism for such increased clearance in AOAH null animals, we hypothesize that, due to their inability to deacylate LPS, they might have a more effective immune response to invading Gram-negative bacteria. A more detailed analysis of such responses to invading Gram-negative uropathogens will be important for understanding the in vivo role of AOAH in the urinary tract.Item Impact of Urine pH on Antibiotic Response in Women with Uropathogenic Eschericia [sic] coli Recurrent Urinary Tract Infections(2019-01-22) Chavez, Jacqueline; Christie, Alana; Zimmern, Philippe E.INTRODUCTION AND OBJECTIVES: As early as Brumfitt in 1948, the relationship between the effectiveness of certain uro-antibiotics and urinary pH levels has been considered.1 Some antibiotics are more effective at a urine pH range 5-6, whereas others work better at a more alkaline (urine pH 7-8) range. We compared the urine pH of women infected with E. coli to their antibiotic treatment response. METHODS: An IRB-approved, prospectively maintained database of well-characterized women with antibiotic-refractory recurrent urinary tract infections (RUTI) managed with electrofulguration (F) at a tertiary care center was reviewed. Included were women with at least 6 months follow-up post-F, an electronic medical record (EMR) documenting urine pH value at the time of each urine culture, and at least one E. coli positive urine culture. Total number of urine cultures post-F, urine pH variability, antibiotics prescribed, and the interval (months) between antibiotic administration and another UTI episode were reviewed. RESULTS: From 2006-2016 23 women met study criteria, with mean follow-up of 2 (1-9) years and mean age of 66 (28-92) years. Total number of urine cultures was 181, including 93 positive (I), 88 negative (NI), and 54 with E. coli. The average number of urine cultures per patient was 7 ± 3.8 (2-16). Median urine pH observed was 6, with no difference between I, NI, or E. coli urine cultures. There was no change in urine pH with aging. Six individuals were prescribed antibiotics for which pH has not been shown to change efficacy, 10 in whom urine pH aligned with the reported best efficacy range for their prescribed antibiotic, and 7 whom urine pH was not in the ideal antibiotic pH range. Mean interval time between first and second positive urine culture was longer for those with the appropriate urine pH for the prescribed antibiotic (26 months, 2-63) compared to those with a mismatch between urine pH and optimal pH range for their antibiotic (18 months, 1-33). CONCLUSION: This observational study explores the possible link between the urine pH of a woman with RUTIs and her response to antibiotic treatment administered without taking her urine pH into account. Future studies are needed to determine if an individual's urine pH needs to match the optimal pH range of a prescribed antibiotic to result in maximum therapeutic efficacy.Item Prognosis in pyelonephritis: promise or progress?(1987-09-10) Smith, James W.Item Recurrent Urinary Tract Infections Due to Bacterial Persistence or Reinfection in Women: Does This Factor Impact Upper Tract Imaging Findings? A Quality Improvement Project(2017-04-03) Rego, Lauren L.; Zimmern, Philippe E.; Reed, W. Gary; Fish, JasonBACKGROUND: It is recommended that women with recurrent urinary tract infections (RUTIs) due to bacterial persistence (same strain) undergo upper urinary tract imaging to evaluate for sources of their infection. OBJECTIVE: To compare the rate of upper tract imaging abnormalities between RUTIs due to bacterial persistence or reinfection. METHODS: Following IRB approval, a prospectively maintained database of women with documented RUTIs (≥ 3 UTI/year) and trigonitis was reviewed for demographic data, urine culture findings, and radiology-interpreted upper tract imaging study (renal ultrasound (US), CT scan, IVP) findings. Patients with irretrievable images, absent or incomplete urine culture results for review, no imaging study performed, an obvious source for RUTI, or history of pyelonephritis were excluded. RESULTS: From 2006 to 2014, 116 of 289 women with symptomatic RUTIs met inclusion criteria. Mean age was 65.0±14.4 with 95% being Caucasian and 81% post-menopausal. Nearly one-third were sexually active and none has prolapse >stage 2. Forty-one percent (48/116) had persistent and 59% (68/116) had reinfection RUTI. Imaging studies included US (52), CT (26), US and CT (31), and IVP with US/CT (7). Of total imaging findings (N=58 in 55 women), 57/58 (98%) were noncontributory. One case (0.9%) of mild hydronephrosis was noted in the persistent RUTI group but not related to any clinical parameters. Escherichia coli was the dominant bacteria in both persistent (71%) and reinfection (47%) RUTI in most recently reported urine culture. CONCLUSION: This study reaffirms that upper tract imaging is not indicated for bacterial reinfection RUTI. However, the same conclusion can be extended to RUTI secondary to bacterial persistence, thus questioning the routine practice of upper tract studies in Caucasian post-menopausal women with RUTI and trigonitis.Item Systematic Review of the Global Literature on Uncomplicated Recurrent Urinary Tract Infections: Underscoring Major Heterogeneity(2024-01-30) Papp, Sara B.; Seyan, Zheyar; Khan, Zara; Kenee, Parker R.M.; Christie, Alana; Zimmern, Philippe E.INTRODUCTION: Urinary tract infections (UTI) are common infections affecting over 60% of women and often become recurrent (rUTI). Despite their prevalence, research on rUTIs is limited and results are heterogenous due to varying definitions and populations. This systematic review examines global literature on uncomplicated rUTI and assesses differences in data based on geographic region. METHODS: Databases PubMed, Embase, WHO Global Index Medicus, and SciELO were searched for the keywords and/or MESH terms for recurrent and UTI, 2000- 2023. Studies were restricted to females ≥18 with uncomplicated rUTIs. Studies were excluded if they did not provide a definition for rUTI or did not cite/report an estimate for rUTI prevalence. The review was registered in PROSPERO and conformed to PRISMA. RESULTS: The search yielded 2,947 studies of which 124 were included (Table 1). Most studies were conducted in Europe (41%) or North America (39%), were prospective (52%), at tertiary centers (49%) and included all age groups (60%). Public institutions were the most common in North America (67%) while multi-center and public institutions were equally frequent in Europe (39% each). The most common definition for rUTI was 2 UTI/6m or 3 UTI/1y (62%). Regardless of study location, most studies cited prevalence estimates for rUTI from U.S.-based populations. Convenience samples were used for 91% of studies and sample sizes were: 30% n<50, 29% n=50-99, 22% n=100-199, 36% n≥200. CONCLUSIONS: This study represents the first formal investigation of the global literature base on uncomplicated rUTI. Studies on rUTIs are globally of small scale and definitions used for rUTI are heterogeneous. More studies are needed to ascertain the true prevalence of rUTI outside of North America and Europe.Item Testing Isogenicity of Recurrent UTI in Postmenopausal Women(2017-01-17) Wong, Daniel; Sarir, Saloomeh; Dao, Ryan; Thomas, Collin; Zimmern, Philippe E.PURPOSE: Due to increase in antibiotic allergies and resistance, the care of older women with recurrent urinary tract infections (UTIs) can be extremely challenging. Antibiotic regimens assume that infections are due to a single genetically identical species or isogen. The aim of this study was to use the classic method of phage typing to test whether the UTI pathogen in a patient is isogenic. Our hypothesis posits that infection may be due to the existence of a complex ecology of simultaneous infection by multiple same-species strains. METHODS: Mid-stream urine samples were taken from postmenopausal women with history of documented recurrent UTIs. Standard urine culture confirmed the presence of Escherichia coli bacterial strain. Urine sample was spread on LB agar plate and incubated for 24hrs at 37 degrees Celsius. 50 separate colonies were picked from the incubated plate and were treated in a patch assay with novel UTI targeting phages from the Rajagopal/Thomas Lab. Transilluminated images where taken with Biorad Image Lab equipment; then sensitivity to each phage was rated. Urine sample from patient 9 was used because our Lab had the most phages specific to lysing it. Phage clearings from the patch were rated on a scale of 0-3 based upon prevailing phage-typing metrics. (Ward et al. year) RESULTS: Differences to phage sensitivity across the 50 colonies numbered 9-1 to 9-50 were noted. Colonies 9-8, 9-44, and 9-46 were notably more resistant to a set of phages that was effective on all the other colonies. DISCUSSION: These findings in one representative older woman with recurrent UTI caused by Escherichia coli may have clinical significance particularly if differential phage sensitivity correlates with virulence, biofilm production, and antibiotic sensitivity variations. Pathogen findings in our urine samples suggest that infection may be an ecology of related, but nonidentical bacteria. CONCLUSION: The observed differences in phage sensitivity suggest there are multiple related, but non isogenic, Escherichia coli in the same bladder, a mechanism possibly contributing to antibiotic resistance and thus leading to UTI recurrence. Next step is to test each colony clone for its antibiotic sensitivity profile to determine if this novel observation could be clinically relevant.Item Urinary tract symptoms and infections in the adult(1973-12-20) Sanford, Jay P.