Urinary Infection Research Articles

Bacteriophage therapy in women with chronic recurrent cystitis caused by multidrug-resistant bacteria: A prospective, observational, comparative study

Abstract Objectives The aim of this study was to evaluate the effects of the combination of bacteriophage therapy with antibiotics and bacteriophage treatment alone on relieving clinical symptoms of chronic recurrent cystitis caused by multidrug-resistant bacteria. Materials and methods This clinical trial compared the treatment methods of 217 female patients with chronic recurrent cystitis caused by multidrug-resistant bacteria, who were investigated from June 2020 to May 2023. Patients were allocated into 4 groups: group I: received bacteriophage (Sextaphage) therapy alone; group II: received a combination of bacteriophages (Sextaphage) and furazidin; group III: received a combination of bacteriophage (Sextaphage) and furazidin with cefixime; and group IV: received furazidin and cefixime (without bacteriophage). The primary outcome included changes in the acute cystitis symptom scale and the pain visual analog scale, which were completed on days 7 and 14 following treatment. Secondary outcome measures included bladder diary records of urinary symptoms, median voided volumes, level of bacteriuria, and degree of leukocyturia. Results Initially, 217 female patients were presented during baseline visits. Those who did not meet the criteria inclusions were excluded, and 178 female patients were included in the final analysis. Statistically significant improvements from baseline in acute cystitis symptom scale scores for differential, typical symptoms, and quality of life domains were observed after 14 days of treatment in groups II, III, and IV. The pain level measured on the 14th day with the visual analog scale significantly decreased in groups II, III, and IV compared with group I. The patients of group I had a reduction of mean level bacteriuria of Escherichia coli from 106 to 102 CFU/mL at 14 days of therapy. Significant improvement of voided volume from baseline was observed in groups II, III, and IV. Episodes of urinary frequency, both daytime and night-time, reduced significantly from baseline in all 4 groups only at 14 days of treatment. Conclusions Bacteriophage cocktail alone or with antibiotics may improve clinical symptoms in women with chronic recurrent cystitis caused by multidrug-resistant bacterial pathogens. In addition to improving clinical symptoms, the therapy with a phage cocktail may restore antibiotic sensitivity and increase the efficacy of antimicrobial agents.

Pelvic Exenteration for locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) in Greece: A national snapshot survey of current practice

Background: Surgical treatment of locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) relies on Pelvic Exenteration, a complex procedure with high morbidity and mortality rates and great disparities in practice across different centers internationally. The aim of this survey is to review the current perioperative management of LARC and LRRC in Greece. Material and Methods: National Snapshot Survey disseminated online by the Hellenic Surgical Society and Greek Society of Coloproctology. Results: Most respondents were surgeons, 22% of whom had received fellowships in pelvic exenteration surgery. 83% of the participants reported holding multidisciplinary team meetings, and typically fewer than 10 pelvic exenteration procedures are conducted annually. A total of 28% of the participants employ a validated classification system to describe the operative approach (Pelvic Exenteration Lexicon). Considering outcomes, surgical factors like length of stay (78%), ICU duration (72%), blood loss (70%) and number of blood transfusions (64%) were prioritised, whereas patient-reported outcomes focused on physical functioning (77%), quality of life (75%), and urinary function (75%). For urological reconstructions, percutaneous nephrostomy (87%), cutaneous ureterostomy (75%) and urinary diversion using an ileal conduit (73%) were utilised the most, while plastic reconstructions involved mainly mesh placement (72%), omental flap with/without a skin graft (70%) and pedicled flaps (58%). Most prevalent complications were perineal wound dehiscence, abdominal wall hernia, postoperative ileus, urinary infection and VTE. Conclusion: Due to its complexity and low volume, experience in LARC/ LRRC is dispersed and differs among individuals. There is a need for structured, validated national guidelines to standardise methods and ensure that patients receive the highest standard of care.

The Role of Stratified Cumulative Antibiograms in the (Choice of Appropriate Antibiotics in Urinary Tract Infection) Management of Urinary Tract Infections

Urinary tract infections (UTIs) are one of the most common bacterial diseases both in communities and in hospitalized patients, and at the same, time they are one of the most common indications for the use of antibiotics. UTI guidelines are generally available nationally or internationally, but they do not address all aspects of UTI treatment for different patient cohorts, age, gender, or comorbidities. The aim of the study was to point out the importance of stratified cumulative antibiograms at the level of individual health care facilities and the significant differences between epidemiological data, not only at the national level, but also at the local level. Our study analyses data from 383 patients with UTIs from a hospital department, General University Hospital (GUH), and 272 patients from an outpatient medical facility, Urocentrum (UC). This analysis focuses on the most common UTI causative agent, Escherichia coli, its representation as the causative agent of UTI in patients with complicated acute cystitis (N30), and its representation in complicated acute cystitis in patients with prostate cancer (C61). In addition to the frequency of occurrence, a sub-analysis of the incidence of resistance of E. coli to commonly used antibiotics by age, gender, diagnosis, and medical facility was performed. Results: The most common causative agent of UTI was E. coli. In patients with N30, it was 70% in GUH and 54% in UC, but in oncological patients with UTI, it was only 39% and 35%, respectively. In patients with UTI in C61, there was a significant difference in susceptibility of E. coli between individual health care facilities. Lower resistance was found in UC opposite to GUH isolates in ampicillin, with 29.8% vs. 65%, p = 0.001; amoxicillin/clavulanic acid, with 8.5% vs. 30%, p = 0.01; with 2.1% vs. 17.5% in pivmecillinam, p = 0.01; with 10.6% vs. 37.5% in co-trimoxazole, p = 0.003; and ciprofloxacin, with 10.6% vs. 30%, p = 0.04. The study shows significant differences in the sensitivity of urinary E. coli isolates in patients in relation to age, gender, medical devices, and the presence of comorbidities.

SPHK1/S1PR1/PPAR-α axis restores TJs between uroepithelium providing new ideas for IC/BPS treatment.

Interstitial cystitis/bladder pain syndrome (IC/BPS) represents a chronic, aseptic inflammatory bladder condition with an unclear etiology and few therapeutic options. A composite barrier structure composed of the uroepithelium and glycosaminoglycan layer forms on the bladder's inner surface to block urine and other harmful substances. Dysfunction of this barrier may initiate the pathogenesis of IC/BPS. Sphingosine-1-phosphate (S1P) plays a crucial role in forming tight junctions. Perfusion of S1P into the bladder restored uroepithelial tight junctions in mice with cyclophosphamide-induced acute cystitis and ameliorated symptoms of the lower urinary tract. Mice lacking sphingosine kinase 1 (SHPK1) exhibited more severe bladder injuries and dysfunction. Concurrent in vitro experiments elucidated S1P's protective effects and its role as a primary messenger through SPHK1 and S1P receptor 1 (S1PR1) knockdown. This study identifies a novel mechanism whereby S1P binding to S1PR1 activates the PPAR-α pathway, thereby enhancing cholesterol transport and restoring tight junctions between uroepithelial cells. These findings elucidate the regulatory role of S1P in the bladder epithelial barrier and highlight a promising therapeutic target for IC/BPS.

Clinical value analysis of integrated care model in reducing bleeding and complications during Da Vinci robot-assisted urology.

This study aims to explore the effect of integrated care mode on patients in Da Vinci robot-assisted urology surgery and provide a new nursing scheme for clinic. A total of 93 patients from August 2022 to March 2024 were selected and divided into intervention group (43 cases) and control group (50 cases). The operation time, blood loss, first postoperative exhaust time, time to get out of bed, pain score (visual analog scale), psychological status (self-rating anxiety scale and self-rating depression scale), quality of life score (36-Item Short Form Survey), catheter retention time, patient satisfaction, incision healing, incidence of urinary system infection, nutritional status, and complication rate were compared between the 2 groups. There were no significant differences in baseline data and operative time between the 2 groups (P > .05), but the amount of intraoperative blood loss in the intervention group (250.32 ± 50.23) mL was less than that in the control group (320.56 ± 65.34) mL (P < .05). The first postoperative exhaust time and getting out of bed time in the intervention group were shorter than those in the control group (P < .05), and the pain visual analog scale score was lower than that in the control group (P < .05). The scores of self-rating anxiety scale and self-rating depression scale of mental state were better than those of the control group (P < .05), and the scores of quality of life were higher (P < .05). The retention time of catheter was shorter than that of the control group (P < .05), the patient satisfaction was 93.02% higher than that of the control group 78.00% (P < .05), and the grade A incision healing rate was 90.70% higher than that of the control group 76.00% (P < .05). The incidence of urinary system infection (4.65%) was lower than that of the control group (16.00%) (P < .05), the changes of serum albumin level and body weight were lower than that of the control group (P < .05), and the complication rate of 6.98% was lower than that of the control group (22.00%) (P < .05). Although the integrated medical care model did not significantly shorten the operation time, it was beneficial to the postoperative recovery of patients in many aspects.

P-1550. Systematic Literature Review of Acute Cystitis or Afebrile Urinary Tract Infection in Men

Abstract Background Acute cystitis in men is classified as complicated urinary tract infection (UTI), despite the absence of functional and/or structural anatomical abnormalities of the urinary tract, associated with a higher risk of treatment failure. We conducted a systematic literature review (SLR) to identify and summarize evidence on the epidemiology (incidence, etiology, antimicrobial resistance [AMR], recurrence) and treatment patterns of acute cystitis or afebrile UTI among men with no signs of systemic infection. Methods Systematic searches for English language articles were conducted Jan 1, 2011–May 12, 2023 in the MEDLINE, MEDLINE In-Process, and Embase databases via OvidSP. Gray literature sources (Table 1) were reviewed. Publications were evaluated by 2 independent reviewers (Table 2). Results Database searches yielded 1025 records with 6 studies eligible for inclusion (Figure 1). Studies were primarily excluded if the population of interest was not included or if outcomes were inseparable for the population of interest. The 6 studies were conducted 2012–2020 in 6 geographic regions (1 US). Sample sizes ranged from 18 to 4876 patients. Four studies reported age (median 44–71 years; Table 3). Population of interest was defined as “uncomplicated” (3 studies) or “acute cystitis”/“afebrile UTI” (3 studies). The incidence of uncomplicated UTI was 6.5/1000 person-years in a retrospective cohort (Netherlands) and increased with age. Relapse, defined as continuation of UTI symptoms ≤ 28 days of stopping treatment, after initial symptom resolution, ranged from 9.9% to 16.9% (referred to as recurrence rates in this study). Escherichia coli (E. coli) were the etiologic bacteria in 39–94% of patients. Nitrofurantoin (56.0%) and fluoroquinolones (62.8%) were the most commonly prescribed antibiotics in the Netherlands and Japan, respectively. AMR among E. coli ranged from 11.8% to 47.1% in 1 study. Conclusion AMR in males with acute cystitis/afebrile UTI may be higher than females in some geographic regions. The SLR identified 6 studies with heterogenous designs, inclusion criteria, and UTI definitions, highlighting the need for research using standard definitions to characterize acute cystitis/afebrile UTI in men, including recurrence rates and the burden of AMR. Funding: GSK study 220916 Disclosures Fanny S. Mitrani-Gold, MPH, GSK: Employee|GSK: Stocks/Bonds (Public Company) Amber Martin, BS, PPD Evidera: Employee of PPD Evidera, which received funding from GSK for this study. Priscilla Wittkopf, PhD, GSK: Grant/Research Support|PPD Evidera: Employee of PPD Evidera, which received funding from GSK for this study.|ThermoFisher Scientific: Stocks/Bonds (Private Company) Joanna Kamar, MPH, PPD Evidera: Employee of PPD Evidera, which received funding from GSK for this study. Madison T. Preib, MPH, GSK: Employee|GSK: Stocks/Bonds (Public Company) Ashish V. Joshi, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Aruni Mulgirigama, MBBS, GSK: Employee|GSK: Stocks/Bonds (Public Company)

P-1649. Nursing Home Clinician Rationales Underlying Antibiotic Decision-Making for Suspected Urinary Tract Infection

Abstract Background The factors underlying antibiotic decision-making in nursing homes (NHs) remains poorly understood. We conducted an analysis of discrete and free text responses from a mixed-methods survey presenting NH clinicians with two patient clinical vignettes on asymptomatic bacteriuria (ASB) and cystitis (CYS) designed to assess clinicians’ treatment (TX) threshold.Table 1:Clinical Vignettes Methods NH clinicians were recruited nationally via professional organizations from December 2021 to April 2022. A web-based survey tool was used to administer the vignettes (Table 1) to participants who were asked to document their TX decision and justification. Treater (TRT) and non-treater (NTRT) responses were stratified by vignette and textual responses were uploaded to NVivo. A hybrid directed and conventional content approach was utilized to develop a codebook using the constant comparison technique.Table 2:Factors Contributing to Clinicians’ Treatment Decisions by Vignette and Treatment Choice Results Among 298 survey respondents; 10.4% treated ASB while 61.1% treated CYS. Seven factors contributing to clinicians’ TX decisions were identified (Table 2). For the ASB vignette (Table 3), TRTs framed the patient’s positive test results as infection (84%) while NTRTs framed it as contamination (79%). TRTs were less likely than NTRTs (26% vs 91%) to note the absence of signs and symptoms (S/S). Both groups cited the patient’s comorbidities and/or medical history (42% vs. 54%) in their TX decision. In the CYS vignette (Table 4), TRTs focused on positive patient S/S (91%) while NTRT did not feel there were sufficient frequency or severity of symptoms to justify immediate therapy (77%). TRTs were more likely to rely on positive test results (59%) and have more concern for patients’ comorbidities and/or medical history (18%).Table 3:Asymptomatic Bacteriuria Vignette Illustrative Quotes Conclusion Both TRTs and NTRTs use urine diagnostics in their decision-making, with TRTs having more confidence in the positive predictive value of urine diagnostics. NTRTs highlighted the lack of S/S as a justification for withholding therapy in both vignettes. TRTs accurately identified S/S for CYS, however, TRTs for ASB expressed concern that S/S might be underreported. This study shows how TRTs and NTRTs justify their rationales, however the next steps involve understanding how these decision-making patterns are amenable to education, information framing and/or risk management interventions.Table 4:Cystitis Vignette Illustrative Quotes Disclosures Robin Jump, MD, PhD, Abacus: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support

P-1566. Healthcare Resource Use and Costs of Acute Uncomplicated Cystitis in Japan

Abstract Background Acute uncomplicated cystitis (AUC) is an area of interest for outpatient antimicrobial stewardship in Japan due to the high prevalence of community antibiotic use. Literature on the cost burden of AUC in Japan is limited. We aimed to quantify real-world healthcare resource utilization (HCRU) and costs of treating AUC in Japan. Methods This retrospective cohort study used Japanese Medical Data Center (JMDC) claims data (1 October 2015−30 November 2021). Eligible patients (≥ 18 to &amp;lt; 75 years) had an outpatient AUC diagnosis claim in the same month as ≥ 1 oral antibiotic prescription (date of prescription = index date). Continuous health plan enrolment, with medical and pharmacy benefits, was required ≥ 12 months pre index (baseline period) and ≥ 12 months post index (follow-up period). Patients with complicated cystitis or pyelonephritis were excluded. The index AUC episode was defined as 28 days from index date and was extended an additional 28 days if treatment failure (TF) was observed (within 28 days from date of TF). Patients were stratified based on evidence of TF or AUC recurrence (full definitions in Table 1). AUC-related costs (Japanese Yen [¥]) and HCRU, per episode, were compared within subgroups. Results Overall, 71,467 patients were included, of whom 3742 (5%) had evidence of TF and 3206 (4%) had recurrent AUC. The mean (standard deviation [SD]) cost of any AUC episode was ¥14,905 (¥31,344) (Table 2), with 1.22 (0.46) outpatient claims and 1.07 (0.27) pharmacy prescription claims per episode (Table 3). Patients with evidence of TF had significantly higher mean (SD) pharmacy (¥2078 [¥2295]) and total costs (¥25,932 [¥64,494]), and a higher number of pharmacy prescription claims (2.03 [0.45]) per episode versus patients without TF (all p&amp;lt; 0.001). Patients with recurrent AUC had higher mean (SD) total costs (¥16,514 [¥35,241]) and higher outpatient claims (1.10 [0.34]) per episode versus patients without recurrence (¥14,830 [¥31,148]) total costs and (¥1037 [¥1281]) outpatient claims; (p=0.008 and p&amp;lt; 0.001, respectively). Conclusion TF rates and recurrence of AUC in Japan were modest; however, the economic burden of AUC was greater in patients who had evidence of TF or recurrence. Disclosures Meg Franklin, PharmaD, PhD, Franklin Pharmaceutical Consulting: Owner and President|Franklin Pharmaceutical Consulting: Ownership Interest|PRECISIONheor (who received funding from GSK to complete this study): Advisor/Consultant Maia R. Emden, BA, PRECISIONheor: Previous employee of PRECISIONheor, who received funding from GSK to complete this study Elise Bauer, MS, PRECISIONheor: Previous employee of PRECISIONheor, who received funding from GSK to complete this study Naomi Sacks, PhD, PRECISIONheor: Previous employee of PRECISIONheor, who received funding from GSK to complete this study Fanny S. Mitrani-Gold, MPH, GSK: Employee|GSK: Stocks/Bonds (Public Company) Shinyoung Ju, MS, GSK: Employee|GSK: Stocks/Bonds (Public Company) Ashish V. Joshi, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Yoshiaki Kawano, MD, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Shinya Kawamatsu, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Madison T. Preib, MPH, GSK: Employee|GSK: Stocks/Bonds (Public Company)

P-1078. Gentamicin-releasing polydopamine catheter coating to prevent urinary catheter-related infections

Abstract Background Catheter-associated urinary infections (CAUTIs) are among the most common healthcare-associated infections in the United States. The risk of CAUTI corresponds to the duration of catheterization; prolonged catheter uses impacts patient morbidity, mortality, and healthcare costs. Pseudomonas aeruginosa is a leading cause of CAUTI and is particularly adept at forming surface-associated biofilms that are difficult to treat. In the present study, we developed a catheter coating using polydopamine (PD) to embed gentamicin on the surface. Bacterial Viability of PAO1 when exposed to PD-gentamicin coating Colony-forming unit (CFU) count of PAO1 exposed to concentration series of PD-only and PD-Gent well plate coating. Methods Coating synthesis: PD-antibacterial coating was synthesized using dopamine hydrochloride salt and antibiotic drugs (i.e., gentamicin) in an alkaline buffer in the presence of polyvinyl chloride (PVC) tubing. A similar procedure was used for the well-plate study using 150 µL of solution per well, followed by heating at 60 °C. Biofilm Quantification: PAO1 was added to a 96-well plate or tubes and incubated statically for 24 h. Biofilms were stained with 0.1% crystal violet, solubilized with 33% glacial acetic acid, and measured at OD590 nm. Cell viability: Colony forming units were measured using 10-fold serial dilutions on TSA agar. Biofilm formation of PAO1 after incubation with PD-gentamicin coating in PVC tubes PAO1 biofilm concentration changes with changing the PD to gentamicin ratio during coating synthesis. Results PD-gentamicin coated tubes and 96-well plates showed elimination of PAO1 viability at PD concentrations of 0.25 mg/mL and above but had little bactericidal effect at lower concentrations (Fig. 1). There was no reduction in viability in PAO1 exposed to PD or gentamicin alone. PAO1 biofilm was reduced in the median PD-gentamicin concentrations 0.1-0.5 mg/mL, but this effect was lost at the extremes of concentration (Fig. 2). Conclusion The PD-gentamicin coating eliminated PAO1 viability and reduced biofilm at PD concentration 0.25 mg/mL. Similar results were observed in 96-well plates and PVC tubes, suggesting versatility in the adherence of the coating material. Additional studies are needed to assess the duration of these effects over time. Disclosures All Authors: No reported disclosures

P-1634. Prescribing Patterns of Antibiotics in an Academic Medical Center Internal Medicine Clinic

Abstract Background Antimicrobial stewardship is critical in the prevention of antibiotic resistance. The CDC estimates nearly 90% of antibiotic use occurs in outpatient settings, with up to half of the prescriptions not carrying appropriate indications. Public health efforts like the National Action Plan for Combating Antibiotic Resistant Bacteria aim to reduce/improve outpatient antibiotic use following the Department of Health and Human Services guidance. Inclusion/Exclusion 350 prescriptions were assessed for inclusion within the study. Prescriptions were excluded if antibiotics were prescribed for prophylaxis, indications outside of preferred list (notably: COPD Exacerbations, prostatitis, pyelonephritis, clearly documented “asymptomatic bacteriuria”), prescriptions continued from inpatient admission, pregnancy, under the age of 18, and infectious disease consults Methods A retrospective descriptive assessment of antimicrobial prescribing practice within one internal medicine clinic was conducted through chart review. Outpatient antibiotic prescriptions from a prespecified list of agents written between March to June of 2023 for cystitis, community-acquired pneumonia, and acute sinusitis were compared to current Infectious Disease Society of America recommendations for treatment. The primary outcome was appropriateness based on indication, drug choice, dose, and duration of therapy. A key secondary outcome assessed was ED or clinic return visits for the same primary problem within 30 days. Prescription Appropriateness Each prescription was assessed for correct indication, drug, dose, and duration based on current IDSA guidelines. Results This study included 166 antibiotic prescriptions written for 147 patients. Of these prescriptions, 67% were inappropriately prescribed. Duration and indication were inappropriate most frequently on prescriptions while drug and dose were appropriately selected by providers. Of the patients with prescription errors, 23.1% (25/108) led to a return visit versus 17.2% (10/58) for patients with antibiotics prescribed correctly (p =0.429). Prescription Inappropriateness by Type of Error This study included 166 antibiotic prescriptions written for 147 patients. Of these prescriptions, 67% were inappropriately prescribed. Duration (33%) and indication (34%) were inappropriate most frequently on prescriptions while drug (16%) and dose (7%) were appropriately selected by providers. Conclusion In conclusion, antibiotics are inappropriately prescribed in the outpatient setting which necessitates the need for increased stewardship efforts. A trend towards increased return visits was observed for patients who received an inappropriate antibiotic prescription. As a secondary outcome, this study was unable to meet statistical significance, but further evaluation should be done to explore this trend. Implementation of institutional prescribing guidelines for common infections such as acute sinusitis or cystitis paired with targeted education for outpatient clinics could help improve antimicrobial prescribing habits. Antibiotic Prescription by Appropriateness The most common antibiotics prescribed included amoxicillin-clavulanate, cephalexin, and nitrofurantoin accounting for 70% of the prescriptions reviewed. Fluroquinolones when prescribed were inappropriate in this study based on indication, dose, duration, or drug. Amoxicillin-clavulanate when prescribed was correct in all four categories for only 50% of prescriptions while nitrofurantoin was appropriate only 29% of the time. Disclosures All Authors: No reported disclosures

P-1675. Antibiotic Inertia Occurs Frequently in Patients Admitted from the Emergency Department on Guideline Non-Concordant Therapy

Abstract Background Antibiotic (abx) inertia is when inpatient providers continue inappropriate empiric abx started in the emergency department (ED) rather than changing to an appropriate regimen. Studies using hypothetical case scenarios estimate that this occurs in 39% of cases, but the phenomenon has not been studied using actual prescribing data. The objective of this study is to evaluate abx inertia in real-world clinical practice. Methods This retrospective chart review of adult inpatients at an 885-bed tertiary care referral center from January - October 2022 evaluated whether guideline non-concordant (GNC) abx therapy started in the ED was continued upon admission to an inpatient team. Patients admitted with a diagnosis of acute uncomplicated cystitis, pyelonephritis, community-acquired pneumonia (PNA), or skin/soft tissue infection (SSTI) who received abx in the ED were eligible for inclusion. ICU admissions were excluded. Ten patients meeting study criteria were randomly chosen from each month. Abx regimens were compared to those listed in corresponding IDSA guidelines. The primary outcome was the continuation of empiric GNC abx by the inpatient team at the time of admission. Results Of the 100 patients evaluated, 56 were started on GNC abx therapy in the ED. Of these, 25 (45%) were continued on GNC regimens. Vancomycin and cefepime, prescribed in 18 (72%) and 10 (40%) cases, were the most commonly continued GNC abx. The majority [23 (92%)] of continued GNC regimens were broader than those listed in the guidelines; 17 (68%) continued an abx not listed in guidelines while also omitting a listed abx. It took a median of 63 hours (95% CI 48-80) for those started on GNC abx in the ED to receive guideline concordant abx (figure 1). There was no difference in age, comorbidities, admission diagnosis, change in diagnosis, prior infections or allergies in patients whose GNC abx were continued versus not. Patients admitted to a hospitalist service were more likely to have GNC abx continued (p &amp;lt; 0.05), table 1. Conclusion Abx inertia occurred in almost half of patients started on GNC abx in the ED. Vancomycin and cefepime as well as a specific inpatient service were often associated with continued GNC abx. These observations offer potential targets for antimicrobial stewardship efforts. Disclosures John C. Williamson, PharmD, Armata Pharmaceuticals: Grant/Research Support|Blue Collar Vaccines and Therapeutics: Board Member|Blue Collar Vaccines and Therapeutics: Ownership Interest|Paratek Pharmaceuticals: Grant/Research Support|ST Pharm Co, Ltd: Grant/Research Support

102. Carbapenemase producing organisms in Positive Blood and urine Cultures in a large New York Health System Reveals Emergence of NDM-Harboring Organisms and Associated Morbidity and Mortality

Abstract Background Infections caused by organisms harboring carbapenemase genes are a significant cause of morbidity and mortality. The prevalence of carbapenemase producing organisms (CPO) has been increasing for several years, with the majority of isolates originating in healthcare settings and containing one of the five most prevalent carbapenemase genes (blaKPC, blaOXA-48-like, blaNDM, blaVIM, blaIMP). Management of patients with CPOs is particularly challenging and knowledge of the specific carbapenemase gene harbored by these organisms is imperative for proper treatment. Methods We conducted a retrospective multicenter study of hospitalized patients with blood and urine cultures positive for a CPO from January 2021 to December 2023 (2021-2023 blood, 2023 for urine). Blood culture PCR results were utilized to identify carbapenemase genes from these specimens. For urine specimens, phenotypic carbapenemase production was assessed by a lateral flow immunoassay (NG-Test CARBA 5). Clinical outcomes including time to appropriate therapy, length of hospital stay, 30-day hospital readmission, and patient mortality were evaluated. Results A total of 71 CPO-positive blood cultures and 50 CPO-positive urine cultures from 10 hospitals were included. Klebsiella pneumoniae was the predominant CPO isolated from both blood and urine samples, urinary tract infections was the most common source of CPO bacteremia. Of the carbapenemase resistance genes detected, blaNDM comprised 39% of CPO isolated from blood and 46% of CPO isolated from urine. Median time to appropriate therapy was 3.9 hours for blood cultures and 16 hours for urine cultures. The median length of hospital stay was 20 days for blood infections and 13 days for urine infections. Thirty-day readmission rates were 16% for blood infections and 50% for urine infections, with mortality rates of 39% for blood infections and 6% for urine infections. Conclusion Timely identification and differentiation of carbapenem resistance genes are crucial for informing adjustments in antimicrobial therapy. Despite appropriate clinical interventions patients with CPO bacteremia had elevated mortality rates, 42% in 2022 and 33% in 2023. Notably, the primary contributor to these high mortality rates was NDM, with rates reaching 54% in 2022 and 50% in 2023. Disclosures All Authors: No reported disclosures

Evaluation of anticancer activity of urotropine surface modified iron oxide nanoparticles using a panel of forty breast cancer cell lines

Urotropine, an antibacterial agent to treat urinary tract bacterial infections, can be also considered as a repurposed drug with formaldehyde-mediated anticancer activity. Recently, we have synthesized urotropine surface modified iron oxide nanoparticles (URO@Fe3O4 NPs) with improved colloidal stability and limited cytotoxicity against human fibroblasts. In the present study, we have investigated URO@Fe3O4 NP-mediated responses in a panel of forty phenotypically different breast cancer cell lines along with three non-cancerous corresponding cell lines. URO@Fe3O4 NPs promoted oxidative stress and FOXO3a-based antioxidant response in breast cancer cells. Elevated levels of GPX4 and decreased levels of ACSL4 in URO@Fe3O4 NP-treated breast cancer cells protected against ferroptotic cell death. On the contrary, URO@Fe3O4 NPs impaired the activity of PERK, a part of unfolded protein response (UPR), especially when the glucose supply was limited, that was accompanied by genetic instability, and apoptotic and/or necrotic cell death in breast cancer cells. In conclusion, this is the first comprehensive analysis of anticancer effects of URO@Fe3O4 NPs against a panel of forty breast cancer cell lines with different receptor status and in glucose replete and deplete conditions. We suggest that presented results might be helpful for designing new nano-based anti-breast cancer strategies.

Personalized optimization of systematic prostate biopsy core number based on mpMRI radiomics features: a large-sample retrospective analysis

BackgroundProstate cancer (PCa) is definitively diagnosed by systematic prostate biopsy (SBx) with 13 cores. This method, however, can increase the risk of urinary retention, infection and bleeding due to the excessive number of biopsy cores.MethodsWe retrospectively analyzed 622 patients who underwent SBx with prostate multiparametric MRI (mpMRI) from two centers between January 2014 to June 2022. The MRI data were collected to manually segment Regions of Interest (ROI) of the tumor layer by layer. ROI reconstructions were fused to form outline of the volume of interest (VOI), which were exported and applied to subsequent extraction of radiomics features. The t-tests, Mann-Whitney U-tests and chi-squared tests were performed to evaluate the significance of features. The logistic regression was used for calculating the PCa risk score (PCS). The PCS model was trained to optimize the SBx core number, utilizing both mpMRI radiomics and clinical features.ResultsThe predicted number of SBx cores was determined by PCS model. Optimal core numbers of SBx for PCS subgroups 1–5 were calculated as 13, 10, 8, 6, and 6, respectively. Accuracies of predicted core numbers were high: 100%, 95.8%, 91.7%, 90.6%, and 92.7% for PCS subgroups 1–5. Optimized SBx reduced core rate by 41.9%. Leakage rates for PCa and clinically significant PCa were 8.2% and 3.4%, respectively. The optimized SBx also demonstrated high accuracy on the validation set.ConclusionThe optimization PCS model described in this study could therefore effectively reduce the number of systematic biopsy cores obtained from patients with high PCS, especially for biopsy cores far away from suspicious lesions. This method can enhance patient experience without reducing tumor detection rate.

Electrolyte Concentration in Urine and Urinary Infection—Is There Any Relation?

Electrolyte Concentration in Urine and Urinary Infection—Is There Any Relation?

OXCT1 succinylation and activation by SUCLA2 promotes ketolysis and liver tumor growth.

Ketone bodies generated in hepatocytes in the adult liver are used for nonhepatic tissues as an energy source. However, ketolysis is reactivated in hepatocellular carcinoma (HCC) cells with largely unelucidated mechanisms. Here, we demonstrate that 3-oxoacid CoA-transferase 1 (OXCT1), a rate-limiting enzyme in ketolysis, interacts with SUCLA2 upon IGF1 stimulation in HCC cells. This interaction results from ERK2-mediated SUCLA2 S124 phosphorylation and subsequent PIN1-mediated cis-trans isomerization of SUCLA2. OXCT1-associated SUCLA2 generates succinyl-CoA, which not only serves as a substrate for OXCT1 but also directly succinylates OXCT1 at K421 and activates OXCT1. SUCLA2-regulated OXCT1 activation substantially enhances ketolysis, HCC cell proliferation, and tumor growth in mice. Notably, treatment with acetohydroxamic acid, an OXCT1 inhibitor used clinically for urinary infection, inhibits liver tumor growth in mice and significantly enhances lenvatinib therapy. Our findings highlight the role of SUCLA2-coupled regulation of OXCT1 succinylation in ketolysis and unveil an unprecedented strategy for treating HCC by interrupting ketolysis.

Candiduria in Pediatric Patients: Two Case Reports and a Review of Management Strategies.

Introduction: Urinary infections, while common in intensive care and surgical units, present a unique challenge when fungal pathogens are involved. These fungal urinary infections, known as fungiuria, require a more intricate and prolonged treatment plan involving antifungal medications. This complexity underscores the need for specialized knowledge and skills in managing such cases. This study aims to present two cases of operated pediatric patients who developed urinary fungal infections following Catheterization and simultaneous treatment with two antibiotics. Results: Two pediatric patients, aged 12 and 16, underwent surgical procedures in our clinic. The first patient was treated for gangrenous appendicitis complicated by generalized peritonitis. The second patient was treated for a perforation of the small intestine caused by gangrene in a segment of the bowel, resulting from twisting around intestinal adhesions, also complicated by generalized peritonitis. Both patients, aged 12 and 16, developed urinary symptoms four days after surgery. Microbiological analysis confirmed the presence of fungal infections caused by Candida albicans. However, with the administration of antifungal medications, we were able to successfully eradicate Candida albicans from their urinary tracts, as confirmed by follow-up microbiological cultures after several weeks of therapy. This successful outcome should instill a sense of accomplishment in the audience. Conclusion: Candidiasis, a significant complication in patients undergoing prolonged Catheterization and simultaneous antibiotic therapy, requires vigilant monitoring. The challenging treatment often necessitates long-term administration of antifungal medications for successful eradication. This underscores the importance of vigilance in monitoring fungal infections in catheterized patients and adopting preventive strategies to minimize their occurrence.

A comparison on safety and efficacy between 24 Fr versus 18 Fr pneumatic balloon dilators for percutaneous treatment of renal stones between 10 and 20mm: results from a contemporary cohort.

To assess differences in safety and efficacy between 24 and 18 Fr pneumatic balloon dilators for percutaneous nephrolithotripsy (PCNL) of renal stones between 10 and 20mm. Patients were randomized to dilatation with a 24 Fr (Group A) versus 18 Fr (Group B) Ultraxx pneumatic dilator (Cook Medical®). In all procedures percutaneous puncture was performed under ultrasound guidance. In both groups the Holmium: YAG Cyber Ho laser generator was used (Quanta System®). Stone-free rate (SFR) and postoperative complications were assessed. 42 and 44 patients were assigned to Groups A and B, respectively. Preoperative features were comparable. Mean stone size was 17.8 vs. 16.6mm in Group A vs. B (p = 0.21). SFR was 95.2% in Group A and 95.4% in Group B (p = 0.19). Postoperative gross haematuria was observed in 5 vs. 2 cases in Group A vs. B (p = 0.04). Mean haemoglobin drop at first postoperative day (POD) was higher in Group A (2.4 vs. 1.1mg/dl, p = 0.04), while comparable at third POD. Blood transfusion was required in 2 cases in Group A and 1 case in Group B. No patients required embolization. No significant difference was observed in terms of postoperative pain and urinary infection. 24 and 18 Fr pneumatic dilators are both effective to access renal cavity during PCNL for the treatment of renal stones between 10 and 20mm. Gross haematuria rate and mean haemoglobin decrease at first POD were significantly higher with 24 Fr dilator, but with no differences in the need for blood transfusions and renal embolization.

Diabetes Mellitus as a Risk Factor for Complicated Urinary Tract Infections in Kidney Transplant Recipients.

Background: Urinary tract infections (UTIs) are a common complication after kidney transplantation. The aim of this study was to evaluate the impact of pre-existing diabetes mellitus and post-transplant diabetes mellitus (PTDM) on the occurrence of pyelonephritis in kidney transplant recipients. Methods: We performed a retrospective analysis which included 299 adult patients transplanted with a kidney between 2018 and 2022. Patients were categorized into pre-transplantation diabetics, PTDM, and non-diabetics. Asymptomatic bacteriuria and lower urinary infections were not included. Results: During a median follow-up time of 31 [17-45] months, 100 UTIs were reported in the total cohort, with a mean time from transplantation to the first UTI episode of 10 ± 11 months. At 48 months, the cumulative incidence of UTIs was 34.9%, 56%, and 47.3% for patients without prior diabetes, pre-transplant diabetes, and PTDM, respectively. Pre-transplant diabetes was independently associated with 79% increased risk of UTIs (adjusted HR = 1.79, 95% CI = 1.14-2.81, p = 0.011). The risk associated with female gender increased to 85%. Patient survival was not significantly affected by the interaction between diabetes and UTI occurrence. Conclusions: Pre-transplant diabetes arises as a significant risk factor for UTIs after kidney transplantation.

Primary obstructive megaureter in an adult: A case report

Primary obstructive megaureter is an uncommon presentation in adults and warrants aggressive surgical management. The disease is characterized by an intrinsic congenital obstruction at the lower 1 to 2 cm of the ureter just before it enters the bladder. A 21-year-old male presented with left loin pain of 2 months duration. A retrograde uretero-pyelography revealed a dilated whole length of the left ureter except for the terminal 1.5 cm. The patient underwent left sided ureteroneocystostomy. Primary obstructive megaureter is associated with complications such as urinary stones, infections and deterioration of renal function. Surgical correction relieves obstruction and improves drainage.