Urinary Tract Infection Research Articles

Designing potential lead compounds targeting aminoglycoside N (6′)-acetyltransferase in Serratia marcescens: A drug discovery strategy

Serratia marcescens is an opportunistic human pathogen that causes urinary tract infections, ocular lens infections, and respiratory tract infections. S. marcescens employs various defense mechanisms to evade antibiotics, one of which is mediated by aminoglycoside N-acetyltransferase (AAC). In this mechanism, the enzyme AAC facilitates the transfer and linkage of the acetyl moiety from the donor substrate acetyl-coenzyme A to specific positions on antibiotics. This modification alters the antibiotic's structure, leading to the inactivation of aminoglycoside antibiotics. In the current scenario, antibiotic resistance has become a global threat, and targeting the enzymes that mediate resistance is considered crucial to combat this issue. The study aimed to address the increasing global threat of antibiotic resistance in Serratia marcescens by targeting the aminoglycoside N-acetyltransferase (AAC (6′)) enzyme, which inactivates aminoglycoside antibiotics through acetylation. Due to the absence of experimental structure, we constructed a homology model of aminoglycoside N (6′)-acetyltransferase (AAC (6′)) of S. marcescens using the atomic structure of aminoglycoside N-acetyltransferase AAC (6′)-Ib (PDB ID: 1V0C) as a template. The stable architecture and integrity of the modelled AAC (6′) structure were analyzed through a 100 ns simulation. Structure-guided high-throughput screening of four small molecule databases (Binding, Life Chemicals, Zinc, and Toslab) resulted in the identification of potent inhibitors against AAC (6′). The hits obtained from screening were manually clustered, and the five hit molecules were shortlisted based on the docking score, which are observed in the range of −17.09 kcal/mol to −11.95 kcal/mol. These selected five molecules displayed acceptable pharmacological properties in ADME predictions. The binding free energy calculations, and molecular dynamics simulations of ligand bound AAC (6′) complexes represented higher affinity and stable binding. The selected molecules demonstrated stable binding with AAC (6′), indicating their strong potential to hamper the binding of aminoglycoside in the respective site. and thereby inhibit. This process mitigates enzyme mediated AAC (6′) activity on aminoglycosides and reverse the bactericidal function of aminoglycosides, and also this method could serve as a platform for the development of potential antimicrobials.

Micropercutaneous nephrostomy for intervention in acute upper urinary tract calculi obstruction with hydronephrosis and infection

To compare the efficacy and advantages of mini percutaneous nephrostomy (MPCN), micropercutaneous nephrostomy (MicroPCN), and retrograde ureteric stenting (RUS) in the treatment of acute upper urinary tract calculi (UUTC) obstruction with hydronephrosis and infection, and verify the safety and indications of clinical application of micropercutaneous nephrostomy. Clinical-epidemiological data of patients with acute upper urinary tract calculi obstruction and infection treated in Ningbo No.2 hospital were retrospectively collected from May 2019 to May 2023. 64 patients (20 patients in MPCN group, 13 patients in MicroPCN group, and 31 patients in RUS group) were eligible for analysis based on inclusion and exclusion criteria. P value < 0.05 was considered statistically significant. There were no significant differences in peri-intervention temperature, multiple infection indicators and complications among the three groups. The nutritional status and peri-intervention coagulation function of patients in MicroPCN and RUS groups were poor, the CRP and proportion of using carbapenem advanced antibiotics were higher. The length of hospital stay and the length of hospital stay after the intervention in MPCN and MicroPCN groups were longer, the length and width of calculi were larger, and the degree of hydronephrosis was heavier. Patients in the MicroPCN group had the worst general condition, the lowest hemoglobin before intervention, the longest withdrawal time of vasoactive drugs. MPCN, MicroPCN, and RUS are safe and effective in relieving acute upper urinary tract calculi obstruction complicated with infection. MicroPCN has more advantages for patients with critical illness or complex obstruction urinary lithiasis.

Safety and effectiveness of sodium-glucose co-transporter 2 inhibitors in active cancer patients with heart failure: results of the observational TOSCA trial

Abstract Background Sodium-glucose co-transporter 2 inhibitors (SGLT2i) currently represent a pillar of heart failure (HF) treatment. However, cancer patients have not been included in landmark randomized controlled trials (RCTs), and data on safety and effectiveness in this population are lacking. Purpose Purpose of present study was to evaluate safety and effectiveness of SGLT2i in active cancer patients with HF. Methods TOSCA is a multi-centre observational trial including patients (≥ 18 years) with active cancer (diagnosis &amp;lt; 3 years) receiving SGLT2i for HF treatment. Patients were enrolled in two (prospective and retrospective) cohorts. The primary endpoint was safety (incidence of known and unexpected side effects). The secondary endpoint was effectiveness (ejection fraction (EF) increase, New York Heart Association (NYHA) class change, HF-related events). Exploratory endpoints included drug-drug interactions with anticancer and supportive care drugs, treatment of cancer therapy-related cardiac dysfunction (CTRCD), and changes in NT-proBNP. Results Eighty-three pts were enrolled (59 prospective - 24 retrospective). Median age was 71 (range 44-92) yrs, M/F 48/52%. The main cancer sites were breast, gastrointestinal tract, and hematological malignancies. Most cases (62%) received an active treatment (mainly chemotherapy) while on SGLT2i. Prevalent aetiology was drug-induced HF (37%) with reduced EF as the prevalent clinical presentation (39%). Prescribed agents were dapagliflozin in 60% and empagliflozin in 40% of cases on top of conventional guideline-directed medical therapy, with a median treatment duration of 3 (range 3-25) months. The incidence of urinary tract infection was 2.5%. No cases of genital infection, hypoglycemia, diabetic ketoacidosis, acute renal injury, thrombosis, and bone fractures were reported. Mean overall EF slightly increased (44.1% vs. 46.6%), and NYHA class improved (class improvement in 16%). Unplanned cardiology visits (1.2%), i.v. diuretics (1.2%), coronary angiography (5%), emergency access (2.5%), and new HF episodes (3.7%) rates were low. SGLT2i appeared effective in 31 cases of CTRCD. A relative reduction in mean NT-proBNP levels (2748 vs 1125pg/mL) was observed. No drug-drug interactions were reported. Conclusions SGLT2i appear to be safe and effective in active cancer patients with HF, with potential cardioprotective effect. No new safety warnings were recorded.

The relationship between neutrophil/lymphocyte ratio, platelet/neutrophil ratio, and risk of urosepsis in patients who present with ureteral stones and suspected urinary tract infection.

Patients presenting with ureteral stones and concurrent urinary tract infections require prompt kidney drainage as per standard care guidelines. However, even in patients who are promptly drained and treated with appropriate antibiotics, the mortality rate due to urosepsis has been reported to be nearly 9%. Therefore, Predictive tools for early sepsis detection have become essential. The Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) are potential biomarkers for predicting infection risk in these patients. A retrospective cohort analysis involving patients diagnosed with obstructing ureteral stones who underwent urgent stent placement due to suspected urinary tract infection (UTI) in the emergency room (ER) was conducted. The baseline characteristics of patients were age, sex, comorbidities, and urological history. Laboratory data collected during hospitalization included total leukocyte and platelet counts and blood cultures. Ratios were calculated from the serum studies obtained upon admission to the ER. A logistic regression model was utilized to predict the incidence of positive qSOFA score (sepsis prediction score), the need for vasopressors, intensive care unit (ICU) admission, and sepsis, using NLR and PLR as independent variables. Between January 2016 and December 2020, 143 patients with a diagnosis of obstructing ureteral stone were admitted to the ER with a suspected UTI. 11.9% showed a positive qSOFA score, 20.3% required vasopressor support for > 1h after ureteral stent placement, 28.7% required ICU admission, and 16.8% met sepsis criteria. Sepsis was defined as patients who were qSOFA positive and vasopressors needed for more than 1h following stent placement. Logistic regression analysis revealed that PLR and positive blood cultures correlated significantly with positive qSOFA scores. Using logistic regression analysis, PLR, NLR, and positive blood culture were each independent predictors of vasopressor requirements, ICU admission, and urosepsis. NLR and PLR may be valuable prognostic markers for predicting urosepsis risk in urolithiasis patients who present with obstructing stones and concern for systemic infection. Their utility may be in helping clinicians in early risk stratification, prompt intervention, and resource allocation.

Extended Spectrum β-Lactamase: Tackling Antibiotic Resistance and Overcoming Treatment Challenges

Antibiotics, also known as antibacterials, kill or inhibit bacterial growth but are ineffective against viruses, fungi, or parasites, often leading to misuse. They are categorized by molecular structure, mode of action, and spectrum of activity. Antimicrobial Resistance (AMR) occurs when pathogens no longer respond to antimicrobial drugs, arising naturally or through acquisition. Resistance mechanisms include enzymatic (most common), genetic and physical. Bacteria produce various β-lactamases, such as Extended Spectrum β-lactamases (ESBLs), AmpC enzymes, and carbapenemase to exert resistance to Beta-Lactam (βL) class of antibiotics. ESBL families include TEM, SHV, and CTX-M, with E. coli being the most prevalent host. Any Gram-Negative Bacteria (GNB) can be an ESBL producer, but most common ones are the Enterobacteriaceae including Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca and Proteus mirabilis. ESBL-producing Enterobacteriaceae (ESBL-E) resist penicillin, aztreonam, and cephalosporins except cephamycins and carbapenems, posing a significant public health risk. Genetic resistance mechanisms involve random mutations and horizontal gene transfer through either of the following processes namely conjugation, transformation, transduction. Physical mechanisms include efflux pump production and decreased porin channels. In some microbiological laboratories, ESBL production are often not determined, rather resistance based on MIC values to third generation Cephalosporins are considered as resistance due to ESBL production. Antibiotic use in agriculture and medicine has increased Multi-drug resistant (MDR) ESBL-producing E. coli and evidenced in retail meat and among meat shop employees. Community-acquired ESBL-E infections are a growing concern, with hospital transmission primarily occurring among patients sharing rooms with ESBL carriers. Empirical and definitive therapies for ESBL-E infections must be adjusted based on Antibiotic Susceptibility Testing (AST). The MERINO trial identified urinary tract infections as the most common source of ESBL-E bacteremia, with E. coli being predominant. For critically ill patients with non-urinary tract infections, Meropenem or Imipenem-cilastatin are recommended. For uncomplicated UTIs, Nitrofurantoin, Cotrimoxazole, and Piperacillin-Tazobactam (Pip-Taz) are effective, while Cotrimoxazole, Fluoroquinolones, and Ceftolozane-tazobactam are suitable for complicated UTIs. New β-lactamase inhibitors like avibactam, vaborbactam, and relebactam are promising for treatment. Misuse of antibiotics, such as inappropriate dosing and duration, contributes to AMR, a growing global challenge. Deaths from AMR, estimated at 1.27 million in 2019, could reach 10 million by 2050. ESBLs drive the use of broad-spectrum antibiotics, accelerating resistance development. Inadequate therapy exacerbates infections, leading to prolonged hospital stays, complications, and increased mortality. Balancing new drug development with resistance emergence is crucial to combat AMR.

Multifaceted Control Interventions for Healthcare-associated Infections in a Kidney Transplant Intensive Care Unit: Clinical Outcome Improvement and Bundle Adherence.

Healthcare-associated infections (HAIs) are preventable complications that overwhelm the healthcare system. The implementation of multifaceted control intervention actions in the intensive care setting modifies clinical outcomes, but its effectiveness has not been specifically investigated for high-risk patients, such as kidney transplant recipients (KTRs). This observational retrospective natural experiment evaluated the effectiveness of multifaceted control interventions (bundles) in reducing HAIs in a KTR intensive care unit. We also measured the bundle adherence rate during 16 mo in the after era. We included 1257 KTRs, 684 before and 573 in the postintervention period. After the bundle implementation, the incidence density of device-associated HAIs decreased from 8.5 to 3.9 per 1000 patient-days (relative risk [RR] = 0.46; 95% confidence interval [CI], 0.25-0.85; P = 0.01), primarily because of the reduction in central line-associated bloodstream infection from 8.0 to 3.4 events per 1000 catheter-days (RR = 0.43; 95% CI, 0.22-0.83; P = 0.012). Reductions in catheter-associated urinary tract infection (2.5 versus 0.6 per 1000 catheter-days; RR = 0.22; 95% CI, 0.03-1.92; P = 0.17) and ventilator-associated pneumonia (3.4 versus 1.0 per 1000 ventilator-days; RR = 0.29; 95% CI, 0.03-2.63; P = 0.27) were not significant. Central venous (P = 0.53) and urinary catheter (P = 0.47) insertion adherence were stable during 16 mo, whereas central venous (P < 0.001) and urinary catheter (P = 0.004) maintenance gradually increased. Finally, ventilator-associated pneumonia prevention bundle adherence slightly decreased over time (P = 0.06). The implementation of comprehensive multifaceted control intervention actions in an intensive care unit dedicated to KTR care was effective in significantly reducing device-associated infections. The impact was in line with the reductions observed in populations that have not undergone transplantation, underscoring the effectiveness of these interventions across different patient groups.

Is it worth using the Comprehensive Complication Index over the Clavien-Dindo classification in elderly patients who underwent percutaneous nephrolithotomy?

To compare the Comprehensive Complication Index (CCI) to the Clavien-Dindo classification (CDC) in an elderly population who underwent percutaneous nephrolithotomy (PCNL) and to identify predictors of postoperative complications in this population. We conducted a retrospective cohort study involving patients 60years and older who underwent PCNL at our Institution between 2009 and 2020. Postoperative complications were considered up to 30days after surgery. Both CDC and CCI were calculated to assess patient outcomes. Length of stay (LOS) and admission to the emergency room (ER) were used as surrogates of postoperative complications. We included 244 patients with a median age of 65 [63-69] years. 15.6% presented postoperative complications, and 2.5% multiple complications. LOS had a correlation coefficient of 0.29 (p < 0.001) and ER admissions had a coefficient of 0.27 (p < 0.001) with both CDC and CCI. Cost of hospitalization based on CDC underestimated CCI-based cost of hospitalization in 0.8% (p = 0.049). Higher American Society of Anesthesiology (ASA) physical status (p = 0.02), Charlson Comorbidity Index (p = 0.008), Guy's classification (p = 0.005), and history of urinary tract infection (UTI, p = 0.047) exhibited significant correlations with postoperative complications. Both CDC and CCI equally correlate with LOS and ER admissions following PCNL in elderly patients. However, CDC underestimates cost of hospitalization in comparison to CCI. We found higher ASA physical status, Charlson Comorbidity Index, Guy's classification, and history of UTI as predictors of postoperative complications after this procedure in this population.

Laparoscopic colon surgery: time to leave the urinary catheter in the operating room?

'Fast track' guidelines have incorporated multimodal measures to optimize perioperative outcomes in surgery, with laparoscopy being a pivotal component for its advantages in early recovery. In this setting,current recommendations regarding the use of aurinary catheter suggest its removal within the first 24-hours postoperatively. However,few studies have assessed the feasibility of leaving the operating room without it. The purpose of this study is to compare the perioperative outcomes of patients undergoing elective laparoscopic colonic resections leaving the operating room with and without a urinary catheter. A retrospective study was conducted utilizing prospectively collected data from patients undergoing elective colon resections over a 17-month period. The patients were classified into two groups based on the presence or absence of a urinary catheter upon leaving the operating room, and subsequently, their perioperative outcomes were compared. A total of 107 patients met the inclusion criteria (n = 28 with a urinary catheter and n = 79 without). Cancer was the most prevalent diagnosis (83.2%), and right hemicolectomy the most frequently performed surgery (32.7%). Two events of urinary catheter reinsertions were reported, both in the no-catheter group (0% vs 2.53%, p = 0.969), andthere were no cases of urinary tract infections. The overall and severe complications ratesexhibited no significant differences (25% vs. 26.6%, p = 1, and 7.14% vs. 5.06%, p = 1)and the length of stay was similar (p = 0.220). Removing the urinary catheter before leaving the operating room appears to be safe and associated with very low rates of urinary retention in selected patients undergoing laparoscopic colonic or upper rectal resections.

Emphysematous pyelonephritis caused by Raoultella ornithinolytica: a case report

BackgroundEmphysematous pyelonephritis is a rare and severe urinary tract infection that is potentially life-threatening and easily progresses to septic shock. In this report, we present a unique case of emphysematous pyelonephritis caused by Raoultella ornithinolytica.Case presentationAn 86-year-old man presented with severe back pain of 3 days’ duration. He had a history of hypertension and diabetes for more than 20 years, and his infection indicators and serum creatinine were elevated. Abdominal computed tomography revealed an abnormal gas shadow around his right kidney and the anterior edge of his right psoas muscle. Consequently, he was initially diagnosed with emphysematous pyelonephritis. There was no evidence of nephrolithiasis or other anatomical or structural abnormalities that could have precipitated this focal renal infection. Both blood and drainage fluid cultures revealed R. ornithinolytica. After early anti-infection treatment, percutaneous drainage and moderate control of blood glucose, the patient gradually recovered.ConclusionsEmphysematous pyelonephritis caused by R. ornithinolytica is rare but has a high drug resistance rate potentially and may cause severe infections. Early diagnosis, prompt use of antibiotics that are sensitive to the organism, and decompression drainage could be the key to treatment.

Mimicking Urinary Tract Infections Caused by Uropathogenic Escherichia coli Using a Human Three-Dimensional Tissue Engineering Model.

Uropathogenic Escherichia coli are the main causal agent of urinary tract infections. These diseases can affect more than half of women during their lifetime. Moreover, recurrent urinary tract infections can affect up to 30% of patients, leading to higher social and economic costs for the community. No efficient treatment against the recurrent form of the disease has been discovered. Due to the low average rate of successful translation from 2D cell culture and in vivo animal models into clinical trials, new models that mimic pathologies, such as those produced by tissue engineering, are needed. A model of human-derived 3D bladder mucosa was produced by tissue engineering techniques using collagen gels and organ-specific primary human stromal and epithelial cell populations. This model was used to mimic the different steps of a urinary tract infection: adhesion, invasion, intracellular bacterial community and quiescent intracellular reservoir formation and, finally, bacteria resurgence after umbrella cell exfoliation through chitosan exposure to mimic the recurrent infection. The uropathogenic strain UTI-89-GFP was used as infectious bacteria and BL-21-GFP strain as a control. Our model is unique and is the first step toward mimicking the different phases of a UTI in a human context.

Urogenital colonization and pathogenicity of E. Coli in the vaginal microbiota during pregnancy

This study explores the role of the vaginal microbiota (VM) in the pathophysiology of asymptomatic bacteriuria (ASB) in a cohort of 1,553 pregnant women. Worldwide, E. coli remains the most common etiological agent of bacteriuria during pregnancy and also a major causative agent of newborn infections. A healthy VM is typically characterized by low diversity and is dominated by lactic acid-producing species, notably those from the Lactobacillus genus. Our results point to decreases in Lactobacillus spp associated with an increase of gut-microbiota-associated species from the Enterobacterales order. Escherichia coli exhibited the most pronounced increase in abundance within the VM during bacteriuria and was notably associated with ASB. Molecular typing and antimicrobial resistance characterization of 72 metagenome assembled E. coli genomes (MAGs) from these pregnant women revealed a genomic signature of extraintestinal pathogenic E. coli (“ExPEC”) strains, which are involved in various extraintestinal infections such as urinary tract infections, newborn infections and bacteremia. Microbial diversity within the vaginal samples from which an E. coli MAG was obtained showed a substantial variation, primarily marked by a decrease in abundance of Lactobacillus species. Overall, our study shows how disruption in key bacterial group within the VM can disrupt its stability, potentially leading to the colonization by opportunistic pathogens.

Kidney Transplantation in Patients with Polycystic Kidney Disease: Increased Risk of Infection Does Not Compromise Graft and Patient Survival

Abstract Background Patients with autosomal dominant polycystic kidney disease (ADPKD) represent &amp;gt;10% of patients awaiting kidney transplantation. These patients are prone to potentially severe urinary tract (UTI) and liver cyst infections after transplantation. Whether such infections compromise outcome is unclear. Methods Between 2000 and 2017 we performed 193 kidney transplantations in patients with ADPKD. In 189 patients we assessed the occurrence, frequency and severity of infection episodes requiring inpatient treatment and their impact on graft and patient outcomes compared with 189 matched controls. Risk factors were analyzed by uni- and multivariable analyses. Results During a mean observation period of 77 months UTIs occurred more frequently in ADPKD patients (39.1% vs. 26.7%, p=0.022; 0.8±1.4 vs. 0.5±1.1 episodes, p&amp;lt;0.001). Eight ADPKD patients suffered from 19 episodes of liver cyst infection. Steroid medication (RR 3.04; p&amp;lt;0.001) and recipient age (RR 1.05; p=0.003) increased the risk for UTI/urosepsis, while nephrectomy reduced it (unilateral: RR 0.60; p=0.088; bilateral: RR 0.45; p=0.020). Patient survival was similar in both groups. The risk of graft failure was lower in ADPKD patients (HR 0.67; p=0.047) due to a lower risk of death-censored graft loss (HR 0.47; p=0.014). Donor age (HR 1.34; p=0.002) and rejection (HR 8.47; p&amp;lt;0.001) were risk factors for death-censored graft loss. Conclusions ADPKD patients are at increased risk of UTI and liver cyst infection after transplantation. Steroid medication and recipient age seem to increase the risk of UTI/urosepsis, while nephrectomy seems to reduce it. Nevertheless, patient survival was similar compared to non-ADPKD patients and death-censored graft survival even better.

Clinical determination of the natural distensibility of the human ureter: initial study.

To define the natural distensibility of the human ureter and evaluate the impact of other possibly favourable factors on ureteric distensibility. A total of 101 patients undergoing ureteroscopic stone removal or percutaneous nephrolithotomy underwent ureteric sizing using sequential passage of 37-cm urethral dilators in 2-F increments while attached to a unique force sensor. Insertion forces were limited to 6 N. After 6 N was attained, an appropriately sized ureteric access sheath was passed. At the conclusion of each procedure, Post-Ureteroscopic Lesion Scale score was determined. Urethral dilators were passed in 61% of patients at ≤14 F; 39% of patients accepted urethral dilators of ≥16 F. The mean dilator size was 14 F. Multivariate logistic regression analysis revealed that preprocedural ureteric stenting and antibiotic use favoured passage of 16-F dilators (odds ratio [OR] 5.16, 95% confidence interval [CI] 1.70-15.62 [P = 0.004] and OR 5.15, 95% CI 1.743-15.243 [P = 0.003], respectively). Neither tamsulosin nor prior urinary tract infection had an impact on ureteric size (OR 0.765, 95% CI 0.281-2.084 [P = 0.601], OR 1.049, 95% CI 0.269-4.089 [P = 0.945], respectively). Using continuous insertion force monitoring and a 6-N threshold, the majority of unstented adult human ureters within our patient population safely accommodated a 14-F dilator. Safe passage of a 16-F dilator at the 6-N threshold was more likely among patients with a preexisting indwelling ureteric stent or patients who were treated with antibiotics within a week of the procedure.

Prescription of antibiotics for urinary tract infections in outpatient care in Bavaria: An analysis of routine data.

Patients with urinary tract infection (UTI) in German outpatient care are usually treated by general practitioners (GPs), as well as by other specialties. To prevent antibiotic resistances and side effects, German guidelines recommend fosfomycin, nitrofurantoin, pivmecillinam and nitroxoline as first-line treatments, and advice against broad-spectrum antibiotics such as fluoroquinolones and cephalosporins. However, data from the European Centre for Disease Prevention and Control indicates a significant proportion of second-line antibiotics in German outpatient care. Our aim was to analyze whether antibiotic prescription has changed over time in accordance with guidelines. In addition, we aimed to investigate whether specialties prescribe different antibiotics for UTIs and whether prescription varies according to patient age and sex. For patients receiving more than one antibiotic, we wanted to determine whether subsequent prescriptions show a change in substances and specialties involved. This retrospective study involved routine data (2013 to 2019) provided by the Bavarian Association of Statutory Health Insurance Physicians. Data on diagnoses and prescriptions were transmitted from outpatient care physicians on a quarterly basis. UTI patients ≥12 years were included. We analyzed 1.7 million UTI prescription cases. In females, shares of fluoroquinolones decreased sharply over time, while shares of first-line substances fosfomycin and pivmecillinam increased. Gynecologists showed the highest shares of first-line substances compared to GPs and urologists. Fluoroquinolone shares decreased in all three specialty groups. In females, older patients showed lower shares of first-line substances than younger patients. If a second or third antibiotic was prescribed, fosfomycin shares decreased, while shares of nitrofurantoin, nitroxoline and cephalosporins increased. Our findings show a trend towards a more guideline-adherent prescribing in the treatment of UTI, with a significant increase of shares of fosfomycin and pivmecillinam, especially in women, and a sharp decrease of shares of fluoroquinolones.

Distinct maternofetal immune signatures delineate preterm birth onset following urinary tract infection.

Preterm birth is the leading cause of infant mortality resulting in over one million neonatal deaths annually. Maternal urinary tract infection (UTI) during pregnancy increases risk for preterm birth; however, biological processes mediating UTI-associated preterm birth are not well-described. We established a murine maternal UTI model in which challenge with uropathogenic E. coli resulted in preterm birth in about half of dams. Dams experiencing preterm birth displayed excessive bladder inflammation and altered uteroplacental T cell polarization compared to non-laboring infected dams, with no differences in bacterial burdens. Additional factors associated with preterm birth included higher proportions of male fetuses and lower maternal serum IL-10. Furthermore, exogenous maternal IL-10 treatment absolved UTI-associated preterm birth but contributed to fetal growth restriction in this model. Using urine samples from a cohort of human pregnancies with or without UTI, we correlated urinary cytokines with birth outcomes and urine culture status. These analyses yielded a non-invasive, highly predictive three-model system for evaluating preterm birth risk implicating cytokines IL-10, IL-15, IL-1β, and IL-1RA. Our unique bimodal murine model coupled with patient samples provides a platform to investigate immunological and microbial factors governing UTI-associated preterm birth, revealing novel therapeutic opportunities to predict or prevent preterm birth.

Consumption of cranberry and probiotics as a natural remedy for urinary tract infections

Introduction and PurposeUrinary tract infections (UTIs) are a prevalent health issue caused primarily by uropathogenic Escherichia coli (UPEC) and other pathogens, affecting millions annually. These infections encompass lower (cystitis) and upper (pyelonephritis) tract manifestations, presenting with symptoms ranging from dysuria to severe complications like sepsis. Traditional antibiotic treatments, while effective, are increasingly challenged by resistance and adverse effects, necessitating exploration of alternative therapies. Cranberry-derived compounds, particularly proanthocyanidins (PACs), are known for their ability to inhibit bacterial adhesion to uroepithelial cells, a critical step in UTI pathogenesis. Clinical studies suggest that cranberry products may reduce UTI incidence, especially in vulnerable populations such as women and catheterized patients. Probiotics, specifically lactobacilli, contribute to urogenital health by competing with uropathogens for epithelial cell binding sites and producing antimicrobial substances. Emerging research highlights the potential synergistic benefits of combining cranberry extracts with probiotics in UTI prevention strategies. Material and MethodsThis review is based on articles from the PubMed database, covering the years 2004-2023, using keywords: urinary tract infections, cranberry, probiotics, E. Coli, antibiotics ConclusionsCranberry products and probiotics offer promising non-antibiotic approaches for UTI prevention, targeting fundamental aspects of bacterial pathogenesis. While preliminary studies indicate promising outcomes, rigorous clinical trials are essential to validate these combinations and optimize therapeutic protocols. Further research is warranted to identify specific bioactive compounds within cranberries, standardize probiotic formulations, and establish comprehensive guidelines for their clinical use in UTI management.

Systematic Review and Meta-Analysis of Total Elbow Arthroplasty in Outpatient Versus Inpatient Settings.

Total joint arthroplasties, including total elbow arthroplasty (TEA), are growing in number and shifting towarda younger age group. These procedures are also moving more towardthe outpatient setting compared to previous years. We are conducting this study to update and summarize the current knowledge about the outcomes of TEA in outpatient versus inpatient settings.We conducted a systematic review and meta-analysis using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework to compare TEA outcomes in outpatient versus inpatient settings. Electronic database searches were performed using PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Google Scholar. Previous studies deemed eligible for this study focused on inpatient cohortsand outpatient cohortsor compared inpatient and outpatient cohorts receiving TEA. Alldata used was obtained from the studiesthat were included.Three studies were deemed eligible and included a total of 1,634 patients, with 1,048 being inpatient and 586 being outpatient. There was a significant increase in total (any) complication rate (log of odds ratio (lnOR): 1.02, 95% CI: 0.35 to 1.68), adverse discharge (lnOR: 1.07, 95% CI: 0.22 to 1.92), and surgical site infection (lnOR: 0.88, 95% CI: 0.05 to 1.71) in the inpatient setting compared to the outpatient setting. There was no significant difference between outpatient and inpatient settings in regard to readmissions (lnOR: 0.85, 95% CI: -0.95 to 2.66), urinary tract infections (UTI)/renal complications (lnOR: 0.04, 95% CI: -0.09 to 0.17), pneumonia/respiratory failure (lnOR: 0.61, 95% CI: -0.29 to 1.51), deep vein thrombosis (DVT)/pulmonary embolism (lnOR: 0.07, 95% CI: -1.31 to 1.44), sepsis (lnOR: 0.86, 95% CI: -0.50 to 2.21), and wound dehiscence (lnOR: 0.55, 95% CI: -0.58 to 1.68).Our results reveal that with careful patient selection, current surgical techniques, and pain control methods, TEA may be performed in the outpatient setting with less risk of complications and lower financial burden compared to inpatient TEA.

ECLIPSES: Early initiation of sodium glucose cotransporter-2 inhibitors for cardiovascular protection in patients with type 2 diabetes following acute coronary syndrome and subsequent coronary artery bypass graft surgery.

There is a paucity of data evaluating early initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with diabetes following acute coronary syndrome (ACS) and coronary artery bypass graft surgery (CABG). To describe the efficacy and safety of SGLT2i initiated early after CABG in patients with type 2 diabetes who experienced ACS. This is a retrospective cohort study of patients with type 2 diabetes (T2DM) who experienced ACS and subsequent CABGwith follow up at 3 and 12 months. Patients who filled a SGLT2i prescription within 14 days of discharge were allocated to the SGLT2i group and those who did not were included in the no SGLT2i group. The primary efficacy end point was first occurrence of a 4-point Major Adverse Cardiovascular Event (MACE), and the primary safety end point was a composite of hypoglycemia, hypotension, diabetic ketoacidosis, acute kidney injury, and urinary tract infection. Secondary end points included a comparative analysis of the primary outcome, 30-day readmission rates, and subgroup analyses of key populations. A total of 1629 patients were included: 226 received a SGLT2i within 14 days of discharge and 1403 did not. At 12 months, 8.9% and 15.3% of patients experienced MACE in the SGLT2i and no SGLT2i groups, respectively (adjusted Hazard Ratio [aHR] 0.65, 95% confidence interval [CI] 0.41-1.04). The primary safety outcome occurred in 12.0% of the SGLT2i group and 19.1% of the no SGLT2i group at 12 months (aHR 0.68, 95% CI 0.45-1.01). Early initiation of SGLT2i use was not associated with a reduction in MACE in patients with T2DM who experienced ACS and underwent subsequent CABG surgery. However, no apparent safety concerns were identified. Adequately powered trials are required to confirm this finding.

MaxEnt modeling of Klebsiella pneumoniae: predicting future distribution and evaluating the risk for public health

Klebsiella pneumoniae is a Gram-negative bacterium known for causing infections such as pneumonia, urinary tract infections, and bloodstream infections in humans. Its increasing drug resistance poses a significant threat. Understanding the effects of climate change on this bacterium is crucial to managing its impacts effectively. In this study, we employed MaxEnt modeling to explore the current and future distribution of K. pneumoniae under different climate change scenarios for 2050 and 2070. Our models utilized 280 valid occurrence points and 19 bioclimatic variables, with Mean Annual Temperature and Mean Annual Precipitation being the most influential variables. The models demonstrated high accuracy, with an AUC of 0.889. Our findings revealed that K. pneumoniae has a cosmopolitan distribution, with the highest suitability observed in Southeastern Asia, Central Africa, and Southern Europe. Future predictions indicated an apparent expansion of its range across almost all continents, particularly in the RCP 8.5 2070 scenario. Results have crucial implications for epidemiology, as they enable the identification of current and potential future disease hotspots and geographical patterns. This knowledge can inform the development of effective infection control strategies. Furthermore, it provides valuable insights for decision-makers and policymakers in allocating resources efficiently for medical control and prevention strategies.

Polypharmacy in elective lumbar spinal surgery for degenerative conditions with 24-month follow-up

We sought to identify long-term associations of medical complications and healthcare utilization related to polypharmacy following spinal surgery for degenerative lumbar pathology. The IBM MarketScan dataset was used to select patients who underwent spinal surgery for degenerative lumbar pathology with 2-year follow-up. Regression analysis compared two matched cohorts: those with and without polypharmacy. Of 118,434 surgical patients, 68.1% met criteria for polypharmacy. In the first 30 days after discharge, surgical site infection was observed in 6% of those with polypharmacy and 4% of those without polypharmacy (p < 0.0001) and at least one complication was observed in 24% for the polypharmacy group and 17% for the non-polypharmacy group (p < 0.0001). At 24 months, patients with polypharmacy were more likely to be diagnosed with pneumonia (48% vs. 37%), urinary tract infection (26% vs. 19%), and surgical site infection (12% vs. 7%), (p < 0.0001). The most prescribed medication was hydrocodone (60% of patients) and more than 95% received opioids. Two years postoperatively, the polypharmacy group had tripled overall healthcare utilization payments ($30,288 vs. $9514), (p < 0.0001). Patients taking 5 or more medications concurrently after spinal surgery for degenerative lumbar conditions were more likely to develop medical complications, higher costs, and return to the emergency department.