Should we review our prophylaxis approach for increased antibiotic resistance in transrectal prostate biopsy?

INTRODUCTION: This study aims to show the bacteriologic picture of acute prostatitis and bacteremia caused by infective agent after transrectal ultrasound-guided prostate biopsy (TRUSBx) and to determine the resistance rates of the infections in patients undergoing transrectal biopsy and to guide prophylaxis approach before biopsy. METHODOLOGY: The retrospective data of 935 patients who underwent TRUSBx between January 2010 to January 2019 were reviewed. Pre-biopsy urine cultures and antimicrobial susceptibility were obtained. Subsequently, patients admitted to the hospital with any complaint after biopsy were examined for severe infection complications. RESULTS: Of the 430 (61.7%) patients who underwent urine culture before the procedure, 45 (10.5%) had growth; 30 (66.7%) of the growing microorganisms were Escherichia coli. Twenty (44.4%) of all Gram-negative agents in pre-biopsy urine culture were susceptible to quinolone. Post TRUSBx bacteremia was present in 18.2%, urinary system infection in 83.6%, and hospitalization in 61.8% of 55 patients who were admitted to the hospital. In the isolated gram-negative microorganisms, fluoroquinolones resistance in urinary system infections was seen in 40% and bacteremia was seen in 70% of the cases. ESBL-producing Gram-negative bacteria were determined in 40% of infections in blood and 38.5% of urinary system infections in the post biopsy period in the current study. CONCLUSIONS: These high antibiotic resistance rates suggest that we better review our pre-procedure prophylaxis approaches.

The Urinary Microbiome: Improving Diagnostics and Management of Urinary Tract Infections in Adult Females.

This article discusses the urinary microbiome in relation to urinary tract infection (UTI) in women. It makes biologic sense that the microbiota of different niches (bladder, vagina, and gut) interact with each other in health, as well as during a UTI event; however, these relationships remain poorly understood. Future research should close knowledge gaps regarding the interactions between the urinary microbiota and the host, amongst the microbiota of adjacent niches, and between the microbes within the same microbiota. The new knowledge should result in improved UTI treatment in the age of antibiotic stewardship.

Cefepime-taniborbactam and CERTAIN-1: Can we treat carbapenem-resistant infections?

Wagenlehner and colleagues1 demonstrated non-inferiority and superiority with respect to a primary endpoint of composite success (microbiological plus clinical) of cefepime/taniborbactam vs. meropenem in treating complicated urinary tract infections and acute pyelonephritis caused by carbapenem-susceptible gram-negative bacteria in adults. A major area of interest in real-world application of cefepime/taniborbactam is its potential role in treating carbapenem-resistant infections, which deserves further investigation.

Turbidimetric bioassays: A solution to antimicrobial activity detection in asymptomatic bacteriuria isolates against uropathogenic Escherichia coli.

Traditional bacteriocin screening methods often face limitations due to diffusion-related challenges in agar matrices, which can prevent the peptides from reaching their target organism. Turbidimetric techniques offer a solution to these issues, eliminating diffusion-related problems and providing an initial quantification of bacteriocin efficacy in producer organisms. This study involved screening the cell-free supernatant (CFS) from eight uncharacterized asymptomatic bacteriuria (ABU) isolates and Escherichia coli 83972 for antimicrobial activity against clinical uropathogenic E. coli (UPEC) strains using turbidimetric growth methods. ABU isolates exhibiting activity against five or more UPEC strains were further characterized (PUTS 37, PUTS 58, PUTS 59, S-07-4, and SK-106-1). The inhibition of the CFS by proteinase K suggested that the antimicrobial activity was proteinaceous in nature, potentially bacteriocins. The activity of E. coli PUTS 58 and SK-106-1 was enhanced in an artificial urine medium, with both inhibiting all eight UPECs. A putative microcin H47 operon was identified in E. coli SK-106-1, along with a previously identified microcin V and colicin E7 in E. coli PUTS 37 and PUTS 58, respectively. These findings indicate that ABU bacteriocin-producers could serve as viable prophylactics and therapeutics in the face of increasing antibiotic resistance among uropathogens.

Bacterial aetiology, antimicrobial susceptibility patterns, and factors associated with urinary tract infection among under-five children at primary health facility, North-Western Tanzania.

BACKGROUND: Urinary tract infections (UTI) are common in under-five children, with significant consequences leading to bacteremia, dehydration, kidney scarring, and renal failure. The incidence of UTI varies with patients' demographics and geographic location. Limited studies have addressed UTI issues, particularly in children. We determined the proportion of UTI, bacterial aetiology, and antimicrobial susceptibility patterns and associated factors among under-five children at the district hospital between March and April 2023. METHODS: We conducted a cross-sectional study using a convenient non-probability sampling technique to collect urine samples from participants with signs and symptoms of UTI. Written informed consent was obtained from parents or guardians. We collected Participants' information using a pretested structured questionnaire. Urine samples were processed at the Regional Referral Hospital. All analyses were conducted using STATA version 15.0. We determined the factors associated with UTI using a modified Poisson model multivariable analysis of the modified Poisson model. The results were presented as a prevalence ratio and 95% confidence interval. The level of significance was specified at 0.05. RESULT: The study recruited 368 under-five children; 194 (52.7%) were males, and the median age (interquartile range) was 24 (13-36) months. Of all, 28.8% (95% CI-24.3-33.6) had culture-confirmed UTI. One hundred and six pathogens were isolated, the majority being Escherichia coli (E. coli), 37 (34.9%), and Staphylococcus aureus (S. aureus), 26 (24.5%). The susceptibility of E. coli to cefepime, piperacillin-tazobactam, nitrofurantoin, and meropenem ranged from 81.1% to 97.3%. S. aureus was most susceptible to nitrofurantoin (96.2%) and ciprofloxacin (92.3%). Multidrug resistance was observed in 33.0% of isolates. The proportion of Methicillin-resistant S. aureus and extended-spectrum beta-lactamases was 23.1% and 25%, respectively. UTI was observed more in patients presenting with vomiting, dysuria, and abdominal pain, patients below 24 months of age, nappy users, and uncircumcised males. CONCLUSION: Our study found a relatively high proportion of UTI among under-five children associated with vomiting, dysuria, abdominal pain, nappy use, and uncircumcision in males. The pathogens were least susceptible to (trimethoprim-sulfamethoxazole, gentamycin, ampicillin, and penicillin) the commonly used antibiotic. We advocate a thorough clinical analysis to detect the predictors of UTI and a periodic review of empirical treatment of UTI based on the antibiotic susceptibility pattern.

Risk Factors for Urinary Tract Infection in Elderly Patients with Type 2 Diabetes: A Retrospective Cohort Study.

OBJECTIVE: The risk factors of urinary tract infection in elderly patients with type 2 diabetes were investigated. METHODS: A total of 72 elderly patients admitted to our hospital from December 2019 to September 2023 because of with type 2 diabetes were retrospectively included. They were divided into the observation group (n = 35) and control group (n = 37) according to whether they had urinary tract infection. The general clinical data, clinical characteristics and the distribution of pathogenic bacteria in the observation group were collected and analysed. Then, t-tests, chi-square tests, regression analysis and receiver operating characteristic curve analysis were conducted. RESULTS: Escherichia coli (E. coli) accounted for 51.43% of the pathogenic bacteria in the observation group, whereas Klebsiella pneumoniae (K. pneumoniae) accounted for 22.86%. The remaining pathogens accounted for 2.86% each. Differences in gender, course of disease, glycosylated haemoglobin and comorbid urinary calculi were found between the groups (p < 0.05); These factors were all risk factors for concurrent urinary infection, and the odds ratios were all >1. The obtained values for gender, disease course, glycosylated haemoglobin and comorbid urinary calculi were respectively 0.594, 0.654, 0.738 and 0.696 (area under the curve); 0.971, 0.714, 0.800 and 0.743 (sensitivity); 0.216, 0.595, 0.676 and 0.649 (specificity); And 0.188, 0.309, 0.476 and 0.392 (Youden index). CONCLUSIONS: Common pathogens in elderly people with type 2 diabetes and comorbid urinary tract infection are E. coli and K. pneumoniae. Risk factors include gender, disease duration, glycosylated haemoglobin and urinary stones. The prompt identification of pathogens and risk factors facilitates clinical treatment, reducing infection incidence.

Epidemiology and risk factors for staphylococcal urinary tract infections in the Moroccan Casablanca area.

PURPOSE: This study aimed to ascertain the prevalence and risk factors for developing staphylococcal urinary tract infections (UTIs) in the Casablanca area of Morocco. METHODS: In Casablanca, Morocco, a retrospective evaluation of 772 UTIs patients was conducted between January 2020 and December 2022. The research included two groups of patients: those with staphylococcal UTIs and those without. Sex, age, chronic illnesses, antibiotic exposure, urinary catheterization, urological surgery, and UTIs history were the risk variables assessed. We employed a logistic regression model to identify the characteristics that were predictive of staphylococcal UTIs. RESULTS: Eight staphylococcal species were responsible for 16.84% of UTIs in 772 non-repeating individuals. Patients infected with S. saprophyticus (35.38%) were the most common, followed by those infected with S. epidermidis (24.61%), S. aureus (13.85%), and S. hemolyticus (10.78%). Multivariate logistic regression analysis revealed that male sex (95% CI: 0.261-0.563), immunosuppression and immunosuppressive treatments (95% CI: 0.0068-0.64), chronic diseases (95% CI: 0.407-0.965), previous UTIs (95% CI: 0.031-0.228), frequency of urination more than 8 times a day (95% CI:1.04-3.29), frequency of urination once or twice a day (95% CI: 1.05-2.39), and urinary catheterization (95% CI: 0.02-0.22) were the most likely predictors of staphylococcal UTIs. In addition, a larger proportion of patients with staphylococcal UTIs were made aware of the risk factors associated with staphylococcal UTIs (52.31%, χ2 = 4.82, = 0.014). CONCLUSIONS: This is the first global study to evaluate the predictive factors for acquiring UTIs caused by staphylococci. Monitoring these factors will enable medical authorities to devise effective strategies for managing UTIs and combating antibiotic resistance.

Gentamicin loaded niosomes against intracellular uropathogenic Escherichia coli strains.

Urinary tract infections (UTIs) are the most common bacterial infections and uropathogenic Escherichia coli (UPEC) is the main etiological agent of UTIs. UPEC can persist in bladder cells protected by immunological defenses and antibiotics and intracellular behavior leads to difficulty in eradicating the infection. The aim of this paper is to design, prepare and characterize surfactant-based nanocarriers (niosomes) able to entrap antimicrobial drug and potentially to delivery and release antibiotics into UPEC-infected cells. In order to validate the proposed drug delivery system, gentamicin, was chosen as "active model drug" due to its poor cellular penetration. The niosomes physical-chemical characterization was performed combining different techniques: Dynamic Light Scattering Fluorescence Spectroscopy, Transmission Electron Microscopy. Empty and loaded niosomes were characterized in terms of size, ζ-potential, bilayer features and stability. Moreover, Gentamicin entrapped amount was evaluated, and the release study was also carried out. In addition, the effect of empty and loaded niosomes was studied on the invasion ability of UPEC strains in T24 bladder cell monolayers by Gentamicin Protection Assay and Confocal Microscopy. The observed decrease in UPEC invasion rate leads us to hypothesize a release of antibiotic from niosomes inside the cells. The optimization of the proposed drug delivery system could represent a promising strategy to significatively enhance the internalization of antimicrobial drugs.

Diagnosing and Managing Urinary Tract Infections in Kidney Transplant Recipients.

In the article, the authors review antibiotic treatment options for both acute uncomplicated UTI and complicated UTI. In addition, they review alternative regimens which are needed in the setting of drug-resistant pathogens including vancomycin-resistant Enterococcus, -extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales, and carbapenem-resistant Pseudomonas, which are encountered with more frequency.

Sepsis risk in diabetic patients with urinary tract infection.

BACKGROUND: Urinary tract infections (UTI) is a prevalent condition in those with diabetes, and in severe cases, it may escalate to sepsis. Therefore, it is important to analyze the risk variables associated with sepsis in diabetes individuals with UTI. METHODS: This research was a retrospective cross-sectional analysis. From January 2011 to June 2022, a group of individuals with diabetes were identified as having UTI at a tertiary hospital situated in Southeastern China. Patient data, including information on urine culture, was collected retrospectively from a clinical record database. The participants were categorized into the sepsis and non-sepsis groups. The risk variables were derived using both uni-and multiple- variable regression analysis. RESULTS: The research included 1919 patients, of whom 1106 cases (57.63%) had positive urine cultures. In total, 445 blood culture samples were tested, identifying 186 positive cases (41.80%). The prevalence of bacteria in urine and blood samples was highest for Escherichia coli and Klebsiella pneumoniae, respectively. Moreover, 268 individuals (13.97%) exhibited sepsis. The regression analysis indicated a positive correlation between sepsis and albumin (ALB)<34.35 g/L, C-reactive protein (CRP)>55.84 mg/L and white blood cell count (WBC) >8.485 X 109/L in diabetic cases with UTIs. By integrating the three aforementioned parameters, the area under the receiver operating characteristic curve was 0.809. CONCLUSIONS: The early detection of sepsis in diabetic individuals with UTI may be achieved using a comprehensive analysis of CRP, WBC, and ALB test findings.

Antibiotic susceptibility patterns and trends of the gram-negative bacteria isolated from the patients in the emergency departments in China: results of SMART 2016-2019.

BACKGROUND: The study aims were to evaluate the species distribution and antimicrobial resistance profile of Gram-negative pathogens isolated from specimens of intra-abdominal infections (IAI), urinary tract infections (UTI), respiratory tract infections (RTI), and blood stream infections (BSI) in emergency departments (EDs) in China. METHODS: From 2016 to 2019, 656 isolates were collected from 18 hospitals across China. Minimum inhibitory concentrations were determined by CLSI broth microdilution and interpreted according to CLSI M100 (2021) guidelines. In addition, organ-specific weighted incidence antibiograms (OSWIAs) were constructed. RESULTS: Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) were the most common pathogens isolated from BSI, IAI and UTI, accounting for 80% of the Gram-negative clinical isolates, while Pseudomonas aeruginosa (P. aeruginosa) was mainly isolated from RTI. E. coli showed < 10% resistance rates to amikacin, colistin, ertapenem, imipenem, meropenem and piperacillin/tazobactam. K. pneumoniae exhibited low resistance rates only to colistin (6.4%) and amikacin (17.5%) with resistance rates of 25-29% to carbapenems. P. aeruginosa exhibited low resistance rates only to amikacin (13.4%), colistin (11.6%), and tobramycin (10.8%) with over 30% resistance to all traditional antipseudomonal antimicrobials including ceftazidime, cefepime, carbapenems and levofloxacin. OSWIAs were different at different infection sites. Among them, the susceptibility of RTI to conventional antibiotics was lower than for IAI, UTI or BSI. CONCLUSIONS: Gram-negative bacteria collected from Chinese EDs exhibited high resistance to commonly used antibiotics. Susceptibilities were organ specific for different infection sites, knowledge which will be useful for guiding empirical therapies in the clinic.

Prevalence of urinary tract infections in pregnant women and antimicrobial resistance patterns in women in Riyadh, Saudi Arabia: a retrospective study.

BACKGROUND: Urinary tract infections (UTIs) are one of the most common health problems worldwide and mainly affect women. This study aimed to evaluate the prevalence of UTIs in pregnant women and determine the antimicrobial resistance patterns of bacterial pathogens isolated from pregnant and nonpregnant women in Riyadh, Saudi Arabia. METHODS: This retrospective cohort study was conducted at an academic medical center in Riyadh, Saudi Arabia, from January to June 2022. The study included all urine cultures performed for adult women during the study period. We excluded urine culture performed for women on antibiotics prescribed for any infection, children, and men. Using the SPSS (version 27) package, descriptive statistics and chi-square tests were used to analyze the data, and p < 0.05 was considered to indicate statistical significance. RESULTS: A total of 2,418 urine cultures performed during the study period were included (985 and 1,433 for pregnant and nonpregnant women, respectively). The overall prevalence of UTIs in pregnant women was 5% (95% CI 3.6-6.4); 10 (1%) women were symptomatic, and 40 (4%) women were asymptomatic. Of the entire cohort, 244 (10.1%) women were diagnosed with UTIs based on bacterial cultures. The predominant bacteria in both pregnant and nonpregnant women were Escherichia coli (134, 54.9%), followed by Klebsiella pneumoniae (48, 19.6%). The antibiotic susceptibility criteria for Escherichia coli and Klebsiella pneumoniae were as follows: nitrofurantoin (94% and 18.8%, respectively), amoxicillin-clavulanic acid (82.8% and 70.8%, respectively), ciprofloxacin (65.7% and 83.3%, respectively), trimethoprim-sulfamethoxazole (65.7% and 79.2%, respectively) and cephalothin (47% and 68.8%, respectively). CONCLUSION: Compared to the findings of other similar studies, the prevalence of UTIs was lower in pregnant women. This may be because the patient population was composed of healthy and educated women who received prenatal education and underwent prenatal assessment as per institutional guidelines. Nitrofurantoin and amoxicillin-clavulanic acid are recommended for use as an empirical therapy for UTIs in pregnant and nonpregnant women because bacteria have the least amount of resistance to these drugs.

Postpartum infections and antimicrobial resistance of responsible pathogens in Ukraine: results a multicenter study (2020-2022).

OBJECTIVE: Aim: To determine the current prevalence of postpartum infections and antimicrobial resistance and antimicrobial resistance of responsible pathogens in Ukraine. PATIENTS AND METHODS: Materials and Methods: Multicenter prospective cohort study was conducted from January 2020 to December 2022 in fifteen hospitals from twelve regions of Ukraine. Definitions of healthcare- associated postpartum infection were adapted from the Centers for Disease Control and Prevention's National Healthcare Safety Network. Antibiotic susceptibility was done by the disc diffusion test as recommended by EUCAST. RESULTS: Results: Among 21,968 women, 6,175 (28.1%) postpartum infections were observed. Of all postpartum infection cases, 83.1% were detected after hospital discharge. The postpartum infection rates were 17.3% after cesarean section and 10.8% after vaginal delivery. The most common postpartum infection types were endometritis (17.3%), followed by urinary tract Infection (3.5%), mastitis (3.4%), surgical site infection (excluding endometritis) (2.4%), and episiotomy site infection (1.5%). The predominant postpartum infection pathogens in Ukraine were: Escherichia coli (10.4%), Enterococcus spp. (9.6%), Staphylococcus aureus (6.7%), Pseudomonas aeruginosa (5.8%), Enterobacter spp. (5.8%). In our study pathogens of postpartum infection had differently levels of resistance to antibiotics. CONCLUSION: Conclusions: Our results indicate that postpartum infections requiring medical attention are common in Ukraine and that most postpartum infections occur after hospital discharge, so that use of routine inpatient surveillance methods alone will lead to underestimation of postpartum infection rates. Optimizing the antibiotic prophylaxis may reduce the burden of postpartum infection, but prevention is the key element.

Fever lasting 48 hours as a predictive factor of ESBL-producing bacteria in non-critically ill patients with urinary tract infection.

Urinary tract infection (UTI) is the most prevalent urological condition worldwide. Choosing appropriate antibiotics for patients who have fever before receiving a culture result is challenging. This retrospective study enrolled patients 394 patients hospitalized at Gangneung Asan Hospital for UTI from May 2017 to April 2021. Fever at 48 h of hospitalization was the analysis point, as this is when the response to antibiotic therapy manifest, although the results of antibiogram are not available. Multivariate analysis was performed to assess the correlation between ESBL producing bacteria (EPB) and fever at 48 h. Overall, 36.3% of patients had EPB and 27.9% had fever at 48 h. In multivariate analysis, a significant positive association was found between EPB and fever (odds ratio 1.17, 95% CI 1.05-1.30, P = 0.004) Female had negative association with multivariate model (OR 0.83, 95% CI 0.73-0.94, P = 0.004). Diabetes did not demonstrate a significant association with EPB. (OR 1.10, 95% CI 0.99-1.22, P = 0.072). Fever at 48 h is associated with EPB and could be considered a predictive factor for EPB infection in patients with UTI. Antibiotic escalation may be considered in patients with fever at 48 h.

Antimicrobial resistance pattern of Uro-Pathogens emphasizing non-lactose fermenting gram negative bacilli.

Objectives: To identify various species of non-lactose fermenting gram-negative bacilli involved in urinary tract infections, and to determine their antimicrobial resistance pattern. METHODS: The retrospective, descriptive, cross-sectional study was conducted from January 1 to April 1, 2022, at the Dow University of Health Sciences, Karachi, and comprised data from the institutional diagnostic laboratory that was related to urine samples regardless of age and gender from January 1, 2020, to December 31, 2021. Data was analysed using SPSS version 25. RESULTS: Of the 103,887 urine samples, 41,280(39.7%) were positive, 51,146(49.2%) showed no bacterial growth, 11,000(10.6%) had non-significant bacterial growth and 461(0.4%) had mixed bacterial growth. Of the positive samples, 18359(44.5%) were positive in 2020, and 22,921(55.5%) in 2021. Gram-negative lactose fermenting bacteria included escherichia coli 23,123(22.3%) and klebsiella pneumoniae 2,993(2.9%), gram-negative non-lactose fermenting bacteria included pseudomonas aeruginosa 1,110(1.07%), and gram-positive bacteria included enterococcus 8,008(7.7%). Pseudomonas aeruginosa was most resistant against tobramycin 880(79.3%) and least resistant against piperacillin-tazobactam 146(13%). CONCLUSIONS: Piperacillin-tazobactam was highly sensitive drug against non-lactose fermenting uro-pathogens.

Prevalence and Resistance Patterns of Urinary Tract Infection in Al-Madinah Al-Munawarah, Saudi Arabia: A Retrospective Study.

BACKGROUND: Urinary tract infections (UTIs) are among the most common infections and can cause numerous complications of the renal system. This study aimed to assess the prevalence of uropathogens and their antibiotic susceptibility patterns in Al-Madinah Al-Munawarah, Saudi Arabia. METHODS: Data was collected from patients with UTIs presented at King Fahad General Hospital in Al-Madinah Al-Munawarah, Saudi Arabia. In this retrospective cross-sectional study, UTI microbial-causing agents and antimicrobial resistance profiles identified using automated systems, Phoenix and VITEK2, were collected between July 2022 and June 2023. In addition, minimal demographic data, including date of collection and sex and age of patients were collected and analyzed using Chi-square test. RESULTS: The study included 1394 patients positive for UTI, comprising 50.57% males and 49.43% females (chi-square goodness-of-fit, p > 0.999). Microbial identification and antimicrobial susceptibility tests were performed on UTI-positive cultures. Among UTIs, mono-infection, caused by a single pathogen, was the most prevalent, accounting for 88.16% of cases, whereas poly-infection (caused by multiple pathogens) presented at 11.9%. The most prevalent UTIs' pathogens were E. coli (30.59%), followed by Klebsiella pneumoniae (21.40%), Enterococcus faecalis (8.46%), Pseudomonas aeruginosa (7.81%), Streptococcus agalactiae (6.35%), Enterococcus faecium (3.01%), Proteus mirabilis (3.01%), Enterobacter cloacae (2.52%), Candida sp. (2.44%), Acinetobacter calcoaceticus-baumannii (1.95%), Staphylococcus aureus (1.79%), and Enterobacter aerogenes (1.30%). The most dominant pathogens that coexisted with other uropathogens to cause UTIs were K. pneumoniae and P. mirabilis (9.32%, chi-square 5.550, p = 0.018), K. pneumoniae and P. aeruginosa (8.07%, chi-square 6.285, p = 0.012), K. pneumoniae and E. faecalis (7.45%, chi-square 5.785, p = 0.016), Candida sp. and Enterococcus faecium (4.97%, chi-square 9.176, p = 0.002, and Candida sp. and Acinetobacter calcoaceticus-baumannii (3.11%, chi-square 4.312, p=0.038)). Among the uropathogens, gram-negative pathogens showed resistance to most of the tested antimicrobials (ampicillins, cephalosporins, fluoroquinolones, trimethoprim-sulfamethoxazole, aztreonam, and nitrofurantoin). High rates of resistance were identified to cephalosporins, amoxicillin-clavulanic acid, and trimethoprim-sulfamethoxazole. CONCLUSION: This study reported UT mono-infection and poly-infection in Al-Madinah Al-Munawarah, Saudi Arabia, with a predominant representation from gram-negative bacteria, Enterobacteriaceae. Most of the UT microbial strains showed a highly resistant profile.

Antimicrobial susceptibility patterns of urinary tract infections causing bacterial isolates and associated risk factors among HIV patients in Tigray, Northern Ethiopia.

BACKGROUND: Urinary tract infections, a prevalent global infectious disease, are clinical issues not well studied in HIV-positive individuals. UTIs have become a global drug resistance issue, but the prevalence and antibiotic susceptibility patterns of UTI-causing bacteria among HIV patients in Tigray, Ethiopia, are poorly understood. This study aims to identify the prevalence of UTI-causing bacteria, their antibiotic susceptibility patterns, and associated risk factors in HIV patients attending ART clinics at Mekelle General Hospital and Ayder Comprehensive Specialized Hospital in Tigray, Northern Ethiopia. METHOD: Clean-catch midstream urine samples (10-15 mL) were collected from HIV patients who are attending ART clinics at Mekelle General Hospital and Ayder Comprehensive Specialized Hospital. Samples were analyzed based on standard microbiological protocols using cysteine-lactose electrolyte deficient (CLED) agar. Pure colonies of bacterial isolates were obtained by sub-culturing into Mac-Conkey, Manitol Salt agar and blood agar plates. The bacterial isolates were then identified using macroscopic, microscopic, biochemical, and Gram staining methods. Gram-negative bacteria were identified using biochemical tests like triple sugar iron agar, Simon's citrate agar, lysine iron agar, urea, motility test, and indol test, whereas Gram-positive isolates were identified using catalase and coagulase tests. The Kirby-Bauer disk diffusion technique was used to analyze the antimicrobial susceptibility pattern of bacterial isolates. Data was analyzed using SPSS version 25.0. RESULTS: Among the 224 patients, 28 (12.5%) of them had been infected by UTIs-causing bacteria. E. coli was the dominant bacterium (16 (57%)) followed by K. pneumoniae (4 (14%)), and S. aureus (3 (11%)). Of the total bacterial isolates, 22 (78.6%) of them developed multi-drug resistance. All Gram-positive (100%) and 75% of Gram-negative bacterial isolates were found to be resistant to two or more drugs. Patients with a history of UTIs, and with CD4 count < 200 cells/ mm3, were more likely to have significant bacteriuria. Compared to male patients, female patients were more affected by the UTIs-causing bacteria. More than 93% of the UTIs-causing bacterial isolates were susceptible to nitrofurantoin, ceftriaxone, ciprofloxacin, and gentamycin; whereas they are highly resistant to ampicillin (96%), cotrimoxazole (82%) and tetracycline (71%). CONCLUSIONS: Most of the bacterial isolates were highly resistant to ampicillin, cotrimoxazole, and tetracycline. Female patients were more affected by the UTIs causing bacteria. The highest prevalence (12.5%) of UTIs in HIV patients needs special attention for better management and monitoring. Previous UTI history and immune suppression are predictors of UTIs, highlighting the need for intervention measures involving molecular studies to identify resistant bacteria genes and promote patient immune reconstitution.

Uropathogenic Escherichia coli infection: innate immune disorder, bladder damage, and Tailin Fang II.

Background: Uropathogenic Escherichia coli (UPEC) activates innate immune response upon invading the urinary tract, whereas UPEC can also enter bladder epithelial cells (BECs) through interactions with fusiform vesicles on cell surfaces and subsequently escape from the vesicles into the cytoplasm to establish intracellular bacterial communities, finally evading the host immune system and leading to recurrent urinary tract infection (RUTI). Tailin Fang II (TLF-II) is a Chinese herbal formulation composed of botanicals that has been clinically proven to be effective in treating urinary tract infection (UTI). However, the underlying therapeutic mechanisms remain poorly understood. Methods: Network pharmacology analysis of TLF-II was conducted. Female Balb/C mice were transurethrally inoculated with UPEC CFT073 strain to establish the UTI mouse model. Levofloxacin was used as a positive control. Mice were randomly divided into four groups: negative control, UTI, TLF-II, and levofloxacin. Histopathological changes in bladder tissues were assessed by evaluating the bladder organ index and performing hematoxylin-eosin staining. The bacterial load in the bladder tissue and urine sample of mice was quantified. Activation of the TLR4-NF-κB pathway was investigated through immunohistochemistry and western blotting. The urinary levels of interleukin (IL)-1ß and IL-6 and urine leukocyte counts were monitored. We also determined the protein expressions of markers associated with fusiform vesicles, Rab27b and Galectin-3, and levels of the phosphate transporter protein SLC20A1. Subsequently, the co-localization of Rab27b and SLC20A1 with CFT073 was examined using confocal fluorescence microscopy. Results: Data of network pharmacology analysis suggested that TLF-II could against UTI through multiple targets and pathways associated with innate immunity and inflammation. Additionally, TLF-II significantly attenuated UPEC-induced bladder injury and reduced the bladder bacterial load. Meanwhile, TLF-II inhibited the expression of TLR4 and NF-κB on BECs and decreased the urine levels of IL-1ß and IL-6 and urine leukocyte counts. TLF-II reduced SLC20A1 and Galectin-3 expressions and increased Rab27b expression. The co-localization of SLC20A1 and Rab27b with CFT073 was significantly reduced in the TLF-II group. Conclusion: Collectively, innate immunity and bacterial escape from fusiform vesicles play important roles in UPEC-induced bladder infections. Our findings suggest that TLF-II combats UPEC-induced bladder infections by effectively mitigating bladder inflammation and preventing bacterial escape from fusiform vesicles into the cytoplasm. The findings suggest that TLF-II is a promising option for treating UTI and reducing its recurrence.