Therapy Of Urinary Tract Infections Research Articles

Short- versus standard-course antibiotic therapy for urinary tract infection in children: a systematic review and meta-analysis.

Urinary tract infections are prevalent among children and are responsible for a significant healthcare burden. Antibiotic therapy is the cornerstone of treatment, but the optimal treatment duration remains elusive. This systematic review and meta-analysis aimed to explore the optimal duration of antibiotic therapy for urinary tract infection (UTI) in pediatric patients. A comprehensive search was performed, including MEDLINE, Embase, and Cochrane Library databases. We included only randomized controlled trials (RCTs) comparing short-course (2 to 5days) and standard-course (≥ 7days) antibiotic treatment in patients < 18years of age. We performed this systematic review and meta-analysis following Cochrane Collaboration recommendations using a random-effects model. Effect estimate was calculated using the risk ratio (RR) with 95% confidence interval (95% CI) for dichotomous and mean difference (MD) with 95% CI for continuous endpoints. Significance was regarded at p-value < 0.05. Statistical analysis was performed using Review Manager 5.4.1. Data from 12 RCTs, encompassing 1442 children, were included. Follow-up ranged from 1 to 12months. The mean age was 5.9years, with approximately 87% female patients. E. coli was the most common pathogen isolated from urine cultures. There was a significant difference in cure rates (RR 0.97; 95% CI 0.95-0.99; p = 0.01) between the groups when only studies that included febrile UTI were analyzed together, favoring 7days or more of treatment, but with high heterogeneity. Otherwise, there was no significant difference in cure rates (RR 0.99; 95% CI 0.91-1.08; p = 0.80) in children with afebrile UTI or recurrence of UTI at any time in children with afebrile (RR 0.98; 95% CI 0.84-1.15; p = 0.80) or febrile UTI (RR 0.52; 95% CI 0.10-2.83; p = 0.45). Also, there was no significant difference in failure rates in children with urinary tract abnormalities and afebrile UTI (RR 0.79; 95% CI 0.47-1.32; p = 0.36), between the short- and the standard-course treatment groups. This analysis was limited by the moderate heterogeneity and the small subgroup of children with urinary tract abnormalities, which could have underpowered our results. The primary outcome of this analysis suggests that a short course of antibiotic therapy is feasible in children with afebrile UTI, but more studies are warranted to safely establish an optimal treatment duration for children with febrile UTI. The study protocol was registered in the PROSPERO platform under the number CRD42023489094.

Bacteriophage P2-71: a promising therapeutic against multidrug-resistant Proteus mirabilis in urinary tract infections.

Proteus mirabilis is a Gram-negative, rod-shaped bacterium widely found in natural environments. It is known for causing a range of severe illnesses in mammals, particularly urinary tract infections (UTIs). This study evaluates the therapeutic efficacy of phage P2-71 against Proteus mirabilis in vivo and in vitro environments. The in vitro therapeutic potential of bacteriophage P2-71 was assessed through the ability of phage to kill Proteus mirabilis by using a plate counting assay, and biofilm inhibition and biofilm lysis assays using a microtitre plate method. Additionally, an in vivo UTI model in C57BL/6Jmice was developed via urethral inoculation of the bacterium. Phage therapy was administered through urethral injection over a period of 5 days. Therapeutic outcomes were measured by analyzing bacterial load, phage titer, inflammatory markers, and histopathological changes in the urine, urogenital tissues, and spleen. In vitro, bacteriophage P2-71 achieved significant reductions in P. mirabilis concentrations, with log reductions of 1.537 and 0.7009 CFU/mL in laboratory and urine environments, respectively (p < 0.001). The phage also decreased biofilm formation by 34-49% and lysed 15-25% of mature biofilms at various multiplicities of infection (MOIs) (p < 0.001). In vivo, phage treatment significantly lowered bacterial concentrations in the urine on Days 1 and 3 (p < 0.0001), achieving a maximum reduction of 4.602 log₁₀ CFU/mL; however, its effectiveness diminished by Day 5 (p > 0.05). Concurrently, phage titers decreased over time. Importantly, phage treatment notably reduced bacterial load in the bladder, kidneys, and spleen (p < 0.001). Inflammatory markers such as IL-6, IL-1β, and TNF-α were significantly lower in the treatment group, especially in the bladder (p < 0.0001), indicating an effective reduction in inflammation. Histopathological analysis showed significant mitigation of tissue damage. The results demonstrated that bacteriophage P2-71 is a promising alternative therapy for UTIs caused by MDR Proteus mirabilis. This bacteriophage therapy offers a viable strategy for managing infections where traditional antimicrobials fail, highlighting its potential in clinical applications.

Isolation and characterization of bacteriophages against E.coli urinary tract infection and evaluating their anti-biofilm activity and antibiotic synergy

Urinary tract infections (UTIs) by Uropathogenic Escherichia coli (UPEC) are a significant health concern, especially due to the increasing prevalence of antibiotic resistance. This study focuses on isolating and characterizing bacteriophages specific to UPEC strains isolated from UTI samples. The isolated phages were assessed for their ability to target and lyse UPEC in vitro, focusing on their efficacy in disrupting biofilms, a key virulence factor contributing to UTI recurrence and antibiotic resistance. The morphological structure observed by TEM belongs to Myoviridae, the phage exhibited icosahedral symmetry with a long non-constricting tail, the approximate measurement of the phage head was 39 nm in diameter, and the phage tail was 105.317 nm in length. One-step growth experiments showed that the latent period was approximately 20 min, followed by a rise period of 40 min, and a growth plateau was reached within 20 min and the burst size observed was 26 phages/infected bacterial cells. These phages were capable of killing cells within the biofilms, leading to a reduction in living cell counts after a single treatment. This study highlights the potential of phages to play a significant role in disrupting, inactivating, and destroying Uropathogenic Escherichia coli (UPEC) biofilms. Such findings could be instrumental in developing treatment strategies that complement antibiotics and disinfectants. The phage-antibiotic synergistic activity was compared to have the possibility to facilitate the advancement of focused and enduring alternatives to traditional antibiotic therapies for UTIs.

Antimicrobial resistance trends among Klebsiella pneumoniae associated with urinary tract infections in Crete, Greece, 2017-2022.

Klebsiella pneumoniae is one of the most prevalent bacteria causing urinary tract infections (UTIs). Its increasing resistance to a wide array of antibiotics limits available treatment options. This study investigated the characteristics and trends of antimicrobial resistance in K. pneumoniae isolated from UTIs in Crete, Greece, during 2017 and 2022. Among the 11,946 Enterobacteriaceae isolated from urine specimens, a total of 1,771 K. pneumoniae isolates were identified (14.8%), with an isolation frequency secondary to Escherichia coli (66.3%). K. pneumoniae isolates increased over the years, with a peak in the year 2022. Higher resistance rates were detected in ciprofloxacin (41%), trimethoprim/sulfamethoxazole (TMP/SMX) (38.1%) and nitrofurantoin (33.9%). Resistance to ciprofloxacin, amoxicillin/clavulanic acid, tigecycline, and TMP/SMX significantly increased from 33.7%, 24%, 6%, and 33.1%, respectively, over the years 2017-2019, to 47.8%, 34.2%, 14.3% and 42.8%, respectively, over the period 2020-2022. ESBL production and carbapenem resistance were decreased by 2.2% and 3.7%, respectively, over the two three-year periods (2017-2019 and 2020-2022). Among the 278 carbapenem-resistant K.pneumoniae (CRKP) isolates, 164 (59%), 66 (23.7%), 18 (6.5%) and 16 (5.8%) were positive for KPC, NDM, VIM and OXA-48 enzymes, respectively. Only 14 (5%) isolates harboured two carbapenemase genes, namely 10 (3.6%) both blaNDM and blaVIM, and 4 (1.4%) both blaKPC and blaNDM. Females, inpatients and the elderly were more frequently affected by CRKP. The frequency of multidrug-resistant (MDR) and extensively drug-resistant (XDR) isolates were 32.6% and 7.7%, respectively. Continuous surveillance of local microbial prevalence and monitoring of antimicrobial resistance patterns provide critical information to guide the empiric therapy for UTIs and control the spread of MDR bacteria.

Analisis Penggunaan Antibiotik Pada Pasien Infeksi Saluran Kemih (ISK) Secara Kuantitatif Di RSUD Provinsi NTB Tahun 2019

Introduction: Urinary Tract Infection (UTI) is a disease that often occurs in developing countries after upper respiratory tract infections. The incidence of UTI in 2018 in Indonesia is quite high, ranging from 39-60%. Antibiotics are the main therapy for UTIs, but excessive and inappropriate use of antibiotics can cause occurrence of antibiotic resistance. Objective: This study aims to quantitatively analyze patterns of antibiotic use in UTI patients at the NTB Provincial Hospital in 2019. Methods: This type of research is descriptive in nature using a cross-sectional design. There were 47 patients in case who were diagnosed with UTI ith the ICD-X code N39.0, which means the UTI suffered by the patient was a non-specidic type of UTI. Quantitative use of antibiotics was calculated using the ATC/DDD method according to WHO standards. Results: The total value of DDD/100 Patient-days was 51.26 with ceftriaxone as an antibiotic with the highest DDD/100 patient-days value of 19.78 and had the largest value in the 90% DU segment, which was 38.59%. Conclusion: Regular evaluation of antibiotic use is needed to minimize excessive use of antibiotics so that rational antibiotic use can be achieved.

Association Between Antibiotic Duration and Recurrence of Urinary Tract Infection in the Neonatal Critical Care Unit.

Urinary tract infection (UTI) is the most common bacterial infection in infants. Current practice guidelines suggest a treatment duration of 7 to 14 days. Suboptimal therapy may increase the risk for recurrent UTIs leading to renal scarring and possibly chronic kidney disease. The primary objective is to evaluate the duration of therapy for UTIs and its association with the incidence of recurrent UTIs in a neonatal intensive care unit (NICU). The secondary objectives are to identify the risk factors and the most common organisms for recurrent UTIs. Patients were identified via the diagnosis codes for UTIs and were included if admitted to the NICU and if they received antibiotics prior to hospital discharge. Patients were divided into 2 groups: antibiotic treatment for 7 days or fewer and antibiotic treatment for greater than 7 days. Eighty-six infants were included in the study. Twenty-six patients received antibiotics for 7 days or fewer, and 60 for more than 7 days. In the study, the median birth weight was 977 g and the median gestational age was 27.6 weeks. There was no significant difference in the rate of recurrent UTIs between the 2 groups (p = 0.66). However, in the subgroup analysis, the incidence was higher for patients receiving antibiotic therapy for fewer than 7 days versus 7 days (p = 0.03). There was no difference in recurrence of UTI between treatment groups (≤7 days versus >7 days), and recurrence was seen in a higher percentage of patients with a urinary tract anomaly.

#2578 Safety profile of dapagliflozin therapy in the kidney peritransplant period

Abstract Background and Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a class of glucose-lowering drugs that have demonstrated important cardio- and nephroprotective effects. These effects, according to preclinical data, may include attenuation of ischemia/reperfusion injury due to downregulation of pro-inflammatory cytokines and necroptosis mediators. This effect could be critical in the peritransplant period, protecting the allograft and potentially reducing delayed graft function (DGF). However, administration of SGLT2i immediately after deceased-donor kidney transplantation (KTx) could potentially be associated with adverse outcomes, such as urinary tract infections (UTI). We report the results of the first 10 patients of an ongoing study aimed at describing the safety profile of dapagliflozin in the peri-KTx period. Method Prospective, uncontrolled pilot study of consecutive, incident KTx patients that received a daily dose of dapagliflozin 10 mg, starting immediately before surgery and continuing until completing the first week post-transplant. All subjects provided informed consent for the study. Those with liver dysfunction, known allergy to SGLT2i, programmed for live-donor or multiorgan kidney transplantation or unable to provide informed consent were excluded. The primary outcome was the development of UTI during index hospitalization, defined either as a positive urine culture and/or symptoms suggestive of UTI. For comparison purposes, a retrospective sample of age- and sex-matched patients that received a KTx prior to the start of this study was included in this analysis. Two controls were selected for each case. Results Demographics and clinical characteristics of both patients in the study and retrospective controls are summarized in Fig. 1. Recipients that received dapagliflozin had similar rates of UTI when compared to controls, and were prescribed less frequently antibiotic therapy for UTI, although none of these differences reached statistical significance. Most cases of both groups consisted in asymptomatic bacteriuria. Of all four cases of documented UTI among treated patients, only one subject developed UTI during the days of dapagliflozin administration (the first 7 days after surgery). This patient did not require antibiotic therapy. The other three cases developed UTI after dapagliflozin discontinuation. Conclusion Results of this preliminary and limited experience lead us to believe that dapagliflozin in the peritransplant period may be a safe and feasible therapy that could help protect the renal allograft from ischemia/reperfusion injury.

Exploring variations in recommended first-choice therapy for complicated urinary tract infections in males: Insights from outpatient settings across age, race, and ethnicity.

There are known disparities in the treatment of infectious diseases. However, disparities in treatment of complicated urinary tract infections (UTIs) are largely uninvestigated. We characterized UTI treatment among males in Veterans Affairs (VA) outpatient settings by age, race, and ethnicity and identified demographic characteristics predictive of recommended first-choice antibiotic therapy. We conducted a national, retrospective cohort study of male VA patients diagnosed with a UTI and dispensed an outpatient antibiotic from January 2010 through December 2020. Recommended first-choice therapy for complicated UTI was defined as use of a recommended first-line antibiotic drug choice regardless of area of involvement (ciprofloxacin, levofloxacin, or sulfamethoxazole/trimethoprim) and a recommended duration of 7 to 10 days of therapy. Multivariable models were used to identify demographic predictors of recommended first-choice therapy (adjusted odds ratio [aOR] > 1). We identified a total of 157,898 males diagnosed and treated for a UTI in the outpatient setting. The average antibiotic duration was 9.4 days (±standard deviation [SD] 4.6), and 47.6% of patients were treated with ciprofloxacin, 25.1% with sulfamethoxazole/trimethoprim, 7.6% with nitrofurantoin, and 6.6% with levofloxacin. Only half of the male patients (50.6%, n = 79,928) were treated with recommended first-choice therapy (first-line drug choice and appropriate duration); 77.6% (n = 122,590) were treated with a recommended antibiotic choice and 65.9% (n = 104,070) with a recommended duration. Age 18-49 years (aOR 1.07, 95% confidence interval [CI] 1.03-1.11) versus age ≥65 years was the only demographic factor predictive of recommended first-choice therapy. Nearly half of the patients included in this study did not receive recommended first-choice therapies; however, racial and ethnic disparities were not identified. Underutilization of recommended first-choice antibiotic therapy in complicated UTIs continues to be an area of focus for antimicrobial stewardship programs.

Biomarkers for urinary tract infection: present and future perspectives.

A prompt diagnosis of urinary tract infection (UTI) is necessary to minimize its symptoms and limit sequelae. The current UTI screening by urine test strip analysis and microscopic examination has suboptimal diagnostic accuracy. A definitive diagnosis of UTI by urine culture takes two to three days for the results. These limitations necessitate a need for better biomarkers for the diagnosis and subsequent management of UTI in children. Here, we review the value of currently available UTI biomarkers and highlight the potential of emerging biomarkers that can facilitate a more rapid and accurate UTI diagnosis. Of the newer UTI biomarkers, the most promising are blood procalcitonin (PCT) and urinary neutrophil gelatinase-associated lipocalin (NGAL). PCT can provide diagnostic benefits and should be considered in patients who have a blood test for other reasons. NGAL, which is on the threshold of clinical care, needs more research to address its scope and utilization, including point-of-care application. Employment of these and other biomarkers may ultimately improve UTI diagnosis, guide UTI therapy, reduce antibiotic use, and mitigate UTI complications.

Shorter versus longer-course of antibiotic therapy for urinary tract infections in pediatric population: an updated meta-analysis.

Urinary tract infections (UTI) affect between 3% to 7.5% of the febrile pediatric population each year, being one of the most common bacterial infections in pediatrics. Nevertheless, there is no consensus in the medical literature regarding the duration of per oral (p.o.) antibiotic therapy for UTI among these patients. Therefore, our meta-analysis aims to assess the most effective therapy length in this scenario. PubMed, Cochrane, and Embase were searched for randomized controlled trials (RCTs) comparing short (≤ 5days) with long-course (≥ 7days) per os (p.o.) antibiotic therapy for children with UTI. Statistical analysis was performed using R Studio version 4.2.1, heterogeneity was assessed with I2 statistics, and the risk of bias was evaluated using the RoB-2 tool. Risk Ratios (RR) with p < 0.05 were considered statistically significant. Seventeen studies involving 1666 pediatric patients were included. Of these, 890 patients (53.4%) were randomized to receive short-course therapy. Patients undergoing short-course therapy showed higher treatment failure rates (RR 1.61; 95% CI 1.15-2.27; p = 0.006). Furthermore, there were no statistically significant differences between groups regarding reinfection (RR 0.73; 95% CI 0.47-1.13; p = 0156) and relapse rates (RR 1.47; 95% CI 0.8-2.71; p = 0.270). Conclusion: In summary, our results suggest that long-course p.o. antibiotic therapy is associated with a lower rate of treatment failure when compared to short-course p.o. antibiotic therapy. There was no statistical difference between both courses regarding reinfection and relapse rates within 15months. PROSPERO identifier: CRD42023456745. What is Known: • Urinary tract infections (UTIs) are common in children, affecting around 7.5% of those under 18. • The optimal duration of antibiotic treatment for pediatric UTIs has been a subject of debate. What is New: • Short-course therapy (5 or fewer days) was associated with a significantly higher failure rate when compared to long-course therapy. • There was no significant difference in reinfection and relapse rates within 15months between short and long-course therapy.

Antimicrobial Resistance in Escherichia coli Causing Urinary Tract Infection: A Four-Year Study

Urinary tract infections (UTIs) are among the most frequently encountered infections for which individuals seek medical attention. They are usually ascending infections and if left untreated the causative agent can ascend the ureters causing pyelonephritis and, furthermore, enter the bloodstream causing systemic infections and urosepsis. Appropriate treatment prevents progression of disease. Escherichia coli is responsible for 80-95% cases of UTI. This study was undertaken to study the antimicrobial resistance among Escherichia coli isolated from patients suffering from UTI over 4 years at a tertiary level medical facility. A retrospective case series study was conducted. All UTI with significant bacteriuria due to E. coli were included in the study. Identification, speciation and antimicrobial susceptibility testing was done as per standard laboratory practices. A total of 555 strains of Escherichia coli were included in the study. Overall highest resistance rates for E. coli were seen among cephalosporins and fluoroquinolones while least overall resistance was seen for nitrofurantoin. There was gradual rise in resistance for carbapenem over the 4 years. The predominant microorganism responsible for all types of infections affecting the urinary tract is Escherichia coli. Empirical antimicrobial therapy for urinary tract infections may be unsuccessful, as resistance rates among E. coli are constantly increasing. The present study provides information regarding the antimicrobial susceptibility pattern over a period of 4 years. It shows that there is a gradual but consistent decrease in antimicrobial susceptibility among the isolates. Hence, it has become necessary that antimicrobial therapy be based on culture reports. Also, frequent and periodic updating of antimicrobial policy is essential.

Comprehensive Review of Urinary Tract Infections in Renal Transplant Recipients: Clinical Insights and Management Strategies.

Urinary tract infections (UTIs) pose a significant challenge in the care of renal transplant recipients. This comprehensive review explores this population's multifaceted landscape of UTIs, emphasizing the importance of early diagnosis and tailored management strategies. Renal transplant recipients face an elevated risk of UTIs due to immunosuppression, altered urinary tract anatomy, and complex comorbidities. Complications of UTIs can lead to graft dysfunction and systemic illness, underscoring the need for effective management. The emergence of multidrug-resistant uropathogens adds complexity to treatment, highlighting the importance of targeted antibiotic therapy. Antibiotics are the most commonly prescribed drugs for UTIs, with nitrofurantoin, fosfomycin, amoxicillin, and amoxicillin-clavulanate potassium being some of the commonly used antibiotics. However, the emergence of multidrug-resistant uropathogens has led to the exploration of alternative treatments, such as bacteriophage therapy, as a potential alternative against multidrug-resistant uropathogenic bacteria. Analgesics such as phenazopyridine can be prescribed to relieve discomfort associated with UTIs. Estrogen therapy has also been suggested as a potential treatment option for UTIs, particularly in postmenopausal women. Trimethoprim-sulfamethoxazole or trimethoprim is recommended as first-line therapy for uncomplicated UTIs. The choice of drug and therapy for UTIs depends on the severity of the infection, the causative organism, and the presence of antibiotic resistance.Preventive measures encompass pre-transplant evaluation, perioperative strategies, post-transplant follow-up, and vaccination. A multidisciplinary approach involving transplant specialists, infectious disease experts, pharmacists, and patient engagement is vital for successful care. The future of UTI management lies in ongoing research, exploring personalized medicine, novel therapies, and innovative prevention strategies. By implementing these strategies and advancing research, healthcare providers can improve graft and patient survival, enhancing the quality of care for renal transplant recipients.

VesiX cetylpyridinium chloride is rapidly bactericidal and reduces uropathogenic Escherichia coli bladder epithelial cell invasion in vitro.

When urinary tract infections (UTIs), which affect over 50% of women, become resistant to available antibiotic therapies dangerous complications like kidney infection and lethal sepsis can occur. New therapeutic paradigms are needed to expand our arsenal against these difficult to manage infections. Our study investigates VesiX, a Cetylpyridinium chloride (CPC)-based therapeutic, as a candidate broad-spectrum antimicrobial agent for use in bladder instillation therapy for antibiotic-resistant UTI. CPC is a cationic surfactant that is FDA-approved for use in mouthwashes and is used as a food additive but has not been extensively evaluated as a UTI therapeutic. Our study is the first to investigate its rapid bactericidal kinetics against diverse uropathogenic bacterial species isolated from postmenopausal women with recurrent UTI and host cytotoxicity. We also report that together with the FDA-approved bladder-instillation agent gentamicin, VesiX was able to significantly reduce intracellular populations of uropathogenic bacteria in cultured bladder epithelial cells.

The rise, fall, and resurgence of phage therapy for urinary tract infection

ABSTRACT In the face of rising antimicrobial resistance, bacteriophage therapy, also known as phage therapy, is seeing a resurgence as a potential treatment for bacterial infections including urinary tract infection (UTI). Primarily caused by uropathogenic Escherichia coli , the 400 million UTI cases annually are major global healthcare burdens and a primary cause of antibiotic prescriptions in the outpatient setting. Phage therapy has several potential advantages over antibiotics including the ability to disrupt bacterial biofilms and synergize with antimicrobial treatments with minimal side effects or impacts on the microbiota. Phage therapy for UTI treatment has shown generally favorable results in recent animal models and human case reports. Ongoing clinical trials seek to understand the efficacy of phage therapy in individuals with asymptomatic bacteriuria and uncomplicated cystitis. A possible challenge for phage therapy is the development of phage resistance in bacteria during treatment. While resistance frequently develops in vitro and in vivo , resistance can come with negative consequences for the bacteria, leaving them susceptible to antibiotics and other environmental conditions and reducing their overall virulence. “Steering” bacteria toward phage resistance outcomes that leave them less fit or virulent is especially useful in the context of UTI where poorly adherent or slow-growing bacteria are likely to be flushed from the system. In this article, we describe the history of phage therapy in treating UTI and its current resurgence, the state of its clinical use, and an outlook on how well-designed phage therapy could be used to “steer” bacteria toward less virulent and antimicrobial-susceptible states.

Свойства бактерий, вызывающих инфекции мочевыводящих путей у пациентов в медицинских учреждениях Болгарии

Pathogenic microorganisms of urinary tract infections are mainly representatives of different bacterial species with a wide variety of virulence factors and multi-drug resistant strains. In connection with determining the empirical therapy of urinary tract infections, it is necessary to know the prevalence and incidence of uropathogens in the region. Objective. To determine the etiological structure of urinary tract infections among Bulgarian patients in the outpatient healthcare setting and their antimicrobial susceptibility and resistance. Patients and methods. A cross-sectional study was conducted among 763 outpatients. There were applied microbiological procedures – urine sample culture and antimicrobial susceptibility test. The principles of the Disc Diffusion Method were applied in determining the sensitivity of microorganisms to antimicrobial chemotherapeutics. Results. The leading contingent were mostly women (75.6%). Predominant working diagnoses as the reason for microbiological analysis were cystitis or tubulointestinal nephritis. A positive urine culture was reported in a significant part of the respondents (46.26%) referred by specialists from primary and secondary health care. Among the isolated strains, Escherichia coli was identified in more than half of the examined individuals (53.3%), with high rates of sensitivity to most antibiotics used in medical practice. 17% and 12.2% were the representations of Enterococcus faecalis and Klebsiella pneumonia in the sample, in which increasing levels of resistance and respectively disturbingly high ones to some of the widely applied antimicrobial agents were measured. Conclusion. E. coli is the most common gram-negative bacteria causing urinary tract infections in the outpatient medical care. An alarming trend of high levels of resistance was reported in E. faecalis, which was the second most common uropathogen of urinary tract infections in the sample. There was a tendency towards significantly increased rates of resistance in less frequently isolated uropathogens in outpatient medical care. Referring to the obtained results of the study, the authors emphasize the need to grade various antimicrobial resistance bacterial profiles in the outpatient healthcare setting. Key words: urinary tract infections, etiology, antibiotic susceptibility

The Ethno-pharmaceuticals Fighting UTI-Resistant Bacteria: Synergistic Potential Exploration

Urinary tract infections (UTIs) are a pressing global health concern, exacerbated by the rise of antibiotic-resistant bacterial strains. Bioprospecting, involving the exploration of natural resources for therapeutic potential, offers a promising approach to tackling this challenge. Ethnopharmaceuticals, traditional medicinal practices and remedies from indigenous communities, present a valuable source for discovering novel bioactive compounds. This review comprehensively evaluates the bioprospecting of ethnopharmaceuticals and their synergistic potential against antibiotic-resistant UTIs. Drawing from existing literature, we analyze a diverse range of ethnopharmaceuticals, elucidating their mechanisms of action and experimental evidence supporting synergistic interactions. Ethno-pharmaceuticals encompass various plant-based extracts, traditional herbal remedies, and indigenous healing practices utilized across generations to manage infections. We examine the scientific evidence supporting their efficacy in treating UTIs, clarifying their bioactive components and modes of action. Integration of traditional knowledge with modern scientific methodologies is crucial to addressing contemporary health challenges. By harnessing the synergistic potential of ethno-pharmaceuticals, we can develop alternative therapies for UTIs, offering hope for improved treatment outcomes amidst antibiotic resistance.

Molecular study of antibiotic resistance gene among nitrofurantoin-resistant gram-negative bacteria isolates from pregnant women

In pregnancy, urinary tract infection (UTIs) is a significant risk factor for morbidity, and nitrofurantoin is a common UTI therapy. The goal was to identify gram-negative UTI isolates and detect antibiotic resistance genes. The research involved 350 pregnant women hospitalised to Al-Zahraa teaching hospital for children’s health and maternity between September and December 2024. Out of 250 pregnant patients, 200 (57.14%) urine samples were bacterial-free, whereas 150 (42.86%) were positive for gram-negative bacteria. The findings showed that 105 isolates (70%) were Escherichia coli, 33 (22%) were Klebsiella pneumoniae, 8 (5.3%) were Pseudomonas aeruginosa, 3 (2%) were Proteus mirabilis, and 1 (0.7%) were Acinetobacter baumannii. The disc diffusion Kirby-Bauer method determined 150 (100%) gramme negative bacteria’s nitrofurantoin sensitivity. 33 (22%) isolates were antibiotic-resistant, 16 (10.66%) intermediate, and 101 (67.33%) susceptible. PCR analysis showed that all 33 out of 33 (100%) gram negative isolates had Ribe, and AcrAB genes. Additionally, a significant prevalence of nfsA-2 genes was discovered in 32 out of 33 isolates (96.96%) the nfsA-1 gene in 78.78% (26/33) of the isolates. The NfsB gene was detected in 30 out of 33 (90.90%) distinct isolates of nitrofurantoin-resistant gram-negative bacteria. The Nucleic acid and amino acid sequence study of NfsA and Ribe genes in some local isolates of K. pneumoniae reveals variations in sequence when compared to other global strains with the same genes.

Prescription pattern of antibiotics in urinary tract infection based on antimicrobial susceptibility test at a tertiary care hospital

Introduction: Urinary tract infection is a common bacterial infection associated with significant morbidity, mortality, and financial burden. This study aimed to identify the causative bacteria, assess their antimicrobial susceptibility patterns and evaluate empirical and definitive antibiotic therapy for urinary tract infection. Methods: A hospital-based crosssectional study was conducted at the outpatient medicine department at a teaching hospital in Nepal from February 15 to July 14, 2022. Two hundred participants with positive urine cultures and antimicrobial susceptibility testing were included. The microorganism causing urinary tract infection and prescription pattern of antibiotics pre-and post-AST report were analyzed. Results: The majority of isolated pathogens were gram-negative bacteria (73%), with Escherichia coli being the most common (53.5%), followed by Staphylococcus aureus among gram-positive bacteria (14.5%). Female patients had a higher incidence of urinary tract infection (59.5%) than males (40.5%). The age group above 60 years had the highest occurrence (34%). Antibiotic susceptibility testing revealed that Escherechia coli exhibited higher sensitivity to nitrofurantoin, amikacin, and meropenem, while resistance was observed against ampicillin, cefixime, and norfloxacin. Empirical antibiotics were commonly prescribed, with levofloxacin and ceftriaxone being the most frequent choices. After antibiotic susceptibility testing, nitrofurantoin and levofloxacin were frequently prescribed. Conclusions: This study provides valuable insights into the etiology of urinary tract infection and antibiotic susceptibility patterns, aiding in selecting appropriate antimicrobial therapy based on local resistance patterns.

Novel BRICHOS-Related Antimicrobial Peptides from the Marine Worm Heteromastus filiformis: Transcriptome Mining, Synthesis, Biological Activities, and Therapeutic Potential.

Marine polychaetes represent an extremely rich and underexplored source of novel families of antimicrobial peptides (AMPs). The rapid development of next generation sequencing technologies and modern bioinformatics approaches allows us to apply them for characterization of AMP-derived genes and the identification of encoded immune-related peptides with the aid of genome and transcriptome mining. Here, we describe a universal bioinformatic approach based on the conserved BRICHOS domain as a search query for the identification of novel structurally unique AMP families in annelids. In this paper, we report the discovery of 13 novel BRICHOS-related peptides, ranging from 18 to 91 amino acid residues in length, in the cosmopolitan marine worm Heteromastus filiformis with the assistance of transcriptome mining. Two characteristic peptides with a low homology in relation to known AMPs-the α-helical amphiphilic linear peptide, consisting of 28 amino acid residues and designated as HfBRI-28, and the 25-mer β-hairpin peptide, specified as HfBRI-25 and having a unique structure stabilized by two disulfide bonds-were obtained and analyzed as potential antimicrobials. Interestingly, both peptides showed the ability to kill bacteria via membrane damage, but mechanisms of their action and spectra of their activity differed significantly. Being non-cytotoxic towards mammalian cells and stable to proteolysis in the blood serum, HfBRI-25 was selected for further in vivo studies in a lethal murine model of the Escherichia coli infection, where the peptide contributed to the 100% survival rate in animals. A high activity against uropathogenic strains of E. coli (UPEC) as well as a strong ability to kill bacteria within biofilms allow us to consider the novel peptide HfBRI-25 as a promising candidate for the clinical therapy of urinary tract infections (UTI) associated with UPEC.

Vitamin D supplementation in children with urinary tract infection

Urinary tract infections (UTIs) are one of the most common bacterial infections in the global population. Vitamin D deficiency is also an urgent and common problem, and the high incidence of hypovitaminosis does not depend on age, sex, nationality, and geographical location. Along with the so-called "classical" effects of cholecalciferol, no less significant non-calcemic functions of cholecalciferol have been actively studied over the past two decades, particularly its effect on inflammation and its role in anti-infectious immunity. More and more data on the relationship between UTIs and vitamin D deficiency supports the possible use of cholecalciferol as an adjuvant to basic UTI therapy.&#x0D; Aim. To analyze the vitamin D status in children with UTI compared to healthy ones.&#x0D; Materials and methods. The study included 75 children from 1 month to 18 years with UTIs of various localization treated in a healthcare institution in Stavropol. The mean age of the study patients was 6.0±0.3 years. Vitamin D status was based on serum calcidiol [25(OH)D3] level.&#x0D; Results. The vitamin D level is statistically significantly higher in children of the control group than in patients with UTI: 36.42 ng/mL [24.92–46.37] vs 24.13 ng/mL [13.75–36.42], respectively (p=0.003). There were no patients with severe vitamin deficiency in the control group, while in the UTI group, it occurred in 20.0% of patients. The vitamin D level was less than 20 ng/mL in 31 (41.3%) children with UTI and only 2 (6.6%) in the control group (p=0.001). Normal vitamin status was found in only 38.7% of patients with UTI compared to 66.7% of healthy children (p0.01). The lowest level was found in patients with acute cystitis – 19.7 ng/mL [9.8–19.7], and the highest in patients with acute pyelonephritis – 31.9 ng/mL [14.3–36.4].&#x0D; Conclusion. Based on the study results, it can be concluded that vitamin D deficiency may be one of the risk factors for developing UTIs in children. Further studies involving more patients are needed.