Search Results (538)

Background: Recurrent urinary tract infections (rUTIs) significantly impair women’s quality of life, making antimicrobial prophylaxis a critical preventative strategy. This retrospective observational study aimed to characterize antibiotic prophylaxis patterns, relapse rates, comparative efficacy of different agents, and tolerability in 908 women (663 postmenopausal, 245 premenopausal) with rUTIs managed at a tertiary university hospital. Methods: Data from medical records (January 2022–December 2024) were analyzed. Patients were stratified by menopausal status. We assessed antibiotic usage, relapse rates (per 100 patient-months), and adverse events. Comparative efficacy of nitrofurantoin-based versus fosfomycin/other prophylaxis was evaluated for rUTIs caused by E. coli, E. faecalis, or E. coli ESBL using weighted and matched analyses to control for covariates. Results: Continuous antimicrobial prophylaxis was the primary strategy, with nitrofurantoin being most frequently used. Premenopausal women showed a greater tendency for intermittent or combined prophylactic approaches. Postmenopausal women exhibited a higher overall crude relapse rate (5.54/100 p-m) compared to premenopausal women (3.14/100 p-m), with E. coli being the most common causative agent in relapses. For rUTIs caused by E. coli, E. faecalis, or E. coli ESBL, nitrofurantoin-based prophylaxis demonstrated significantly lower adjusted relapse rates than fosfomycin/other regimens (rate ratio: 0.47 for postmenopausal, 0.35 for premenopausal women). This observed efficacy for nitrofurantoin was robust against potential unmeasured confounding. Prophylaxis was generally well-tolerated (3.0% gastrointestinal adverse events overall); however, premenopausal women reported a higher adverse event incidence. Conclusions: Our findings strongly suggest that nitrofurantoin is an effective prophylactic choice for rUTIs caused by common uropathogens (E. coli, E. faecalis, E. coli ESBL), particularly in postmenopausal women. The diverse prophylactic strategies highlight the need for individualized care. While generally well-tolerated, adverse event profiles vary between menopausal groups, necessitating careful monitoring. Full article

Background: The treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections is extremely challenging due to its antibiotic resistance, and the combination of plant active ingredients with antibiotics represents a potential strategy to address this issue. Methods: We determined the combinatorial relationship between baicalin (BA) and kanamycin (KM) using the checkerboard dilution method. The antibacterial activity of the baicalin–kanamycin (BA/KM) combination was evaluated through growth curve determination assays and scanning electron microscopy (SEM). The effects of the BA/KM combination on the cell membrane and cell wall of MRSA were analyzed using reactive oxygen species (ROS) detection assays, intracellular protein leakage experiments, alkaline phosphatase (AKP) activity assays, laser scanning confocal microscopy (LSCM) observations, and molecular docking simulations. The antibiofilm activity and related mechanisms of the BA/KM combination were elucidated via crystal violet staining, MTT assay, phenol-sulfuric acid method, congo red staining, staphyloxanthin determination assays, and quantitative real-time polymerase chain reaction (qPCR). The safety of the BA/KM combination was assessed through hemolytic activity analysis, and its anti-MRSA efficacy was evaluated on lettuce. Results: BA/KM combination showed a synergistic antibacterial effect on MRSA USA300. Mechanistic studies revealed that BA may interact with amino acid residues of peptidoglycan synthetase PBP2a to hinder peptidoglycan synthesis, thereby facilitating KM penetration through the cell wall. Subsequently, BA binds to amino acid residues of the membrane transporter NorA, leading to disruption of cell membrane homeostasis and enhancing KM’s ability to induce intracellular ROS accumulation in MRSA. Furthermore, the BA/KM combination reduced MRSA biofilm formation by 77.85% and decreased the metabolic activity of biofilm cells by 42.93% through inhibiting the synthesis of biofilm components EPS and PIA. Additionally, this combination suppressed the synthesis of staphyloxanthin and downregulated the expression of agrA and agrC genes. When 1/8 MIC BA was combined with 1/4 MIC KM, the count of MRSA on lettuce surfaces was reduced by 0.88 log CFU/cm², an effect comparable to that of 0.2% (v/v) hydrogen peroxide. Conclusions: According to these findings, the BA/KM combination may offer a promising option for enhancing antibacterial efficacy through synergism, reducing antibiotic usage concentrations, and limiting MRSA transmission in fresh agricultural products. Full article

Colibacillosis, caused by avian pathogenic Escherichia coli (APEC), represents a major threat to poultry production, leading to significant mortality and economic losses. This study aimed to characterize an APEC strain, HPVN24, isolated from diarrheic chickens at a farm in Hai Phong, Vietnam. The strain was investigated through phenotypic assays, antibiotic susceptibility profiling, and whole-genome sequencing using the Illumina platform. HPVN24 exhibited β-hemolytic activity and resistance to trimethoprim, ampicillin, and ciprofloxacin. Whole-genome analysis identified the strain as serotype O78:H9 and sequence type ST23, with a genome size of 5.05 Mb and a GC content of 50.57%. Genome annotation revealed a wide repertoire of genes involved in metabolism, secretion systems, virulence, and biofilm formation. Virulence-associated genes included those related to adhesion, iron acquisition, hemolysin production, and stress response. Analysis predicted multidrug resistance to 18 antibiotic classes, with particularly strong resistance to fluoroquinolones. Phylogenetic comparison demonstrated that HPVN24 clustered closely with O78:H9 strains isolated from poultry in other regions, suggesting potential transmission across populations. These findings indicate that HPVN24 is a multidrug-resistant and highly virulent APEC strain linked to colibacillosis outbreaks in Vietnam and highlight the need for ongoing surveillance, judicious antibiotic usage, and alternative strategies to ensure poultry health and food safety. Full article

The global escalation of antimicrobial resistance (AMR) among Gram-negative bacteria poses a severe threat to public health. Traditional antibiotic development struggles to keep pace with emerging resistant strains, necessitating innovative strategies to enhance therapeutic options. This review explores the potential of drug repurposing as a strategic approach to combat Gram-negative bacterial infections, focusing on clinically approved drugs with antibacterial properties or the capacity to enhance antibiotic efficacy through direct or host-directed mechanisms. Within the review, a special section is dedicated to the potential usage of repurposed drugs against bacteria that can be used as biological warfare agents, exposure to which may lead to mass casualties, in particular if these pathogens are resistant to antibiotics. Repurposed drugs exhibit diverse antibacterial mechanisms, including membrane disruption, efflux pump inhibition, iron metabolism interference, quorum sensing suppression, and biofilm inhibition. Additionally, many agents demonstrated host-directed therapeutic effects by modulating inflammatory responses, enhancing autophagy, or boosting innate immune functions. Drug repurposing offers a promising avenue to mitigate the AMR crisis by providing rapid, cost-effective therapeutic solutions. Combining repurposed drugs with existing antibiotics or employing them as host-directed therapies holds significant potential for treating infections caused by multidrug-resistant Gram-negative pathogens. Continued research and clinical validation are essential to translate these findings into effective treatment regimens. Full article

Background/Objectives: The prevalence of ESBL-producing Escherichia coli (E. coli) has increased significantly, impacting prognoses due to delayed or limited treatment options. We aimed to determine the demographic patterns, risk factors, and clinical outcomes of ESBL-producing E. coli in a top-referral hospital in Indonesia. Methods: This study was observational in design and focused on hospitalized patients with bacteremia due to E. coli during 2022–2024. Results: We identified 224 patients during the study period. The median of length of stay was 7 (3–13) days. Mortality occurred in 149 (66.55%) patients, and there was no difference in the mortality between patients with ESBL E. coli and those with non-ESBL E. coli. The severity of illness, as defined by the Pitt bacteremia score (PBS), was higher in the ESBL E. coli group. Urinary tract infection (UTI), previous antibiotic use, and central venous catheter (CVC) insertion were independent risk factors for bacteremia due to ESBL E. coli bacteremia. Male gender, shorter length of stay (LOS), solid tumor, pneumonia, mechanical ventilation, CVC insertion, inappropriate initial antibiotic therapy (IIAT), and sequential organ failure assessment (SOFA) score were risk factors for mortality in bacteremia caused by E. coli, including both ESBL and non-ESBL producers. Male gender, shorter LOS, CVC usage, and SOFA score were independent risk factors for mortality in bacteremia due to ESBL E. coli. Conclusions: ESBL-producing E. coli increases the severity of bacteremia. Recognizing patients at high risk for ESBL-producing E. coli infections is crucial for initiating appropriate empirical antibiotic treatment targeting ESBL-producing pathogens. Full article

Candida albicans is the primary etiological agent of vulvovaginal candidiasis (VVC), a widespread fungal infection affecting millions of women worldwide. Although often self-limiting, VVC can become recurrent or severe, significantly impacting quality of life. The pathogenesis of C. albicans is driven by key virulence factors, including hyphal transformation, biofilm formation, and immune evasion, which all facilitate persistence and resistance to host defenses. Epidemiological data indicate that up to 75% of women experience at least one episode of VVC, with 5–10% developing recurrent vulvovaginal candidiasis. The condition typically presents with vaginal itching, burning, erythema, edema, and an abnormal discharge. Diagnosis relies on both clinical presentation and microbiological confirmation; however, misdiagnosis remains common due to symptom overlap with other vaginal infections and conditions in general. Azole antifungals remain the cornerstone of treatment; however, increasing resistance (particularly in non-albicans Candida species) poses substantial therapeutic challenges. Consequently, the emergence of antifungal-resistant strains underscores the need for novel treatment strategies, including probiotics and natural antifungal agents. Preventive measures—including maintaining vaginal microbiota balance, avoiding unnecessary antibiotic usage, and improving hygiene practices—play a pivotal role in reducing disease burden due to C. albicans. Given the rising incidence of VVC and the burden of recurrent cases, further research is essential to develop targeted therapeutic interventions. This comprehensive review highlights the evolving epidemiology, pathogenesis, and clinical challenges of C. albicans-associated VVC, emphasizing the need for improved diagnostic strategies, alternative therapeutic approaches, and targeted preventive measures to reduce disease burden and enhance patient outcomes. Full article

Antimicrobial resistance (AMR) constitutes a serious public health issue, and the European Union (EU) requires reduction in the sales of antibiotics in farmed animals of 50% by 2030. A scoping review was conducted in PubMed for the years from 2000 to 2024, limited to the English and German languages, with the aims to (1) provide an overview of factors on commercial poultry farms potentially associated with health-related endpoints such as mortality, disease prevalence, carcass condemnation, performance as well as AMR/antimicrobial usage at different hierarchical levels (animal, flock/batch, stable, farm), and (2) identify inconsistencies with respect to these potential risk factors. Overall, 34 peer-reviewed publications met the inclusion criteria for the review. Significant associations identified in the uni- or multivariable statistical analysis were summarised using graphs and bar charts. The results highlight that risk factor–outcome associations often are complex, inconsistent with regards to the direction of the influence especially for some ordinal or categorical variables. In some associations such as the sex of the animals and performance, contrary directions were reported in different studies—illustrating the multifactorial dynamics of commercial poultry production. This research enhances the understanding of the complexity of commercial poultry production, which is essential when designing future studies and interpreting their results. Full article

Background: Various predisposing factors contribute to the emergence and dissemination of the multidrug-resistant (MDR) phenotype in Escherichia coli and Klebsiella pneumoniae. Understanding these factors is crucial for guiding appropriate antimicrobial therapy and infection control strategies. This study investigated the predisposing factors contributing to the MDR characteristics of E. coli and K. pneumoniae isolated in a community hospital in northeastern Thailand. Methods: This case–control study utilized retrospective data from bacterial culture, as well as demographic, clinical, and antibiotic susceptibility records collected during 5 years (January 2016–December 2020). E. coli and K. pneumoniae isolates were analyzed from various clinical samples, including blood, urine, pus, sputum, and other body fluids. Data were analyzed using descriptive statistics and univariate logistic regression. Results: In total, 660 clinical isolates were analyzed (421 E. coli and 239 K. pneumoniae). Blood was the most common source of the detection of E. coli (63.0%) and sputum was the most common source of K. pneumoniae (51.0%). The median ages of patients were 67 and 63 years for E. coli and K. pneumoniae, respectively. E. coli cases were significantly associated with prior antibiotic use (OR = 1.79, 95% CI: 1.17–2.74 p = 0.008). MDR was observed in 50.1% of E. coli and 29.7% of K. pneumoniae (p < 0.001). E. coli compared to K. pneumoniae had lower resistance to third-gen cephalosporins (64.9% versus 95.8%) and carbapenems (8.0% versus 6.9%). ICU admission was the only factor significantly associated with MDR E. coli (OR = 2.40, 95% CI: 1.11–5.20 p = 0.026). No significant differences were observed in gender, age, or comorbidities between MDR cases. Antibiotic usage patterns also differed, with E. coli more likely to receive third-gen cephalosporins compared to carbapenems (OR = 3.02, 95% CI:1.18–7.74 p = 0.021). Conclusions: The use of third-generation cephalosporin may drive MDR E. coli more than K. pneumoniae. Prior antibiotic exposure was linked to E. coli bloodstream infections, while MDR E. coli showed greater clinical severity. These findings highlighted the need for improved antibiotic stewardship in rural hospitals. Full article

Background: Studies have demonstrated a positive correlation between high body mass index (BMI) and an increased risk of Clostridioides difficile infection (CDI), independent of antibiotic usage or healthcare exposures. Aim: To compare the outcomes of obese (BMI ≥ 30 kg/m²) and non-obese (BMI < 30 kg/m²) hospitalized patients with CDI. Methods: This retrospective cohort study included patients with CDI hospitalized in Beilinson hospital between January 2013 and January 2020. The primary outcome was 90-day all-cause mortality. Secondary outcomes included 30-day mortality, colectomy, intensive care unit (ICU) admission and length of hospital stay (LOS). Multivariate analysis was performed to identify the risk factors independently associated with 90-day mortality. Results: The study included 889 patients: 131 (15%) obese and 758 (85%) non-obese. The obese group was younger (median age 65 years vs. 73 years (p < 0.01)) and with a higher rate of diabetes mellitus (57/131 (44%) vs. 180/758 (24%) (p < 0.01)). The 90-day mortality was lower in the obese group: 19/131 (15%) vs. 170/752 (23%) (p = 0.04). The 30-day mortality was 8/131 (6%) vs. 96/757 (13%) (p = 0.03). ICU admission was 9/131 (7%) vs. 23/758 (3%) (p = 0.03), and median LOS was 19 vs. 12 days (p < 0.01) in obese and non-obese groups, respectively. In the multivariable analysis, after adjustment for age, Charlson’s comorbidity index ≥3, assistance in activities of daily living, treatment with proton pump inhibitors and severity of illness, obesity was not a significant risk factor for 90-day mortality (OR = 0.65, 95% CI: 0.38–1.01; p = 0.1). Conclusions: In this study, obesity was not significantly associated with 90-day mortality after adjustment for other risk factors; however, ICU admission was higher and LOS longer in this group. Full article

Background/Objectives: Antibiotic use is common among hospitalized pediatric patients. However, inappropriate use, including excessive use of Watch antibiotics, can contribute to antimicrobial resistance, adverse events, and increased healthcare costs. Consequently, there is a need to continually assess their usage among this vulnerable population. This was the objective behind this study. Methods: The medical records of all pediatric patients (under 12 years) admitted and treated with antibiotics at a Ghanaian Teaching Hospital between January 2022 and March 2022 were extracted from the hospital’s electronic database. The prevalence and appropriateness of antibiotic use were based on antibiotic choices compared with current guidelines. Influencing factors were also assessed. Results: Of the 410 admitted patients, 319 (77.80%) received at least one antibiotic. The majority (68.65%; n = 219/319) were between 0 and 2 years, and males (54.55%; n = 174/319). Ceftriaxone was the most commonly prescribed antibiotic (20.69%; n = 66/319), and most of the systemic antibiotics used belonged to the WHO Access and Watch groups, including a combination of Access and Watch groups (42.90%; n = 136/319). Neonatal sepsis (24.14%; n = 77/319) and pneumonia (14.42%; n = 46/319) were the most common diagnoses treated with antibiotics. Antibiotic appropriateness was 42.32% (n = 135/319). Multivariate analysis revealed ceftriaxone prescriptions (aOR = 0.12; CI = 0.02–0.95; p-value = 0.044) and surgical prophylaxis (aOR = 0.07; CI = 0.01–0.42; p-value = 0.004) were associated with reduced antibiotic appropriateness, while a pneumonia diagnosis appreciably increased this (aOR = 15.38; CI = 3.30–71.62; p-value < 0.001). Conclusions: There was high and suboptimal usage of antibiotics among hospitalized pediatric patients in this leading hospital. Antibiotic appropriateness was influenced by antibiotic type, diagnosis, and surgical prophylaxis. Targeted interventions, including education, are needed to improve antibiotic utilization in this setting in Ghana and, subsequently, in ambulatory care. Full article

The rise in antibiotic-resistant bacteria has made the management of bacterial diseases increasingly challenging. As a result, bacteriophages have gained attention as a promising alternative to antibiotics for combating bacterial pathogens. However, the usage of phages as biocontrol agents faces many challenges, including environmental stability, delivery efficiency, host specificity, and potential bacterial resistance. Advancements in genetic engineering and nanotechnology have been explored to enhance the stability, efficacy, and adaptability of phage-based treatments. In this review, we discuss the key barriers to the effective implementation of phage therapy and highlight innovative strategies to overcome these challenges. By addressing these limitations, this review aims to provide insights into optimizing phage-based approaches for widespread therapeutic and biocontrol applications. Full article

The role of Enterococcus spp. in food is debated since this group of lactic acid bacteria contains opportunistic pathogenic strains, some of which exhibit a multidrug-resistant profile. In livestock farms, the use of antibiotics is the most common practice to deal with mastitis-causing bacteria. However, the heavy usage and/or misuse of antibiotics has led to the emergence of antibiotic resistance. This study aimed to genetically and phenotypically characterize Enterococcus strains isolated from raw sheep milk. Samples were collected over one year from the bulk tank of a dairy sheep farm and cultured on selective media. Isolates were purified and analyzed by whole-genome sequencing and antimicrobial susceptibility testing. The isolates were divided into clusters and the corresponding species were identified along with their genes related to virulence and antibiotic resistance. The pan-, core- and accessory-genomes of the strains were determined. Finally, the antibiotic-resistant profile of selected strains was examined and associated with their genomic characterization. These findings contribute to a better understanding of Enterococci epidemiology, providing comprehensive profiles of their virulence and resistance genes. The presence of antibiotic-resistant bacteria in raw sheep milk destined for the production of cheese should raise awareness. Full article

Necrotic enteritis, caused by Clostridium perfringens (C. perfringens) is a disease present worldwide and causes major economic losses. The re-emergence of the disease, in recent years, is mainly due to the ban of the usage of antibiotics as growth promoters in the EU. The aim of this study was to establish a reliable, robust challenge model. Ross hybrid broilers were divided into randomized groups: a positive and a negative control group, a group receiving antibiotic treatment and three groups fed with assorted feed supplements, all receiving the same basal diet. The birds in the treatment groups were vaccinated twice using a 10-times dose of an Infectious Bursitis live vaccine and the animals were challenged four times with a NetB toxin producing C. perfringens strain. The presence of clinical signs and body weight gain were monitored. At the end of the study necropsy was performed and the gut lesions were scored. During the experiment, clinical signs were absent in the negative control group and in the antibiotic treated group. The other animals displayed diarrhea and feather loss. These symptoms were the most pronounced in the positive control group. The gut lesion scores showed significant differences between the negative and positive control groups, with the former scoring the lowest. Based on these results, the challenge model establishment was successful and in this setup the assessment of the potency of feed additives is also possible. Full article

Background: The European League Against Rheumatism (EULAR), in collaboration with the European Scleroderma Trial and Research group (EUSTAR), published the first set of treatment recommendations for systemic sclerosis (SSc) in 2009, with subsequent updates in 2016 and 2023. Objectives: This study aimed to evaluate how rheumatologists’ clinical approaches to the treatment of SSc evolved following the 2016 update of the clinical management guidelines. Methods: Medication use for SSc was analyzed in a cohort of 378 patients. The patients were stratified based on enrollment before (233 patients) and after (145 patients) the guideline update, and medication usage was compared between the two groups. Results: Although all patients presented with Raynaud’s phenomenon (RP), only 35% received calcium channel blockers. Medications such as iloprost, phosphodiesterase type 5 (PDE-5) inhibitors, fluoxetine, and bosentan, recommended for the treatment of RP and digital ulcers, were not approved for SSc by the Republic Health Insurance Fund. Treatment for pulmonary arterial hypertension (PAH) was administered to only 16 patients (4.2%), including 2 who received bosentan, 10 who received PDE-5 inhibitors, and 4 who were treated with riociguat. The use of PDE-5 inhibitors increased following the 2016 update of the guidelines. Cyclophosphamide was consistently prescribed for interstitial lung disease (ILD), with an increased frequency observed after the guideline update. No significant differences were observed in the use of methotrexate for skin involvement, ACE inhibitors for scleroderma renal crisis, or antibiotics for gastrointestinal symptoms. Proton pump inhibitors (PPIs) were prescribed to 87.3% of patients with gastrointestinal involvement, with an increase in use of both PPIs and prokinetic agents following the guideline update. Conclusions: Rheumatologists’ adherence to the EULAR/EUSTAR guidelines varied considerably, with 25% to 100% of eligible patients receiving the recommended treatments. Concordance improved in the management of PAH, ILD, and gastrointestinal involvement after the 2016 guideline update. Full article

Grazing is a free-range farming model commonly practiced in low-external-input agricultural systems. The widespread use of veterinary antibiotics in livestock farming has led to significant environmental accumulation of antibiotic residues and antibiotic resistance genes (ARGs), posing global health risks. This study investigated the antibiotic residues, bacterial community, ARG profiles, and mobile genetic elements (MGEs) in cattle feces from three provinces in western China (Ningxia, Xinjiang, and Inner Mongolia) under grazing modes. The HPLC-MS detection showed that the concentration of tetracycline antibiotics was the highest in all three provinces. Correlation analysis revealed a significant negative correlation between antibiotic residues and the diversity and population abundance of intestinal microbiota. However, the abundance of ARGs was directly proportional to antibiotic residues. Then, the Sankey analysis revealed that the ARGs in the cattle fecal samples were concentrated in 15 human pathogenic bacteria (HPB) species, with 9 of these species harboring multiple drug resistance genes. Metagenomic sequencing revealed that carbapenemase-resistant genes (bla_KPC and bla_VIM) were also present in considerable abundance, accounting for about 10% of the total ARGs detected in three provinces. Notably, Klebsiella pneumoniae strains carrying bla_CTX-M-55 were detected, which had a possibility of IncFII plasmids harboring transposons and IS19, indicating the risk of horizontal transfer of ARGs. This study significantly advances the understanding of the impact of antibiotic residues on the fecal microbiota composition and ARG profiles in grazing cattle from northwestern China. Furthermore, it provides critical insights for the development of rational antibiotic usage strategies and comprehensive public health risk assessments. Full article