Search Results (439)

Aim: Antibiotic de-escalation (ADE) is essential, but appears to be underperformed although being possible, which we refer to as a ‘missed opportunity’. We aimed to analyze the ADE missed opportunities in Gram-negative bloodstream infections (BSIs) in a setting with a high antimicrobial resistance profile. Methods: A retrospective, two-centered cohort study was performed from 1 January 2018 to 30 June 2019, including adults with mono- or polymicrobial Gram-negative BSIs. All ADE episodes and 30-day mortality were noted. Results/Discussion: Out of 273 BSIs (43 ADE vs. 230 no-ADE episodes), 101 were considered a ‘missed’ opportunity of ADE (36.9%, 101/273). In multivariate analysis, ADE opportunities were missed 4.4 times more (OR = 4.4; 95% CI 1.24–15.9) in the presence of hematological malignancy and 6.2 times more (OR = 6.2; 95% CI 1.76–22.2) in ESBL. Contrary to this, ADE opportunities were missed 0.24 times less (OR = 0.24; 95% CI 0.09–0.61) among patients with E. coli BSIs, and 0.17 less (OR = 0.17; 95% CI 0.05–0.67) if ertapenem was used as an empirical agent. The ADE missed opportunity group had a higher mortality rate, which is statistically significant in univariate analysis, but not in multivariate analysis. Conclusion: The presence of ESBL and hematological malignancy were the significant barriers to appropriate ADE practice in our study. A good stewardship program must address physician hesitation in ADE practice. Full article

Feline urinary tract infections (UTIs) present a common challenge in veterinary practice, underscoring the importance of understanding local bacterial pathogens and antimicrobial resistance (AMR). This study determined bacterial prevalence and antimicrobial susceptibility in cats at Kasetsart University’s Veterinary Teaching Hospital in Bangkok, Thailand. Of the 543 cystocentesis urine samples collected from 428 cats, 115 (21.2%) tested positive for bacterial cultures, leading to a diagnosis of UTIs in 95 cats (22.2%). The most prevalent isolates included Escherichia coli (24.8%), Staphylococcus species (19.2%), Proteus mirabilis (13.6%), Pseudomonas aeruginosa (12.0%), and Enterococcus species (12.0%). Staphylococcus felis (8.8%) and Staphylococcus pseudintermedius (5.6%) were the predominant Staphylococcus species. Rare pathogens such as Corynebacterium urealyticum and Lactococcus garvieae were also identified. Antimicrobial testing revealed alarming resistance, with 69.2% of isolates exhibiting multidrug resistance (MDR). Escherichia coli and Proteus mirabilis showed high resistance to amoxicillin/clavulanic acid (AMC) (45.2–70.6%) and sulfamethoxazole/trimethoprim (SXT) (51.6–52.9%). Enterococcus faecium exhibited 85.7% resistance to AMC. Methicillin resistance was identified in 41.7% of Staphylococcus isolates, particularly high in Staphylococcus epidermidis (75.0%) and Staphylococcus pseudintermedius (71.4%). High fluoroquinolone resistance among MDR isolates further exacerbates AMR concerns. These results indicate that MDR Gram-negative, Staphylococcus, and Enterococcus species complicate the empirical treatment of feline UTIs, highlighting significant implications for AMR in veterinary practice. Full article

Sepsis remains a leading global cause of mortality, with delayed recognition and empirical antibiotic overuse fueling poor outcomes and rising antimicrobial resistance. This systematic scoping review evaluates the current landscape of artificial intelligence (AI) and machine learning (ML) applications in sepsis care, focusing on early detection, personalized antibiotic management, and resistance forecasting. Literature from 2019 to 2025 was systematically reviewed following PRISMA-ScR guidelines. A total of 129 full-text articles were analyzed, with study quality assessed via the JBI and QUADAS-2 tools. AI-based models demonstrated robust predictive performance for early sepsis detection (AUROC 0.68–0.99), antibiotic stewardship, and resistance prediction. Notable tools, such as InSight and KI.SEP, leveraged multimodal clinical and biomarker data to provide actionable, real-time support and facilitate timely interventions. AI-driven platforms showed potential to reduce inappropriate antibiotic use and nephrotoxicity while optimizing outcomes. However, most models are limited by single-center data, variable interpretability, and insufficient real-world validation. Key challenges remain regarding data integration, algorithmic bias, and ethical implementation. Future research should prioritize multicenter validation, seamless integration with clinical workflows, and robust ethical frameworks to ensure safe, equitable, and effective adoption. AI and ML hold significant promise to transform sepsis management, but their clinical impact depends on transparent, validated, and user-centered deployment. Full article

In acute lymphoblastic leukemia (ALL), neutropenia and fever of unknown origin may occur, indicating the use of antimicrobials to control a probable infection. However, in 60–70% of cases there is no obvious infectious focus so treatment is empirical, increasing the risk of developing systemic inflammatory response syndrome (SIRS). The construction of a prognostic model of fever and development of SIRS based on the identification of endogenous molecules, called alarmins or damage-associated molecular patterns (DAMPs) and inflammatory cytokines, can help identify children with ALL and fever or SIRS and who do not have an infection. A cohort of 30 children with recently diagnosed ALL and absence of infectious microorganisms before starting the remission induction phase was studied. Two groups were identified: (1) a group with SIRS (fever, tachycardia, tachypnea, and leukopenia, without focus of infection) and (2) a group without SIRS. The DAMPs, namely HMGB1 and S100A8 proteins, were quantified by ELISA and inflammatory mediators were determined by multiple protein analysis. The medians of DAMPs and inflammatory mediators in children with SIRS were higher than in children who did not have SIRS, and the delta values of the biomarkers studied in patients with and without SIRS showed important differences, with statistically higher medians in patients with SIRS compared to those without SIRS. HMGB1 together with IL-1β, IL-8, IL-10, and MCP-1 can serve as biomarkers to identify children with ALL and fever or SIRS who should not receive antimicrobial treatment because the origin of their fever is not due to an infectious agent. Full article

Background: Infectious complications are common after percutaneous nephrolithotomy (PCNL). Clinical guidelines recommend, previous to surgery, prolonged antibiotic regimens in patients with preoperative positive urine cultures to reduce infectious risk. However, such strategies may increase selective pressure and promote antimicrobial resistance. Evidence supporting the use of a single antibiotic dose tailored to culture sensitivity in these cases is limited but emerging. Methods: We conducted a retrospective observational study including 187 PCNL procedures performed between 2021 and 2023 under an individualized antibiotic prophylaxis protocol. Patients with negative or contaminated urine cultures received a single empirical dose, while those with recent positive cultures received a single dose based on antimicrobial susceptibility testing. Postoperative complications—including fever, sepsis, and a composite outcome—were analyzed through multivariable logistic regression, comparing high- and low-risk patients. Results: A total of 67.9% of procedures were performed in patients meeting at least one high-risk criterion, including a positive preoperative urine culture in 32.1%. The overall incidence of infectious complications was 11.9% (fever 8.7%, sepsis 3.2%), with no significant differences between risk groups. A low concordance was observed between preoperative and intraoperative urine cultures (Spearman = 0.3954). Conclusions: A single preoperative antibiotic dose adjusted to the antibiogram, even in patients with a positive urine culture, was not associated with increased infectious complications. This approach is an initial step that supports a rational and individualized prophylactic strategy aligned with the goals of antimicrobial stewardship programs (ASPs). Full article

Background: Urinary tract infections (UTIs) are among the most common types of infections during childhood. Limited data are available on the prevalence of UTI in children from Romania, with most being available for hospitalized children. For this reason, we conducted a retrospective observational study in consecutive non-hospitalized children to assess the number of positive UTI samples and the antibacterial resistance of causative pathogens. Methods: This study included 7222 consecutive urine cultures collected from children aged 1 to 18 years who are residents of Arad County, Western Romania. Urine samples were analyzed for leukocyturia and cultures for the presence of monomorphic bacteria. Results: The overall number of positive UTI samples was 10.44%. A higher number of positive UTI samples was observed in females when compared to males and in children aged 6–12 and 12 to 18 years when compared to those aged 1–5 years. The antibiotic susceptibility testing of E. coli isolates revealed high sensitivity to most tested antibacterials. Near-complete susceptibility was observed for fosfomycin (99.71%) and nitrofurantoin (96.01%), while high susceptibility rates were also observed for ciprofloxacin (85.43%) and amoxicillin–clavulanic acid (75.05%). In contrast, high resistance was found for ampicillin (62.28% resistant) and trimethoprim–sulfamethoxazole (36.53% resistant). Conclusions: Given the clinical risks associated with UTI in children, our findings underscore the urgent need for the continued monitoring of multidrug-resistant strains. Our study provides important epidemiological and resistance data to guide empirical treatment and strengthen pediatric antimicrobial resistance surveillance. Future studies should focus on different regions and regularly update resistance patterns to keep treatment and prevention strategies aligned with local conditions. Full article

Introduction: Urinary tract infections (UTIs) remain a significant public health issue worldwide, particularly affecting the geriatric population with increased morbidity and mortality. Aging-related immune changes, comorbidities, and urogenital abnormalities contribute to the higher incidence and complexity of UTIs in elderly patients. Antimicrobial resistance, especially extended-spectrum beta-lactamase (ESBL) production and carbapenem resistance, poses a major challenge in managing UTIs in this group. Methods: This retrospective, multicenter study included 776 patients aged 65 and older, hospitalized with a diagnosis of urinary tract infection between January 2019 and August 2024. Clinical, laboratory, and microbiological data were collected and analyzed. Urine samples were obtained under sterile conditions and pathogens identified using conventional and automated systems. Antibiotic susceptibility testing was performed according to CLSI standards. Logistic regression analyses were conducted to identify factors associated with ESBL production, carbapenem resistance, and mortality. Results: Among the patients, the median age was 78.9 years, with 45.5% female. ESBL production was detected in 56.8% of E. coli isolates and carbapenem resistance in 1.2%. Klebsiella species exhibited higher carbapenem resistance (37.8%). Independent predictors of ESBL production included the presence of urogenital cancer and antibiotic use within the past three months. Carbapenem resistance was associated with recent hospitalization, absence of kidney stones, and infection with non-E. coli pathogens. Mortality was independently associated with intensive care admission at presentation, altered mental status, Gram-positive infections, and comorbidities such as chronic obstructive pulmonary disease and urinary incontinence. Discussion: Our findings suggest that urinary pathogens and resistance patterns in elderly patients are similar to those in younger adults reported in the literature, highlighting the need for age-specific awareness in empiric therapy. The identification of risk factors for multidrug-resistant organisms emphasizes the importance of targeted antibiotic stewardship, especially in high-risk geriatric populations. Multicenter data contribute to regional understanding of resistance trends, aiding clinicians in optimizing management strategies for elderly patients with UTIs. Conclusions: This study highlights that E. coli and Klebsiella species are the primary causes of UTIs in the elderly, with resistance patterns similar to those seen in younger adults. The findings also contribute important data on risk factors for ESBL production and carbapenem resistance, supported by a robust patient sample. Full article

Molecular methods allow for a rapid identification of the main causative agents of pneumonia along with the most frequent resistance genes. Prolonged broad-spectrum antibiotic therapy without microbiological evidence of infection drives antimicrobial resistance. We evaluated if the result provided by the molecular method is helpful for antimicrobial de-escalation. All respiratory samples collected and directly processed via Real-Time PCR from patients with suspected pneumonia, of whom clinical data were available, were included in this study. In 82 patients out of a total of 174 (47.1%), antimicrobial therapy was modified after the molecular test, and in 28/82 (34.1%), antimicrobial de-escalation was carried out. Among the 92 patients in whom therapy was not modified, 33 (35.9%) were did not receive any antimicrobial therapy before the molecular test and no antibiotics were prescribed after the test. Therefore, in 61 (28 + 33) out of the 174 (35%) patients, unnecessary antimicrobials were discontinued or avoided. The syndromic panel used at our institution can be of help in better choosing when empiric antibiotic de-escalation therapy could be feasible. Full article

Objectives: In the context of the global rise in antimicrobial resistance (AMR), this study aimed to investigate temporal trends in AMR among pathogens isolated from endometrial cultures of patients diagnosed with chronic endometritis (CE). Methods: This cross-sectional study included 244 women consecutively diagnosed with CE at the Gynecology Unit of the University of Bari, Italy, between January 2020 and June 2024. Exclusion criteria were (i) previous CE diagnosis or treatment; (ii) antimicrobial use in the month prior to hysteroscopy and biopsy; (iii) use of oral or vaginal prebiotics/probiotics or contraceptives in the three months prior; (iv) known immunosuppression; and (v) hypersensitivity to quinolones or macrolides. CE was diagnosed using hysteroscopy combined with endometrial histology and microbial culture. Specifically, in cases with hysteroscopic signs suggestive of CE, endometrial biopsies were obtained using a Novak curette and processed for histological and immunohistochemical analyses, as well as for microbial identification and antimicrobial susceptibility testing in accordance with EUCAST guidelines. The primary outcomes were the prevalence of CE-associated pathogens and their AMR profiles. Results: The median age at CE diagnosis was 33 years (range 26–44). The most frequently isolated pathogens were Enterococcus faecalis (26.2%), Escherichia coli (19.3%), and Ureaplasma urealyticum (16.4%). High AMR rates were observed, with increasing trends over time. Ampicillin resistance reached 98.5% (63/64), penicillin resistance 30.8% (16/52), and extended-spectrum beta-lactamase (ESBL) positivity 34.7% (25/72), all with statistically significant trends (p < 0.001). Resistance to commonly used first-line antimicrobials, such as tetracyclines, quinolones, and nitroimidazoles, was also substantial. Conclusions: This study highlights a significant increase in AMRs among microorganisms responsible for CE between 2020 and 2024. As a result, empirical first-line antimicrobial therapies commonly used to treat patients with CE may be increasingly ineffective in a growing number of cases. This underscores the need for improved and targeted diagnostic and therapeutic strategies to effectively manage CE and prevent treatment failures. Strengthening surveillance systems, implementing antimicrobial stewardship programs, and enhancing patient education may help counter the growing threat of AMR. Full article

Background: Metronidazole is the preferred anaerobic agent for empiric treatment of intra-abdominal infections (IAI). Although dosed every 8 h (q8hr), blood concentrations exceed the in vitro minimum inhibitory concentration (MIC) for anaerobic organisms at 12 h (q12hr). A drug shortage of intravenous (IV) metronidazole prompted the conversion to every 12 h dosing in qualifying patients treated for IAI. Objective: To determine efficacy outcomes of metronidazole dosed every 12 h versus every 8 h in patients treated for IAI. Methods: This was a multi-center, retrospective, cohort study of 201 patients from January to July 2021 (q8hr) and January to November 2023 (q12hr) at five hospitals through the greater Houston area. Included patients were adults with a diagnosis of IAI confirmed by radiographic evidence and a white blood count (WBC) > 12,000 cells/µL and/or temperature > 100.4 °F at the time of diagnosis. The primary outcome was clinical cure of IAI, defined as resolution of signs/symptoms of IAI and normalization of WBC or temperature. Results: A total of 201 patients were included, 103 patients in the q8hr group and 98 patients in the q12hr group. Clinical cure of IAI occurred in 72 patients (69.9%) in the q8hr group and 62 patients (63.2%) in the q12hr group (p = 0.318). The median duration of therapy days was similar for both groups (4.0 [4.0–6.0] vs. 4.0 [3.0–6.0] (p = 0.509)). The frequency of clinical failure was higher in the q12hr group (8.7% vs. 21.4%; p = 0.01). Seven patients in the q8hr group and fourteen patients in the q12hr group required escalation of antibiotics due to the need for broader-spectrum antimicrobial therapy by clinical failure definition. Conclusions: There was no difference in clinical cure of IAI with an extended dosing interval. Clinical failure and escalation in antibiotics was higher in the q12h group due to the need for broader-spectrum gram-negative coverage and not related to the need for anaerobic coverage. Findings suggest that every 12 h dosing has similar outcomes. Full article

Background: Antimicrobial resistance (AMR) poses a significant threat to public health, especially in low- and middle-income countries (LMICs), where surveillance infrastructure is underdeveloped. Bihar, India’s third most populous state and one of its least-resourced states, has remained largely absent from national AMR monitoring initiatives. Methods: This study aimed to characterize the AMR infection landscape across five public tertiary care hospitals in Bihar over three years (2022–2024) and to assess the feasibility of integrating digital workflows for real-time microbiological reporting. Standardized antimicrobial susceptibility testing (AST) was performed on >48,000 urine, pus, and blood samples using CLSI guidelines. Facility-level data were digitized into an open-source AMR reporting system, enabling automated antibiogram generation. Results: The findings revealed substantial resistance: high resistance to beta-lactams, carbapenems, and fluoroquinolones across pathogens. For instance, E. coli sensitivity to nitrofurantoin varied from 86.5% at NMCH (Patna) to 44.7% at JLNMCH (Bhagalpur), while cephalosporin sensitivity in Klebsiella spp. dropped below 2% in several hospitals. MRSA prevalence exceeded 65% in two facilities, far above the national average of 47.8%. Digital integration led to a four-fold increase in culture testing in all facilities and improved data completeness and turnaround times. Spatial analysis and microbiology laboratory assessment revealed significant geographic disparities in diagnostic access, with facilities in remote districts facing delays of over four hours for basic testing. Conclusions: Our study is the first study from India to create such a broad, facility-associated AMR picture over time at a state level. Policy implications include the need for a state-level AMR surveillance dashboard, alignment of procurement with facility-specific resistance patterns, and routine stewardship audits. Clinically, this study demonstrates the utility of localized antibiograms for guiding empirical therapy in resource-limited settings. This study provides a scalable framework for embedding AMR surveillance into routine health system workflows in LMICs. Full article

To determine the incidence, causative organisms, and treatment effectiveness for microbial keratitis (MK) in the Southwest of England. Retrospective analysis of 872 corneal scrapes (January 2018–December 2022). Microbiology results were evaluated for organism growth and antimicrobial sensitivity. Data were divided into two groups for trend analysis (A: 2018–2020, B: 2021–2022). Of the 872 scrapes, 357 (39.6%) were culture positive. Bacteria accounted for 90.2% of cases, followed by viruses (2.8%), fungi (2.5%), mixed bacterial growth (2.5%), and Acanthamoeba (2.0%). The estimated incidence of MK was 9.69/100,000/year. Group B had a significantly higher overall MK incidence, with no change in pathogen distribution. Pseudomonas aeruginosa was the most frequent isolate (69 cases, 19.3%). In vitro sensitivity to fluoroquinolones was 94.4% for Gram-positive and 98.6% for Gram-negative bacteria. All fungal isolates were sensitive to at least one antifungal. Bacterial pathogens dominate MK in the Southwest of England, with over 90% sensitivity to chloramphenicol, fluoroquinolones, and aminoglycosides, indicating low antimicrobial resistance. Fluoroquinolones remain the recommended first-line therapy for MK. Fungal and protozoal keratitis are rare (<3% of cases), supporting bacteria-focused empirical treatment with close monitoring. Full article

Solanum nigrum L., a widely consumed Asian medicinal edible plant, is a promising source of bioactive saponins for functional food applications. This study optimized the extraction of saponins from S. nigrum fruits (8.59% total saponin yield), followed by isolation via column chromatography and structural elucidation using spectroscopic analyses (IR, NMR, and MS). Concurrently, the antioxidant properties and antibacterial activity of the purified substances were detected and analyzed. The three saponins (SNL1, SNL2, SNL3) were identified as γ₂-Solamargine , Diosgenin, and β-Solanine. The  n-butanol -purified fraction demonstrated a remarkable capacity to scavenge DPPH, hydroxyl, and ABTS radicals (DPPH IC50 = 0.0096 mg/mL; hydroxyl radical IC50 = 0.8 mg/mL; ABTS IC50 = 0.061 μg/mL), indicating the inhibition of a multi-pathway oxidative chain reaction. Concurrently, the saponins exhibited selective antimicrobial efficacy against key foodborne pathogens, particularly Escherichia coli. To the best of our knowledge, this work provides the first empirical evidence of S. nigrum fruit saponins as dual-functional natural preservatives, synergistically suppressing lipid oxidation and microbial growth. These findings highlight their potential as safer, multi-mechanistic alternatives to synthetic additives, aligning with clean-label food industry demands. Full article

Klebsiella pneumoniae, a zoonotic pathogen of global concern, poses significant threats to both veterinary and public health. Here, a comparative study characterized 14 clinical isolates (7 avian-derived, 7 human-derived) from Jiangsu, China, through integrated genomic and phenotypic analyses. Firstly, multilocus sequence typing (MLST) revealed distinct epidemiological patterns: the same ST type in avian isolates was circulating between different species and different regions, whereas it was not found in human isolates. In addition, hypervirulent Klebsiella pneumoniae (hvKP) phenotypes confirmed by string test were exclusive to two human isolates (KP15, KP20). Secondly, biofilm detection demonstrated 78.6% (11/14) of isolates possessed biofilm-forming capacity, with cellulose but not curli as the predominant matrix component. Human-derived KP15 and KP20 had the strongest biofilm formation ability in all isolates. Antimicrobial susceptibility profiling identified serious multidrug resistance in both avian and human isolates. Virulence gene analysis revealed striking disparities, with human isolates harboring 10–20 virulence factors (median 15) versus 6–7 (median 6.5) in avian counterparts. Finally, functional pathogenesis assessments demonstrated human-derived strains exhibited stronger epithelial cell adhesion (2-fold higher) and invasion (1.97-fold higher) in Calu-3 cell models and paradoxically showed reduced macrophage phagocytosis (2.85-fold lower at 2 h) for immune escape. In vivo models confirmed dose-dependent mortality, with human isolates demonstrating higher lethality in both Galleria mellonella and mice. Virulence gene burden positively correlated with mortality outcomes. These findings delineate critical host adaptation differences in Klebsiella pneumoniae populations and provide empirical evidence for pathogen transmission dynamics at the human-animal interface. Full article

Background: Antimicrobial resistance (AMR) is a public health concern worldwide, particularly in low-to-middle-income countries with few antimicrobial stewardship programs and few laboratories equipped for diagnosis. Methods: As point-prevalence surveys (PPSs) are a well-known tool for assessing antimicrobial use, we adjusted standardized Global-PPS for use in two hospitals in Benin and included an analysis based on the 2021 WHO AWaRe classification. Results: Of the 450 patients enrolled, 148 received antimicrobials (AMs) (overall prevalence 32.9%), most of them orally (54.2%). Both hospitals had a high rate of Access and Watch antibiotics use, and both prescribed mainly metronidazole. In four prescriptions, hospital A used a non-recommended association of antibiotics, such as ceftriaxone + sulbactam and ofloxacin + ornidazole. While hospital A prescribed predominantly amoxicillin + clavulanic acid (19/92; 21%) and ceftriaxone (14/92; 15%), hospital B prescribed ampicillin (24/120; 20%) and cefuroxime (14/120; n = 12%). In hospital B, surgical antimicrobial prophylaxis (SAP) was suboptimal. While there were no single-dose prophylaxis prescriptions, all one-day prophylaxis (SP2) involved ampicillin for cesarean sections. In patients in intensive care units, prolonged prophylaxis (>1 day, SP3) accounted for all postoperative prescriptions. Conclusions: These findings highlight the critical need for implementing antimicrobial stewardship programs, expanding diagnostic laboratory capacity to minimize empirical prescribing, and strengthening medical student training to ensure quality and rational antibiotic use, thereby addressing the growing challenge of resistance in resource-limited settings. Full article