[Combating antimicrobial resistance: audits of practices to target actions]. / Lutte contre l'antibiorésistance : audits des pratiques pour cibler les actions.

Antibiotic resistance is a public health emergency requiring a concerted approach and motivating the implementation of antibiotic stewardship programmes. As part of an institutional project at the Centre hospitalier universitaire vaudois, we collected data on the appropriateness of antimicrobial prescriptions in various medical and surgical departments in order to identify areas for improvement. The results show that there is room for improvement and that there are differences between departments, particularly regarding surgical prophylaxis administered beyond the operating time, adaptation of the spectrum and duration. Prescribing appropriateness data is an essential complement to consumption data for adapting effective intervention strategies.

L'antibiorésistance constitue une urgence de santé publique justifiant une approche concertée et motivant la mise en place de programmes de gestion des antibiotiques (Antibiotic Stewardship). Dans le cadre d'un projet institutionnel conduit au Centre hospitalier universitaire vaudois, nous avons collecté dans différents services médico-chirurgicaux des données d'adéquation des prescriptions afin d'identifier les domaines d'amélioration. Les résultats obtenus montrent qu'il existe une marge d'amélioration et des différences interservices, en particulier concernant les prophylaxies chirurgicales administrées au-delà du temps opératoire, l'adaptation du spectre et la durée. Les données d'adéquation des prescriptions sont un complément essentiel aux données de consommation pour adapter des stratégies d'intervention efficaces.

Concomitant bedaquiline and delamanid therapy in patients with drug-resistant extra-pulmonary tuberculosis in Mumbai, India.

Background: World Health Organization suggests concurrent bedaquiline-delamanid (BDQ-DLM) as part of individualised regimens for eligible patients with pulmonary drug-resistant tuberculosis (DR-TB); however, data for patients with drug-resistant extrapulmonary tuberculosis (EPTB) is extremely limited. This study documents the treatment outcomes and adverse events associated with concurrent BDQ-DLM-based regimens in patients with drug-resistant EPTB at a Médecins Sans Frontières clinic in Mumbai, India. Methods: Retrospective cohort study based on routinely collected programmatic data. Individualised regimens were based on drug-susceptibility testing and previous drug exposure. Drug-resistant EPTB patients initiated on regimens containing concurrent BDQ and DLM from April 2016 to October 2019 were included. Patients who completed treatment were followed up at 12 months. Results: Of 17 patients, median age was 23 years (IQR = 21-30 years) and 12/17 (71 %) were female. Pre-extensively drug-resistant tuberculosis and extensively drug-resistant TB was reported in 13/17 (76.4 %) and 2/17 (11.7 %) patients respectively. Microbiological reports were unavailable for two patients with central nervous system TB. Lymph node TB was the commonest form of EPTB in 9/17 (53 %) of patients. Median duration of treatment was 18.9 months. At least one grade three or four severe adverse event (SAE) was reported by 13/17 (76.4 %) patients. Thirteen (76.4 %) patients had favourable outcomes. None of the patients relapsed or died in the one-year period of post-treatment follow-up. Conclusion: Concurrent BDQ-DLM-based regimens in drug-resistant EPTB were effective and associated with manageable adverse events.

Enigmatic exosomal connection in lung cancer drug resistance.

Lung cancer remains a significant global health concern with limited treatment options and poor prognosis, particularly in advanced stages. Small extracellular vesicles such as exosomes, secreted by cancer cells, play a pivotal role in mediating drug resistance in lung cancer. Exosomes have been found to facilitate intercellular communication by transferring various biomolecules between cancer cells and their microenvironment. Additionally, exosomes can transport signaling molecules promoting cancer cell survival and proliferation conferring resistance to chemotherapy. Moreover, exosomes can modulate the tumor microenvironment by inducing phenotypic changes hindering drug response. Understanding the role of exosomes in mediating drug resistance in lung cancer is crucial for developing novel therapeutic strategies and biomarkers to overcome treatment limitations. In this review, we summarize the current knowledge on conventional and emerging drug resistance mechanisms and the involvement of exosomes as well as exosome-mediated factors mediating drug resistance in lung cancer.

Blue-Light-Activated Water-Soluble Sn(IV)-Porphyrins for Antibacterial Photodynamic Therapy (aPDT) against Drug-Resistant Bacterial Pathogens.

Antimicrobial resistance has emerged as a global threat to the treatment of infectious diseases. Antibacterial photodynamic therapy (aPDT) is a promising alternative approach and is highly suitable for the treatment of cutaneous bacterial infections through topical applications. aPDT relies on light-responsive compounds called photosensitizer (PS) dyes, which generate reactive oxygen species (ROS) when induced by light, thereby killing bacterial cells. Despite several previous studies in this area, the molecular details of targeting and cell death mediated by PS dyes are poorly understood. In this study, we further investigate the antibacterial properties of two water-soluble Sn(IV) tetrapyridylporphyrins that were quaternized with methyl and hexyl groups (1 and 2). In this follow-up study, we demonstrate that Sn(IV)-porphyrins can be photoexcited by blue light (a 427 nm LED) and exhibit various levels of bactericidal activity against both Gram-(+) and Gram-(-) strains of bacteria. Using localization studies through fluorescence microscopy, we show that 2 targets the bacterial membrane more effectively than 1 and exhibits comparatively higher aPDT activity. Using multiple fluorescence reporters, we demonstrate that photoactivation of 1 and 2 results in extensive collateral damage to the bacterial cells including DNA cleavage, membrane damage, and delocalization of central systems necessary for bacterial growth and division. In summary, this investigation provides deep insights into the mechanism of bacterial killing mediated by the Sn(IV)-porphyrins. Moreover, our approach offers a new method for evaluating the activity of PS, which may inspire the discovery of new PS with enhanced aPDT activity.

Changing Landscape of Antimicrobial Resistance in Neonatal Sepsis: An in silico Analyses of Multidrug Resistance in Klebsiella pneumoniae.

BACKGROUND: Neonatal sepsis poses a critical healthcare concern, as multidrug-resistant Klebsiella pneumoniae (K. pneumoniae) infections are on the rise. Understanding the antimicrobial susceptibility patterns and underlying resistance mechanism is crucial for effective treatment. OBJECTIVES: This study aimed to comprehensively investigate the antimicrobial susceptibility patterns of K. pneumoniae strains responsible for neonatal sepsis using in silico tools. We sought to identify trends and explore reasons for varying resistance levels, particularly for ß-lactams and fluoroquinolone. METHODS: K. pneumoniae isolated from neonates at Kanchi Kamakoti CHILDS Trust Hospital (2017-2020) were analyzed for antimicrobial resistance. Elevated resistance to ß-lactam and fluoroquinolone antibiotics was further investigated through molecular docking and interaction analysis. ß-lactam affinity with penicillin-binding proteins and ß-lactamases was examined. Mutations in ParC and GyrA responsible for quinolone resistance were introduced to investigate ciprofloxacin interactions. RESULTS: Of 111 K. pneumoniae blood sepsis isolates in neonates, high resistance was detected to ß-lactams such as cefixime (85.91%, n = 71), ceftriaxone (84.9%, n = 106), cefotaxime (84.9%, n = 82) and fluoroquinolone (ciprofloxacin- 79.44%, n = 107). Molecular docking revealed low ß-lactam binding toward penicillin-binding proteins and higher affinities for ß-lactamases, attributing to the reduced ß-lactam efficiency. Additionally, ciprofloxacin showed decreased affinity toward mutant ParC and GyrA in comparison to their corresponding wild-type proteins. CONCLUSION: Our study elucidates altered resistance profiles in neonatal sepsis caused by K. pneumoniae, highlighting mechanisms of ß-lactam and fluoroquinolone resistance. It underscores the urgent need for the development of sustainable therapeutic alternatives to address the rising antimicrobial resistance in neonatal sepsis.

Assessment of Antimicrobial Resistance Laboratory-based Surveillance Capacity of Hospitals in Zambia: Findings and Implications for System Strengthening.

BACKGROUND: A well-established antimicrobial resistance (AMR) laboratory-based surveillance (LBS) is of utmost importance in a country like Zambia which bears a significant proportion of the world's communicable disease burden. This study assessed the capacity of laboratories in selected hospitals to conduct AMR surveillance in Zambia. METHODS: This cross-sectional exploratory study was conducted among eight (8) purposively selected hospitals in Zambia between August 2023 and December 2023. Data were collected using the self-scoring Laboratory Assessment of Antibiotic Resistance Testing Capacity (LAARC) tool. FINDINGS: Of the assessed facilities, none had full capacity to conduct AMR surveillance with varying capacities ranging from moderate [63% (5/8)] to low [38% (3/8)]. Some of the barriers of AMR-LBS were the lack of electronic laboratory information system (LIS) [63% (5/8)] and the lack of locally generated antibiograms [75% (6/8)]. Quality control for antimicrobial susceptibility testing (AST), pathogen identification and media preparation had the lowest overall score among all the facilities with a score of 14%, 20% and 44% respectively. The highest overall scores were in specimen processing (79%), data management (78%), specimen collection, transport, and management (71%) and safety (70%). Most facilities had standard operating procedures (SOPs) in place but lacked specimen-specific SOPs. CONCLUSION: The absence of laboratories with full capacity to conduct AMR surveillance hinders efforts to combat AMR and further complicates the treatment outcomes of infectious diseases. Establishing and strengthening LBS systems are essential in quantifying the burden of AMR and supporting the development of local antibiograms and treatment guidelines.

[Metagenomic next-generation sequencing-based retrospective investigation of the drug resistance sites of mycoplasma pneumoniae in children].

Objective: To analyze the drug-resistant gene loci of Mycoplasma pneumoniae (MP) using metagenomic next-generation sequencing (mNGS). Methods: From November 2022 to October 2023, 697 clinical samples (including sputum, alveolar lavage fluid and blood) of 686 children with Mycoplasma pneumoniae positive detected by mNGS were retrospectively analyzed. Samples were divided into intensive care unit (ICU) group and non-ICU group, Chi-square test was used to compare groups, and Mann-Kendall trend test was used to analyze the change trend of the detection rate of drug resistance gene loci over time. Results: Of the 697 samples, 164 were from the ICU group and 533 were from the non-ICU group. The detection rate of Mycoplasma pneumoniae resistance gene was 44.3% (309/697), and all detected drug-resistant gene loci of MP were A2063G. The detection rate of Mycoplasma pneumoniae in ICU group was 50.0% (82/164), and the detection rates of Mycoplasma pneumoniae resistance gene loci in sputum, alveolus lavage fluid and blood samples were 75.0% (18/24) and 48.4% (62/128), respectively. The detection rate in sputum was higher than alveolus lavage fluid samples (χ2=5.72,P=0.017). The detection rate of Mycoplasma pneumoniae in non-ICU group was 42.6% (227/533), the detection rate of Mycoplasma pneumoniae resistance gene loci in sputum and alveolar lavage fluid was 40.0% (16/40), 44.3% (201/454), and no detection rate in blood samples (0/12). There was no significant difference in the detection rate of alveolar lavage fluid and sputum (χ2=0.27, P=0.602). From November 2022 to October 2023, the detection rate of submitted samples showed an increasing trend month by month (overall: Z=3.99, ICU inspection group: Z=2.93, non-ICU group: Z=3.01, all P<0.01). Among the bacteria commonly detected with Mycoplasma pneumoniae, Streptococcus pneumoniae accounted for the highest proportion, the detection rate was 15.5% (108/697), and Epstein-Barr virus accounted for the highest proportion of 17.6% (123/697). Conclusions: From November 2022 to October 2023, the detection rate of Mycoplasma pneumoniae drug resistance gene loci showed an increasing trend. The detection rate of drug resistance gene loci in sputum samples of ICU group was higher than alveolus lavage fluid. No new drug resistance site were detected.

Antimicrobial resistance prediction by clinical metagenomics in pediatric severe pneumonia patients.

BACKGROUND: Antimicrobial resistance (AMR) is a major threat to children's health, particularly in respiratory infections. Accurate identification of pathogens and AMR is crucial for targeted antibiotic treatment. Metagenomic next-generation sequencing (mNGS) shows promise in directly detecting microorganisms and resistance genes in clinical samples. However, the accuracy of AMR prediction through mNGS testing needs further investigation for practical clinical decision-making. METHODS: We aimed to evaluate the performance of mNGS in predicting AMR for severe pneumonia in pediatric patients. We conducted a retrospective analysis at a tertiary hospital from May 2022 to May 2023. Simultaneous mNGS and culture were performed on bronchoalveolar lavage fluid samples obtained from pediatric patients with severe pneumonia. By comparing the results of mNGS detection of microorganisms and antibiotic resistance genes with those of culture, sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: mNGS detected bacterial in 71.7% cases (86/120), significantly higher than culture (58/120, 48.3%). Compared to culture, mNGS demonstrated a sensitivity of 96.6% and a specificity of 51.6% in detecting pathogenic microorganisms. Phenotypic susceptibility testing (PST) of 19 antibiotics revealed significant variations in antibiotics resistance rates among different bacteria. Sensitivity prediction of mNGS for carbapenem resistance was higher than penicillins and cephalosporin (67.74% vs. 28.57%, 46.15%), while specificity showed no significant difference (85.71%, 75.00%, 75.00%). mNGS also showed a high sensitivity of 94.74% in predicting carbapenem resistance in Acinetobacter baumannii. CONCLUSIONS: mNGS exhibits variable predictive performance among different pathogens and antibiotics, indicating its potential as a supplementary tool to conventional PST. However, mNGS currently cannot replace conventional PST.

Identification of KDM4C as a gene conferring drug resistance in multiple myeloma.

Bortezomib (BTZ), a proteasome inhibitor, is a promising therapeutic option for multiple myeloma (MM) patients. However, drug resistance often occurs, leading to disease relapse and poor prognosis. In this study, we aimed to identify novel genes associated with drug resistance and investigate their roles in BTZ resistance. Through the screening of 26 genes frequently associated with chemosensitivity or drug resistance, we discovered that KDM4C, a histone demethylase, exhibited increased expression in BTZ-resistant MM cells compared to their sensitive counterparts. Overexpression of KDM4C enhanced the tolerance of a MM cell line to the drug, whereas the knockdown of KDM4C, using shRNA, increased the sensitivity of resistant cells to BTZ treatment. This suggests that KDM4C plays a pivotal role in conferring BTZ resistance. Our study offers fresh insights into BTZ resistance in MM and highlights KDM4C as a potential target for overcoming drug resistance.

Comprehensive analysis of antimicrobial resistance in the Southwest Indian Ocean: focus on WHO critical and high priority pathogens.

The spread of antimicrobial resistance (AMR) is a major global concern, and the islands of the Southwest Indian Ocean (SWIO) are not exempt from this phenomenon. As strategic crossroads between Southern Africa and the Indian subcontinent, these islands are constantly threatened by the importation of multidrug-resistant bacteria from these regions. In this systematic review, our aim was to assess the epidemiological situation of AMR in humans in the SWIO islands, focusing on bacterial species listed as priority by the World Health Organization. Specifically, we examined Enterobacterales, Acinetobacter spp., Pseudomonas spp. resistant to carbapenems, and Enterococcus spp. resistant to vancomycin. Our main objectives were to map the distribution of these resistant bacteria in the SWIO islands and identify the genes involved in their resistance mechanisms. We conducted literature review focusing on Comoros, Madagascar, Maldives, Mauritius, Mayotte, Reunion Island, Seychelles, Sri Lanka, and Zanzibar. Our findings revealed a growing interest in the investigation of these pathogens and provided evidence of their active circulation in many of the territories investigated. However, we also identified disparities in terms of data availability between the targeted bacteria and among the different territories, emphasizing the need to strengthen collaborative efforts to establish an efficient regional surveillance network.

Antimicrobial resistance trends in clinical Escherichia coli and Klebsiella pneumoniae in Ethiopia.

Background: Clinicians rely on local antimicrobial resistance pattern data to guide empiric treatment for seriously ill patients when culture and antimicrobial susceptibility testing results are not immediately available. Objective: This study aimed to analyse 5-year trends in antimicrobial resistance profiles of Escherichia coli and Klebsiella pneumoniae isolates. Methods: Bacteriology reports from 2017 to 2021 at the Ethiopian Public Health Institute were analysed retrospectively. Isolates were identified using either the VITEK 2 Compact system, the BD Phoenix M50 instrument, or conventional biochemical tests. Antimicrobial susceptibility testing was conducted using either the Kirby-Bauer disk diffusion method or the VITEK 2 Compact system and BD Phoenix M50 systems available at the time of testing. The Cochran Armitage trend test was employed to test the significance of antimicrobial resistance trends over time. P-values less than 0.05 were considered statistically significant. Results: Of the 5382 bacteriology reports examined, 458 (9%) were on E. coli and 266 (5%) were on K. pneumoniae. Both K. pneumoniae (88%) and E. coli (65%) demonstrated high resistance to extended-spectrum cephalosporins. However, both K. pneumoniae (14%) and E. coli (5%) showed lower rates of resistance to carbapenems compared to other antimicrobials. In K. pneumoniae, resistance to carbapenems (from 0% to 38%; p < 0.001) and ciprofloxacin (from 41% to 90%; p < 0.001) increased significantly between 2017 and 2021. Conclusion: Both organisms showed very high resistance to broad-spectrum antibiotics. Additionally, K. pneumoniae demonstrated a statistically significant rise in ciprofloxacin and carbapenem resistance. What this study adds: This study emphasises the significance of regular reporting of local antimicrobial resistance patterns as this information can guide appropriate empiric therapy and efforts to address antimicrobial resistance issues.

Epidemiology and antimicrobial susceptibility profiles of Enterobacterales causing bloodstream infections before and during COVID-19 pandemic: Results of the Study for Monitoring Antimicrobial Resistance Trends (SMART) in Taiwan, 2018-2021.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has contributed to the spread of antimicrobial resistance, including carbapenem-resistant Enterobacterales. METHODS: This study utilized data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program in Taiwan. Enterobacterales from patients with bloodstream infections (BSIs) were collected and subjected to antimicrobial susceptibility testing and ß-lactamase gene detection using a multiplex PCR assay. Statistical analysis was conducted to compare susceptibility rates and resistance genes between time periods before (2018-2019) and during the COVID-19 pandemic (2020-2021). RESULTS: A total of 1231 Enterobacterales isolates were collected, predominantly Escherichia coli (55.6%) and Klebsiella pneumoniae (29.2%). The proportion of nosocomial BSIs increased during the COVID-19 pandemic (55.5% vs. 61.7%, p < 0.05). Overall, susceptibility rates for most antimicrobial agents decreased, with Enterobacterales from nosocomial BSIs showing significantly lower susceptibility rates than those from community-acquired BSIs. Among 123 Enterobacterales isolates that underwent molecular resistance mechanism detection, ESBL, AmpC ß-lactamase, and carbapenemase genes were detected in 43.1%, 48.8% and 16.3% of the tested isolates, respectively. The prevalence of carbapenemase genes among carbapenem-resistant Enterobacterales increased during the pandemic, although the difference was not statistically significant. Two novel ß-lactamase inhibitor combinations, imipenem-relebactam and meropenem-vaborbactam, preserved good efficacy against Enterobacterales. However, imipenem-relebactam showed lower in vitro activity against imipenem-non-susceptible Enterobacterales than that of meropenem-vaborbactam. CONCLUSIONS: The COVID-19 pandemic appears to be associated with a general decrease in antimicrobial susceptibility rates among Enterobacterales causing BSIs in Taiwan. Continuous surveillance is crucial to monitor antimicrobial resistance during the pandemic and in the future.

Environmental Drivers of Antimicrobial Resistance in Low and Middle-Income Countries: The Impacts of a Changing World.

This letter highlights the impact of environmental drivers on antimicrobial resistance (AMR) in low and middle-income countries (LMICs) and highlights the need for a comprehensive approach to address this global health threat. Key factors, such as agricultural practices, wastewater treatment, and pollution, contribute to the development and spread of resistant pathogens. Utilizing the One Health approach, the paper emphasizes the importance of promoting responsible antimicrobial use, strengthening public health systems, investing in innovative research, and raising public awareness. By understanding and addressing these environmental drivers, we can work toward safeguarding global health and ensuring a sustainable future.

Virulence Genes, Antimicrobial Resistance, and Genotypes of Campylobacter jejuni Isolated from Chicken Slaughterhouses in South Korea.

Campylobacter jejuni represents one of the leading causes of bacterial gastroenteritis in humans and is primarily linked to chicken meat contamination. In the present study, we analyzed the virulence and survival genes, antimicrobial resistance, and the clonal distribution of 50 C. jejuni isolates obtained from various sources in 14 chicken slaughterhouses across 8 provinces in South Korea from 2019 to 2022. Furthermore, we determined their genetic relatedness to human-derived isolates registered in PubMLST using multilocus sequence typing (MLST). All isolates harbored various virulence and survival genes (flhA, cadF, cdtA, cdtC, cmeA, and sodB) out of 17 tested genes, as confirmed via polymerase chain reaction analysis. Adherence factor gene virB11 was not detected in any isolate. All isolates harbored 12 or more virulence and survival genes. Antimicrobial susceptibility testing indicated that ciprofloxacin resistance was the most prevalent (84.0%), followed by nalidixic acid (82.0%) and tetracycline (52.0%) resistance. MLST analysis of the isolates revealed 18 sequence types (STs), including four new ones. Overlapping STs between chicken slaughterhouse and human-derived isolates included ST42, ST45, ST50, ST137, ST354, and ST464. Our study identified 11 clonal complexes (CCs), with CC-21 being the most prevalent in both human and chicken slaughterhouse-derived isolates. This study provides comprehensive insights into recent C. jejuni isolates from chicken slaughterhouses, including data on quinolone resistance and virulence factors. The MLST-based genetic relatedness between isolates from humans and chicken slaughterhouses in this study suggests the potential of C. jejuni transmission from chickens to humans through the food chain. This study suggests the need for improved management practices in chicken slaughterhouses to reduce the transmission of chicken slaughterhouse-derived C. jejuni to humans.

Needles in haystacks: monitoring the potential escape of bioaerosolised antimicrobial resistance genes from wastewater treatment plants with air and phyllosphere sampling.

Wastewater treatment plants are well known point sources of emissions of antimicrobial resistance genes (ARGs) into the environment. Although most work to date has focused on ARG dispersal via effluent, aerial dispersal in bioaerosols is a poorly understood, but likely important vector for ARG dispersal. Recent evidence suggests that ARG profiles of the conifer needle phyllosphere could be used to measure bioaerosol dispersal from anthropogenic sources. Here we assessed airborne dispersal of ARGs from wastewater treatment plants in Wales, UK and Quebec, Canada, using conifer needles as passive bioaerosol monitors. ARG profiles of wastewater were compared to those of conifer phyllosphere using high-throughput qPCR. ARG richness was significantly lower in conifer phyllosphere samples than wastewater samples, though no differences were observed across the dispersal gradients. Mean copy number of ARGs followed a similar trend. ARG profiles showed limited, but consistent patterns with increasing distance from wastewater treatment plants, but these did not align with those of wastewater samples. For example, proportional abundance of aminoglycosides decreased over the dispersal gradient in Wales, whereas mobile genetic elements showed the inverse relationship. In summary, while distinct ARG profiles exist along dispersal gradients, links to those of wastewater were not apparent.

Responsive neurostimulation of thalamic nuclei for regional and multifocal drug-resistant epilepsy in children and young adults.

OBJECTIVE: Responsive neurostimulation (RNS) is a US FDA-approved form of neuromodulation to treat patients with focal-onset drug-resistant epilepsy (DRE) who are ineligible for or whose condition is refractory to resection. However, the FDA approval only extends to use in patients with one or two epileptogenic foci. Recent literature has shown possible efficacy of thalamic RNS in patients with Lennox-Gastaut syndrome and multifocal epilepsy. The authors hypothesized that RNS of thalamic nuclei may be effective in seizure reduction for patients with multifocal or regionalized-onset DRE. METHODS: The authors performed a retrospective chart review of all patients who had an RNS device managed at Texas Children's Hospital between July 2016 and September 2023, with at least one active electrode in the thalamic nuclei and ≥ 12 months of postimplantation follow-up. Information conveyed by the patient or their caregiver provided data on the change in the clinical seizure frequency, quality of life (QOL), and seizure severity between the preimplantation baseline visit and the last office visit (LOV). RESULTS: Thirteen patients (ages 8-24 years) were identified with active RNS leads in thalamic nuclei (11 centromedian and 2 anterior nucleus). At LOV, 46% of patients reported 50%-100% clinical seizure reduction (classified as responders), 15% reported 25%-49% reduction, and 38% reported < 25% reduction or no change. Additionally, 42% of patients reported subjective improvement in QOL and 58% reported improved seizure severity. Patients with focal cortical dysplasia (FCD) responded strongly: 3 of 5 (60%) reported ≥ 80% reduction in seizure burden and improvement in seizure severity and QOL. Patients with multifocal epilepsy and bilateral thalamocortical leads also did well, with all 3 reporting ≥ 50% reduction in seizures. CONCLUSIONS: RNS of thalamic nuclei shows promising results in reducing seizure burden for patients with multifocal or regional-onset DRE, particularly in a bilateral thalamocortical configuration or when addressing an underlying FCD.

Copper selenide nanosheets with photothermal therapy-related properties and multienzyme activity for highly effective eradication of drug resistance.

Bacterial infections are among the most significant causes of death in humans. Chronic misuse or uncontrolled use of antibiotics promotes the emergence of multidrug-resistant superbugs that threaten public health through the food chain and cause environmental pollution. Based on the above considerations, copper selenide nanosheets (CuSe NSs) with photothermal therapy (PTT)- and photodynamic therapy (PDT)-related properties have been fabricated. These CuSe NSs possess enhanced PDT-related properties and can convert O2 into highly toxic reactive oxygen species (ROS), which can cause significant oxidative stress and damage to bacteria. In addition, CuSe NSs can efficiently consume glutathione (GSH) at bacterial infection sites, thus further enhancing their sterilization efficacy. In vitro antibacterial experiments with near-infrared (NIR) irradiation have shown that CuSe NSs have excellent photothermal bactericidal properties. These experiments also showed that CuSe NSs exerted excellent bactericidal effects on wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) and significantly promoted the healing of infected wounds. Because of their superior biological safety, CuSe NSs are novel copper-based antimicrobial agents that are expected to enter clinical trials, serving as a modern approach to the major problem of treating bacterially infected wounds.

The Impact of Colonization by Multi Drug Resistant Bacteria on Graft Survival, Risk of Infection, and Mortality in Recipients of Solid Organ Transplant: Systematic Review and Meta-analysis.

BACKGROUND: The Global increase in colonization by multidrug-resistant (MDR) bacteria poses a significant concern. The precise impact of MDR colonization in solid organ transplant recipients (SOTR) remains not well established. OBJECTIVES: Assess the impact of MDR colonization on SOTR's mortality, infection, or graft-loss. METHODS: . DATA SOURCE: Data from PROSPERO, OVID Medline, Ovid EMBASE, Wiley Cochrane Library, ProQuest Dissertations, Theses Global, and SCOPUS, were systematically reviewed spanning from inception until March 20, 2023. The study protocol was registered with PROSPERO (CRD42022290011) and followed the PRISMA guidelines. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, INTERVENTIONS, AND ASSESSMENT OF RISK OF BIAS: Cohorts and case-control studies that reported on adult SOTR colonized by Methicillin-resistant Staphylococcus-aureus (MRSA), Vancomycin-resistant Enterococci (VRE), Extended-spectrum beta-lactamase (ESBL) or carbapenem-resistant Enterobacteriaceae (CRE), or MDR-Pseudomonas, and compared to non-colonized, were included. Two reviewers assessed eligibility, conducted risk of bias evaluation using the Newcastle-Ottawa scale, and rated certainty of evidence using the GRADE approach. METHODS OF DATA SYNTHESIS: We employed RevMan for a meta-analysis using random-effects models to compute pooled odds-ratios (OR) and 95% confidence-intervals (CI). Statistical heterogeneity was determined using the I2 statistic. RESULTS: 15,202 SOTR (33 cohort, 6 case-control studies) were included, where Liver transplant and VRE colonization (25 and 14 studies) were predominant. MDR colonization significantly increased post-transplant one-year mortality (OR= 2.35, 95%CI 1.63-3.38) and mixed-infections (OR=10.74, 95%CI 7.56-12.26) across transplant types (p<0.001 and I2= 58%), but no detected impact on graft-loss (p=0.41, I2= 0%). Subgroup analysis indicated a higher association between CRE or ESBL colonization with outcomes (CRE: death OR=3.94, mixed-infections OR=24.8; ESBL: mixed-infections OR=10.3, no mortality data) compared to MRSA (Death: OR=2.25; Mixed-infection: OR=7.75) or VRE colonization (Death: p=0.20, Mixed-infections: OR=5.71). CONCLUSIONS: MDR colonization in SOTR, particularly CRE, is associated with increased mortality. Despite the low certainty of evidence, actions for preventing MDR colonization in transplant candidates are warranted.