Antimicrobial resistance (AMR) develops into a worldwide health emergency through genetic and biochemical adaptations which enable microorganisms to resist antimicrobial treatment. β-lactamases (blaNDM, blaKPC) and efflux pumps (MexAB-OprM) working with mobile genetic elements facilitate fast proliferation of multidrug-resistant (MDR) and exttreme drug-resistant (XDR) phenotypes thus creating major concerns for healthcare systems and community health as well as the agricultural sector.

The review dissimilarly unifies molecular resistance pathways with public health implications through the study of epidemiological data and monitoring approaches and innovative therapeutic solutions. Previous studies separating their attention between molecular genetics and clinical outcomes have been combined into our approach which delivers an all-encompassing analysis of AMR.

The report investigates the resistance mechanisms which feature enzymatic degradation and efflux pump overexpression together with target modification and horizontal gene transfer because these factors represent important contributors to present-day AMR developments. This review investigates AMR effects on hospital and community environments where it affects pathogens including MRSA, carbapenem-resistant Klebsiella pneumoniae, and drug-resistant Pseudomonas aeruginosa. This document explores modern AMR management methods that comprise WHO GLASS molecular surveillance systems and three innovative strategies such as CRISPR-modified genome editing and bacteriophage treatments along with antimicrobial peptides and artificial intelligence diagnostic tools.

The resolution of AMR needs complete scientific and global operational methods alongside state-of-the-art therapeutic approaches. Worldwide management of drug-resistant infection burden requires both enhanced infection prevention procedures with next-generation antimicrobial strategies to reduce cases effectively.

Urinary tract infections (UTIs) are common globally, and are developing increased antibiotic resistance. Despite being the diagnostic "gold standard," urine culture is limited by slow results and a high rate of false negative findings, leading to treatment delays, higher costs, and overuse of empirical antibiotics. Our study aims to develop a rapid and reliable model to predict clinical outcomes.

From January 1st to October 31st, 2023, we enrolled patients with symptoms suggesting UTI from the Outpatient Department of our hospital. Inclusion criteria were patients aged ≥18, initially diagnosed with UTI, available urinalysis, flow cytometry, and urinary culture. Exclusion criteria included failed sample collection and cultures, and pregnant women. A case-control study was conducted, with UTI cases defined as ≥ 10^5 CFU/ µ L and controls as < 10^5 CFU/ µ L, matched for age and sex in a 1:1 ratio. For validation, retrospective cases from July to December 2022 were selected with matching controls. Using urine culture as the gold standard, the predictive model was developed with backward stepwise logistic regression. Model discrimination was assessed using area under the curve (AUC).

In our discovery cohort, we included 1,335 UTI cases and 1,282 non-UTI controls, with mean ages of 52.9 ± 17.1 years and 51.9 ± 16.4 years, and females of 76.9% and 77.7%. Using 100 cells/uL as a threshold, bacterial counts demonstrated a sensitivity of 91.0% and specificity of 45.7%. Our novel UTIRisk score, developed from urinalysis and flow cytometry parameters, showed strong discrimination for UTI, with a AUC of 0.82 (95% CI: 0.81-0.84). In the validation cohort, the AUC was 0.77 (95% CI: 0.74-0.80). The UTIRisk score exhibited excellent specificity (96.5%) and high positive predictive value (92.6%). The score performed strongly across subgroups, particularly in males and patients aged ≥65.

Our UTIRisk score can improve diagnosis, reduce unnecessary urine cultures, optimize antibiotic use, and help control antibiotic resistance in LMICs. Multicenter, and intervention-based studies are warranted before clinical implementation.

Ventilator-associated pneumonia is one of the most common infections in Intensive Care Units (ICU). It is frequently caused by multidrug-resistant pathogens (including carbapenems) and is an important health issue. It may result in severe clinical consequences, with higher healthcare utilization and high economic burden. Timely and appropriate treatment is key to obtaining better outcomes and allocational efficiency. Currently, the treatment options for carbapenem-resistant pathogen infections are limited, usually based on polymyxin, aminoglycosides, or combination therapy, as well as novel antibiotic therapies including Ceftazidime/Avibactam (CAZ-AVI). CAZ-AVI has shown activity against gram-negative pathogens and is currently used for the treatment of Ventilator-Associated Pneumonia (VAP). To better inform healthcare professionals and help promote a rational use of antibiotic therapy, a cost-effectiveness analysis was conducted to compare the cost-effectiveness of CAZ-AVI versus polymyxin B in ICU patients with VAP from the Brazilian National Supplementary Health Agency perspective over a 5-year time horizon. CAZ-AVI had higher total costs and resulted in more Quality-Adjusted Life Years (QALY) gained when compared with polymyxin B. At a willingness-to-pay threshold of BRL 40,000.00/QALY gained, CAZ-AVI was the cost-effective strategy (ICER: BRL 35,298.65/QALY gained). Nephrotoxicity in patients treated with polymyxin B, hospitalization utility, and treatment duration were the variables that most influenced the results. In the probabilistic sensitivity analysis, CAZ-AVI was cost-effective in 55 %-89 % of the interactions. The evidence suggests that CAZ-AVI results in lower mortality and nephrotoxicity rates, which might have contributed to more QALYs gained and a favorable ICER, despite the higher costs. This study was registered on the Open Science Framework database (Protocol https://doi.org/10.17605/OSF.IO/SP2EJ).

The rising prevalence of antimicrobial resistance (AMR) poses a critical global health challenge. Healthcare workers (HCWs) play a pivotal role in combating AMR by implementing effective preventive strategies and adhering to good practices. This study aimed to evaluate the global knowledge, attitudes, and practices (KAP) of HCWs towards AMR.

A comprehensive search of PubMed/MEDLINE, ScienceDirect, Scopus, Web of Science, Cochrane Library, and Google Scholar was conducted for English-language articles published up to August 2024. Inclusion criteria were observational studies reporting KAP data among HCWs related to AMR. Study quality was assessed using the Joanna Briggs Institute critical appraisal checklist. Statistical analyses, including heterogeneity (I² statistic, Cochran Q), were conducted using STATA version 14. Random-effects models were applied for pooled estimates, and subgroup analyses, meta-regression, and sensitivity analyses were performed. Publication bias was assessed via Egger's test and adjusted using the trim-and-fill method. Geographical distribution was analyzed with ArcGIS 10.3 software, and evidence certainty was evaluated using the GRADE framework.

A meta-analysis of 108 studies involving 29,433 HCWs assessed their knowledge of AMR. Additionally, 51 studies with 13,660 HCWs evaluated attitudes, and 43 studies with 10,569 HCWs examined practices regarding AMR. The pooled proportion of HCWs with good knowledge of AMR was 56.5% (95% CI: 50.4-62.6%, I² = 99.5%), with the highest prevalence in Europe (70.3%) and the lowest in the Western Pacific (45.9%). Positive attitudes towards AMR were reported in 60.4% (95% CI: 48.5-72.3%, I² = 99.8%), with the highest prevalence in the Eastern Mediterranean Region (64.5%) and among those with less than five years of experience (77.8%). Good practices were observed in 48.5% (95% CI: 36.5-60.5%, I² = 99.7%), with the highest adherence in Europe (56.6%) and the lowest in Africa (39.1%). Subgroup analysis revealed that younger HCWs (under 30 years) showed better KAP scores across all domains.

The findings underscore the need for targeted interventions to enhance the knowledge, attitudes, and practices of HCWs regarding AMR. Priority should be given to designing and implementing robust training programs tailored to the specific needs of HCWs in resource-constrained settings. Strengthening AMR-related education and practice among HCWs is crucial for combating the global AMR crisis effectively.

Antimicrobial resistance threatens human and animal health, with antimicrobial usage being a key driver of selection, transmission, and spread of resistant bacteria. Livestock represents a potential reservoir for human transmission, leading authorities to restrict veterinary usage of fluoroquinolones and certain cephalosporins. However, growing evidence indicates that the corresponding resistance determinants can be retained even in the drugs' absence. To obtain data on the magnitude and dynamics of this phenomenon in pig farming, we quantitatively and qualitatively assessed fluoroquinolone- and cephalosporin-resistant Escherichia coli in Thuringian pigsties practicing a closed management system to minimize the impact of externally introduced strains. Pooled fecal samples from consecutive fattening runs at one conventional and two organic farms and from 25 piglet groups from another conventional farm were collected over 16 months and screened for E. coli on plates containing enrofloxacin, ceftiofur, or cefquinome. Resistant bacteria were isolated on all farms; their counts varied strongly but were generally higher in piglets and declined with increasing animal age. Phylogenetic comparison of 393 isolates was performed via multiple-locus variable number tandem repeat analysis (MLVA) to follow strain dynamics and persistence. The isolates displayed large phylogenetic heterogeneity, featuring 52 different MLVA patterns. Still, conserved MLVA patterns indicated long-term persistence of specific strains in each farm's environment. This suggests that resistant strains appear well-adapted to the particular farm and its management practices, implying that, beyond restricting usage, further measures, including, e.g., consideration of the type of resistance as well as its persistence and transmission dynamics, will be indispensable to reduce the antimicrobial resistance load in pork production.IMPORTANCEAntimicrobial resistance (AMR) represents a global threat to human and animal health, with animals considered a reservoir for transmission of AMR to humans. Because antimicrobial usage is a driver for resistance, one approach to decrease the AMR burden is to reduce its usage. However, this can, but does not necessarily, lead to lower AMR prevalence. German and EU legislation restrict the use of fluoroquinolones and certain cephalosporins, substance classes designated as highest priority critically important antimicrobials for human medicine, in animal husbandry. Longitudinal sampling of organic and conventional farms in Thuringia for resistance to these antibiotic classes revealed that certain resistant Escherichia coli strains can persist in the farm environment over extended time periods. These strains displayed farm specificity, indicating adaptation to the particular farm and its management practices, so that their elimination might be difficult, requiring either procedures acting generally against Enterobacterales or targeted action against the specific strains.

This study aimed to assess the attitudes, and practices (AP) of general physicians (GPs) regarding antibiotic prescribing and antimicrobial resistance (AMR). A cross-sectional, descriptive AP study was conducted by surveying GPs treating community acquired respiratory tract infections (RTIs) across nine countries, including India, Pakistan, Algeria, Thailand, Vietnam, Egypt, Morocco, the United Arab Emirates, and Saudi Arabia. A 29-item, web-based questionnaire was used to collect data between October-2023 and December-2023. Overall, 9249/14207 invited GPs responded, and 1008 responses were included in the analysis after quality control (3341 terminated due to eligibility, 4764 dropped out without completion, 136 excluded for quality concern). Of the included respondents, 78.8% were male and 98% were aged ≥35 years. 41% of GPs agreed, 33% disagreed, and 27% were neutral to questions regarding whether or not antibiotics are helpful in treating infectious respiratory diseases. In total, 62% of GPs agreed that AMR is a concern in their country and 63% agreed that prescribing antibiotics in primary care results in AMR. Pregnant women and patients with comorbidities were populations for whom selecting an appropriate antibiotic was most challenging; 38% of GPs found prescribing antibiotics to children was difficult. Difficulty in correlating susceptibility data (53%), limited availability of information on antibiotics (52%), and lack of availability of appropriate antibiotics (51%) were important challenges for appropriate antibiotic selection. Overall, 94% of GPs agreed that there is a need for frequent training on antibiotic therapy, with 33% and 49% recommending quarterly and biannual trainings, respectively. This study identified current practices, and possible gaps in appropriate antibiotic prescribing for RTIs. As an outcome, specific training needs could be identified to assist GPs with appropriate antibiotic prescribing in an outpatient setting.

Dispensing antibiotics without a prescription is common among community pharmacists in low- and middle-income countries despite its association with antibiotic resistance. This study describes the prevalence and nature of dispensing antibiotics without prescription among community pharmacists in Nigeria and its associated factors.

A cross-sectional study was conducted among community pharmacists in Nigeria with a validated, online, self-administered questionnaire. Reliability was assessed with Cronbach's alpha. Descriptive and inferential statistics were performed with SPSS Version 2023 at a 0.05% significance level.

A total of 420 community pharmacists participated in the study. The Reliability result was 0.860, implying the data collection tool's perfect internal consistency. Independent pharmacies represented 87.4% of the respondents, and most were in urban areas (71.4%). Most respondents (98.1%) dispensed antibiotics without prescription, with (84.2%) sometimes requesting laboratory investigations before dispensing antibiotics. Cephalosporin (74.8%), penicillin (70.2%), and quinolones (68.3%) were the major classes of antibiotics dispensed. The pharmacists' confidence in their clinical skills (78.8%), ability of the antibiotics to cover a broader range of microorganisms (78.0%), inability of patients to access healthcare services in other places (67.3%), emergencies (58.3%), affordability (49.0%), patients' demand (38.2%), absence of sanctions (34%), not getting prescriptions (33.1%), were the key deciding factors for the pharmacists to dispense antibiotics without prescription or substitute class of antibiotics. Factors like financial incentives, fear of losing clients, fear of expiry, competition from other pharmacies, and trust in patients' self-diagnosis were low in driving decisions to dispense antibiotics without prescriptions.

Non-prescription dispensing of antibiotics is high among community pharmacists in Nigeria, and is related to various factors. A strategic approach, including mandatory health insurance schemes, prescription and dispensing policies, and enforcement of antimicrobial stewardship regulations by the Nigerian government, is necessary to improve ethical practice and address the irrational dispensing and use of antibiotics in Nigeria.

According to the World Health Organization (WHO), surveillance programs have become essential at national, regional, and global levels to adjust empirical treatments and target interventions to prevent and control the emergence of antimicrobial resistance (AMR). Therefore, this study aimed to conduct the first systematic review and meta-analysis of clinical Enterobacterales resistance to 11 representative antimicrobials from the WHO AWaRe (Access, Watch, Reserve) list, and to provide recommendations to tackle AMR more efficiently in Togo.

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (The PRISMA 2020) were used to conduct this study and the protocol was registered with PROSPERO (CRD42024606897). Keywords were used to conduct a systematic literature review of electronic databases. Data analysis was conducted using Stata software version 17.0.

Twenty research articles reporting 9,327 clinical Enterobacterales isolates obtained from 1991 to 2020 were included in this review and were mainly Escherichia coli (6,639; 71.2%), and Klebsiella spp. (2,542; 27.3%), mainly isolated from urine (14 studies; 70%), and pus/wounds (12; 60%). The pooled Enterobacterales resistance rates ranged from 1% (95% CI: 0, 2) imipenem, 3% (95% CI: 1, 5) amikacin, 4% (95% CI: 2, 7) fosfomycin, 50% (95% CI: 40, 60) chloramphenicol, 55% (95% CI: 45, 64) gentamicin, 68% (95% CI: 59, 76) ciprofloxacin, 73% (95% CI: 66, 80) amoxicillin/clavulanic acid (AMC), 79% (95% CI: 71, 86) third-generation cephalosporins (3GC), to 90% (95% CI: 86, 93) sulfamethoxazole/trimethoprim (SXT). The most significant upward trend over 30 years was reported for SXT (R2 = 73.24%, p < 0.001), ciprofloxacin (R2 = 61.44%, p < 0.001), and 3GC (R2 = 18.49%, p < 0.001). Klebsiella spp. strains were significantly more resistant to chloramphenicol (p = 0.03) than E. coli isolates, whereas E. coli isolates were significantly more resistant to amikacin (p = 0.04) than Klebsiella spp. isolates.

This study revealed high first-line AMR rates with drastic upward trends in clinical Enterobacterales isolated in Togo over the past 30 years. Thus, the adjustment of empirical antimicrobial treatments in Togo becomes crucial. Moreover, the implementation of prevention policies, whole-genome sequencing approaches, and the promotion of antibiotic stewardship must be enhanced. Finally, alternative therapeutic approaches, such as phytotherapy and phage therapy, were discussed.

Not applicable.

The escalating threat of antibiotic resistance demands innovative strategies against multidrug-resistant (MDR) microorganisms, particularly in hospital settings where such infections represent a major global health challenge. Since the rapid growth of nanotechnology interdisciplinary research and funding programs in the 2000s, silver ions have re-emerged as potent antimicrobial agents, offering a promising complement to conventional therapies. This therapeutic potential is nowadays explored through the use of silver nanoparticles (AgNPs) as sources for silver ions release. Recent studies have shown that controlled silver ion release enhances the efficacy of common antibiotics. This can be attributed to the energetically demanding nature of the bacterial response to silver, which weakens bacterial metabolism and, in turn, overwhelms bacterial defenses and increases antibiotic effectiveness. Herein, historical insights into the use of colloidal silver and AgNPs are combined with a review of recent research on the exploitation of the synergistic effect between AgNPs and antibiotics as a promising strategy against MDR pathogens.

Antimicrobial resistance (AMR) poses a significant threat, particularly in low- and middle-income countries (LMICs), exacerbated by inappropriate antibiotic use, access to quality antibiotics and weak antimicrobial stewardship (AMS). There is a need to review current evidence on antibiotic use, access, and AMR, in primary care across key countries.

This narrative review analyzes publications from 2018 to 2024 regarding access, availability, and use of appropriate antibiotics.

There were very few studies focussing on a lack of access to antibiotics in primary care. However, there was considerable evidence of high rates of inappropriate antibiotic use, including Watch antibiotics, typically for minor infections, across studied countries exacerbated by patient demand. The high costs of antibiotics in a number of LMICs impact on their use, resulting in short courses and sharing of antibiotics. This can contribute to AMR alongside the use of substandard and falsified antibiotics. Overall, limited implementation of national action plans, insufficient resources, and knowledge gaps affects sustainable development goals to provide routine access to safe, effective, and appropriate antibiotics.

There is a clear need to focus health policy on the optimal use of essential AWaRe antibiotics in primary care settings to reduce AMR in LMICs.

The occurrence of antibiotic-resistant bacteria (ARB) has become a global menace and therefore increases morbidity, mortality and healthcare costs. Globally, hospital wastewater (HWW) has been identified as a significant source of antibiotic-resistant elements.

This review aims to systematically review and to perform meta-analyses from evidence on antibiotic resistance studies in HWW in West Africa.

The review was conducted in compliance with PRISMA and included studies published between 1990 and 2024 in West Africa from the Scopus, PubMed, and Web of Science databases. Eligible studies that characterized resistant bacteria, genes, or antibiotic residues in HWW were included. Meta-analyses for resistant bacteria and genes as well risk of bias using the Newcastle-Ottawa scale were conducted.

Out of 23 studies reviewed, resistant bacteria were reported in 39% (E. coli), 26% (K. pneumoniae), and 17% (P. aeruginosa), while 17 studies reported ARGs, with blaTEM (29%), blaOXA- 48 (18%), blaSHV (18%), and mecA (18%) being the most common. Only 4% and 9% of studies focused on toxin genes and antibiotic residues, respectively. Meta-analysis showed pooled prevalence rates for resistant bacteria: E. coli 42.6% (95% CI: 26.7%-60.3%) and K. pneumoniae 32.1% (95% Cl: 28.8%- 36.5%), and ARGs: blaTEM 76.0% (95% CI = 64.6%-84.6%) and blaSHV 59.3% (95% CI = 19.5%-89.8%).

This systematic review highlights significant findings of high levels of ARGs and ARBs of public health concern in HWW in West Africa. This highlights the need to improve upon the monitoring of antibiotic resistance and treatment of HWW in West Africa.

A multicomponent Biginelli reaction was used to produce biologically active dihydropyrimidones that were then combined with ZnO nanoparticles. Biginelli compounds synthesized with various alkyl chains were characterized using high-resolution mass spectrometry as well as 1H- and 13C-NMR spectroscopy. Efficient antibacterial gels were developed by introducing the prepared Biginelli compounds and ZnO nanoparticles into a carbomer polymer matrix. Antibacterial screening revealed that the ABS-G4 gel exhibited the highest antibacterial potential, with minimum inhibitory concentrations of 16 ± 2 and 12 ± 2 μg mL-1 against Escherichia coli and Staphylococcus aureus, respectively. The ABS-G4 gel was characterized using rheological studies, field-emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, powder X-ray diffraction, and atomic force microscopy. The ABS-G4 gel was showing more antibacterial efficacy toward Gram-positive strains of bacteria than Gram-positive ones. An antibacterial dressing was formed by coating the developed gel onto a gauze dressing.

Antimicrobial resistance (AMR) is one of the biggest problems facing the scientific and medical communities. According to WHO, this growing issue might make once-effective antibiotics obsolete and pose a substantial risk to public health. Estimates indicate that multimillion deaths were either directly or indirectly caused by AMR, making it one of the most substantial risks to public health and development in the world. The issue of AMR is primarily caused by healthcare workers' excessive and inappropriate use of antimicrobial agents. Dentists are believed to prescribe a considerable portion of all antibiotics globally. The emergence of AMR, its causes, and its effects on human health are examined in this article, with special attention to dental offices and medical facilities. It draws attention to the rising issue of antibiotic overprescription and abuse, particularly in low- and middle-income countries, where improper antibiotic use is an everyday practice around the globe. The article discusses the role of antimicrobial stewardship programs and the importance of implementing precise, evidence-based practices in preventing AMR. Since antibiotic abuse in livestock greatly accelerates the spread of resistance, the role of antibiotics in animal agriculture is also investigated. To address AMR, the paper highlights the necessity of a global, coordinated response that bolsters surveillance systems, cuts back on needless antibiotic use, and expands access to alternative treatments. Recent research has called into question the efficacy of preventive antibiotic medication in these situations. According to other researchers, it might not help avoid surgical site infections. However, other experts say disrupting deeper tissues and local mucosal defenses during an intraoral surgical operation may raise the risk of infection even when antibiotics are used.

There are concerns globally with rising rates of antimicrobial resistance (AMR), particularly in low- and middle-income countries (LMICs). AMR is driven by high rates of inappropriate prescribing and dispensing of antibiotics, particularly Watch antibiotics. To develop future interventions, it is important to document current knowledge, attitudes and practices (KAP) among key stakeholder groups in LMICs.

We undertook a narrative review of published papers among four WHO Regions including African and Asian countries. Relevant papers were sourced from 2018 to 2024 and synthesized by key stakeholder group, country, WHO Region, income level and year. The findings were summarized to identify pertinent future activities for all key stakeholder groups.

We sourced 459 papers, with a large number coming from Africa (42.7%). An appreciable number dealt with patients' KAP (33.1%), reflecting their influence on the prescribing and dispensing of antibiotics. There was marked consistency of findings among key stakeholder groups across the four WHO Regions, all showing concerns with high rates of prescribing of antibiotics for viral infections despite professed knowledge of antibiotics and AMR. There were similar issues among dispensers. Patients' beliefs regarding the effectiveness of antibiotics for self-limiting infectious diseases were a major challenge, although educational programmes did improve knowledge. The development of the AWaRe (Access, Watch and Reserve) system, including practical prescribing guidance, provides a future opportunity for the standardization of educational inputs.

Similar KAP regarding the prescribing and dispensing of antibiotics across LMICs and stakeholder groups presents clear opportunities for standardization of educational input and practical training programmes based on the AWaRe system.

The ubiquitous opportunistic pathogen Pseudomonas aeruginosa (P. aeruginosa) causes biofilm-associated drug-resistant infections that often lead to treatment failure. Targeting the bacterium's quorum sensing (QS) and iron homeostasis presents a promising strategy to combat biofilm formation. This study synthesized benzothiazole-conjugated hydroxamic acid derivatives as dual-acting biofilm inhibitors, and compound JH21 was identified as the hit compound with potent submicromolar biofilm inhibitory activity (IC50 = 0.4 μM). Further mechanistic studies demonstrated not only that the production of virulence was decreased through mainly inhibiting QS system but also that JH21 competed for iron with the high-affinity siderophore pyoverdine, inducing iron deficiency and inhibiting biofilm. Moreover, JH21 significantly enhanced the efficacy of tobramycin and ciprofloxacin by 200- and 1000-fold, respectively, in a mouse wound infection model. These results emphasized the feasibility of dual-acting biofilm inhibitors against resistant P. aeruginosa infections and the potential of JH21 as a novel antibacterial synergist.

Antibiotic resistance is a growing global health threat, and understanding local trends in bacterial isolates and their susceptibility patterns is crucial for effective infection control and antimicrobial stewardship. The coronavirus disease 2019 (COVID-19) pandemic has introduced additional complexities, potentially influencing these patterns.

To analyze trends in bacterial isolates and their antibiotic susceptibility patterns at Salmaniya Medical Complex from 2018 to 2023, with a specific focus on the impact of the COVID-19 pandemic on these trends.

A retrospective analysis of microbiological data was conducted, covering the period from 2018 to 2023. The study included key bacterial pathogens such as Escherichia coli (E. coli), Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus, among others. The antibiotic susceptibility profiles of these isolates were assessed using standard laboratory methods. To contextualize the findings, the findings were compared with similar studies from other regions, including China, India, Romania, Saudi Arabia, the United Arab Emirates, Malaysia, and United States.

The study revealed fluctuating trends in the prevalence of bacterial isolates, with notable changes during the COVID-19 pandemic. For example, a significant increase in the prevalence of Staphylococcus aureus was observed during the pandemic years, while the prevalence of E. coli showed a more variable pattern. Antibiotic resistance rates varied among the different pathogens, with a concerning rise in resistance to commonly used antibiotics, particularly among Klebsiella pneumoniae and E. coli. Additionally, the study identified an alarming increase in the prevalence of multidrug-resistant (MDR) strains, especially within Klebsiella pneumoniae and E. coli isolates. The impact of the COVID-19 pandemic on these trends was evident, with shifts in the frequency, resistance patterns, and the emergence of MDR bacteria among several key pathogens.

This study highlights the dynamic nature of bacterial isolates and their antibiotic susceptibility patterns at Salmaniya Medical Complex, particularly in the context of the COVID-19 pandemic. The findings underscore the need for continuous monitoring and effective anti-microbial stewardship programs to combat the evolving threat of antibiotic resistance. Further research and policy initiatives are required to address the identified challenges and improve patient outcomes in the face of these ongoing challenges.

Limited data is available concerning the patterns of antifungal use and Invasive fungal infection (IFI)-associated mortality risk factors in patients with IFI prior to and during the Coronavirus disease 2019 (COVID-19) pandemic in resource-limited settings.

A single-center retrospective cohort study was conducted. All patients age >18 years diagnosed with IFIs were prospectively followed during a 3-year pre-COVID-19 pandemic period and a 3-year during COVID-19 pandemic period. Patient characteristics, the patterns of antifungal use, IFI-associated mortality risk factors, and adverse drug events were collected.

There was a total of 133 patients in this study: 60 (45.1%) were in period 1 and 73 (54.9%) were in period 2. Pre-emptive antifungal therapy was commonly practiced in period 2 (21.7% vs 37%, P = .05). The presence of a central venous catheter (aOR 3.19, P = .007), hematologic adverse drug events (aOR 17.9, P = .008) were preventable risks for the overall IFI mortality in both periods. Appropriate antifungal use was protective against the overall IFI mortality in period 2 (aOR 0.09, P = .009).

Several preventable risk factors associated with mortality were identified and served as a key for improvement of infection prevention, national policy to access antifungal agents, and antifungal stewardship in resource-limited settings.

The high cost of antimicrobials presents critical challenges for healthcare providers managing infections amidst the growing threat of antimicrobial resistance (AMR). High costs hinder access to necessary treatments, disproportionately affecting disadvantaged populations and exacerbating health disparities. High drug prices necessitate the use of less effective or more toxic alternatives, leading to suboptimal outcomes and prolonged hospitalizations. This, in turn, increases healthcare costs and undermines efforts to combat AMR. Equitable policies, national formularies, and cost caps for essential antimicrobials can ensure universal access to life-saving treatments and enable antimicrobial stewardship programs to ensure the best possible outcomes.

This national study assessed the economic impact of treating patients with antimicrobial resistance (AMR) pathogens within Malaysia's Ministry of Health (MoH) hospitals.

A cross-sectional study design and top-down costing approach, analysing Malaysian diagnosis-related group (DRG) data for AMR patients admitted to MoH hospitals from 2017 to 2020.

A total of 1190 cases were identified using International Statistical Classification of Diseases-10 version 2010 codes for AMR pathogens.

The study aims to estimate direct healthcare costs for treating AMR patients. Costs per admission were calculated based on each patient's length of stay (LOS). A binary logistic regression model identified cost determinants, with significant factors (p<0.05) further analysed using a multivariate multiple logistic regression. ORs with 95% CIs were determined, and treatment costs were categorised as above or below the annual national base rate.

Findings showed that costs are influenced by the volume of cases identified through DRG codes and LOS, which averaged between 21.7 and 36.4 days. Median admission costs for AMR patients ranged from RM12 476.28 (IQR RM 15 655.93) to RM19 295.11 (IQR RM20 200.28). Both LOS and total costs increased annually, from RM3 711 046.10 in 2017 to RM9 700 249.08 in 2019. Patients over 56 years old and those with severity levels II and III were more likely exceeding the national base rate.

These findings, explaining 9.3% of the variance in the regression model, can inform policies to reduce the economic burden of AMR and improve patient outcomes, highlighting the need for a comprehensive strategy to address this global health threat.

Antimicrobial resistance remains a public health problem of global concern with a great health and financial burden. Its recognition as a threat by political leadership has boosted the research and development of new antibiotics and particularly novel combinations of β-lactams/β-lactamase inhibitors against multidrug-resistant (MDR) Gram-negative pathogens, which remain the major concern in clinical practice. The incorporation of ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, and imipenem/cilastatin/relebactam has provided new therapeutic options in the treatment of patients with infections due to MDR pathogens. Cefiderocol along with cefepime/enmetazobactam, avibactam/aztreonam, and sulbactam/durlobactam have been recently added to these agents as therapeutic choices, particularly for metallo-β-lactamase producing Gram-negative bacteria. Currently, many combinations are being studied for their in vitro activity against both serine- and metallo-β-lactamases. However, only a few have advanced through phase 1, 2, and 3 clinical trials. Among them, in this article, we focus on the most promising combinations of cefepime/zidebactam, cefepime/taniborbactam, and imipenem/cilastatin/funobactam, which are currently under investigation in phase 3 trials.

Background/Objectives: Antibiotic resistance in chronic lung infections caused by Pseudomonas aeruginosa requires alternative approaches to improve antibiotic efficacy. One promising approach is the use of adjuvant compounds that complement antibiotic therapy. This study explores the potential of menadione as an adjuvant to azithromycin against planktonic cells and biofilms of P. aeruginosa, focusing on its mechanisms of action and cytotoxicity in pulmonary cell models. Methods: The effect of menadione in improving the antibacterial and antibiofilm potency of azithromycin was tested against P. aeruginosa. Mechanistic studies in P. aeruginosa and AZMr-E. coli DH5α were performed to probe reactive oxygen species (ROS) production and bacterial membrane disruption. Cytotoxicity of antibacterial concentrations of menadione was assessed by measuring ROS levels and membrane integrity in Calu-3 and A549 lung epithelial cells. Results: Adding 0.5 µg/mL menadione to azithromycin reduced the minimum inhibitory concentration (MIC) by four-fold and the minimum biofilm eradication concentration (MBEC) by two-fold against P. aeruginosa. Adjuvant mechanisms of menadione involved ROS production and disruption of bacterial membranes. Cytotoxicity tests revealed that antibacterial concentrations of menadione (≤64 µg/mL) did not affect ROS levels or membrane integrity in lung cell lines. Conclusions: Menadione enhanced the efficacy of azithromycin against P. aeruginosa while exhibiting a favorable safety profile in lung epithelial cells at antibacterial concentrations. These findings suggest that menadione is a promising antibiotic adjuvant. However, as relevant data on the toxicity of menadione is sparse, further toxicity studies are required to ensure its safe use in complementing antibiotic therapy.

Antimicrobial resistance (AMR) in bacteria is a global issue requiring serious attention and management. The indiscriminate use of antibiotics in livestock for growth promotion, disease prevention, and treatment has led to the dissemination of AMR bacteria and resistance genes into the environment. In addition, unethical antibiotic sales without prescriptions, poor sanitation, and improper disposal cause significant amounts of antibiotics used in livestock to enter the environment, causing the emergence of resistant bacteria. Intensive livestock farming is an important source of AMR genes, environmental bacteria contamination, and possible transfer to human pathogens. Bacteria intrinsically antibiotic resistant, which are independent of antibiotic use, further complicate AMR and increase the risk of morbidity and mortality following infections by AMR bacteria. Escherichia coli, Salmonella spp., and Staphylococcus spp. are commonly found in livestock that carry resistance genes and have a risk of human infection. The impact of AMR, if left unchecked, could lead to substantial public health burdens globally, with a predicted mortality rate higher than cancer by 2050. "One Health" integrates strategies across human, animal, and environmental health domains, including improving antibiotic stewardship in livestock, preventing infection, and raising awareness regarding the judicious use of antibiotics. The use of antibiotic alternatives, such as prebiotics, probiotics, bacteriophages, bacteriocins, and vaccinations, to control or prevent infections in livestock will help to avoid over-reliance on antibiotics. Coordinated international actions are needed to mitigate the spread of AMR through improved regulations, technology improvements, and awareness campaigns.

Antimicrobial resistance (AMR) has emerged as a priority for both public health and the global economy. Moreover, information on AMR is scarce, particularly in low/middle-income countries. We evaluated the direct economic cost of microorganisms and AMR.

We performed a cross-sectional study to assess the economic costs of neonatal cases diagnosed with bacteremia at the Instituto Nacional Materno Perinatal in Lima, Peru, from January 2017 to June 2018. We used cost invoices calculated by the micro-costing bottom-up approach, as well as the strain identification and antimicrobial susceptibility data, to estimate the direct costs.

The average costs of bacteremia were US$349 (SD 403) for multidrug-resistant (MDR) strains and US$276 (SD 349) for non-MDR strains. Costs were higher for microorganisms associated with late-onset sepsis (LOS). We found that LOS, multidrug resistance and age were significantly associated with bloodstream infection (BSI) costs. Also, all microorganism groups were associated with increased costs, with the highest average costs for Acinetobacter, followed by Pseudomonas.

In Peru, BSI costs are strongly associated with AMR. Furthermore, costs increase significantly with LOS, multidrug resistance and the patient's age. We urge health authorities to strengthen measures and strategies against the pressing threat of AMR.

In this review, we present the efforts made so far in developing effective solutions to prevent infections caused by seven major respiratory pathogens: influenza virus, respiratory syncytial virus (RSV), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Bordetella pertussis, Streptococcus pneumoniae (pneumococcus), Mycobacterium tuberculosis, and Pseudomonas aeruginosa. Advancements driven by the recent coronavirus disease 2019 (COVID-19) crisis have largely focused on viruses, but effective prophylactic solutions for bacterial pathogens are also needed, especially in light of the antimicrobial resistance (AMR) phenomenon. Here, we discuss various innovative key technologies that can help address this critical need, such as (a) the development of Lung-on-Chip ex vivo models to gain a better understanding of the pathogenesis process and the host-microbe interactions; (b) a more thorough investigation of the mechanisms behind mucosal immunity as the first line of defense against pathogens; (c) the identification of correlates of protection (CoPs) which, in conjunction with the Reverse Vaccinology 2.0 approach, can push a more rational and targeted design of vaccines. By focusing on these critical areas, we expect substantial progress in the development of new vaccines against respiratory bacterial pathogens, thereby enhancing global health protection in the framework of the increasingly concerning AMR emergence.

Antimicrobial stewardship programs (ASPs) and diagnostic stewardship programs (DSPs) are essential strategies for effectively managing infectious diseases and tackling antimicrobial resistance (AMR). These programs can have a complementary impact, i.e., ASPs optimize antimicrobial use to prevent resistance, while DSPs enhance diagnostic accuracy to guide appropriate treatments. This review explores the current landscape of ASPs and DSPs in pediatric care, focusing on key factors, influencing their development, implementation, and evaluation across various settings. A multidisciplinary approach is necessary, involving multiple healthcare professionals to support comprehensive stewardship practices in pediatric care. No single intervention suits all settings, or even the same setting, in different countries; interventions must be tailored to each specific context, considering factors such as hospital capacity, patient complexity, and the parent-child dynamic. It is essential to educate caregivers on optimal antibiotic use through clear, concise messages adapted to their socioeconomic status and level of understanding. The cost-effectiveness of ASPs and DSPs should also be assessed, and standardized metrics should be employed to evaluate success in pediatric settings, focusing on outcomes beyond just antibiotic consumption, such as AMR rates. This manuscript further discusses emerging opportunities and challenges in ASP implementation, offering insights into future research priorities. These include large-scale studies to evaluate the long-term impact of ASPs, cost-effectiveness assessments of pediatric-specific diagnostic tools, and the integration of artificial intelligence to support clinical decision making. Addressing these areas will enhance the effectiveness and sustainability of ASPs, contributing to global efforts to combat AMR and improve pediatric health outcomes.

Background/Objectives: Given the magnitude and urgency of the global antimicrobial resistance (AMR) problem and the insufficiency of strategies to reduce antimicrobial use, there is a need for novel strategies. Traditional, Complementary, and Integrative Healthcare (TCIH) provides strategies and solutions that contribute to reducing (inappropriate) antimicrobial use, preventing or treating infections in both human and veterinary medicine, and may contribute to promoting the health/resilience of humans and animals and reducing AMR. The aims of this study were to present the core results of a global TCIH research agenda for AMR and its added value to two existing global AMR research agendas published in 2023. Methods: A survey, interviews, and consensus meetings among network members, as an adapted version of the nominal group technique, were executed to develop the global TCIH research agenda. A comparison of the global TCIH research agenda with the two existing global AMR research agendas was performed. The TCIH additions to these two existing global AMR research agendas were determined. Results: The global TCIH research agenda adds to 19 of 40 research priorities of the World Health Organization (WHO) AMR research agenda 2023 and three of the five pillars of the WHO/Food and Agriculture Organization of the United Nations (FAO)/United Nations Environment Programme (UNEP)/World Organisation for Animal Health (WOAH) research agenda 2023. In addition, the TCIH research agenda adds two new research themes with four new research priorities and three new research priorities to already existing themes of the two global AMR research agendas. Conclusions: The global TCIH research agenda fits with and adds to two global AMR research agendas and can be used as an additional strategy to reduce AMR and (inappropriate) use of antibiotics.

Antimicrobial resistance (AMR) is a major global health challenge, particularly in low- and middle-income countries (LMICs). Understanding the knowledge, attitudes, motivations, and expectations of community members regarding antimicrobial use is essential for effective stewardship interventions. This scoping review aimed to identify key themes relating to the critical areas regarding antimicrobial use among community members in primary healthcare (PHC), with a particular focus on LMICs.

OVID Medline, PubMed, and CINAHL databases were searched using Boolean operators and Medical Subject Headings (MeSH) terms relevant to antimicrobial use and community behaviors. The Population, Intervention, Comparison, Outcome, and Study Design (PICOS) framework guided study selection, which focused on community members seeking care in PHC in LMICs. Data management and extraction were facilitated using the Covidence platform, with the Critical Appraisal Skills Programme (CASP) qualitative checklist applied for qualitative studies. A narrative synthesis identified and grouped key themes and sub-themes.

The search identified 497 sources, of which 59 met the inclusion criteria, with 75% of the studies conducted in outpatient primary care settings. Four key themes were identified: (1) the 'patient' theme, highlighting beliefs, knowledge, and expectations, which was the most prominent (40.5%); (2) the 'provider' theme, emphasizing challenges related to clinical decision-making, knowledge gaps, and adherence to guidelines; (3) the 'healthcare systems' theme, highlighting resource limitations, lack of infrastructure, and policy constraints; and (4) the 'intervention/uptake' theme, emphasizing strategies to improve future antibiotic use and enhance access to and quality of healthcare.

Stewardship programs in PHC settings in LMICs should be designed to be context-specific, community-engaged, and accessible to individuals with varying levels of understanding, involving the use of information and health literacy to effectively reduce AMR.

Surveillance of antibiotic use is crucial for identifying targets for antibiotic stewardship programs (ASPs), particularly in pediatric populations within countries like Pakistan, where antimicrobial resistance (AMR) is escalating. This point prevalence survey (PPS) seeks to assess the patterns of antibiotic use in pediatric patients across Punjab, Pakistan, employing the WHO AWaRe classification to pinpoint targets for intervention and encourage rational antibiotic usage.

A PPS was conducted across 23 pediatric wards of 14 hospitals in the Punjab Province of Pakistan using the standardized Global-PPS methodology developed by the University of Antwerp. The study included all pediatric inpatients receiving antibiotics at the time of the survey, categorizing antibiotic prescriptions according to the WHO Anatomical Therapeutic Chemical classification and the AWaRe classification system.

Out of 498 pediatric patients, 409 were receiving antibiotics, representing an antibiotic use prevalence of 82.1%. A substantial majority (72.1%) of the prescribed antibiotics fell under the WHO's Watch category, with 25.7% in the Access category and 2.2% in the Reserve group. The predominant diagnoses were respiratory infections, notably pneumonia (32.4%). The most commonly used antibiotics were ceftriaxone (37.2%) and Vancomycin (13.5%). Only 2% of antibiotic uses were supported by culture sensitivity reports, highlighting a reliance on empirical therapy.

The high prevalence of antibiotic use, particularly from the Watch category, and low adherence to culture-based prescriptions underscore the critical need for robust antibiotic stewardship programs in Pakistan. Strengthening these programs could help mitigate AMR and optimize antibiotic use, aligning with global health objectives.

Antimicrobial resistance is a critical global challenge in the 21st century, validating Sir Alexander Fleming's warning about the misuse of antibiotics leading to resistant microbes. With a dwindling arsenal of effective antibiotics, it is imperative to concentrate on alternative antimicrobial strategies. Previous studies have not comprehensively discussed the advantages and limitations of various strategies, including bacteriophage therapy, probiotics, immunotherapies, photodynamic therapy, essential oils, nanoparticles and antimicrobial peptides (AMPs) within a single review. This review addresses that gap by providing an overview of these various non-antibiotic antimicrobial strategies, highlighting their pros and cons, with a particular emphasis on antimicrobial peptides (AMPs). We explore the mechanism of action of AMPs against bacteria, viruses, fungi and parasites. While these peptides hold significant promise, their application in mainstream drug development is hindered by challenges such as low bioavailability and potential toxicity. However, advancements in peptide engineering and chemical modifications offer solutions to enhance their clinical utility. Additionally, this review presents updates on strategies aimed at improving the cost, stability and selective toxicity of AMPs through the development of peptidomimetics. These molecules have demonstrated effective activity against a broad range of pathogens, making them valuable candidates for integration into surface coatings to prevent device-associated infections. Furthermore, we discuss various approaches for attaching and functionalising these peptides on surfaces. Finally, we recommend comprehensive in vivo studies to evaluate the efficacy of AMPs and their mimetics, investigate their synergistic combinations with other molecules and assess their potential as coatings for medical devices.

This study investigated the antibacterial and anti-biofilm properties of postbiotics derived from Lactobacillus plantarum and their effect on the expression of antibiotic resistance genes (ermB and blaKPC) in Enterococcus faecalis and Pseudomonas aeruginosa, respectively. Cell-free supernatants (CFSs) were analyzed through gas chromatography-mass spectrometry (GC-MS), which showed that butyric acid (14.31%) was the major compound, other metabolites present in CFSs included lactic acid (5.94%), hdroxyacetone (5,21%), benzoic acid (3.12%), Pyrrolo[1,2-a] pyrazine-1,4-dione (1.91%), 2,3-Butanediol (1.04%), and 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one (0.73.%). To investigate the effect of postbiotics on bacterial growth and biofilm formation, minimal inhibitory concentration (MIC) and microtiter plate assays were used. MIC results showed that resistant En. faecalis and P. aeruginosa can grow at concentrations of 2.5 and 5 mg/ml, respectively, after exposure to postbiotics. Furthermore, the microtiter plate results showed that postbiotics significantly reduced biofilm formation: 51%, 45%, and 39% in En. faecalis and 46%, 38%, and 27% in P. aeruginosa at different concentrations. Real-time polymerase chain reaction also confirmed the reduction of resistance genes (ermB; P = 0.007 and blaKPC; P = 0.02) expression. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay showed that the cell survival rate was 80%. These findings suggest that postbiotics from L. plantarum may be a promising approach for combating bacterial growth, biofilm formation, and antibiotic resistance.

Antibiotic-resistant bloodstream infections (ARB BSI) cause an enormous disease and economic burden. We assessed the impact of ARB BSI caused by high- and critical-priority pathogens in hospitalised Chilean patients compared to BSI caused by susceptible bacteria.

We conducted a retrospective cohort study from 2018 to 2022 in three Chilean hospitals and measured the association of ARB BSI with in-hospital mortality, length of hospitalisation (LOS), and intensive care unit (ICU) admission. We focused on BSI caused by Acinetobacter baumannii, Enterobacterales, Staphylococcus aureus, Enterococcus species, and Pseudomonas aeruginosa. We addressed confounding using propensity scores, inverse probability weighting, and multivariate regressions. We stratified by community- and hospital-acquired BSI and assessed total hospital and productivity costs.

We studied 1218 adult patients experiencing 1349 BSI episodes, with 47.3% attributed to ARB. Predominant pathogens were Staphylococcus aureus (33% Methicillin-resistant 'MRSA'), Enterobacterales (50% Carbapenem-resistant 'CRE'), and Pseudomonas aeruginosa (65% Carbapenem-resistant 'CRPA'). Approximately 80% of BSI were hospital-acquired. ARB was associated with extended LOS (incidence risk ratio IRR = 1.14, 95% CI = 1.05-1.24), increased ICU admissions (odds ratio OR = 1.25; 1.07-1.46), and higher mortality (OR = 1.42, 1.20-1.68) following index blood culture across all BSI episodes. In-hospital mortality risk, adjusted for time-varying and fixed confounders, was 1.35-fold higher (1.16-1.58) for ARB patients, with higher hazard ratios for hospital-acquired MRSA and CRE at 1.37 and 1.48, respectively. Using a societal perspective and a 5% discount rate, we estimated excess costs for ARB at $12,600 per patient, with an estimated annual excess burden of 2270 disability-adjusted life years (DALYs) and $9.6 (5.0-16.4) million.

It is urgent to develop and implement interventions to reduce the burden of ARB BSIs, particularly from MRSA and CRE.

Agencia Nacional de Investigación y Desarrollo ANID, Chile.

In addition to affecting animal health and production, antimicrobial resistance (AMR) in livestock can have far-reaching social and economic consequences, including on human health and the environment. Given the diversity of data needs and the absence of standardised methodologies, the scale of antimicrobial use (AMU) and AMR's social and economic burden on livestock is complex to gauge. Yet, quantifying this impact can be an essential input for farm-level decision-making and, more widely, for policy development, public awareness, resource allocation to interventions and research and development prioritisation, particularly in a One Health context. This work proposes a conceptual framework to guide the assessment of the burden of AMU and AMR in livestock using the Global Burden of Animal Diseases (GBADs) approach. Its development identified and mapped critical socio-economic concepts in AMU and AMR in livestock and their relationships. The Animal Health Loss Envelope (AHLE), a monetary metric that sets a boundary for overall losses from health hazards and allows an understanding of the relative importance of health problems in livestock, was used as the metric in which the concepts and data needs for the AMU and AMR assessment were anchored. The proposed framework identifies pathways for losses and data inputs needed to estimate the burden of AMU and AMR within this wider envelope of losses. These include information on health expenditure and mortality and morbidity effects related to AMR in livestock. This work highlights the need for improved health and production data collection in livestock production as an essential stepping stone to accurately producing AMU and AMR burden estimates.

The One Health concept recognises the interconnectedness of humans, plants, animals and the environment. Recent research strongly supports the idea that the environment serves as a significant reservoir for antimicrobial resistance (AMR). However, the complexity of natural environments makes efforts at AMR public health risk assessment difficult. We lack sufficient data on key ecological parameters that influence AMR, as well as the primary proxies necessary for evaluating risks to human health. Developing environmental AMR 'early warning systems' requires models with well-defined parameters. This is necessary to support the implementation of clear and targeted interventions. In this review, we provide a comprehensive overview of the current tools used globally for environmental AMR human health risk assessment and the underlying knowledge gaps. We highlight the urgent need for standardised, cost-effective risk assessment frameworks that are adaptable across different environments and regions to enhance comparability and reliability. These frameworks must also account for previously understudied AMR sources, such as horticulture, and emerging threats like climate change. In addition, integrating traditional ecotoxicology with modern 'omics' approaches will be essential for developing more comprehensive risk models and informing targeted AMR mitigation strategies.

Usage of antibiotics in agriculture has increased dramatically recently, significantly raising the influx of antibiotic resistance genes (ARGs) into river systems through organic manure runoff, seriously threatening water security. However, the dynamics, transmission mechanisms, and potential water security risk of ARGs, as well as their response to land use spatial scale and seasonal variations in agricultural river systems remain unclear. To address these challenges, this work employed metagenomic technique to systematically evaluate the pollution and dissemination of ARGs in overlying water and sediment within a typical agricultural catchment in China. The results demonstrated significant differences between overlying water and sediment ARGs. Overlying water dominated by multidrug ARGs exhibited higher diversity, whereas sediment predominantly containing sulfonamide ARGs had higher abundance. The dynamics of ARGs in overlying water were more responsive to seasonal variations compared to sediment due to greater changes in hydrodynamics and nutrient conditions. The profiles of ARGs in overlying water were largely regulated by microbiota, whereas mobile genetic elements (MGEs) were the main forces driving the dissemination of ARGs in sediment. The variation in dissemination mechanisms led to different resistance risks, with sediment presenting a higher resistance risk than overlying water. Furthermore, Mantel test was applied to discover the impact of land use spatial scale and composition on the transmission of ARGs in river systems. The findings showed that cultivated land within 5 km of the riverbank was the key influencing factor. Cultivated land exacerbated ARGs spread by increasing MGEs abundance and nutrient concentrations, resulting in the abundance of ARGs in high-cultivated sites being twice that in low-cultivated sites, and raising the regional water security risk, with a more pronounced effect in sediment. These findings contribute to a better understanding of ARGs dissemination in agricultural watersheds, providing a basis for implementing effective resistance control measures and ensuring water security.

A pandemic known as anti-microbial resistance (AMR) poses a challenge to contemporary medicine. To stop AMR's rise and quick worldwide spread, urgent multisectoral intervention is needed. This review will provide insight on new and developing treatment approaches for AMR. Future therapy options may be made possible by the development of novel drugs that make use of developments in "omics" technology, artificial intelligence, and machine learning. Vaccines, immunoconjugates, antimicrobial peptides, monoclonal antibodies, and nanoparticles may also be intriguing options for treating AMR in the future. Combination therapy may potentially prove to be a successful strategy for combating AMR. To lessen the impact of AMR, ideas like drug repurposing, antibiotic stewardship, and the one health approach may be helpful.

Antimicrobial resistance is a growing health threat, but standard methods for determining antibiotic susceptibility are slow and can delay optimal treatment, which is especially consequential in severe infections such as bacteremia. Novel approaches for rapid susceptibility profiling have emerged that characterize either bacterial response to antibiotics (phenotype) or detect specific resistance genes (genotype). Genotypic and Phenotypic AST through RNA detection (GoPhAST-R) is a novel assay, performed directly on positive blood cultures, that integrates rapid transcriptional response profiling with the detection of key resistance gene transcripts, thereby providing simultaneous data on both phenotype and genotype. Here, we performed the first clinical pilot of GoPhAST-R on 42 positive blood cultures: 26 growing Escherichia coli, 15 growing Klebsiella pneumoniae, and 1 with both. An aliquot of each positive blood culture was exposed to nine different antibiotics, lysed, and underwent rapid transcriptional profiling on the NanoString platform; results were analyzed using an in-house susceptibility classification algorithm. GoPhAST-R achieved 95% overall agreement with standard antimicrobial susceptibility testing methods, with the highest agreement for beta-lactams (98%) and the lowest for fluoroquinolones (88%). Epidemic resistance genes including the extended spectrum beta-lactamase blaCTX-M-15 and the carbapenemase blaKPC were also detected within the population. This study demonstrates the clinical feasibility of using transcriptional response profiling for rapid resistance determination, although further validation with larger and more diverse bacterial populations will be essential in future work. GoPhAST-R represents a promising new approach for rapid and comprehensive antibiotic susceptibility testing in clinical settings.IMPORTANCEExposure to antibiotics causes differential transcriptional signatures in susceptible vs resistant bacteria. These differences can be leveraged to rapidly predict resistance profiles of Escherichia coli and Klebsiella pneumoniae in clinically positive blood cultures.