Comprehensive genomics reveals novel sequence types of multidrug resistant Klebsiella oxytoca with uncharacterized capsular polysaccharide K- and lipopolysaccharide O-antigen loci from the National Hospital of Uganda.

The Klebsiella oxytoca complex comprises diverse opportunistic bacterial pathogens associated with hospital and community-acquired infections with growing alarming antimicrobial resistance. We aimed to uncover the genomic features underlying the virulence and antimicrobial resistance of isolates from Mulago National Hospital in Uganda. We coupled whole genome sequencing with Pathogenwatch multilocus sequence typing (MLST) and downstream bioinformatic analysis to delineate sequence types (STs) capsular polysaccharide K- and O-antigen loci, along with antimicrobial resistance (AMR) profiles of eight clinical isolates from the National Referral Hospital of Uganda. Our findings revealed that only two isolates (RSM6774 and RSM7756) possess a known capsular polysaccharide K-locus (KL74). The rest carry various unknown K-loci (KL115, KL128, KLI52, KL161 and KLI63). We also found that two isolates possess unknown loci for the lipopolysaccharide O-antigen (O1/O2v1 type OL104 and unknown O1). The rest possess known O1 and O3 serotypes. From MLST, we found four novel sequence types (STs), carrying novel alleles for the housekeeping genes glyceraldehyde-6-phosphate dehydrogenase A (gapA), glucose-6-phosphate isomerase (pgi), and RNA polymerase subunit beta (rpoB). Our AMR analysis revealed that all the isolates are resistant to ampicillin and ceftriaxone, with varied resistance to other antibiotics, but all carry genes for extended-spectrum beta-lactamases (ESBLs). Notably, one strain (RSM7756) possesses outstanding chromosomal and plasmid-encoded AMR to beta-lactams, cephalosporins, fluoroquinolones and methoprims. Conclusively, clinical samples from Mulago National Referral Hospital harbor novel STs and multidrug resistant K. oxytoca strains, with significant public health importance, which could have been underrated.

Butyricimonas faecihominis: an atypically resistant bacterium implicated in abscess formation - a case report.

BACKGROUND: This case report presents a unique instance of abscesses with an uncommon pathogen isolated from blood cultures. CASE PRESENTATION: We present the case of a perianal abscess in a 50-year-old man with a history of cocaine abuse and bilateral hip replacements. The rapid progression led to septic shock and multi-organ failure, requiring intensive care unit admission, surgery including protective transversostomy. Blood cultures showed growth of Butyricimonas spp. with resistance to penicillin and piperacillin-tazobactam. The immediate switch to meropenem led to a significant improvement in the patient's condition. The patient was discharged after 40 days of hospitalization in good general condition and the reversal of the transversostomy was performed six months later. CONCLUSION: The identification of Butyricimonas faecihominis, a rarely reported pathogen, emphasizes the challenges of diagnosing and treating unusual infections. This case emphasizes the importance of rapid microbiological diagnosis, interdisciplinary collaboration, and targeted antibiotic therapy in the treatment of abscesses and sepsis.

The importance of "one health approach" to the AMR study and surveillance in Angola and other African countries.

The dissemination of multidrug-resistant (MDR) bacterial isolates in low- and middle-income countries, including several African countries, is a major concern. The poor sanitary conditions of rural and urban families observed in certain regions may favor the transmission of bacterial infections between animals and humans, including those promoted by strains resistant to practically all available antibiotics. In Angola, in particular, the presence of these strains in human hospitals has already been described. Nevertheless, the information on antimicrobial resistance (AMR) prevalence in Angola is still scarce, especially regarding veterinary isolates. This review aimed to synthesize data on antimicrobial resistance in African countries, with a special focus on Angola, from a One Health perspective. The main goals were to identify research gaps that may require further analysis, and to draw attention to the importance of the conscious use of antimicrobials and the establishment of preventive strategies, aiming to guarantee the safeguarding of public health. To understand these issues, the available literature on AMR in Africa was reviewed. We searched PubMed for articles pertinent to AMR in relevant pathogens in Angola and other African countries. In this review, we focused on AMR rates and surveillance capacity. The principal findings were that, in Africa, especially in sub-Saharan countries, AMR incidence is high due to the lack of legislation on antibiotics, to the close interaction of humans with animals and the environment, and to poverty. The information about current resistance patterns of common pathogenic bacteria is sparse, and the number of quality studies is limited in Angola and in some other Sub-Saharan African countries. Also, studies on the "One Health Approach" focusing on the environment, animals, and humans, are scarce in Africa. The surveillance capacity is minimal, and only a low number of AMR surveillance programs and national health programs are implemented. Most international and cooperative surveillance programs, when implemented, are not properly followed, concluded, nor reported. In Angola, the national health plan does not include AMR control, and there is a consistent omission of data submitted to international surveillance programs. By identifying One Health strengths of each country, AMR can be controlled with a multisectoral approach and governmental commitment.

Traces of pandemic fluoroquinolone-resistant Escherichia coli clone ST131 transmitted from human society to aquatic environments and wildlife in Japan.

Transmission of antimicrobial-resistant bacteria among humans, animals, and the environment is a growing concern worldwide. The distribution of an international high-risk fluoroquinolone-resistant Escherichia coli clone, ST131, has been documented in clinical settings. However, the transmission of ST131 from humans to surrounding environments remains poorly elucidated. To comprehend the current situation and identify the source of ST131 in nature, we analyzed the genetic features of ST131 isolates from the aquatic environment (lake/river water) and wildlife (fox, raccoon, raccoon dog, and deer) and compared them with the features of isolates from humans in Japan using accessory and core genome single nucleotide polymorphism (SNP) analyses. We identified ST131 isolates belonging to the same phylotype and genome clusters (four of eight clusters were concomitant) with low SNP distance between the human isolates and those from the aquatic environment and wildlife. These findings warn of ST131 transmission between humans and the surrounding environment in Japan.

Point prevalence survey of antibiotics use among hospitalised neonates and children in Saudi Arabia: findings and implications.

Background: Neonates and children are more susceptible to a variety of infections, leading to frequent antibiotic prescriptions. However, the inappropriate use of antibiotics leads to antibiotic resistance and higher mortality rates. Therefore, this study aimed to determine the prevalence of antibiotic use, and current antibiotic prescribing practices among neonates and children admitted in the selected hospitals of Saudi Arabia. Methods: A cross-sectional study was conducted from September to November 2023 to assess the prevalence of antibiotic use, and the current antibiotic prescribing practices across six hospitals of Saudi Arabia. Results: The study included 499 children and neonates, with 94.6% receiving antibiotic prescriptions. The most frequently prescribed antibiotic class was third-generation cephalosporin (31.5%), with ceftriaxone being the most commonly prescribed antibiotic (15%). The majority of patients were prescribed one antibiotic (81.4%), and the intravenous route (96.4%) was the primary route for administration. The majority of patients were prescribed antibiotics empirically (69.7%), and community-acquired infections (64.2%) were the most common type of infection for antibiotic prescription. Similarly, sepsis (39.2%) was the most common indication for antibiotics, and the majority of prescribed antibiotics (61.7%) belonged to the 'Watch' category as per WHO AWaRe classification. Conclusion: Our study revealed excessive antibiotic consumption in neonates and children, therefore quality improvement programmes including antimicrobial stewardship programmes are urgently needed to address ongoing issues.

Comparison of vonoprazan bismuth-containing triple therapy with quadruple therapy in Helicobacter pylori-infected treatment-naive patients: a prospective multicenter randomized controlled trial.

BACKGROUND AND AIM: Helicobacter pylori infection is linked to various gastrointestinal conditions, such as chronic active gastritis, peptic ulcers, and gastric cancer. Traditional treatment options encounter difficulties due to antibiotic resistance and adverse effects. Therefore, the aim of this study was to explore the effectiveness of a new treatment plan that combines vonoprazan (VPZ), amoxicillin, and bismuth for the eradication of H. pylori. METHODS: A total of 600 patients infected with H. pylori were recruited for this multicenter randomized controlled trial. Patients treated for H. pylori elimination were randomly assigned at a 1:1 ratio to receive 14 days of vonoprazan-based triple therapy (vonoprazan + amoxicillin + bismuth, group A) or standard quadruple therapy (esomeprazole + clarithromycin + amoxicillin + bismuth, group B). Compliance and adverse effects were tracked through daily medication and side effect records. All patients underwent a 13C/14C-urea breath test 4 weeks after treatment completion. RESULTS: Intention-to-treat (ITT) and per-protocol (PP) analyses revealed no substantial differences in H. pylori eradication rates between groups A and B (ITT: 83.7% vs 83.2%; PP: 90.9% vs 89.7%). However, significant differences were observed in the assessment of side effects (13.7% vs 28.6%, P < 0.001). Specifically, group A had significantly fewer "bitter mouths" than group B did (3.7% vs 16.2%, P < 0.001). CONCLUSION: Triple therapy comprising vonoprazan (20 mg), amoxicillin (750 mg), and bismuth potassium citrate (220 mg) achieved a PP eradication rate ≥90%, paralleling standard quadruple therapy, and had fewer adverse events and lower costs (¥306.8 vs ¥645.8) for treatment-naive patients.

Development of a luciferase-based Gram-positive bacterial reporter system for the characterization of antimicrobial agents.

Mechanistic investigations are of paramount importance in elucidating the modes of action of antibiotics and facilitating the discovery of novel drugs. We reported a luciferase-based reporter system using bacterial cells to unveil mechanisms of antimicrobials targeting transcription and translation. The reporter gene Nluc encoding NanoLuciferase (NanoLuc) was integrated into the genome of the Gram-positive model organism, Bacillus subtilis, to generate a reporter strain BS2019. Cellular transcription and translation levels were assessed by quantifying the amount of Nluc mRNA as well as the luminescence catalyzed by the enzyme NanoLuc. We validated this system using three known inhibitors of transcription (rifampicin), translation (chloramphenicol), and cell wall synthesis (ampicillin). The B. subtilis reporter strain BS2019 successfully revealed a decline in Nluc expression by rifampicin and NanoLuc enzyme activity by chloramphenicol, while ampicillin produced no observable effect. The assay was employed to characterize a previously discovered bacterial transcription inhibitor, CUHK242, with known antimicrobial activity against drug-resistant Staphylococcus aureus. Production of Nluc mRNA in our reporter BS2019 was suppressed in the presence of CUHK242, demonstrating the usefulness of the construct, which provides a simple way to study the mechanism of potential antibiotic candidates at early stages of drug discovery. The reporter system can also be modified by adopting different promoters and reporter genes to extend its scope of contribution to other fields of work. IMPORTANCE: Discovering new classes of antibiotics is desperately needed to combat the emergence of multidrug-resistant pathogens. To facilitate the drug discovery process, a simple cell-based assay for mechanistic studies is essential to characterize antimicrobial candidates. In this work, we developed a luciferase-based reporter system to quantify the transcriptional and translational effects of potential compounds and validated our system using two currently marketed drugs. Reporter strains generated in this study provide readily available means for identifying bacterial transcription inhibitors as prospective novel antibacterials. We also provided a series of plasmids for characterizing promoters under various conditions such as stress.

Phage therapy: an alternative treatment modality for MDR bacterial infections.

The increasing global incidence of multidrug-resistant (MDR) bacterial infections threatens public health and compromises various aspects of modern medicine. Recognising the urgency of this issue, the World Health Organisation has prioritised the development of novel antimicrobials to combat ESKAPEE pathogens. Comprising Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli, such pathogens represent a spectrum of high to critical drug resistance, accounting for a significant proportion of hospital-acquired infections worldwide. In response to the waning efficacy of antibiotics against these resilient pathogens, phage therapy (PT) has emerged as a promising therapeutic strategy. This review provides a comprehensive summary of clinical research on PT and explores the translational journey of phages from laboratory settings to clinical applications. It examines recent advancements in pre-clinical and clinical developments, highlighting the potential of phages and their proteins, alone or in combination with antibiotics. Furthermore, this review underlines the importance of establishing safe and approved routes of phage administration to patients. In conclusion, the evolving landscape of phage therapy offers a beacon of hope in the fight against MDR bacterial infections, emphasising the imperative for continued research, innovation and regulatory diligence to realise its full potential in clinical practice.

Aspirin altered antibiotic resistance genes response to sulfonamide in the gut microbiome of zebrafish.

Pharmaceuticals are widespread in aquatic environments and might contribute to the prevalence of antibiotic resistance. However, the co-effect of antibiotics and non-antibiotic pharmaceuticals on the gut microbiome of fish is poorly understood. In this study, we characterized the variation of the zebrafish gut microbiome and resistome after exposure to sulfamethoxazole (SMX) and aspirin under different treatments. SMX contributed to the significant increase in the antibiotic resistance genes (ARGs) richness and abundance with 46 unique ARGs and five mobile genetic elements (MGEs) detected. Combined exposure to SMX and aspirin enriched total ARGs abundance and rearranged microbiota under short-term exposure. Exposure time was more responsible for resistome and the gut microbiome than exposure concentrations. Perturbation of the gut microbiome contributed to the functional variation related to RNA processing and modification, cell motility, signal transduction mechanisms, and defense mechanisms. A strong significant positive correlation (R=0.8955, p<0.001) was observed between total ARGs and MGEs regardless of different treatments revealing the key role of MGEs in ARGs transmission. Network analysis indicated most of the potential ARGs host bacteria belonged to Proteobacteria. Our study suggested that co-occurrence of non-antibiotics and antibiotics could accelerate the spread of ARGs in gut microbial communities and MGEs played a key role.

New arsenals for old armour: Biogenic nanoparticles in the battle against drug-resistant Candida albicans.

Candida albicans is a common commensal fungus and fourth most frequent causative agent of nosocomial infections including life-threatening invasive candidiasis in humans. The effectiveness of present antifungal therapies using azoles, polyenes, flucytosine and echinocandins has plateaued in managing fungal infections. The limitations of these drugs are related to polymorphic morphology, biofilm formation, emergence of drug-resistant strains and production of several virulence factors. Development of new antifungal agents, which can particularly targeting multiple cellular targets and limiting evolving resistant strains are needed. Recently, metal nanoparticles have emerged as a source of new antifungal agents for antifungal formulations. Furthermore, green nanotechnology deals with the use of biosynthetic routes that offer new avenue for synthesizing antifungal nanoparticles coupled with less toxic chemical inventory and environmental sustainability. This article reviews the recent developments on C. albicans pathogenesis, biofilm formation, drug resistance, mode of action of antifungal drugs and antifungal activities of metal nanoparticles. The antifungal efficacy and mode of action of metal nanoparticles are described in the context of prospective therapeutic applications.

Antimicrobial Resistance in Uropathogenic Escherichia coli Strains Isolated from Relapses from Recurrent Urinary Tract Infections.

Little is known about the characteristics of uropathogenic Escherichia coli (UPEC) associated with recurrent urinary tract infections (RUTIs). The present study aimed to analyze the phenotypic antimicrobial resistance of recurrent UPEC isolates attributable to either relapse or reinfection. A total of 140 E. coli strains were isolated from 70 outpatients with RUTIs. All isolates were analyzed by random amplified polymorphic DNA-polymerase chain reaction to evaluate genetic similarity between the first and second isolates. We found that 64.2% (45/70) of outpatients had a relapse with the primary infecting E. coli strain and 35.7% (25/70) had reinfection with a new E. coli strain. Compared with reinfecting strains, relapse UPEC isolates exhibited much higher antimicrobial resistance; 89% of these isolates were multidrug-resistant and 46.6% were extended-spectrum ß-lactamase producers. Our study provides evidence that RUTIs are mainly driven by the persistence of the original strain in the host (relapses) despite appropriate antibiotic treatments, and only RUTIs attributed to relapses seem to favor multidrug resistance in UPEC isolates.

Antibiotic resistance: Assessing knowledge and misconceptions among Portuguese students and science teachers.

Antimicrobial resistance poses one of the most significant medical challenges for humanity. The current burden is overwhelming and is projected to escalate rapidly, with predictions for 2050 indicating 10 million deaths per year due to antibiotic-resistant microorganisms. Enhancing public awareness and education on this topic is crucial in efforts to mitigate this issue. In our study, we translated an existing questionnaire on antimicrobial resistance into Portuguese, validated it, and applied it between December 2020 and March 2021 to a group of Portuguese students (n = 112) and science teachers (n = 95). A majority of the students surveyed (65.1%) incorrectly believed that antibiotics could treat colds/flus. As anticipated, the teachers outperformed the students in the questionnaire. However, difficulties with this topic were evident in both groups. Most notably, the misconception that the human body becomes resistant to antibiotics was prevalent among most participants (77.0% of students and 68.4% of teachers). Consistent with previous studies in other populations and geographic locations, our research reveals a worrying lack of knowledge about antimicrobial resistance among Portuguese students and science teachers. Consequently, it is deemed urgent to implement effective measures to raise awareness and educate on this topic.

Distributive justice and value trade-offs in antibiotic use in aged care settings.

Residential aged care facilities (RACF) are sites of high antibiotic use in Australia. Misuse of antimicrobial drugs in RACF contributes to antimicrobial resistance (AMR) burdens that accrue to individuals and the wider public, now and in the future. Antimicrobial stewardship (AMS) practices in RACF, e.g. requiring conformation of infection, are designed to minimise inappropriate use of antibiotics. We conducted dialogue groups with 46 participants with a parent receiving aged care to better understand families' perspectives on antibiotics and care in RACF. Participants grappled with value trade offs in thinking about their own parents' care, juggling imagined population and future harms with known short term comfort of individuals and prioritising the latter. Distributive justice in AMR relies on collective moral responsibility and action for the benefit of future generations and unknown others. In RACF, AMS requires value trade-offs and compromise on antimicrobial use in an environment that is heavily reliant on antimicrobial drugs to perform caring functions. In the context of aged care, AMS is a technical solution to a deeply relational and socio-structural problem and there is a risk that carers (workers, families) are morally burdened by system failures that are not addressed in AMS solutions.

Colistin-, cefepime-, and levofloxacin-resistant Salmonella enterica serovars isolated from Egyptian chicken carcasses.

OBJECTIVES: The emergence of multidrug-resistant (MDR) Salmonella strains, especially resistant ones toward critically important antimicrobial classes such as fluoroquinolones and third- and fourth-generation cephalosporins, is a growing public health concern. The current study, therefore, aimed to determine the prevalence, and existence of virulence genes (invA, stn, and spvC genes), antimicrobial resistance profiles, and the presence of ß-lactamase resistance genes (blaOXA, blaCTX-M1, blaSHV, and blaTEM) in Salmonella strains isolated from native chicken carcasses in Egypt marketed in Mansoura, Egypt, as well as spotlight the risk of isolated MDR, colistin-, cefepime-, and levofloxacin-resistant Salmonella enterica serovars to public health. METHODS: One hundred fifty freshly dressed native chicken carcasses were collected from different poultry shops in Mansoura City, Egypt between July 2022 and November 2022. Salmonella isolation was performed using standard bacteriological techniques, including pre-enrichment in buffered peptone water (BPW), selective enrichment in Rappaport Vassiliadis broth (RVS), and cultivating on the surface of xylose-lysine-desoxycholate (XLD) agar. All suspected Salmonella colonies were subjected to biochemical tests, serological identification using slide agglutination test, and Polymerase Chain Reaction (PCR) targeting the invasion A gene (invA; Salmonella marker gene). Afterward, all molecularly verified isolates were screened for the presence of virulence genes (stn and spvC). The antimicrobial susceptibility testing for isolated Salmonella strains towards the 16 antimicrobial agents tested was analyzed by Kirby-Bauer disc diffusion method, except for colistin, in which the minimum inhibition concentration (MIC) was determined by broth microdilution technique. Furthermore, 82 cefotaxime-resistant Salmonella isolates were tested using multiplex PCR targeting the ß-lactamase resistance genes, including blaOXA, blaCTX-M1, blaSHV, and blaTEM genes. RESULTS: Salmonella enterica species were molecularly confirmed via the invA Salmonella marker gene in 18% (27/150) of the freshly dressed native chicken carcasses. Twelve Salmonella serotypes were identified among 129 confirmed Salmonella isolates with the most predominant serotypes were S. Kentucky, S. Enteritidis, S. Typhimurium, and S. Molade with an incidence of 19.4% (25/129), 17.1% (22/129), 17.1% (22/129), and 10.9% (14/129), respectively. All the identified Salmonella isolates (n = 129) were positive for both invA and stn genes, while only 31.8% (41/129) of isolates were positive for the spvC gene. One hundred twenty-one (93.8%) of the 129 Salmonella-verified isolates were resistant to at least three antibiotics. Interestingly, 3.9%, 14.7%, and 75.2% of isolates were categorized into pan-drug-resistant, extensively drug-resistant, and multidrug-resistant, respectively. The average MAR index for the 129 isolates tested was 0.505. Exactly, 82.2%, 82.2%, 63.6%, 51.9%, 50.4%, 48.8%, 11.6%, and 10.1% of isolated Salmonella strains were resistant to cefepime, colistin, cefotaxime, ceftazidime/clavulanic acid, levofloxacin, ciprofloxacin, azithromycin, and meropenem, respectively. Thirty-one out (37.8%) of the 82 cefotaxime-resistant Salmonella isolates were ß-lactamase producers with the blaTEM as the most predominant ß-lactamase resistance gene, followed by blaCTX-M1 and blaOXA genes, which were detected in 21, 16, and 14 isolates respectively). CONCLUSION: The high prevalence of MDR-, colistin-, cefepime-, and levofloxacin-resistant Salmonella serovars among Salmonella isolates from native chicken is alarming as these antimicrobials are critically important in treating severe salmonellosis cases and boost the urgent need for controlling antibiotic usage in veterinary and human medicine to protect public health.

Antimicrobial resistance and its risks evaluation in wetlands on the Qinghai-Tibetan Plateau.

Amidst the global antimicrobial resistance (AMR) crisis, antibiotic resistance has permeated even the most remote environments. To understand the dissemination and evolution of AMR in minimally impacted ecosystems, the resistome and mobilome of wetlands across the Qinghai-Tibetan Plateau and its marginal regions were scrutinized using metagenomic sequencing techniques. The composition of wetland microbiomes exhibits significant variability, with dominant phyla including Proteobacteria, Actinobacteria, Bacteroidetes, and Verrucomicrobia. Notably, a substantial abundance of Antibiotic Resistance Genes (ARGs) and Mobile Genetic Elements (MGEs) was detected, encompassing 17 ARG types, 132 ARG subtypes, and 5 types of MGEs (Insertion Sequences, Insertions Sequences, Genomic Islands, Transposons, and Integrative Conjugative Elements). No significant variance was observed in the prevalence of resistome and mobilome across different wetland types (i.e., the Yellow River, other rivers, lakes, and marshes) (R=-0.5882, P=0.607). The co-occurrence of 74 ARG subtypes and 22 MGEs was identified, underscoring the pivotal role of MGEs in shaping ARG pools within the Qinghai-Tibetan Plateau wetlands. Metagenomic binning and analysis of assembled genomes (MAGs) revealed that 93 out of 206 MAGs harbored ARGs (45.15 %). Predominantly, Burkholderiales, Pseudomonadales, and Enterobacterales were identified as the primary hosts of these ARGs, many of which represent novel species. Notably, a substantial proportion of ARG-carrying MAGs also contained MGEs, reaffirming the significance of MGEs in AMR dissemination. Furthermore, utilizing the arg_ranker framework for risk assessment unveiled severe contamination of high-risk ARGs across most plateau wetlands. Moreover, some prevalent human pathogens were identified as potential hosts for these high-risk ARGs, posing substantial transmission risks. This study aims to investigate the prevalence of resistome and mobilome in wetlands, along with evaluating the risk posed by high-risk ARGs. Such insights are crucial for informing environmental protection strategies and facilitating the management of water resources on the Qinghai-Tibetan Plateau.

Effect of meddling ARBs on ARGs dynamics in fungal infested soil and their selective dispersal along spatially distant mycelial networks.

During the recent times, environmental antibiotic resistance genes (ARGs) and their potential transfer to other bacterial hosts of pathogenic importance are of serious concern. However, the dissemination strategies of such ARGs are largely unknown. We tested that saprotrophic soil fungi differentially enriched antibiotic resistant bacteria (ARBs) and subsequently contributed in spatial distribution of selective ARGs. Wafergen qPCR analysis of 295 different ARGs was conducted for manure treated pre-sterilized soil incubated or not with selected bacterial-fungal consortia. The qPCR assay detected unique ARGs specifically found in the mycosphere of ascomycetous and basidiomycetous fungi. Both fungi exerted potentially different selection pressures on ARBs, resulting in different patterns of ARGs dissemination (to distant places) along their respective growing fungal highways. The relative abundance of mobile genetic elements (MGEs) was significantly decreased along fungal highways compared to the respective inoculation points. Moreover, the decrease in MGEs and ARGs (along fungal highways) was more prominent over time which depicts the continuous selection pressure of growing fungi on ARBs for enrichment of particular ARGs in mycosphere. Such data also indicate the potential role of saprotrophic soil fungi to facilitate horizontal gene transfer within mycospheric environmental settings. Our study, therefore, advocates to emphasize the future investigations for such (bacteria-fungal) interactive microbial consortia for potential (spatial) dissemination of resistance determinants which may ultimately increase the exposure risks of ARGs.

Determining a future policy focus to support antimicrobial stewardship in community pharmacy: A modified Delphi study.

Background: Over the past decade, the pharmacy sector's policy, academic and professional spheres have increasingly drawn attention to the opportunities to better leverage the untapped potential of the community pharmacy sector in contributing to global efforts to reduce antimicrobial resistance (AMR). While efforts are in train, progress is slow. Objective: To draw insights from global experts in the field to identify a broad range of potential future policy directions to support community pharmacists' involvement in antimicrobial stewardship (AMS). Methods: A modified Delphi technique, comprising two survey rounds to build consensus amongst global community pharmacy sector stakeholders and opinion leaders. In Round 1, participants rated their level of agreement with 28 statements across the three domains of policy design, implementation design, and monitoring and evaluation. Participants were also invited to contribute feedback in Round 1, which was reflected as new statements (n = 10) in Round 2. In Round 2, participants were asked to re-assess Round 1 statements in view of the group consensus and to rate the new statements. Results: 289 participants were invited to participate. 48/289 (17% response rate) completed Round 1, and 25/42 (60% response rate) completed Round 2. Consensus (defined as >70% agreement) was achieved for 79% (n = 30) of the statements across the three domains. Conclusion: Pharmacy sector experts agreed that acknowledging community pharmacists in AMS national action plans is an important component, signalling a recognition of the sector's contribution to whole-of-nation AMS efforts. Implementation components that achieved consensus reflect the profession's evolution to a professional service driven model, particularly in complementary AMS initiatives including infection prevention and control measures. Context-specific adjustments to support implementing these AMS measures will be required, in addition to striking the appropriate balance to support the pace of increased community pharmacists'involvement in AMS with building whole-of-profession buy-in.

Antimicrobial resistance in China across human, animal, and environment sectors - a review of policy documents using a governance framework.

Antimicrobial resistance (AMR) poses a multifaceted threat to the human, animal, and environment sectors. In response, China has formulated a series of policies since the 2000s. Thus far, there has been no comprehensive assessment of these policy documents. This study aims to review the content of AMR policy documents at the national level using a governance framework covering three areas: Policy Design; Implementation Tools; and Monitoring and Evaluation. We identified 44 AMR documents from 2003 to 2022 sourced from government agency websites. Our findings have revealed noticeable discrepancies across the three governance areas. The Policy Design and Monitoring and Evaluation areas should be strengthened, particularly in the domains of 'Coordination', 'Accountability', 'Sustainability', and 'Effectiveness'. From a 'One Health' perspective, the environment sector has received less attention compared to the human and animal sectors. Effectively addressing these challenges requires a stronger commitment and widespread support from diverse stakeholders.

Patient characteristics and antimicrobial susceptibility profiles of Escherichia coli and Klebsiella pneumoniae infections in international travellers: a GeoSentinel analysis.

BACKGROUND: Antimicrobial resistance (AMR) is a global health crisis, with Enterobacterales including Escherichia coli and Klebsiella pneumoniae playing significant roles. While international travel to low- and middle-income countries is linked to colonisation with AMR Enterobacterales, the clinical implications, particularly the risk of subsequent infection, remain unclear due to limited data. We aimed to characterise E. coli and K. pneumoniae infections in travellers and the antimicrobial susceptibility profiles of their isolates. METHODS: We analysed data on E. coli and K. pneumoniae infections in travellers collected at GeoSentinel sites between 2015 and 2022, focusing on epidemiological, clinical and microbiological characteristics. We defined multi-drug resistance (MDR) as non-susceptibility to agents from at least three drug classes. RESULTS: Over the 8-year period, we included 655 patients (median age 41 years; 74% female) from 57 sites in 27 countries, with 584 E. coli and 72 K. pneumoniae infections. Common travel regions included Sub-Saharan Africa, Southeast Asia, and South-Central Asia. Urinary tract infections predominated. Almost half (45%) were hospitalised. Among infections with antimicrobial susceptibility data across three or more drug classes, 203/544 (37%) E. coli and 19/67 (28%) K. pneumoniae demonstrated MDR. Over one-third of E. coli and K. pneumoniae isolates were non-susceptible to third-generation cephalosporins and cotrimoxazole, with 38% and 28% non-susceptible to fluoroquinolones, respectively. Travellers to South-Central Asia most frequently had isolates non-susceptible to third-generation cephalosporins, fluoroquinolones and carbapenems. We observed increasing frequencies of phenotypic extended spectrum beta-lactamase and carbapenem resistance over time. CONCLUSIONS: E. coli and K. pneumoniae infections in travellers, particularly those to Asia, may be challenging to empirically treat. Our analysis highlights the significant health risks these infections pose to travellers and emphasises the escalating global threat of AMR. Enhanced, systematic AMR surveillance in travellers is needed, along with prospective data on infection risk post travel-related AMR organism acquisition.

Epidemiology and antimicrobial resistance of Mycobacterium spp. in the United Arab Emirates: a retrospective analysis of 12 years of national antimicrobial resistance surveillance data.

Introduction: The Eastern Mediterranean Regional Office (EMRO) region accounts for almost 8% of all global Mycobacterium tuberculosis (TB) cases, with TB incidence rates ranging from 1 per 100,000 per year in the United Arab Emirates (UAE) to 204 per 100,000 in Djibouti. The national surveillance data from the Middle East and North Africa (MENA) region on the epidemiology and antimicrobial resistance trends of TB, including MDR-TB remains scarce. Methods: A retrospective 12-year analysis of N = 8,086 non-duplicate diagnostic Mycobacterium tuberculosis complex (MTB complex) isolates from the UAE was conducted. Data were generated through routine patient care during the 2010-2021 years, collected by trained personnel and reported by participating surveillance sites to the UAE National Antimicrobial Resistance (AMR) Surveillance program. Data analysis was conducted with WHONET, a windows-based microbiology laboratory database management software developed by the World Health Organization Collaborating Center for Surveillance of Antimicrobial Resistance, Boston, United States (https://whonet.org/). Results: A total of 8,086 MTB-complex isolates were analyzed. MTB-complex was primarily isolated from respiratory samples (sputum 80.1%, broncho-alveolar lavage 4.6%, pleural fluid 4.1%). Inpatients accounted for 63.2%, including 1.3% from ICU. Nationality was known for 84.3% of patients, including 3.8% Emiratis. Of UAE non-nationals, 80.5% were from 110 countries, most of which were Asian countries. India accounted for 20.8%, Pakistan 13.6%, Philippines 12.7%, and Bangladesh 7.8%. Rifampicin-resistant MTB-complex isolates (RR-TB) were found in 2.8% of the isolates, resistance to isoniazid, streptomycin, pyrazinamide, and ethambutol, was 8.9, 6.9, 3.4 and 0.4%, respectively. A slightly increasing trend of resistance among MTB-complex was observed for rifampicin from 2.5% (2010) to 2.8% (2021). Conclusion: Infections due to MTB-complex are relatively uncommon in the United Arab Emirates compared to other countries in the MENA region. Most TB patients in the UAE are of Asian origin, mainly from countries with a high prevalence of TB. Resistance to first line anti-tuberculous drugs is generally low, however increasing trends for MDR-TB mainly rifampicin linked resistance is a major concern. MDR-TB was not associated with a higher mortality, admission to ICU, or increased length of hospitalization as compared to non-MDR-TB.