Universal access to safe water, whether at households or health centres, is central to achieving the sixth sustainable development goal by 2030. A hospital-based survey was conducted to screen for antimicrobial resist...Universal access to safe water, whether at households or health centres, is central to achieving the sixth sustainable development goal by 2030. A hospital-based survey was conducted to screen for antimicrobial resistance among coliforms in samples collected from tap water (n = 54) at surgical wards in Gaza and to investigate the association with free residual chlorine and pH levels. Total coliforms (TC) were detected in 48.1% (26/54) of tested samples and FCs were detected in 25.9% (14/54). Free residual chlorine test ranged from zero to 0.2 mg/l (average: 0.08 mg/l), of which more than half of the samples (53.7%) 29/54 showed no free residual chlorine. The mean value of free residual chlorine in samples tested positive for growth on m-Endo (0.03) was lower than the mean for negative samples (0.14). The pH values were within the acceptable range (average: 7.6) and there was a statistically significant variation between the mean of pH values for samples tested positive on m-Endo (7.29) and that tested negative (7.84). Among coliform positive samples, 23.1% (6/26) had coliform isolates with resistance patterns. More than two-thirds of antimicrobial resistant (AMR) isolates were resistant to amikacin, ceftazidime, ceftriaxone, and imipenem. Moreover, 50% of the isolates were resistant to piperacillin-tazobactam. One-third (33.3%) of isolates were resistant to cefoxitin, and fosfomycin, 16.7% were resistant to ciprofloxacin, and nitrofurantoin. Intermediate resistance was shown in 16.7% of the isolates to cefoxitin and ciprofloxacin. The ESBL and carbapenem resistance genes detected in isolates were TEM (66.7%), NDM (33.3%), OXA (25%), blaCTXM (16.7%), and blaCTXM-3 (16.7%). The finding highlighted the level of contamination with AMR coliform in samples collected from tap water and pointed out the importance of managing water safety through identifying the main source of contamination, in addition to maintaining proper water disinfection at healthcare facilities for the patient, staff and environmental safety.展开更多
Economic losses and market constraints caused by bacterial diseases such as colibacillosis due to avian pathogenic Escherichia coli and necrotic enteritis due to Clostridium perfringens remain major problems for poult...Economic losses and market constraints caused by bacterial diseases such as colibacillosis due to avian pathogenic Escherichia coli and necrotic enteritis due to Clostridium perfringens remain major problems for poultry producers,despite substantial efforts in prevention and control.Antibiotics have been used not only for the treatment and prevention of such diseases,but also for growth promotion.Consequently,these practices have been linked to the selection and spread of antimicrobial resistant bacteria which constitute a significant global threat to humans,ani-mals,and the environment.To break down the antimicrobial resistance(AMR),poultry producers are restricting the antimicrobial use(AMU)while adopting the antibiotic-free(ABF)and organic production practices to satisfy consum-ers’demands.However,it is not well understood how ABF and organic poultry production practices influence AMR profiles in the poultry gut microbiome.Various Gram-negative(Salmonella enterica serovars,Campylobacter jejuni/coli,E.coli)and Gram-positive(Enterococcus spp.,Staphylococcus spp.and C.perfringens)bacteria harboring multiple AMR determinants have been reported in poultry including organically-and ABF-raised chickens.In this review,we discussed major poultry production systems(conventional,ABF and organic)and their impacts on AMR in some potential pathogenic Gram-negative and Gram-positive bacteria which could allow identifying issues and opportuni-ties to develop efficient and safe production practices in controlling pathogens.展开更多
Antimicrobial resistance in the laying hen production industry has become a serious public health problem.The antimicrobial resistance and phylogenetic relationships of the common conditional pathogen Enterococcus alo...Antimicrobial resistance in the laying hen production industry has become a serious public health problem.The antimicrobial resistance and phylogenetic relationships of the common conditional pathogen Enterococcus along the laying hen production chain have not been systematically clarified.105 Enterococcus isolates were obtained from 115 environmental samples (air,dust,feces,fies,sewage,and soil) collected along the laying hen production chain (breeding chicken,chick,young chicken,and commercial laying hen).These Enterococcus isolates exhibited resistance to some clinically relevant antibiotics,such as tetracycline (92.4%),streptomycin (92.4%),and erythromycin (91.4%),and all strains had multidrug resistance phenotypes.Whole genome sequencing characterized 29 acquired antibiotic resistance genes (ARGs) that conferred resistance to 11 classes of antibiotics in 51pleuromutilin-resistant Enterococcus isolates,and lsa(E),which mediates resistance to pleuromutilins,always co-occurred with lnu(B).Alignments with the Mobile Genetic Elements database identified four transposons (Tn554,Tn558,Tn6261,and Tn6674) with several ARGs(erm(A),ant(9)-la,fex(A),and optrA) that mediated resistance to many clinically important antibiotics.Moreover,we identified two new transposons that carried ARGs in the Tn554 family designated as Tn7508 and Tn7492.A complementary approach based on conventional multi-locus sequence typing and whole genome single nucleotide polymorphism analysis showed that phylogenetically related pleuromutilin-resistant Enterococcus isolates were widely distributed in various environments on different production farms.Our results indicate that environmental contamination by antimicrobial-resistant Enterococcus requires greater attention,and they highlight the risk of pleuromutilin-resistant Enterococcus and ARGs disseminating along the laying hen production chain,thereby warranting effective disinfection.展开更多
Objective:To determine the clinical distribution of multi-drug resistant organism(MDRO)in Jiangyan Hospital and the monitoring and warning of drug-resistance bacteria to provide an important basis for guiding the appl...Objective:To determine the clinical distribution of multi-drug resistant organism(MDRO)in Jiangyan Hospital and the monitoring and warning of drug-resistance bacteria to provide an important basis for guiding the application of broad-spectrum antibiotics in clinical treatment and reducing the occurrence of nosocomial infection.Methods:Retrospective screening and analysis were conducted on the pathogenic strains of hospitalized patients in our hospital in 2022.Results:A total of 2,769 strains of pathogenic bacteria and 390 strains of MDRO were detected and isolated in our hospital in 2022;the detection rate of MDRO was 14.08%.A total of 516 strains(18.64%)Klebsiella pneumoniae(KP)and 62 strains(12.02%)of carbapenem-resistant Klebsiella pneumoniae(CR-KP)were detected;436 strains(15.75%)of Escherichia coli(ECO)were detected,including 8 strains(1.83%)of CR-ECO;342 strains(12.35%)of Pseudomonas aeruginosa(PA)and 116 strains(33.92%)of CR-PA were detected;there were 194 strains(7.01%)of Acinetobacter baumannii(AB),among which 125 strains(64.43%)were CR-AB;there were 291 strains(10.51%)of Staphylococcus aureus,among which 79 strains(27.15%)of methicillin-resistant Staphylococcus aureus(MRSA)were detected;78 strains(2.82%)of Enterococcus faecalis were detected,and vancomycin-resistant enterococcus(VRE)was not detected.The first five MDROs were CR-AB,CR-PA,MRSA,CR-KP,and CR-ECO.The top five departments with the highest MDRO detection rate in 2022 were the ICU(37.44%),the Pulmonology Department(ward 13;31.03%),the Department of Rehabilitation(ward 5;6.67%),the Department of Neurosurgery(ward 11;4.62%),and the Department of General Surgery(ward 10;3.59 The resistance rate of antibacterial drugs is divided into four levels for early warning:30%to 40%,41%to 50%,51%to 75%,and 75%or more.Conclusion:Our hospital should strengthen the monitoring of antimicrobial resistance warning related to MDRO and the abuse of antimicrobial drugs.Based on the results of drug sensitivity and antimicrobial resistance warning,the use of antibiotics should be standardized in clinical practice to reduce nosocomial infection。展开更多
BACKGROUND In the absence of effective antimicrobials,transplant surgery is not viable,and antirejection immunosuppressants cannot be administered,as resistant infections compromise the life-saving goal of organ trans...BACKGROUND In the absence of effective antimicrobials,transplant surgery is not viable,and antirejection immunosuppressants cannot be administered,as resistant infections compromise the life-saving goal of organ transplantation.AIM To evaluate the efficacy of antimicrobials in preventing resistance in solid organ transplant recipients.METHODS A systematic review was conducted using a search methodology consistent with the preferred reporting items for systematic reviews and meta-analyses.This review included randomized clinical trials that evaluated the efficacy of antimicrobial agents(prophylactic or therapeutic)aimed at preventing antimicrobial resistance.The search strategy involved analyzing multiple databases,including PubMed/MEDLINE,Web of Science,Embase,Scopus,and SciELO,as well as examining gray literature sources on Google Scholar.A comprehensive electronic database search was conducted from the databases’inception until May 2024,with no language restrictions.RESULTS After the final phase of the eligibility assessment,this systematic review ultimate-ly included 7 articles.A total of 2318 patients were studied.The most studied microorganisms were cytomegalovirus,although vancomycinresistant enterococci,Clostridioides difficile,and multidrug-resistant Enterobacterales were also analyzed.The antimicrobials used in the interventions were mainly maribavir,valganciclovir,gancic-lovir,and colistin-neomycin.Of concern,all clinical trials showed significant proportions of resistant microorga-nisms after the interventions,with no statistically significant differences between the groups(mean resistance 13.47%vs 14.39%),except for two studies that demonstrated greater efficacy of maribavir and valganciclovir(mean resistance 22.2%vs 41.1%in the control group;P<0.05).The total reported deaths in three clinical trials were 75,and there were 24 graft rejections in two studies.CONCLUSION All clinical trials reported significant proportions of antimicrobial-resistant microorganisms following interventions.More high-quality randomized clinical trials are needed to corroborate these results.展开更多
TEM and SHV are among the most prevalentβ-lactamases contributing toβ-lactam antibiotic resistance in clinical settings,leading to treatment challenges and increased mortality rates.Except for penicillin and early c...TEM and SHV are among the most prevalentβ-lactamases contributing toβ-lactam antibiotic resistance in clinical settings,leading to treatment challenges and increased mortality rates.Except for penicillin and early cephalosporins,TEM and SHV variants have evolved with the ability to hydrolyze the second-and third-generation cephalosporins,monobactams,and evenβ-lactamase inhibitors.Accurate detection ofβ-lactamases is of paramount importance for optimizing antibiotic use and combating antimicrobial resistance(AMR).While genetic detection methods,such as polymerase chain reaction(PCR),are widely employed,their positive results may lack phenotypic correlation due to the low or absent expression of blaSHV and blaTEM in many strains[1].Therefore,a direct protein-level detection method such as targeted proteomics is more precise and clinically relevant.This study highlights the development of a rapid detection method using targeted proteomics with high-resolution accurate mass(HRAM)Orbitrap MS for the direct detection of TEM and SHV in Enterobacteriaceae strains,which offers greater clinical relevance compared to conventional genetic approaches.展开更多
Antimicrobial resistance(AMR)has become a critical global public health challenge in the 21st century.Since the initial isolation of a blaNDM-1-carrying and carbapenem-resistant Klebsiella pneumoniae from an Indian ho...Antimicrobial resistance(AMR)has become a critical global public health challenge in the 21st century.Since the initial isolation of a blaNDM-1-carrying and carbapenem-resistant Klebsiella pneumoniae from an Indian hospital in 2009[1],the escalating prevalence of New Delhi metallo-β-lactamase(NDM)-encoding genes(blaNDM)has transformed carbapenem resistance into a worldwide phenomenon,transcending national and regional boundaries[2].Up to 90 distinct NDM variants have been reported globally according to the NCBI GenBank Pathogens database.Plasmidmediated horizontal gene transfer(HGT),which occurs both within and across bacterial species,has significantly accelerated the global dissemination of blaNDM-related genes and the associated resistance[3].Carbapenem-resistant pathogens were responsible for 200,000 deaths globally in 2019[4].Although NDM-1 has been relatively well characterized[5],the epidemiological profiles of other NDM variants require continued surveillance and indepth investigation.The novel NDM-9 variant(GenBank accession no.KC999080)was first identified in 2013 from a clinically significant isolate of Klebsiella pneumoniae ST107 strain PPH1303 with a high level of resistance to carbapenems recovered from the urine culture of a pediatric patient in Beijing,China,who had acute lymphocytic leukemia and had undergone allogeneic stem cell transplantation[6].展开更多
Background: The irrational use of medicines remains a key health problem in many developing countries. The overuse of antibiotics is a key driver of antimicrobial resistance (AMR). This study surveyed antibiotic use a...Background: The irrational use of medicines remains a key health problem in many developing countries. The overuse of antibiotics is a key driver of antimicrobial resistance (AMR). This study surveyed antibiotic use and adherence to the World Health Organization (WHO) prescribing indicators at the Request Muntanga Hospital in the Kalomo District of Southern Province, Zambia. Materials and Methods: This cross-sectional study was conducted from July 2023 to September 2023 at Request Muntanga Hospital in Zambia and reviewed 600 medical record prescriptions which were issued from July 1, 2022 to June 30, 2023 using the WHO prescribing indicators. The collected data were analyzed using Statistical Package for Social Sciences version 23.0. Results: From the 600 prescriptions sampled, 1246 medicines were prescribed, with antibiotics making up 86.7% of the encounters. Additionally, the average number of drugs prescribed per encounter was 2.1 and the prevalence of polypharmacy was 61.3%. Further, 17.8% of medicines were prescribed as injectables. Furthermore, 76.7% of the drugs were prescribed from the Zambia Essential Medicines List and 38.9% by generic names. Conclusions: This study found a high use of antibiotics and deviations from the WHO/International Network of Rational Use of Drugs (INRUD) core prescribing indicators at the Request Muntanga Hospital indicating non-adherence to the prescribing indicators. There is a need to promote adherence to the WHO/INRUD core prescribing indicators to promote the rational use of antibiotics and prevent the emergence and spread of AMR.展开更多
The One Health concept acknowledges the importance of multiple dimensions in controlling antimicrobial resistance(AMR).However,our understanding of how anthropological,socioeconomic,and environmental factors drive AMR...The One Health concept acknowledges the importance of multiple dimensions in controlling antimicrobial resistance(AMR).However,our understanding of how anthropological,socioeconomic,and environmental factors drive AMR at a national level remains limited.To explore associations between potential contributing factors and AMR,this study analyzed an extensive database comprising 13 major antibioticresistant bacteria and over 30 predictors(e.g.,air pollution,antibiotic usage,economy,husbandry,public services,health services,education,diet,climate,and population)from 2014 to 2020 across China.The multivariate analysis results indicate that fine particulate matter with a diameter of 2.5 μm or less(PM_(2.5))is associated with AMR,accounting for 12%of the variation,followed by residents’income(10.3%)and antibiotic usage density(5.1%).A reduction in PM_(2.5)of 1 μg·m^(-3)is linked to a 0.17%decrease in aggregate antibiotic resistance(p<0.001,R^(2)=0.74).Under different scenarios of China’s PM_(2.5)airquality projections,we further estimated the premature death toll and economic burden derived from PM_(2.5)-related antibiotic resistance in China until 2060.PM_(2.5)-derived AMR is estimated to cause approximately 27000(95%confidence interval(CI):646848830)premature deaths and about 0.51(95%CI;0.12-0.92)million years of life lost annually in China,equivalent to an annual welfare loss of 8.4(95%CI;2.0-15.0)billion USD.Implementing the“Ambitious Pollution 1.5℃ Goals”scenario to reduce PM_(2.5)concentrations could prevent roughly 14000(95%CI;3324-26320)premature deaths—with a potential monetary value of 9.8(95%CI;2.2-17.6)billion USD—from AMR by 2060.These results suggest that reducing air pollution may offer co-benefits in the health and economic sectors by mitigating AMR.展开更多
Background:Antimicrobial resistance(AMR)poses a significant and growing public health challenge in East and Southern Africa.Despite formal commitments to the National Action Plans,domestic financing for AMR remains cr...Background:Antimicrobial resistance(AMR)poses a significant and growing public health challenge in East and Southern Africa.Despite formal commitments to the National Action Plans,domestic financing for AMR remains critically limited,with most countries continuing to depend heavily on external donor funding.Objective:This narrative review examines the current extent to which domestic fiscal commitments align with national AMR policy goals across the two regions.Methods:Government websites for ministries of health and finance,donor platforms,and three academic databases(Scopus,JSTOR,Google Scholar)were searched for eligible articles.National budget statements and media reports were also reviewed where available.Three researchers independently screened titles and summaries,followed by full-text reviews to confirm eligibility.Results:The findings reveal that while several countries have developed National Action Plans,very few have allocated domestic funding to implement them.Only Malawi,Nigeria and Uganda reported modest domestic contributions,while in other countries such as Zambia,Ethiopia,and South Africa,AMR programs remain largely donor-financed or lack dedicated budget lines altogether.Veterinary and laboratory sectors are particularly underfunded,with minimal integration into broader AMR strategies.While this review has several limitations including restricted access to current,comprehensive national budget data and a reliance on secondary sources such as donor and World Health Organization reports,which may introduce bias,the patterns identified in this review still offer valuable insight into regional funding dynamics and can inform future policy and research efforts.Conclusion:We conclude that without dedicated domestic financing and accountability mechanisms,AMR efforts in the region may face significant sustainability challenges observed in other health responses such as human immunodeficiency virus.Strengthening AMR governance requires clear budgetary commitments,sustainable cofinancing models,and policy instruments to reduce dependency on external support.展开更多
The rapid emergence of drug-resistant microbial pathogens has posed challenges to global health in the twenty-first century.This development has significantly made most antibiotics ineffective in the treatment of infe...The rapid emergence of drug-resistant microbial pathogens has posed challenges to global health in the twenty-first century.This development has significantly made most antibiotics ineffective in the treatment of infections they cause,resulting in increasing treatment costs and annual death rates.To address the challenge posed by these pathogens,we explore the potential of secondary metabolites from Aspergillus species as a source of new and effective therapeutic agents to treat drug-resistant infections.Terpenoids,a distinct group of natural products,are extensively distributed in plants and fungi,and have been attributed with significant antibacterial,anticancer,and antiviral activities.In this review,we present an overview of Aspergillus species,and review the novel terpenoids isolated from them from 2019 to April 2024,highlighting anti-infective activity against members of the ESKAPE pathogens.We further focus on the strategies through which the structural framework of these new terpenoids could be modified and/or optimized to feed a pipeline of new lead compounds targeting microbial pathogens.Overall,this review provides insight into the therapeutic applications of terpenoids sourced from Aspergillus species and the potential for the discovery of new compounds from these fungi to combat antimicrobial resistance.展开更多
Background:Community-acquired bacterial pneumonia(CABP)poses a serious public health threat,particularly with the emergence of drug-resistant bacterial strains.This study aims to investigate the molecular interactions...Background:Community-acquired bacterial pneumonia(CABP)poses a serious public health threat,particularly with the emergence of drug-resistant bacterial strains.This study aims to investigate the molecular interactions of Nafithromycin(Miqnaf®),India’s first indigenous next-generation macrolide antibiotic,and evaluate its potential against Streptococcus pneumoniae,a key pathogen responsible for CABP.Targeting 23S rRNA is critical for overcoming antibiotic resistance since it is involved in bacterial protein production.Many antibiotics,including macrolides target this rRNA.Mutations in 23S rRNA frequently result in resistance;therefore,designing medicines that bind new or conserved areas of 23S rRNA can circumvent current resistance mechanisms and restore antibiotic potency.Nafithromycin has excellent therapeutic potential,with a short three-day regimen and much higher efficacy than conventional macrolides.Its high lung tissue penetration and robust effectiveness against drug-resistant respiratory bacteria make it a promising next-generation antibiotic.Methods:To elucidate the interaction of Nafithromycin with bacterial ribosomal RNA,molecular docking studies were performed using AutoDock Vina.The three-dimensional structure of Streptococcus pneumoniae 23S rRNA was retrieved from the Protein Data Bank(PDB).The ligand structure of Nafithromycin was obtained from the PubChem database and prepared using Open Babel.Docking simulations targeted key functional regions-Domains II and V of 23S rRNA-known to be critical for bacterial protein synthesis.Binding affinities were calculated,and molecular interactions such as hydrogen bonds,hydrophobic contacts,and conformational stabilities were analyzed using Discovery Studio and PyMOL.Results:Nafithromycin exhibited a high binding affinity of-10.3 kcal/mol toward S.pneumoniae 23S rRNA.The compound formed stable interactions with both Domain II and Domain V,crucial regions involved in the inhibition of bacterial protein synthesis.Hydrogen bonding and hydrophobic interactions further stabilized the ligand-receptor complex.Compared to azithromycin,Nafithromycin demonstrated superior binding efficacy and a greater potential to inhibit resistant bacterial strains,indicating its structural advantages and enhanced ribosomal targeting.Conclusion:Nafithromycin demonstrates significant potential as a potent therapeutic agent against drug-resistant CABP.Its strong binding affinity,stable interactions with bacterial rRNA,favorable pharmacokinetic profile,and reduced resistance risk support its clinical utility and suggest its advantage over traditional macrolide antibiotics such as azithromycin.展开更多
BACKGROUND Sepsis is a critical medical condition,and poses a substantial global health burden,with significant morbidity,mortality,and economic costs,particularly pronounced in low-and middle-income countries.Effecti...BACKGROUND Sepsis is a critical medical condition,and poses a substantial global health burden,with significant morbidity,mortality,and economic costs,particularly pronounced in low-and middle-income countries.Effective management of sepsis relies on early recognition and appropriate intervention,underscoring the importance of accurate classification to guide treatment decisions.The correct diagnosis will lead to effective antimicrobial stewardship practices.AIM To assess the distribution of sepsis categories and the use of empirical antibiotics classified by the World Health Organization(WHO)Access,Watch,and Reserve(AWaRe)system in a tertiary care hospital in Northern India and to correlate antibiotic usage with sepsis classifications.METHODS This longitudinal observational study in the Department of General Medicine,in a tertiary care hospital in Northern India,from 2023 to 2024,aimed to assess the use of empirical antibiotics classified by the WHO AWaRe system.The study also aimed to correlate antibiotic usage.Patients were categorized into sepsis classes(Asepsis,Possible Sepsis,Probable Sepsis,Confirmed Sepsis)and followed until discharge or Day-28.Descriptive and inferential statistical analyses were employed to assess sepsis categories and empirical antibiotic usage classified by the WHO AWaRe system.RESULTS A total of 1867 patients admitted with suspected sepsis were screened,with 230 meeting the inclusion criteria.Among the study cohort(mean age 40.70±14.49 years,50.9% female),initial sepsis classification predominantly included probable sepsis(51.3%)and possible sepsis(35.7%),evolving to asepsis(57.8%)upon final classification,but all received antibiotics.Empirical antibiotic use showed a predominance of Watch group antibiotics(72.2%),with ceftriaxone and piperacillin-tazobactam being the most commonly prescribed;however,no statistical association could be established among the different classes of sepsis with the AWaRe groups.CONCLUSION Accurate sepsis classification is pivotal for clinical decision-making,optimizing antibiotic use,and combating antimicrobial resistance.The majority of the asepsis category was labelled as probable or possible sepsis and given antibiotics at initial hospitalization.The high reliance on Watch group antibiotics in empirical therapy signals a need for enhanced diagnostic strategies to refine treatment initiation,potentially reducing unnecessary antibiotic exposure.Future efforts should focus on establishing sepsis classification checklists as in this study and promoting adherence to antimicrobial stewardship principles to mitigate the global threat of antimicrobial resistance.展开更多
BACKGROUND Outpatient parenteral antimicrobial therapy(OPAT)offers a crucial method for administering intravenous/intramuscular antimicrobials outside of hospital settings,allowing patients to complete treatment safel...BACKGROUND Outpatient parenteral antimicrobial therapy(OPAT)offers a crucial method for administering intravenous/intramuscular antimicrobials outside of hospital settings,allowing patients to complete treatment safely while avoiding many hospital-acquired complications.This is a major boost or low-hanging fruit intervention in antimicrobial stewardship practices with multiple targets like decreasing hospital stays,its related complications,the economy,the burden on hospitals,etc.However,resource-constrained countries like India practices rarely OPAT in an evidence-based way.AIM To evaluate the effectiveness,safety,and feasibility along with barriers and facilitators of OPAT practices in resource-poor settings,with a focus on its role in antimicrobial stewardship.METHODS This pilot longitudinal observational study included patients who met OPAT checklist criteria and were committed to post-discharge follow-up.Pre-discharge education and counselling were provided,and demographic data were recorded.Various outcome measures,including barriers and facilitators,were identified through an extensive literature review,fishbone diagram preparation,data collection and analysis,and patient feedback.All healthcare workers who were taking care of the patients discharged with OPAT were contacted with openended questions to get data on feasibility.The study was approved by the Institutional Ethics Committee of All India Institute of Medical Sciences,Rishikesh.We used descriptive analysis and theχ2 test to analyze data.P value<0.05 was considered significant.RESULTS Out of 20 patients,the mean age was 37 years.The cohort comprised 13 males.OPAT was administered at home in 15 cases and at nursing homes in 5 cases,with nine patients receiving treatment from family members and 11 patients receiving care from a local nurse.The infections requiring OPAT included:Kidney-urinary tract(6 cases),gastrointestinal tract(4 cases),respiratory tract(4 cases),meningitis(3 cases),endocarditis(2 cases),and multiple visceral abscesses(1 case).Nineteen out of 20 patients achieved afebrile status.Half of the patients did not receive education,counselling,or demonstrations prior to discharge,but all patients rated the service as good/excellent.According to doctors’feedback,OPAT is highly beneficial and effective for patients when systematically implemented with daily telephonic monitoring,but faces challenges due to the lack of standardized protocols,dedicated teams,and adequate resources.The implementation of OPAT resulted in a reduction of hospitalization duration by an average of two weeks.CONCLUSION This pilot study proves that OPAT is safe,feasible,and efficacious by reducing two weeks of hospitalization in resource-poor settings.OPAT contributes directly to antimicrobial stewardship by reducing hospital stays and hospital-acquired complications,which is vital in combating antimicrobial resistance(AMR)and aligns with the global action plan for AMR in infection prevention and optimal antimicrobial utilization.展开更多
Background: Antimicrobial Resistance (AMR) has been recognized as a global public health problem of utmost importance that needs to be tackled. Low-income countries such as Uganda have the greatest burden of severe an...Background: Antimicrobial Resistance (AMR) has been recognized as a global public health problem of utmost importance that needs to be tackled. Low-income countries such as Uganda have the greatest burden of severe and life-threatening infections and are most likely to suffer more from the spread of untreatable resistant bacteria. Despite the generally increasing trends in AMR, there is hardly any documented data on AMR in orthopedic care. Methods: We analyzed data from the pathogenic isolates from pus and tissue from the laboratory from 2019 to 2023. We calculated the proportions of isolates resistant to commonly used antimicrobial classes. We used the chi-square test for trends to evaluate changes in AMR across the study period. Results: Out of the 286 isolates, 104 (43.5%) were from pus, 112 (46.9%) were from tissue samples and the remaining 9.6% were from different fluid aspirates like synovial fluid. Most of the isolates were from males (64.2%) and aged between 19 and 45 years (46.2%). The distribution of whether the bacteria were gram-positive or negative was relatively equal with 114 (45.2%) being gram-negative and 120 (47.6%) gram-positive. Generally, there was increased AMR across all antibiotics from 2019 to 2021 e.g. for Imipinem, it went from 0% in 2019 to 70.8% in 2021 and for Amoxyclav, it went from 10% in 2019 to 93.2% in 2021. There was a general decline in AMR noted from 2021 to 2023. However, currently, the highest resistance is noted in ceftriaxone (80.0%) and the lowest in Imipinem (11.76%). Conclusion: There is a general decreasing trend in AMR, most probably due to increasing policies governing the use of antibiotics. However, there is still high resistance to commonly used and affordable antibiotics. Continuous monitoring of AMR is still recommended to reduce the AMR problem in Uganda at large through public health policy and planning.展开更多
The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR...The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR.However,their clinical translation is hindered by their inherently low immunogenicity,often requiring potent adjuvants and advanced delivery systems.Biomembrane nanostructures(e.g.,liposomes,exosomes,and cell membrane-derived nanostructures),characterized by superior biocompatibility,intrinsic targeting ability,and immune-modulating properties,could serve as versatile platforms that potentiate vaccine efficacy by increasing antigen stability,enabling codelivery of immunostimulants,and facilitating targeted delivery to lymphoid tissues/antigen-presenting cells.This intrinsic immunomodulation promotes robust humoral and cellular immune responses to combat bacteria.This review critically reviews(1)key biomembrane nanostructure classes for bacterial protein antigens,(2)design strategies leveraging biomembrane nanostructures to enhance humoral and cellular immune responses,(3)preclinical efficacy against diverse pathogens,and(4)translational challenges and prospects.Biomembrane nanostructure-driven approaches represent a paradigm shift in the development of next-generation bacterial protein vaccines against resistant infections.展开更多
This study was conducted to determine genetic diversity and antimicrobial susceptibility profiles of Staphylococcus aureus recovered from bovine mastiffs in Zhejiang Province, China. Out of 3178 quarter milk samples f...This study was conducted to determine genetic diversity and antimicrobial susceptibility profiles of Staphylococcus aureus recovered from bovine mastiffs in Zhejiang Province, China. Out of 3178 quarter milk samples from 846 lactating cows, among which 459 cows （54.3%） were found HMT positive, 890 quarters （28%） were found having subclinical mastitis. From 75 representative S. aureus isolates, 16 distinct types were identified by pulsed-field gel electrophoresis （PFGE）. Four major PFGE types （A, B, C, and D） accounted for 82.7% of all isolates, and type A （41.3%） was observed in multiple herds across the studied areas. Each region was found to have a predominant type： Hangzhou type A （64.1%）, Ningbo type C （34.5%） and type B （23.1%）, Jinhua type D （53.3%）, and Taizhou type C （62.5%）. Results of antimicrobial susceptibility tests showed that 90.7% of the isolates were resistant to at least one antimicrobial. Resistance to penicillin and ampicillin （77.3%）, tetracycline （60.0%）, or erythromycin （48.0%） was observed. The bacteria resistant to multiple antibiotics such as penicillin, ampicillin, tetracycline, and erythromycin were commonly found. The information obtained from this study is useful for designing specific control programs for bovine S. aureus mastitis in this region.展开更多
The management of Helicobacter pylori(H. pylori) infection treatment differs from the common treatment protocol for other infectious diseases. Because culture-or molecular-guided approaches face several practical issu...The management of Helicobacter pylori(H. pylori) infection treatment differs from the common treatment protocol for other infectious diseases. Because culture-or molecular-guided approaches face several practical issues, such as the invasive procedures required to obtain gastric biopsy specimens and the lack of availability of routine laboratory testing in some places, H. pylori treatment includes the administration of two or three empirically selected antibiotics combined with a proton pump inhibitor rather than evidence-based eradication treatment. The efficacy of empirical therapy is decreasing, mostly due to increasing multiple resistance. Multiresistance to levofloxacin, clarithromycin, and metronidazole, which are commonly used in empirical treatments, appears to have increased in many countries. Mutations play a primary role in the antimicrobial resistance of H. pylori, but many different mechanisms can be involved in the development of antibiotic resistance. Determining and understanding these possible mechanisms might allow the development of new methods for the detection of H. pylori and the determination of antimicrobial resistance. A treatment based on the detection of antimicrobial resistance is usually more effective than empirical treatment. Nevertheless, such an approach before treatment is still not recommended in the Maastricht guidelines due to the difficulty associated with the routine application of available cultureor molecular-based susceptibility tests, which are usually administered in cases of treatment failure. The management of first and rescue treatments requires further research due to the steadily increase in antimicrobial resistance.展开更多
Staphylococcus aureus is the most common etiological pathogen of bovine mastitis. The resistant strains make the disease difficult to cure. The aim of this study was to characterize the genetic nature of the antimicro...Staphylococcus aureus is the most common etiological pathogen of bovine mastitis. The resistant strains make the disease difficult to cure. The aim of this study was to characterize the genetic nature of the antimicrobial resistance in S. aureus cultured from bovine mastitis in Northwest China in 2014. A total of 44 S. aureus were isolated for antimicrobial resistance and resistance-related genes. Antimicrobial resistance was determined by disc diffusion and the corresponding resistance genes were detected by PCR. Phenotype indicated that S. aureus isolates were resistant to penicillin （84.09%）, erythromycin （20.45%）, tetracycline （15.91%）, gentamicin （9.09%）, tobramycin （6.82%）, kanamycin （6.82%） and methicillin （2.27%）. 9.09% of the S. aureus isolates were classified as multidrug resistant. In addition, genotypes showed that the isolates were resistant to rifampicin （100%, rpoB）, penicillin （95.45%, blaZ）, tetracycline （22.73%, tetK, tetM, alone or in combination）, erythromycin （22.73%, ermB or ermC）, gentamicin/tobramycin/kanamycin （2.27%, aacA-aphD）, methicillin （2.27%, mecA） and vancomycin （2.27%, vanA）. Resistance to tetracycline was attributed to the genes tetK and tetM （r=0.558, P〈0.001）. This study noted high-level geno- and phenotypic antimicrobial resistance in S. aureus isolates from bovine mastitis cases in Northwest China.展开更多
The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria.As an excellent candidate to overcome antibiotic resistance,antimicrobial pepti...The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria.As an excellent candidate to overcome antibiotic resistance,antimicrobial peptides(AMPs)that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity.These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action.This comprehensive review provides a broad overview of AMPs from the origin,structural characteristics,mechanisms of action,biological activities to clinical applications.We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.展开更多
文摘Universal access to safe water, whether at households or health centres, is central to achieving the sixth sustainable development goal by 2030. A hospital-based survey was conducted to screen for antimicrobial resistance among coliforms in samples collected from tap water (n = 54) at surgical wards in Gaza and to investigate the association with free residual chlorine and pH levels. Total coliforms (TC) were detected in 48.1% (26/54) of tested samples and FCs were detected in 25.9% (14/54). Free residual chlorine test ranged from zero to 0.2 mg/l (average: 0.08 mg/l), of which more than half of the samples (53.7%) 29/54 showed no free residual chlorine. The mean value of free residual chlorine in samples tested positive for growth on m-Endo (0.03) was lower than the mean for negative samples (0.14). The pH values were within the acceptable range (average: 7.6) and there was a statistically significant variation between the mean of pH values for samples tested positive on m-Endo (7.29) and that tested negative (7.84). Among coliform positive samples, 23.1% (6/26) had coliform isolates with resistance patterns. More than two-thirds of antimicrobial resistant (AMR) isolates were resistant to amikacin, ceftazidime, ceftriaxone, and imipenem. Moreover, 50% of the isolates were resistant to piperacillin-tazobactam. One-third (33.3%) of isolates were resistant to cefoxitin, and fosfomycin, 16.7% were resistant to ciprofloxacin, and nitrofurantoin. Intermediate resistance was shown in 16.7% of the isolates to cefoxitin and ciprofloxacin. The ESBL and carbapenem resistance genes detected in isolates were TEM (66.7%), NDM (33.3%), OXA (25%), blaCTXM (16.7%), and blaCTXM-3 (16.7%). The finding highlighted the level of contamination with AMR coliform in samples collected from tap water and pointed out the importance of managing water safety through identifying the main source of contamination, in addition to maintaining proper water disinfection at healthcare facilities for the patient, staff and environmental safety.
基金supported by Agriculture and Agri-Food Canada to M.S.Diarra through the Genomics Research and Development Initiative (PSS#1858 J-001262) and A-Base (PSS#3441,J-002363) projects on “Mitigating Antimicrobial Resistance”.
文摘Economic losses and market constraints caused by bacterial diseases such as colibacillosis due to avian pathogenic Escherichia coli and necrotic enteritis due to Clostridium perfringens remain major problems for poultry producers,despite substantial efforts in prevention and control.Antibiotics have been used not only for the treatment and prevention of such diseases,but also for growth promotion.Consequently,these practices have been linked to the selection and spread of antimicrobial resistant bacteria which constitute a significant global threat to humans,ani-mals,and the environment.To break down the antimicrobial resistance(AMR),poultry producers are restricting the antimicrobial use(AMU)while adopting the antibiotic-free(ABF)and organic production practices to satisfy consum-ers’demands.However,it is not well understood how ABF and organic poultry production practices influence AMR profiles in the poultry gut microbiome.Various Gram-negative(Salmonella enterica serovars,Campylobacter jejuni/coli,E.coli)and Gram-positive(Enterococcus spp.,Staphylococcus spp.and C.perfringens)bacteria harboring multiple AMR determinants have been reported in poultry including organically-and ABF-raised chickens.In this review,we discussed major poultry production systems(conventional,ABF and organic)and their impacts on AMR in some potential pathogenic Gram-negative and Gram-positive bacteria which could allow identifying issues and opportuni-ties to develop efficient and safe production practices in controlling pathogens.
基金supported by the National Key Research and Development Program of China (Nos.2022YFC2303900 and2022YFD1800400)the General Program of National Natural Science Foundation of China (Nos.U21A20257 and 31830098)+1 种基金the National System of Layer Production Technology (No.CARS-40-K-14)the Key R&D Program of Sichuan Province (Nos.2022ZDZX0017 and 2021YFH0192)。
文摘Antimicrobial resistance in the laying hen production industry has become a serious public health problem.The antimicrobial resistance and phylogenetic relationships of the common conditional pathogen Enterococcus along the laying hen production chain have not been systematically clarified.105 Enterococcus isolates were obtained from 115 environmental samples (air,dust,feces,fies,sewage,and soil) collected along the laying hen production chain (breeding chicken,chick,young chicken,and commercial laying hen).These Enterococcus isolates exhibited resistance to some clinically relevant antibiotics,such as tetracycline (92.4%),streptomycin (92.4%),and erythromycin (91.4%),and all strains had multidrug resistance phenotypes.Whole genome sequencing characterized 29 acquired antibiotic resistance genes (ARGs) that conferred resistance to 11 classes of antibiotics in 51pleuromutilin-resistant Enterococcus isolates,and lsa(E),which mediates resistance to pleuromutilins,always co-occurred with lnu(B).Alignments with the Mobile Genetic Elements database identified four transposons (Tn554,Tn558,Tn6261,and Tn6674) with several ARGs(erm(A),ant(9)-la,fex(A),and optrA) that mediated resistance to many clinically important antibiotics.Moreover,we identified two new transposons that carried ARGs in the Tn554 family designated as Tn7508 and Tn7492.A complementary approach based on conventional multi-locus sequence typing and whole genome single nucleotide polymorphism analysis showed that phylogenetically related pleuromutilin-resistant Enterococcus isolates were widely distributed in various environments on different production farms.Our results indicate that environmental contamination by antimicrobial-resistant Enterococcus requires greater attention,and they highlight the risk of pleuromutilin-resistant Enterococcus and ARGs disseminating along the laying hen production chain,thereby warranting effective disinfection.
文摘Objective:To determine the clinical distribution of multi-drug resistant organism(MDRO)in Jiangyan Hospital and the monitoring and warning of drug-resistance bacteria to provide an important basis for guiding the application of broad-spectrum antibiotics in clinical treatment and reducing the occurrence of nosocomial infection.Methods:Retrospective screening and analysis were conducted on the pathogenic strains of hospitalized patients in our hospital in 2022.Results:A total of 2,769 strains of pathogenic bacteria and 390 strains of MDRO were detected and isolated in our hospital in 2022;the detection rate of MDRO was 14.08%.A total of 516 strains(18.64%)Klebsiella pneumoniae(KP)and 62 strains(12.02%)of carbapenem-resistant Klebsiella pneumoniae(CR-KP)were detected;436 strains(15.75%)of Escherichia coli(ECO)were detected,including 8 strains(1.83%)of CR-ECO;342 strains(12.35%)of Pseudomonas aeruginosa(PA)and 116 strains(33.92%)of CR-PA were detected;there were 194 strains(7.01%)of Acinetobacter baumannii(AB),among which 125 strains(64.43%)were CR-AB;there were 291 strains(10.51%)of Staphylococcus aureus,among which 79 strains(27.15%)of methicillin-resistant Staphylococcus aureus(MRSA)were detected;78 strains(2.82%)of Enterococcus faecalis were detected,and vancomycin-resistant enterococcus(VRE)was not detected.The first five MDROs were CR-AB,CR-PA,MRSA,CR-KP,and CR-ECO.The top five departments with the highest MDRO detection rate in 2022 were the ICU(37.44%),the Pulmonology Department(ward 13;31.03%),the Department of Rehabilitation(ward 5;6.67%),the Department of Neurosurgery(ward 11;4.62%),and the Department of General Surgery(ward 10;3.59 The resistance rate of antibacterial drugs is divided into four levels for early warning:30%to 40%,41%to 50%,51%to 75%,and 75%or more.Conclusion:Our hospital should strengthen the monitoring of antimicrobial resistance warning related to MDRO and the abuse of antimicrobial drugs.Based on the results of drug sensitivity and antimicrobial resistance warning,the use of antibiotics should be standardized in clinical practice to reduce nosocomial infection。
文摘BACKGROUND In the absence of effective antimicrobials,transplant surgery is not viable,and antirejection immunosuppressants cannot be administered,as resistant infections compromise the life-saving goal of organ transplantation.AIM To evaluate the efficacy of antimicrobials in preventing resistance in solid organ transplant recipients.METHODS A systematic review was conducted using a search methodology consistent with the preferred reporting items for systematic reviews and meta-analyses.This review included randomized clinical trials that evaluated the efficacy of antimicrobial agents(prophylactic or therapeutic)aimed at preventing antimicrobial resistance.The search strategy involved analyzing multiple databases,including PubMed/MEDLINE,Web of Science,Embase,Scopus,and SciELO,as well as examining gray literature sources on Google Scholar.A comprehensive electronic database search was conducted from the databases’inception until May 2024,with no language restrictions.RESULTS After the final phase of the eligibility assessment,this systematic review ultimate-ly included 7 articles.A total of 2318 patients were studied.The most studied microorganisms were cytomegalovirus,although vancomycinresistant enterococci,Clostridioides difficile,and multidrug-resistant Enterobacterales were also analyzed.The antimicrobials used in the interventions were mainly maribavir,valganciclovir,gancic-lovir,and colistin-neomycin.Of concern,all clinical trials showed significant proportions of resistant microorga-nisms after the interventions,with no statistically significant differences between the groups(mean resistance 13.47%vs 14.39%),except for two studies that demonstrated greater efficacy of maribavir and valganciclovir(mean resistance 22.2%vs 41.1%in the control group;P<0.05).The total reported deaths in three clinical trials were 75,and there were 24 graft rejections in two studies.CONCLUSION All clinical trials reported significant proportions of antimicrobial-resistant microorganisms following interventions.More high-quality randomized clinical trials are needed to corroborate these results.
基金supported by the National Natural Science Foundation of China(Grant Nos.:32141003,82330110,and 81803593)the CAMS Innovation Fund for Medical Sciences(CIFMS),China(Grant Nos.:2021-I2M-1-030,and 2021-I2M-1-039)+1 种基金the Fundamental Research Funds for the Central Universities,China(Grant No.:3332018094)the National Science and Technology Infrastructure of China(Project No.:National Pathogen Resource Center-NPRC-32).
文摘TEM and SHV are among the most prevalentβ-lactamases contributing toβ-lactam antibiotic resistance in clinical settings,leading to treatment challenges and increased mortality rates.Except for penicillin and early cephalosporins,TEM and SHV variants have evolved with the ability to hydrolyze the second-and third-generation cephalosporins,monobactams,and evenβ-lactamase inhibitors.Accurate detection ofβ-lactamases is of paramount importance for optimizing antibiotic use and combating antimicrobial resistance(AMR).While genetic detection methods,such as polymerase chain reaction(PCR),are widely employed,their positive results may lack phenotypic correlation due to the low or absent expression of blaSHV and blaTEM in many strains[1].Therefore,a direct protein-level detection method such as targeted proteomics is more precise and clinically relevant.This study highlights the development of a rapid detection method using targeted proteomics with high-resolution accurate mass(HRAM)Orbitrap MS for the direct detection of TEM and SHV in Enterobacteriaceae strains,which offers greater clinical relevance compared to conventional genetic approaches.
基金supported financially by the National Key Research and Science Program of the Ministry of Science and Technology of the People’s Republic of China(2022YFC2303900)the Beijing Natural Science Foundation(7232242).
文摘Antimicrobial resistance(AMR)has become a critical global public health challenge in the 21st century.Since the initial isolation of a blaNDM-1-carrying and carbapenem-resistant Klebsiella pneumoniae from an Indian hospital in 2009[1],the escalating prevalence of New Delhi metallo-β-lactamase(NDM)-encoding genes(blaNDM)has transformed carbapenem resistance into a worldwide phenomenon,transcending national and regional boundaries[2].Up to 90 distinct NDM variants have been reported globally according to the NCBI GenBank Pathogens database.Plasmidmediated horizontal gene transfer(HGT),which occurs both within and across bacterial species,has significantly accelerated the global dissemination of blaNDM-related genes and the associated resistance[3].Carbapenem-resistant pathogens were responsible for 200,000 deaths globally in 2019[4].Although NDM-1 has been relatively well characterized[5],the epidemiological profiles of other NDM variants require continued surveillance and indepth investigation.The novel NDM-9 variant(GenBank accession no.KC999080)was first identified in 2013 from a clinically significant isolate of Klebsiella pneumoniae ST107 strain PPH1303 with a high level of resistance to carbapenems recovered from the urine culture of a pediatric patient in Beijing,China,who had acute lymphocytic leukemia and had undergone allogeneic stem cell transplantation[6].
文摘Background: The irrational use of medicines remains a key health problem in many developing countries. The overuse of antibiotics is a key driver of antimicrobial resistance (AMR). This study surveyed antibiotic use and adherence to the World Health Organization (WHO) prescribing indicators at the Request Muntanga Hospital in the Kalomo District of Southern Province, Zambia. Materials and Methods: This cross-sectional study was conducted from July 2023 to September 2023 at Request Muntanga Hospital in Zambia and reviewed 600 medical record prescriptions which were issued from July 1, 2022 to June 30, 2023 using the WHO prescribing indicators. The collected data were analyzed using Statistical Package for Social Sciences version 23.0. Results: From the 600 prescriptions sampled, 1246 medicines were prescribed, with antibiotics making up 86.7% of the encounters. Additionally, the average number of drugs prescribed per encounter was 2.1 and the prevalence of polypharmacy was 61.3%. Further, 17.8% of medicines were prescribed as injectables. Furthermore, 76.7% of the drugs were prescribed from the Zambia Essential Medicines List and 38.9% by generic names. Conclusions: This study found a high use of antibiotics and deviations from the WHO/International Network of Rational Use of Drugs (INRUD) core prescribing indicators at the Request Muntanga Hospital indicating non-adherence to the prescribing indicators. There is a need to promote adherence to the WHO/INRUD core prescribing indicators to promote the rational use of antibiotics and prevent the emergence and spread of AMR.
基金funded by the National Natural Science Foun-dation of China(22406168,W2411031,and 52270201)the China Postdoctoral Science Foundation(2023M733061)the Zhejiang University Global Partnership Fund(100000-11320/198).
文摘The One Health concept acknowledges the importance of multiple dimensions in controlling antimicrobial resistance(AMR).However,our understanding of how anthropological,socioeconomic,and environmental factors drive AMR at a national level remains limited.To explore associations between potential contributing factors and AMR,this study analyzed an extensive database comprising 13 major antibioticresistant bacteria and over 30 predictors(e.g.,air pollution,antibiotic usage,economy,husbandry,public services,health services,education,diet,climate,and population)from 2014 to 2020 across China.The multivariate analysis results indicate that fine particulate matter with a diameter of 2.5 μm or less(PM_(2.5))is associated with AMR,accounting for 12%of the variation,followed by residents’income(10.3%)and antibiotic usage density(5.1%).A reduction in PM_(2.5)of 1 μg·m^(-3)is linked to a 0.17%decrease in aggregate antibiotic resistance(p<0.001,R^(2)=0.74).Under different scenarios of China’s PM_(2.5)airquality projections,we further estimated the premature death toll and economic burden derived from PM_(2.5)-related antibiotic resistance in China until 2060.PM_(2.5)-derived AMR is estimated to cause approximately 27000(95%confidence interval(CI):646848830)premature deaths and about 0.51(95%CI;0.12-0.92)million years of life lost annually in China,equivalent to an annual welfare loss of 8.4(95%CI;2.0-15.0)billion USD.Implementing the“Ambitious Pollution 1.5℃ Goals”scenario to reduce PM_(2.5)concentrations could prevent roughly 14000(95%CI;3324-26320)premature deaths—with a potential monetary value of 9.8(95%CI;2.2-17.6)billion USD—from AMR by 2060.These results suggest that reducing air pollution may offer co-benefits in the health and economic sectors by mitigating AMR.
文摘Background:Antimicrobial resistance(AMR)poses a significant and growing public health challenge in East and Southern Africa.Despite formal commitments to the National Action Plans,domestic financing for AMR remains critically limited,with most countries continuing to depend heavily on external donor funding.Objective:This narrative review examines the current extent to which domestic fiscal commitments align with national AMR policy goals across the two regions.Methods:Government websites for ministries of health and finance,donor platforms,and three academic databases(Scopus,JSTOR,Google Scholar)were searched for eligible articles.National budget statements and media reports were also reviewed where available.Three researchers independently screened titles and summaries,followed by full-text reviews to confirm eligibility.Results:The findings reveal that while several countries have developed National Action Plans,very few have allocated domestic funding to implement them.Only Malawi,Nigeria and Uganda reported modest domestic contributions,while in other countries such as Zambia,Ethiopia,and South Africa,AMR programs remain largely donor-financed or lack dedicated budget lines altogether.Veterinary and laboratory sectors are particularly underfunded,with minimal integration into broader AMR strategies.While this review has several limitations including restricted access to current,comprehensive national budget data and a reliance on secondary sources such as donor and World Health Organization reports,which may introduce bias,the patterns identified in this review still offer valuable insight into regional funding dynamics and can inform future policy and research efforts.Conclusion:We conclude that without dedicated domestic financing and accountability mechanisms,AMR efforts in the region may face significant sustainability challenges observed in other health responses such as human immunodeficiency virus.Strengthening AMR governance requires clear budgetary commitments,sustainable cofinancing models,and policy instruments to reduce dependency on external support.
基金supported by grants awarded to RAD by the South African Medical Research Council(SAMRC),with funds received from the South African National Department of Health,and the UK Medical Research Council,with funds received from the UK Government's Newton Fund(Grant No.:96185)by South African National Research Foundation(NRF)through the DSI/NRF South African Research Chair Initiative(NRF UID 87583)+2 种基金OO was supported by a Rhodes University Post-Doctoral FellowshipIN and TS received Post-Doctoral Fellowships from the SAMRCDA was supported by DAAD Scholarship(Reference number:91758998).
文摘The rapid emergence of drug-resistant microbial pathogens has posed challenges to global health in the twenty-first century.This development has significantly made most antibiotics ineffective in the treatment of infections they cause,resulting in increasing treatment costs and annual death rates.To address the challenge posed by these pathogens,we explore the potential of secondary metabolites from Aspergillus species as a source of new and effective therapeutic agents to treat drug-resistant infections.Terpenoids,a distinct group of natural products,are extensively distributed in plants and fungi,and have been attributed with significant antibacterial,anticancer,and antiviral activities.In this review,we present an overview of Aspergillus species,and review the novel terpenoids isolated from them from 2019 to April 2024,highlighting anti-infective activity against members of the ESKAPE pathogens.We further focus on the strategies through which the structural framework of these new terpenoids could be modified and/or optimized to feed a pipeline of new lead compounds targeting microbial pathogens.Overall,this review provides insight into the therapeutic applications of terpenoids sourced from Aspergillus species and the potential for the discovery of new compounds from these fungi to combat antimicrobial resistance.
文摘Background:Community-acquired bacterial pneumonia(CABP)poses a serious public health threat,particularly with the emergence of drug-resistant bacterial strains.This study aims to investigate the molecular interactions of Nafithromycin(Miqnaf®),India’s first indigenous next-generation macrolide antibiotic,and evaluate its potential against Streptococcus pneumoniae,a key pathogen responsible for CABP.Targeting 23S rRNA is critical for overcoming antibiotic resistance since it is involved in bacterial protein production.Many antibiotics,including macrolides target this rRNA.Mutations in 23S rRNA frequently result in resistance;therefore,designing medicines that bind new or conserved areas of 23S rRNA can circumvent current resistance mechanisms and restore antibiotic potency.Nafithromycin has excellent therapeutic potential,with a short three-day regimen and much higher efficacy than conventional macrolides.Its high lung tissue penetration and robust effectiveness against drug-resistant respiratory bacteria make it a promising next-generation antibiotic.Methods:To elucidate the interaction of Nafithromycin with bacterial ribosomal RNA,molecular docking studies were performed using AutoDock Vina.The three-dimensional structure of Streptococcus pneumoniae 23S rRNA was retrieved from the Protein Data Bank(PDB).The ligand structure of Nafithromycin was obtained from the PubChem database and prepared using Open Babel.Docking simulations targeted key functional regions-Domains II and V of 23S rRNA-known to be critical for bacterial protein synthesis.Binding affinities were calculated,and molecular interactions such as hydrogen bonds,hydrophobic contacts,and conformational stabilities were analyzed using Discovery Studio and PyMOL.Results:Nafithromycin exhibited a high binding affinity of-10.3 kcal/mol toward S.pneumoniae 23S rRNA.The compound formed stable interactions with both Domain II and Domain V,crucial regions involved in the inhibition of bacterial protein synthesis.Hydrogen bonding and hydrophobic interactions further stabilized the ligand-receptor complex.Compared to azithromycin,Nafithromycin demonstrated superior binding efficacy and a greater potential to inhibit resistant bacterial strains,indicating its structural advantages and enhanced ribosomal targeting.Conclusion:Nafithromycin demonstrates significant potential as a potent therapeutic agent against drug-resistant CABP.Its strong binding affinity,stable interactions with bacterial rRNA,favorable pharmacokinetic profile,and reduced resistance risk support its clinical utility and suggest its advantage over traditional macrolide antibiotics such as azithromycin.
文摘BACKGROUND Sepsis is a critical medical condition,and poses a substantial global health burden,with significant morbidity,mortality,and economic costs,particularly pronounced in low-and middle-income countries.Effective management of sepsis relies on early recognition and appropriate intervention,underscoring the importance of accurate classification to guide treatment decisions.The correct diagnosis will lead to effective antimicrobial stewardship practices.AIM To assess the distribution of sepsis categories and the use of empirical antibiotics classified by the World Health Organization(WHO)Access,Watch,and Reserve(AWaRe)system in a tertiary care hospital in Northern India and to correlate antibiotic usage with sepsis classifications.METHODS This longitudinal observational study in the Department of General Medicine,in a tertiary care hospital in Northern India,from 2023 to 2024,aimed to assess the use of empirical antibiotics classified by the WHO AWaRe system.The study also aimed to correlate antibiotic usage.Patients were categorized into sepsis classes(Asepsis,Possible Sepsis,Probable Sepsis,Confirmed Sepsis)and followed until discharge or Day-28.Descriptive and inferential statistical analyses were employed to assess sepsis categories and empirical antibiotic usage classified by the WHO AWaRe system.RESULTS A total of 1867 patients admitted with suspected sepsis were screened,with 230 meeting the inclusion criteria.Among the study cohort(mean age 40.70±14.49 years,50.9% female),initial sepsis classification predominantly included probable sepsis(51.3%)and possible sepsis(35.7%),evolving to asepsis(57.8%)upon final classification,but all received antibiotics.Empirical antibiotic use showed a predominance of Watch group antibiotics(72.2%),with ceftriaxone and piperacillin-tazobactam being the most commonly prescribed;however,no statistical association could be established among the different classes of sepsis with the AWaRe groups.CONCLUSION Accurate sepsis classification is pivotal for clinical decision-making,optimizing antibiotic use,and combating antimicrobial resistance.The majority of the asepsis category was labelled as probable or possible sepsis and given antibiotics at initial hospitalization.The high reliance on Watch group antibiotics in empirical therapy signals a need for enhanced diagnostic strategies to refine treatment initiation,potentially reducing unnecessary antibiotic exposure.Future efforts should focus on establishing sepsis classification checklists as in this study and promoting adherence to antimicrobial stewardship principles to mitigate the global threat of antimicrobial resistance.
文摘BACKGROUND Outpatient parenteral antimicrobial therapy(OPAT)offers a crucial method for administering intravenous/intramuscular antimicrobials outside of hospital settings,allowing patients to complete treatment safely while avoiding many hospital-acquired complications.This is a major boost or low-hanging fruit intervention in antimicrobial stewardship practices with multiple targets like decreasing hospital stays,its related complications,the economy,the burden on hospitals,etc.However,resource-constrained countries like India practices rarely OPAT in an evidence-based way.AIM To evaluate the effectiveness,safety,and feasibility along with barriers and facilitators of OPAT practices in resource-poor settings,with a focus on its role in antimicrobial stewardship.METHODS This pilot longitudinal observational study included patients who met OPAT checklist criteria and were committed to post-discharge follow-up.Pre-discharge education and counselling were provided,and demographic data were recorded.Various outcome measures,including barriers and facilitators,were identified through an extensive literature review,fishbone diagram preparation,data collection and analysis,and patient feedback.All healthcare workers who were taking care of the patients discharged with OPAT were contacted with openended questions to get data on feasibility.The study was approved by the Institutional Ethics Committee of All India Institute of Medical Sciences,Rishikesh.We used descriptive analysis and theχ2 test to analyze data.P value<0.05 was considered significant.RESULTS Out of 20 patients,the mean age was 37 years.The cohort comprised 13 males.OPAT was administered at home in 15 cases and at nursing homes in 5 cases,with nine patients receiving treatment from family members and 11 patients receiving care from a local nurse.The infections requiring OPAT included:Kidney-urinary tract(6 cases),gastrointestinal tract(4 cases),respiratory tract(4 cases),meningitis(3 cases),endocarditis(2 cases),and multiple visceral abscesses(1 case).Nineteen out of 20 patients achieved afebrile status.Half of the patients did not receive education,counselling,or demonstrations prior to discharge,but all patients rated the service as good/excellent.According to doctors’feedback,OPAT is highly beneficial and effective for patients when systematically implemented with daily telephonic monitoring,but faces challenges due to the lack of standardized protocols,dedicated teams,and adequate resources.The implementation of OPAT resulted in a reduction of hospitalization duration by an average of two weeks.CONCLUSION This pilot study proves that OPAT is safe,feasible,and efficacious by reducing two weeks of hospitalization in resource-poor settings.OPAT contributes directly to antimicrobial stewardship by reducing hospital stays and hospital-acquired complications,which is vital in combating antimicrobial resistance(AMR)and aligns with the global action plan for AMR in infection prevention and optimal antimicrobial utilization.
文摘Background: Antimicrobial Resistance (AMR) has been recognized as a global public health problem of utmost importance that needs to be tackled. Low-income countries such as Uganda have the greatest burden of severe and life-threatening infections and are most likely to suffer more from the spread of untreatable resistant bacteria. Despite the generally increasing trends in AMR, there is hardly any documented data on AMR in orthopedic care. Methods: We analyzed data from the pathogenic isolates from pus and tissue from the laboratory from 2019 to 2023. We calculated the proportions of isolates resistant to commonly used antimicrobial classes. We used the chi-square test for trends to evaluate changes in AMR across the study period. Results: Out of the 286 isolates, 104 (43.5%) were from pus, 112 (46.9%) were from tissue samples and the remaining 9.6% were from different fluid aspirates like synovial fluid. Most of the isolates were from males (64.2%) and aged between 19 and 45 years (46.2%). The distribution of whether the bacteria were gram-positive or negative was relatively equal with 114 (45.2%) being gram-negative and 120 (47.6%) gram-positive. Generally, there was increased AMR across all antibiotics from 2019 to 2021 e.g. for Imipinem, it went from 0% in 2019 to 70.8% in 2021 and for Amoxyclav, it went from 10% in 2019 to 93.2% in 2021. There was a general decline in AMR noted from 2021 to 2023. However, currently, the highest resistance is noted in ceftriaxone (80.0%) and the lowest in Imipinem (11.76%). Conclusion: There is a general decreasing trend in AMR, most probably due to increasing policies governing the use of antibiotics. However, there is still high resistance to commonly used and affordable antibiotics. Continuous monitoring of AMR is still recommended to reduce the AMR problem in Uganda at large through public health policy and planning.
基金the National Natural Science Foundation of China(82573571)the Shanghai 2025 Basic Research Plan Natural Science Foundation(25ZR1401393)the First Batch of Open Topics of the Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices(2025QN13)。
文摘The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR.However,their clinical translation is hindered by their inherently low immunogenicity,often requiring potent adjuvants and advanced delivery systems.Biomembrane nanostructures(e.g.,liposomes,exosomes,and cell membrane-derived nanostructures),characterized by superior biocompatibility,intrinsic targeting ability,and immune-modulating properties,could serve as versatile platforms that potentiate vaccine efficacy by increasing antigen stability,enabling codelivery of immunostimulants,and facilitating targeted delivery to lymphoid tissues/antigen-presenting cells.This intrinsic immunomodulation promotes robust humoral and cellular immune responses to combat bacteria.This review critically reviews(1)key biomembrane nanostructure classes for bacterial protein antigens,(2)design strategies leveraging biomembrane nanostructures to enhance humoral and cellular immune responses,(3)preclinical efficacy against diverse pathogens,and(4)translational challenges and prospects.Biomembrane nanostructure-driven approaches represent a paradigm shift in the development of next-generation bacterial protein vaccines against resistant infections.
基金Project (No. 2005C12015) supported by the Science and Technology Department of Zhejiang Province, China
文摘This study was conducted to determine genetic diversity and antimicrobial susceptibility profiles of Staphylococcus aureus recovered from bovine mastiffs in Zhejiang Province, China. Out of 3178 quarter milk samples from 846 lactating cows, among which 459 cows （54.3%） were found HMT positive, 890 quarters （28%） were found having subclinical mastitis. From 75 representative S. aureus isolates, 16 distinct types were identified by pulsed-field gel electrophoresis （PFGE）. Four major PFGE types （A, B, C, and D） accounted for 82.7% of all isolates, and type A （41.3%） was observed in multiple herds across the studied areas. Each region was found to have a predominant type： Hangzhou type A （64.1%）, Ningbo type C （34.5%） and type B （23.1%）, Jinhua type D （53.3%）, and Taizhou type C （62.5%）. Results of antimicrobial susceptibility tests showed that 90.7% of the isolates were resistant to at least one antimicrobial. Resistance to penicillin and ampicillin （77.3%）, tetracycline （60.0%）, or erythromycin （48.0%） was observed. The bacteria resistant to multiple antibiotics such as penicillin, ampicillin, tetracycline, and erythromycin were commonly found. The information obtained from this study is useful for designing specific control programs for bovine S. aureus mastitis in this region.
文摘The management of Helicobacter pylori(H. pylori) infection treatment differs from the common treatment protocol for other infectious diseases. Because culture-or molecular-guided approaches face several practical issues, such as the invasive procedures required to obtain gastric biopsy specimens and the lack of availability of routine laboratory testing in some places, H. pylori treatment includes the administration of two or three empirically selected antibiotics combined with a proton pump inhibitor rather than evidence-based eradication treatment. The efficacy of empirical therapy is decreasing, mostly due to increasing multiple resistance. Multiresistance to levofloxacin, clarithromycin, and metronidazole, which are commonly used in empirical treatments, appears to have increased in many countries. Mutations play a primary role in the antimicrobial resistance of H. pylori, but many different mechanisms can be involved in the development of antibiotic resistance. Determining and understanding these possible mechanisms might allow the development of new methods for the detection of H. pylori and the determination of antimicrobial resistance. A treatment based on the detection of antimicrobial resistance is usually more effective than empirical treatment. Nevertheless, such an approach before treatment is still not recommended in the Maastricht guidelines due to the difficulty associated with the routine application of available cultureor molecular-based susceptibility tests, which are usually administered in cases of treatment failure. The management of first and rescue treatments requires further research due to the steadily increase in antimicrobial resistance.
基金supported by the Central Public-Interest Scientific Institution Basal Research Fund,China (1610322015007)the Key Technology R&D Program of China during the 12th Five-Year Plan period (2012BAD12B03)the Natural Science Foundation of Gansu Province,China (145RJYA311)
文摘Staphylococcus aureus is the most common etiological pathogen of bovine mastitis. The resistant strains make the disease difficult to cure. The aim of this study was to characterize the genetic nature of the antimicrobial resistance in S. aureus cultured from bovine mastitis in Northwest China in 2014. A total of 44 S. aureus were isolated for antimicrobial resistance and resistance-related genes. Antimicrobial resistance was determined by disc diffusion and the corresponding resistance genes were detected by PCR. Phenotype indicated that S. aureus isolates were resistant to penicillin （84.09%）, erythromycin （20.45%）, tetracycline （15.91%）, gentamicin （9.09%）, tobramycin （6.82%）, kanamycin （6.82%） and methicillin （2.27%）. 9.09% of the S. aureus isolates were classified as multidrug resistant. In addition, genotypes showed that the isolates were resistant to rifampicin （100%, rpoB）, penicillin （95.45%, blaZ）, tetracycline （22.73%, tetK, tetM, alone or in combination）, erythromycin （22.73%, ermB or ermC）, gentamicin/tobramycin/kanamycin （2.27%, aacA-aphD）, methicillin （2.27%, mecA） and vancomycin （2.27%, vanA）. Resistance to tetracycline was attributed to the genes tetK and tetM （r=0.558, P〈0.001）. This study noted high-level geno- and phenotypic antimicrobial resistance in S. aureus isolates from bovine mastitis cases in Northwest China.
基金supported by grants from the National Natural Science Foundation of China (81770176)the special support plan for Zhejiang Province High-Level Talents (2019R52011)。
文摘The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria.As an excellent candidate to overcome antibiotic resistance,antimicrobial peptides(AMPs)that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity.These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action.This comprehensive review provides a broad overview of AMPs from the origin,structural characteristics,mechanisms of action,biological activities to clinical applications.We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.
