Production systems and important antimicrobial resistant-pathogenic bacteria in poultry:a review

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.

Antimicrobial Resistant Coliforms in Tap Water with Low Free Residual Chlorine Levels in Two Hospitals: Case Study in Gaza, Palestine

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.

Core and variable antimicrobial resistance genes in the gut microbiomes of Chinese and European pigs

Monitoring the prevalence of antimicrobial resistance genes(ARGs)is vital for addressing the global crisis of antibiotic-resistant bacterial infections.Despite its importance,the characterization of ARGs and microbiome structures,as well as the identification of indicators for routine ARG monitoring in pig farms,are still lacking,particularly concerning variations in antimicrobial exposure in different countries or regions.Here,metagenomics and random forest machine learning were used to elucidate the ARG profiles,microbiome structures,and ARG contamination indicators in pig manure under different antimicrobial pressures between China and Europe.Results showed that Chinese pigs exposed to high-level antimicrobials exhibited higher total and plasmid-mediated ARG abundances compared to those in European pigs(P<0.05).ANT(6)-Ib,APH(3')-IIIa,and tet(40)were identified as shared core ARGs between the two pig populations.Furthermore,the core ARGs identified in pig populations were correlated with those found in human populations within the same geographical regions.Lactobacillus and Prevotella were identified as the dominant genera in the core microbiomes of Chinese and European pigs,respectively.Forty ARG markers and 43 biomarkers were able to differentiate between the Chinese and European pig manure samples with accuracies of 100%and 98.7%,respectively.Indicators for assessing ARG contamination in Chinese and European pigs also achieved high accuracy(r=0.72-0.88).Escherichia flexneri in both Chinese and European pig populations carried between 21 and 37 ARGs.The results of this study emphasize the importance of global collaboration in reducing antimicrobial resistance risk and provide validated indicators for evaluating the risk of ARG contamination in pig farms.

Analysis of Multi-Drug Resistant Organism Surveillance and Antimicrobial Resistance Early Warning in a Hospital in 2022

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。

Burden of severe infections due to carbapenem-resistant pathogens in intensive care unit

Intensive care units(ICU)for various reasons,including the increasing age of admitted patients,comorbidities,and increasingly complex surgical procedures(e.g.,transplants),have become"the epicenter"of nosocomial infections,these are characterized by the presence of multidrug-resistant organisms(MDROs)as the cause of infection.Therefore,the perfect match of fragile patients and MDROs,as the cause of infection,makes ICU mortality very high.Furthermore,carbapenems were considered for years as last-resort antibiotics for the treatment of infections caused by MDROs;unfortunately,nowadays carbapenem resistance,mainly among Gram-negative pathogens,is a matter of the highest concern for worldwide public health.This comprehensive review aims to outline the problem from the intensivist's perspective,focusing on the new definition and epidemiology of the most common carbapenem-resistant MDROs(Acinetobacter baumannii,Pseudomonas aeruginosa and Enterobacterales)to emphasize the importance of the problem that must be permeating clinicians dealing with these diseases.

Global Strategies to Combat Antimicrobial Resistance: A One Health Perspective

Background: Antimicrobial resistance (AMR) is a global health challenge that has escalated due to the inappropriate use of antimicrobials in humans, animals, and the environment. Developing and implementing strategies to reduce and combat AMR is critical. Purpose: This study aimed to highlight some global strategies that can be implemented to address AMR using a One Health approach. Methods: This study employed a narrative review design that included studies published from January 2002 to July 2023. The study searched for literature on AMR and antimicrobial stewardship (AMS) in PubMed and Google Scholar using the 2020 PRISMA guidelines. Results: This study reveals that AMR remains a significant global public health problem. Its severity has been markedly exacerbated by inappropriate use of antimicrobials in humans, animals, and the broader ecological environment. Several strategies have been developed to address AMR, including the Global Action Plan (GAP), National Action Plans (NAPs), AMS programs, and implementation of the AWaRe classification of antimicrobials. These strategies also involve strengthening surveillance of antimicrobial consumption and resistance, encouraging the development of new antimicrobials, and enhancing regulations around antimicrobial prescribing, dispensing, and usage. Additional measures include promoting global partnerships, combating substandard and falsified antimicrobials, advocating for vaccinations, sanitation, hygiene and biosecurity, as well as exploring alternatives to antimicrobials. However, the implementation of these strategies faces various challenges. These challenges include low awareness and knowledge of AMR, a shortage of human resources and capacity building for AMR and AMS, in adequate funding for AMR and AMS initiatives, limited laboratory capacities for surveillance, behavioural change issues, and ineffective leadership and multidisciplinary teams. Conclusion: In conclusion, this study established that AMR is prevalent among humans, animals, and the environment. Successfully addressing AMR calls for a collaborative, multifaceted One Health approach. Despite this, some gaps remain effectively implementing strategies currently recommended to combat AMR. As a result, it is essential to reinforce the strategies that are deployed to counter AMR across the human, animal, and environmental sectors.

Encapsulated peracetic acid as a valid broad‑spectrum antimicrobial alternative,leading to beneficial microbiota compositional changes and enhanced performance in broiler chickens

Background Antimicrobial alternatives are urgently needed,including for poultry production systems.In this study,we tested the potential broad-range antimicrobial alternative peracetic acid,delivered in feed via the hydrolysis of encapsulated precursors through a 28-day study using 375 Ross 308 broiler chickens.We tested two peracetic acid concentrations,30 and 80 mg/kg on birds housed on re-used litter,and we evaluated the impact of both levels on gut microbial communities,bacterial concentration,antimicrobial resistance genes relative abundance and growth performance when compared to control birds housed on either clean or re-used litter.Results Body weight gain and feed conversion ratio improved in peracetic acid fed birds.At d 28,birds given 30 mg/kg of peracetic acid had a decreased Firmicutes and an increased Proteobacteria abundance in the jejunum,accompanied by an increase in Bacillus,Flavonifractor and Rombustia in the caeca,and a decreased abundance of tetracycline resistance genes.Chicken given 80 mg/kg of peracetic acid had greater caecal abundance of macrolides lincosamides and streptogramins resistance genes.Growth performance on clean litter was reduced compared to reused litter,which concurred with increased caecal abundance of Blautia,decreased caecal abundance of Escherichia/Shigella,Anaerostipes and Jeotgalicoccus,and greater gene abundance of vancomycin,tetracycline,and macrolides resistance genes.Conclusions Peracetic acid could be used as a safe broad-spectrum antimicrobial alternative in broilers.Encapsulated precursors were able to reduce the bacterial concentration in the jejunum whilst promoting the proliferation of probiotic genera in the caeca,especially at the low peracetic acid concentrations tested,and improve growth performance.Moreover,our findings offer further insights on potential benefits of rearing birds on re-used litter,suggesting that the latter could be associated with better performance and reduced antimicrobial resistance risk compared to clean litter rearing.

Design methods for antimicrobial peptides with improved performance

The recalcitrance of pathogens to traditional antibiotics has made treating and eradicating bacterial infections more difficult.In this regard,developing new antimicrobial agents to combat antibiotic-resistant strains has become a top priority.Antimicrobial peptides(AMPs),a ubiquitous class of naturally occurring compounds with broadspectrum antipathogenic activity,hold significant promise as an effective solution to the current antimicrobial resistance(AMR)crisis.Several AMPs have been identified and evaluated for their therapeutic application,with many already in the drug development pipeline.Their distinct properties,such as high target specificity,potency,and ability to bypass microbial resistance mechanisms,make AMPs a promising alternative to traditional antibiotics.Nonetheless,several challenges,such as high toxicity,lability to proteolytic degradation,low stability,poor pharmacokinetics,and high production costs,continue to hamper their clinical applicability.Therefore,recent research has focused on optimizing the properties of AMPs to improve their performance.By understanding the physicochemical properties of AMPs that correspond to their activity,such as amphipathicity,hydrophobicity,structural conformation,amino acid distribution,and composition,researchers can design AMPs with desired and improved performance.In this review,we highlight some of the key strategies used to optimize the performance of AMPs,including rational design and de novo synthesis.We also discuss the growing role of predictive computational tools,utilizing artificial intelligence and machine learning,in the design and synthesis of highly efficacious lead drug candidates.

Identification of blaIMI-mediated carbapenem-resistant Enterobacter from a duck farm in China

Carbapenem-and colistin-resistant Enterobacter has been a clinical and therapy problem in recent years.Here,we report the carbapenem-and colistin-resistant Enterobacter harboring bla_(IMI) isolated from intestinal samples and the environment of a duck farm in China.Four bla_(IMI)-positive Enterobacter isolates were resistant to carbapenem and colistin.Three bla_(IMI) subtypes were detected in different molecular categories of Enterobacter.The detection of the various IMI producers highlights the diversity of carbapenemases in a duck farm.Whole-genome sequencing demonstrated the bla_(IMI) genes were present in chromosomes or plasmids in these strains.The conjugation experiment demonstrated the ability of bla_(IMI)-carrying plasmid to transmit horizontally.The molecular evolution characteristics were examined through comparative genetic analysis.The study demonstrated the presence of chromosomal and plasmid bla_(IMI) and the bla_(IMI)-carrying plasmid exhibits a horizontal transmission between Enterobacter and Escherichia coli C600.The similar genetic content was discovered between two bla_(IMI-16)-positive Enterobacter asburiae.In addition,a bla_(IMI-16)-carrying plasmid is an IncFII(Yp)plasmid,and a substantial amount of mobile genetic elements were identified around bla_(IMI-16).The IS-like elements and IncFII(Yp)plasmid are significant in the propagation of bla_(IMI).Our study provides evidence for the transmission of diverse bla_(IMI) genes in China and supplies additional reference data for bla_(IMI)-positive antimicrobialresistant Enterobacter.Routine surveys of bla_(IMI)-positive Enterobacter from animal-raising environments must be given more focus.

Disease burden,antimicrobial resistance and molecular characterization of invasive group B Streptococcus among non-pregnant adults in Malaysia:A protocol study

and pili genes are also investigated.Methods:This multicentre,prospective,observational study is conducted in seven major tertiary hospitals in Malaysia among non-pregnant adults.Simultaneously,a retrospective study is conducted in the selected hospitals with similar approaches.GBS isolates are subjected to phenotyping,serotyping by multiplex PCR,antimicrobial susceptibility testing and PCR-detection of GBS virulence and pilus genes.Seven housekeeping genes are amplified and sequenced for multi-locus sequence typing.Discussion:Findings from the study may contribute to the management of clinical practice to diagnose and prevent GBS related diseases in a timely manner.Prudent use of antibiotics is encouraged by monitoring antimicrobial resistance.

Antimicrobial resistance and molecular typing of Salmonella in the chicken production chain in Hubei Province, China

Salmonella is a significant foodborne zoonotic pathogen that endangers both human and animal health.The goal of this research is to gain a preliminary understanding of Salmonella contamination and antimicrobial resistance in the chicken production chain in Hubei Province,China.1149 animal and environmental samples were collected from chicken farms,slaughterhouses,and retail markets in six cities across Hubei Province in China from 2019 to 2020,yielding Salmonella isolation rates of 4.68%(28/598),12.21%(47/385),and 9.64%(16/166),respectively.Seventeen distinct serotypes were detected among 53 non-clonal Salmonella strains,of which Meleagridis(26.42%,14/53)was the dominant serotype.Almost half of the strains(49.06%,26/53)were multi-drug resistant(MDR).Whole-genome sequencing(WGS)showed that 10 resistance genes(tetA,bla_(TEM),parC,qnrs1,floR,aac(6'-ly,aph(6)-ld,aph(3")-b,aac(6')-laa and sul2)and 7 categories of virulence genes were present in all three links in 22 non-clonal dominant serotype strains.It was shown that Salmonella in the chicken production chain in Hubei Province had a high resist-ance rate to Tetracycline(TET,73.58%),Ofloxacin(OFL,69.81%),Florfenicol(FFC,60.38%)and Ampicillin(AMP,39.62%)which was consistent with the widespread use of these drugs in the husbandry industry in China.Salmonella ST types determined by MLST and serotypes determined by WGS had a one-to-one correlation.Minimum spanning tree analysis revealed that there was cross contamination of Salmonella in farms and slaughterhouses,slaughterhouses and markets,animal samples and environmental samples.This work provides useful information for the prevention and control of contamination and antimicrobial resistance of Salmonella in the chicken production chain,as well as demonstrating the dependable role of WGS in Salmonella molecular typing.

Knowledge, Attitudes, and Practices of Poultry Farmers on Antimicrobial Use and Resistance in Kitwe, Zambia: Implications on Antimicrobial Stewardship

Introduction: The inappropriate antimicrobial usage (AMU) in chicken production has led to an increase in the prevalence of antimicrobial resistance (AMR). In Zambia, there is little information documented regarding the knowledge, attitude, and practices of poultry farmers on AMU and AMR. Therefore, this study assessed the knowledge, attitude and practices regarding AMU and AMR among poultry farmers in Kitwe, Zambia. Methods: This was a cross-sectional study conducted among 106 poultry farmers from November to December 2021 using a structured questionnaire. Data analysis was done using IBM Statistical Package for Social Sciences (SPSS) version 26. Results: Overall, of the 106 participants, 90.6% knew what antimicrobials were, but only 29.2% were aware of AMR. The study showed that 46.2% of the participants had low knowledge, 71.7% had negative attitudes, and 61.3% had poor practices regarding AMR. The prevalence of antibiotic use in poultry production was 83%. The most used antimicrobials were tetracycline (84%) and gentamicin (35.2%). The commonly reported reason for the use of antimicrobials was for the treatment (93.2%) and prevention (89.8%) of diseases. Further, 76.9% of the administered antimicrobials were usually done without veterinarian consultation or prescription. Conclusion: The study shows that there was high AMU in poultry farms in Kitwe. However, there was low knowledge, negative attitude, and poor practices towards AMU and AMR. Therefore, there is a need for educational and sensitisation programmes regarding AMU and AMR among poultry farmers in Kitwe, Zambia. Alongside this, antimicrobial stewardship and surveillance systems should be strengthened in the livestock production sector. This will ensure food safety and public health.

Knowledge, Attitudes, and Practices of Antimicrobial Use and Resistance among Village Animal Health Workers and Veterinary Drug Retailers in Cambodia

Misuse, overuse, and missed prescription of antimicrobials are the driving factors to antimicrobial resistance (AMR) leading to a globally increasing public health concern. This study was conducted to assess the current knowledge, attitudes, and practices (KAP) of village animal health workers (VAHWs) and veterinary drug retailers (VDRs) on antimicrobial use (AMU) and antimicrobial resistance (AMR). The sample size was calculated following [1]. KAP data were scored and categorized following Bloom’s cut-off score. A total of 108 study populations (66 VAHWs and 42 VDRs) were purposively surveyed using a validated KAP questionnaire in 5 provinces across Cambodia. This study found that VAHWs and VDRs have moderate levels of knowledge (61% to 65%) and good attitudes towards AMU (83% to 84%) but employed moderate practices (59% to 74%) on AMU. VAHWs had moderate (66%);while DVRs had poor knowledge (58%) on AMR. Thus, regular awareness education specifically on proper use, prudent use, and stewardships on AMU and AMR in the form of refresher training or awareness events must be provided to VAHWs and VDRs to avoid inappropriate use of antimicrobials and spreading the AMR knowledge across Cambodia.

Antimicrobial Stewardship: Knowledge and Attitudes of Pharmacy Staff on Antibiotic Dispensing Patterns, Use and Resistance in Benin

Background: One of the key drivers for the emergence and spread of antimicrobial resistance (AMR) is non-prudent antibiotic use, which results in selection pressure toward relevant bacteria. Pharmacy staffs have pivotal roles in facilitating the prudent use of antibiotics through antimicrobial stewardship programs. Due to limited information in Benin, this study assessed the knowledge and attitudes of pharmacy staffs on antibiotic use and resistance. Materials and Methods: This cross-sectional study was conducted among 159 pharmacy staffs using a structured questionnaire from August 2018 to December 2018 in Benin. Data analysis was done by using Stata version 13.0. Results: Of the 159 participants, 54.8% knew the definition of antibiotic therapy and 66.9% knew the definition of probabilistic antibiotic therapy. The majority (88.1%) of the participants thought that the choice of antibiotics was made according to the pathology, while 60.4% thought that it depended on the pathology and the germ involved. 49.02% of dispensers in pharmacies stated that half of the patients had requested treatment without providing a prescription at the pharmacy. The top three antibiotics that were dispensed without a prescription include amoxicillin (98.1%), cloxacillin (76.7%) and metronidazole (57.2%), all from the Access group of antibiotics. Conclusion: These results underscore the need for educational and training interventions targeting specific professional groups. There is an urgent need for regulatory measures and public awareness through improved antimicrobial stewardship to limit this practice.

Prevalence and Antimicrobial Susceptibility Status of Gram-Negative and Gram-Positive Bacteria on Handheld Shopping Trolleys and Baskets in Supermarkets in Ndola, Zambia

Background: Supermarkets are a place visited by individuals with different health conditions daily where microbiological contaminants through touch onto fomites such as trolleys and baskets can be passed on to other people hence potentially spreading infectious diseases. This study aimed to investigate the presence of Gram-negative and Gram-positive bacteria on handheld shopping trolleys and baskets and their antimicrobial susceptibility status against commonly used antibiotics in Zambia. Methods: A cross-sectional study was conducted. Trolleys and basket handles were swabbed and standard microbiological methods were used to identify the bacteria and disc diffusion to determine their antimicrobial susceptibility status. Data was collected from December 2021 to April 2022. Data was analysed using IBM Statistical Package for Social Sciences (SPSS) Version 22. Results: Twenty-eight percent of the 200 total samples were found to be culture-positive and predominant isolates were Staphylococcus aureus (17.3%), Pseudomonas species (4.5%), Escherichia coli (2%), Corynebacterium species (2%), Staphylococcus species (1.5%) and Enterobacter aerogenes (0.5%). Staphylococcus aureus showed the most resistance to azithromycin (17%) followed by ciprofloxacin (2.8%), nitrofurantoin (2.8%) and chloramphenicol (2.8%). Escherichia coli showed 100% resistance to amoxicillin, cloxacillin and ampicillin, 75% resistance to ciprofloxacin and the least resistance to azithromycin (25%) while it was susceptible to nitrofurantoin. Staphylococcus species, Corynebacterium species, Enterobacter aerogenes and Pseudomonas species showed no resistance to any antibiotics. Conclusion: The study showed the presence of microorganisms with considerable antimicrobial resistance to antibiotics in Zambia on trolley and basket handles indicating the need for more initiatives to address proper hygiene in public environmental sites for better infection prevention and control.

Prevalence of Antimicrobial Resistance of ESKAPE Pathogens before and during Pandemic COVID-19 Pandemic in a University Affiliated Hospital in Tangerang, Indonesia

Introduction: Antimicrobial resistance is the most important health problems currently. Antibiotic prophylaxis to prevent bacterial co-infections in hospitalized COVID-19 patients, and lack of surveillance were associated with antimicrobial resistance. ESKAPE pathogens consisting of E. faecium, S. aureus, K. pneumoniae, A. baumanii, P. aeruginosa and Enterobacter spp. are associated with healthcare-associated infections. Patients and Methods: This descriptive, retrospective, longitudinal study aims to describe the resistance rates of bloodstream infection due to ESKAPE pathogens from patients admitted in Siloam Hospital Karawaci, before and during COVID-19 pandemic (January 1st, 2019 until December 31st, 2022). Out of 296 ESKAPE pathogens collected from blood samples, S. aureus was the most frequent species, followed by K. pneumoniae, A. baumannii, P. aeruginosa, Enterobacter spp., and E. faecium. Results: Resistance rates of E. faecium were alarmingly high from 2019 until 2021, but in 2022 no sample was found. Resistance rates of S. aureus and MRSA decreased from 2019 until 2021 and then increased again in 2022 while for K. pneumoniae it peaked in 2020 and reached the lowest in 2022. Resistance pattern of A. baumanii was not favorable from 2019 until 2021, but decreased dramatically in 2022. Resistance pattern of P. aeruginosa was quite variable in 2021 and 2022 while for Enterobacter spp. it was variable in 2020 to 2022. Conclusion: The COVID-19 pandemic affected the antimicrobial resistance pattern of ESKAPE pathogens in Banten province, Indonesia. Resistance rates increased as the pandemic peaked in 2020 to 2021, and decreased as the pandemic resolves in 2022.

Towards an Antimicrobial Stewardship Program in a Young Tertiary Hospital in Southern Nigeria: A Point Prevalence Survey of Antimicrobial Usage

Background: Antimicrobial resistance (AMR) is one of the top 10 global public health threats facing humanity and this burden is borne largely by low and middle-income countries. As part of efforts to combat AMR, the World Health Organization has identified Antimicrobial Stewardship as one of the strategic objectives of its global action plan on antimicrobial resistance. This survey aimed to observe antimicrobial prescribing and usage patterns in the Rivers State University Teaching Hospital with the purpose of identifying gaps to inform the specific antimicrobial stewardship interventions necessary to address our specific needs. Methodology: A point prevalence survey was conducted using the protocol and web-based automated data management system designed by the Global Point Prevalence Survey of Antimicrobial Consumption and Resistance, University of Antwerp, Belgium, in November 2021. Results: A total of 69 adult medical and surgical patients were surveyed;27 males and 18 females. Antimicrobial prevalence was 65.2%. Third generation cephalosporins (24.4%;33.3%), fluoroquinolones (17.8%;22.2%) and imidazole derivatives (20%;36.1%) were most prescribed on the medical and surgical wards. Antimicrobial guidelines were completely unavailable, most antimicrobials (93.8%) were prescribed empirically and 64.4% of these remained empirical after 72 hours of commencement. Conclusion: Antimicrobial stewardship interventions are necessary to minimize sub-optimal antimicrobial prescribing practices in our facility. Most critical are education on appropriate use of antimicrobials, support for development of antimicrobial guidelines, diagnostic stewardship, and the drive for improved use of the laboratory to guide antimicrobial prescriptions. The antimicrobial stewardship committee and team must drive this, having the requisite support from the management and prescribers, with the primary outcomes being reduced antimicrobial prevalence and improved antimicrobial prescription patterns.

The Triple Combination of Meropenem,Avibactam,and a Metallo-β-Lactamase Inhibitor Optimizes Antibacterial Coverage Against Different β-Lactamase Producers

This work explores the potential of a triple combination of meropenem(MEM),a novel metallo-blactamase(MBL)inhibitor(indole-2-carboxylate 58(InC58)),and a serine-b-lactamase(SBL)inhibitor(avibactam(AVI))for broad-spectrum activity against carbapenemase-producing bacteria.A diverse panel comprising MBL-and SBL-producing strains was used for susceptibility testing of the triple combination using the agar dilution method.The frequency of resistance(FoR)to MEM combined with InC58 was investigated.Mutants were sequenced and tested for cross resistance,fitness,and the stability of the resistance phenotype.Compared with the double combinations of MEM plus an SBL or MBL inhibitor,the triple combination extended the spectrum of activity to most of the isolates bearing SBLs(oxacillinase-48(OXA-48)and Klebsiella pneumoniae carbapenemase-2(KPC-2))and MBLs(New Delhi metallo-blactamases(NDMs)),although it was not effective against Verona integron-encoded metallo-blactamase(VIM)-carrying Pseudomonas aeruginosa(P.aeruginosa)and OXA-23-carrying Acinetobacter baumannii(A.baumannii).The FoR to MEM plus InC58 ranged from 2.22×10^(-7)to 1.13×10^(-6).The resistance correlated with mutations to ompC and comR,affecting porin C and copper permeability,respectively.The mutants manifested a fitness cost,a decreased level of resistance during passage without antibiotic pressure,and cross resistance to another carbapenem(imipenem)and a b-lactamase inhibitor(taniborbactam).In conclusion,compared with the dual combinations,the triple combination of MEM with InC58 and AVI showed a much wider spectrum of activity against different carbapenemaseproducing bacteria,revealing a new strategy to combat b-lactamase-mediated antimicrobial resistance.

Antimicrobial resistance characteristics and phylogenetic relationships of pleuromutilin-resistant Enterococcus isolates from different environmental samples along a laying hen production chain

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.

An Update on the Clinical Pipelines of New Antibacterial Drugs Developed in China

Antibacterial resistance is a global health threat that requires further concrete action on the part of all countries.In this context,one of the biggest concerns is whether enough new antibacterial drugs are being discovered and developed.Although several high-quality reviews on clinical antibacterial drug pipelines from a global perspective were published recently,none provides comprehensive information on original antibacterial drugs at clinical stages in China.In this review,we summarize the latest progress of novel antibacterial drugs approved for marketing and under clinical evaluation in China since 2019.Information was obtained by consulting official websites,searching commercial databases,retrieving literature,asking personnel from institutions or companies,and other means,and a considerable part of the data covered here has not been included in other reviews.As of June 30,2023,a total of 20 antibacterial projects from 17 Chinese pharmaceutical companies or developers were identified and updated.Among them,two new antibacterial drugs that belong to traditional antibiotic classes were approved by the National Medical Products Administration(NMPA)in China in 2019 and 2021,respectively,and 18 antibacterial agents are in clinical development,with one under regulatory evaluation,five in phase-3,six in phase-2,and six in phase-1.Most of the clinical candidates are new analogs or monocomponents of traditional antibacterial pharmacophore types,including two dual-acting hybrid antibiotics and a recombinant antibacterial protein.Overall,despite there being 17 antibacterial clinical candidates,our analysis indicates that there are still relatively few clinically differentiated antibacterial agents in stages of clinical development in China.Hopefully,Chinese pharmaceutical companies and institutions will develop more innovative and clinically differentiated candidates with good market potential in the future research and development(R&D)of original antibacterial drugs.