Pub Date : 2024-05-08DOI: 10.3389/frabi.2024.1362516
Mousumi Shyam, Abhishek Thakur, Caroline Velez, Chris Daniel, Orlando Acevedo, S. Bhakta, Venkatesan Jayaprakash
In response to continued public health emergency of antimicrobial resistance (AMR), a significant key strategy is the discovery of novel mycobacterial efflux-pump inhibitors (EPIs) as potential adjuvants in combination drug therapy. Interest in identifying new chemotypes which could potentially synergize with the existing antibiotics and can be deployed as part of a combination therapy. This strategy could delay the emergence of resistance to existing antibiotics and increase their efficacy against resistant strains of mycobacterial species. In recent decades, notable approaches have been accounted for EPI development and have resulted in the discovery of several EPIs including SQ109 and AU1235. In context, to accelerate newer EPIs with novel mode of action here we have discussed mycobactin analogues and highlighted in silico binding orientation with siderophore efflux-pump proteins MmpL4/5.3-(2-hydroxyphenyl)-5-(aryl)-pyrazoline series was investigated for whole-cell efflux-pump inhibitory activity against Mycobacterium smegmatis and Mycobacterium abscessus. Machine learning and molecular dynamics were performed to construct a MmpL4/5 complex embedded in a lipid bilayer to identify the putative binding site and to predict ligand-protein binding energetics. Furthermore, the identified HIT compound was investigated in synergistic assay with bedaquiline.Compound Il, 2-(5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenol, was identified as the most potent efflux pump inhibitor against M. smegmatis in whole-cell efflux-pump investigation. Followed HIT Il employed against M. abscessus for efflux-pump inhibition investigations and notable whole-cell efflux-pump inhibitory profile has been observed. The theoretical investigations predicted compound Il to be selective towards MmpL4, with significant hydrogen bonding and π-π stacking interactions effectively blocking a critical Asp-Tyr dyad interaction network necessary for proton translocation. Compound Il with bedaquiline highlighted an additive profile against the M. abscessus pathogen.MD simulations and whole-cell assays are indicating potential development of compound Il as an adjunct to the existing therapeutic regimen against mycobacterial infections.
为应对抗菌药耐药性（AMR）这一持续的公共卫生紧急状况，一项重要的关键战略是发现新型分枝杆菌外排泵抑制剂（EPIs），作为联合药物疗法的潜在辅助剂。研究人员有兴趣发现可能与现有抗生素产生协同作用的新化学类型，并将其作为联合疗法的一部分。这种策略可以延缓现有抗生素耐药性的产生，并提高其对耐药性分枝杆菌菌株的疗效。近几十年来，用于 EPI 开发的方法引人注目，并发现了包括 SQ109 和 AU1235 在内的几种 EPI。3-(2-hydroxyphenyl)-5-(aryl)-pyrazoline 系列研究了对烟曲霉分枝杆菌和脓肿分枝杆菌的全细胞外排泵抑制活性。研究人员利用机器学习和分子动力学方法构建了嵌入脂质双分子层的 MmpL4/5 复合物，从而确定了可能的结合位点，并预测了配体与蛋白质的结合能。在全细胞外排泵研究中，化合物 Il，2-(5-(4-氟苯基)-4,5-二氢-1H-吡唑-3-基)苯酚被鉴定为对 M. smegmatis 最有效的外排泵抑制剂。在对脓肿霉菌进行外排泵抑制研究时，使用了 HIT Il，并观察到了显著的全细胞外排泵抑制特征。理论研究预测化合物 Il 对 MmpL4 具有选择性，其显著的氢键和 π-π 堆叠相互作用有效地阻断了质子转运所必需的关键 Asp-Tyr 二元相互作用网络。MD 模拟和全细胞实验表明，化合物 Il 有可能发展成为现有霉菌感染治疗方案的辅助药物。
{"title":"Mycobactin analogue interacting with siderophore efflux-pump protein: insights from molecular dynamics simulations and whole-cell assays","authors":"Mousumi Shyam, Abhishek Thakur, Caroline Velez, Chris Daniel, Orlando Acevedo, S. Bhakta, Venkatesan Jayaprakash","doi":"10.3389/frabi.2024.1362516","DOIUrl":"https://doi.org/10.3389/frabi.2024.1362516","url":null,"abstract":"In response to continued public health emergency of antimicrobial resistance (AMR), a significant key strategy is the discovery of novel mycobacterial efflux-pump inhibitors (EPIs) as potential adjuvants in combination drug therapy. Interest in identifying new chemotypes which could potentially synergize with the existing antibiotics and can be deployed as part of a combination therapy. This strategy could delay the emergence of resistance to existing antibiotics and increase their efficacy against resistant strains of mycobacterial species. In recent decades, notable approaches have been accounted for EPI development and have resulted in the discovery of several EPIs including SQ109 and AU1235. In context, to accelerate newer EPIs with novel mode of action here we have discussed mycobactin analogues and highlighted in silico binding orientation with siderophore efflux-pump proteins MmpL4/5.3-(2-hydroxyphenyl)-5-(aryl)-pyrazoline series was investigated for whole-cell efflux-pump inhibitory activity against Mycobacterium smegmatis and Mycobacterium abscessus. Machine learning and molecular dynamics were performed to construct a MmpL4/5 complex embedded in a lipid bilayer to identify the putative binding site and to predict ligand-protein binding energetics. Furthermore, the identified HIT compound was investigated in synergistic assay with bedaquiline.Compound Il, 2-(5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenol, was identified as the most potent efflux pump inhibitor against M. smegmatis in whole-cell efflux-pump investigation. Followed HIT Il employed against M. abscessus for efflux-pump inhibition investigations and notable whole-cell efflux-pump inhibitory profile has been observed. The theoretical investigations predicted compound Il to be selective towards MmpL4, with significant hydrogen bonding and π-π stacking interactions effectively blocking a critical Asp-Tyr dyad interaction network necessary for proton translocation. Compound Il with bedaquiline highlighted an additive profile against the M. abscessus pathogen.MD simulations and whole-cell assays are indicating potential development of compound Il as an adjunct to the existing therapeutic regimen against mycobacterial infections.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"209 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141002048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-24DOI: 10.3389/frabi.2024.1405401
Francesco Di Gennaro
{"title":"Prescriptive appropriateness of dalbavancin in acute bacterial skin and skin structure infections in adults: an integrated approach between clinical profile, patient- and health system-related factors and focus on environmental impact","authors":"Francesco Di Gennaro","doi":"10.3389/frabi.2024.1405401","DOIUrl":"https://doi.org/10.3389/frabi.2024.1405401","url":null,"abstract":"","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"8 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140661663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-16DOI: 10.3389/frabi.2024.1222580
L. Veerapa-Mangroo, Harena Rasamoelina-Andriamanivo, M.I. Issack, Eric Cardinale
This study aims at determining the pattern of antibiotic consumption and resistance in Mauritius, a tropical island in the Indian Ocean.Antibiotic consumption was measured in kilograms of purchased antibiotics and also in defined daily dose (DDD) in different health institutions from 2015 to 2017. Data on antibiotic resistance was collected at the Central Health Laboratory (CHL) at Victoria Hospital and at Jeetoo Hospital Laboratory, where antibiotic sensitivity testing is done for all public health institutions. For this study, Escherichia coli, Klebsiella species, Acinetobacter species, and Pseudomonas aeruginosa isolates from blood samples of patients from 2015 to 2023 were included. The resistance rate and prevalence of multi-drug-resistant (MDR) organisms were calculated.The amount of antibiotics (in kilograms) distributed to the human sector was between 11,000 to 13,000 kg, compared to only 700 to 1,500 kg in the animal sector. The DDD per 1,000 inhabitants per day was 20.9, 22.1, and 21.7 in 2015, 2016, and 2017, respectively, with a greater consumption of WATCH and RESERVE group antibiotics in the private sector. In public health institutions, health centers in the northern region had the highest DDD per 1,000 outpatients per day for beta-lactams penicillins and quinolones. Concerning antibiotic resistance, the proportion of MDR Acinetobacter baumannii and Pseudomonas aeruginosa has increased from 58% to 74% and from 33% to 45%, respectively, from 2015 to 2023. During the same period, the proportion of E. coli and K. pneumoniae isolates sensitive to ceftriaxone decreased from 55% to 39% and from 37% to 22%, respectively, while the proportion of E. coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa isolates sensitive to meropenem decreased from 98% to 94%, 83% to 53%, 45% to 28%, and 63% to 47%, respectively.This study provides valuable insights on antibiotic consumption and resistance in the country and emphasizes the significance of adopting a One Health approach to combat antimicrobial resistance (AMR) effectively. These findings will aid policymakers in formulating targeted strategies to address the challenge of AMR and should be integrated into the National Action Plan on AMR in Mauritius.
{"title":"Epidemiology of antibiotic consumption and resistance in Mauritius","authors":"L. Veerapa-Mangroo, Harena Rasamoelina-Andriamanivo, M.I. Issack, Eric Cardinale","doi":"10.3389/frabi.2024.1222580","DOIUrl":"https://doi.org/10.3389/frabi.2024.1222580","url":null,"abstract":"This study aims at determining the pattern of antibiotic consumption and resistance in Mauritius, a tropical island in the Indian Ocean.Antibiotic consumption was measured in kilograms of purchased antibiotics and also in defined daily dose (DDD) in different health institutions from 2015 to 2017. Data on antibiotic resistance was collected at the Central Health Laboratory (CHL) at Victoria Hospital and at Jeetoo Hospital Laboratory, where antibiotic sensitivity testing is done for all public health institutions. For this study, Escherichia coli, Klebsiella species, Acinetobacter species, and Pseudomonas aeruginosa isolates from blood samples of patients from 2015 to 2023 were included. The resistance rate and prevalence of multi-drug-resistant (MDR) organisms were calculated.The amount of antibiotics (in kilograms) distributed to the human sector was between 11,000 to 13,000 kg, compared to only 700 to 1,500 kg in the animal sector. The DDD per 1,000 inhabitants per day was 20.9, 22.1, and 21.7 in 2015, 2016, and 2017, respectively, with a greater consumption of WATCH and RESERVE group antibiotics in the private sector. In public health institutions, health centers in the northern region had the highest DDD per 1,000 outpatients per day for beta-lactams penicillins and quinolones. Concerning antibiotic resistance, the proportion of MDR Acinetobacter baumannii and Pseudomonas aeruginosa has increased from 58% to 74% and from 33% to 45%, respectively, from 2015 to 2023. During the same period, the proportion of E. coli and K. pneumoniae isolates sensitive to ceftriaxone decreased from 55% to 39% and from 37% to 22%, respectively, while the proportion of E. coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa isolates sensitive to meropenem decreased from 98% to 94%, 83% to 53%, 45% to 28%, and 63% to 47%, respectively.This study provides valuable insights on antibiotic consumption and resistance in the country and emphasizes the significance of adopting a One Health approach to combat antimicrobial resistance (AMR) effectively. These findings will aid policymakers in formulating targeted strategies to address the challenge of AMR and should be integrated into the National Action Plan on AMR in Mauritius.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"8 3‐4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140698559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-10DOI: 10.3389/frabi.2024.1367936
Alann Caderhoussin, D. Couvin, Gaëlle Gruel, Isaure Quétel, M. Pot, Rémy Arquet, Alexis Dereeper, J. Bambou, Antoine Talarmin, Séverine Ferdinand
This study aimed to understand the origin and to explain the maintenance of extended-spectrum β-lactamase (ESBL) Enterobacteriaceae isolated from food-producing animals in a third-generation cephalosporin (3GC)-free farm.Culture and molecular approaches were used to test molecules other than 3GC such as antibiotics (tetracycline and oxytetracycline), antiparasitics (ivermectin, flumethrin, fenbendazol, and amitraz), heavy metal [arsenic, HNO3, aluminum, HNO3, cadmium (CdSO4), zinc (ZnCl2), copper (CuSO4), iron (FeCl3), and aluminum (Al2SO4)], and antioxidant (butylated hydroxytoluene) as sources of selective pressure. Whole-genome sequencing using short read (Illumina™) and long read (Nanopore™) technologies was performed on 34 genomes. In silico gene screening and comparative analyses were used to characterize the genetic determinants of resistance, their mobility, and the genomic relatedness among isolates.Our analysis unveiled a low diversity among the animal ESBL-producing strains. Notably, E. coli ST3268 was recurrently isolated from both flies (n = 9) and cattle (n = 5). These E. coli ST3268/blaCTX-M-15/blaTEM-1B have accumulated multiple plasmids and genes, thereby representing a reservoir of resistance and virulence factors. Our findings suggest that flies could act as effective mechanical vectors for antimicrobial gene transfer and are capable of transporting resistant bacteria across different environments and to multiple hosts, facilitating the spread of pathogenic traits. A significantly higher mean minimum inhibitory concentration of oxytetracycline (841.4 ± 323.5 mg/L vs. 36.0 ± 52.6 mg/L, p = 0.0022) in ESBL E. coli than in non-ESBL E. coli and blaCTX-M-15 gene overexpression in oxytetracycline-treated vs. untreated ESBL E. coli (RQOxy = 3.593, p = 0.024) confirmed oxytetracycline as a source of selective pressure in ESBL E. coli.The occurrence of ESBL E. coli in a farm without 3GC use is probably due to an as yet undefined human origin of Enterobacteriaceae blaCTX-M-15 gene transmission to animals in close contact with cattle farm workers and the maintenance of the local ESBL E. coli reservoir by a high fly diversity and oxytetracycline selective pressure. These findings highlight the critical need for stringent vector control to mitigate antimicrobial resistance spread for preserving public health. Addressing this issue necessitates a multifaceted approach combining microbial genetics, vector ecology, and farm management practices.
{"title":"The fly route of extended-spectrum-β-lactamase-producing Enterobacteriaceae dissemination in a cattle farm: from the ecosystem to the molecular scale","authors":"Alann Caderhoussin, D. Couvin, Gaëlle Gruel, Isaure Quétel, M. Pot, Rémy Arquet, Alexis Dereeper, J. Bambou, Antoine Talarmin, Séverine Ferdinand","doi":"10.3389/frabi.2024.1367936","DOIUrl":"https://doi.org/10.3389/frabi.2024.1367936","url":null,"abstract":"This study aimed to understand the origin and to explain the maintenance of extended-spectrum β-lactamase (ESBL) Enterobacteriaceae isolated from food-producing animals in a third-generation cephalosporin (3GC)-free farm.Culture and molecular approaches were used to test molecules other than 3GC such as antibiotics (tetracycline and oxytetracycline), antiparasitics (ivermectin, flumethrin, fenbendazol, and amitraz), heavy metal [arsenic, HNO3, aluminum, HNO3, cadmium (CdSO4), zinc (ZnCl2), copper (CuSO4), iron (FeCl3), and aluminum (Al2SO4)], and antioxidant (butylated hydroxytoluene) as sources of selective pressure. Whole-genome sequencing using short read (Illumina™) and long read (Nanopore™) technologies was performed on 34 genomes. In silico gene screening and comparative analyses were used to characterize the genetic determinants of resistance, their mobility, and the genomic relatedness among isolates.Our analysis unveiled a low diversity among the animal ESBL-producing strains. Notably, E. coli ST3268 was recurrently isolated from both flies (n = 9) and cattle (n = 5). These E. coli ST3268/blaCTX-M-15/blaTEM-1B have accumulated multiple plasmids and genes, thereby representing a reservoir of resistance and virulence factors. Our findings suggest that flies could act as effective mechanical vectors for antimicrobial gene transfer and are capable of transporting resistant bacteria across different environments and to multiple hosts, facilitating the spread of pathogenic traits. A significantly higher mean minimum inhibitory concentration of oxytetracycline (841.4 ± 323.5 mg/L vs. 36.0 ± 52.6 mg/L, p = 0.0022) in ESBL E. coli than in non-ESBL E. coli and blaCTX-M-15 gene overexpression in oxytetracycline-treated vs. untreated ESBL E. coli (RQOxy = 3.593, p = 0.024) confirmed oxytetracycline as a source of selective pressure in ESBL E. coli.The occurrence of ESBL E. coli in a farm without 3GC use is probably due to an as yet undefined human origin of Enterobacteriaceae blaCTX-M-15 gene transmission to animals in close contact with cattle farm workers and the maintenance of the local ESBL E. coli reservoir by a high fly diversity and oxytetracycline selective pressure. These findings highlight the critical need for stringent vector control to mitigate antimicrobial resistance spread for preserving public health. Addressing this issue necessitates a multifaceted approach combining microbial genetics, vector ecology, and farm management practices.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"2006 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140718487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-08DOI: 10.3389/frabi.2024.1384390
Christopher Campion, Godefroid Charbon, Peter E. Nielsen, A. Løbner‐Olesen
Initiation of chromosome replication is an essential stage of the bacterial cell cycle that is controlled by the DnaA protein. With the aim of developing novel antimicrobials, we have targeted the initiation of DNA replication, using antisense peptide nucleic acids (PNAs), directed against DnaA translation. A series of anti-DnaA PNA conjugated to lysine-rich bacterial penetrating peptides (PNA-BPPs) were designed to block DnaA translation. These anti-DnaA PNA-BPPs inhibited growth of wild-type Escherichia coli cells at low micromolar concentrations, and cells exposed to anti-DnaA PNA-BPPs exhibited characteristic hallmarks of chromosome replication inhibition. These results present one of very few compounds successfully targeting initiation of chromosome replication, an essential step in the bacterial cell cycle.
{"title":"Targeting synthesis of the Chromosome Replication Initiator Protein DnaA by antisense PNA-peptide conjugates in Escherichia coli","authors":"Christopher Campion, Godefroid Charbon, Peter E. Nielsen, A. Løbner‐Olesen","doi":"10.3389/frabi.2024.1384390","DOIUrl":"https://doi.org/10.3389/frabi.2024.1384390","url":null,"abstract":"Initiation of chromosome replication is an essential stage of the bacterial cell cycle that is controlled by the DnaA protein. With the aim of developing novel antimicrobials, we have targeted the initiation of DNA replication, using antisense peptide nucleic acids (PNAs), directed against DnaA translation. A series of anti-DnaA PNA conjugated to lysine-rich bacterial penetrating peptides (PNA-BPPs) were designed to block DnaA translation. These anti-DnaA PNA-BPPs inhibited growth of wild-type Escherichia coli cells at low micromolar concentrations, and cells exposed to anti-DnaA PNA-BPPs exhibited characteristic hallmarks of chromosome replication inhibition. These results present one of very few compounds successfully targeting initiation of chromosome replication, an essential step in the bacterial cell cycle.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"30 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140729176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-03DOI: 10.3389/frabi.2024.1364946
Shaila Haque, Md. Yusuf Jamil, Md. Shahinul Haque Khan, Md. Sajib Al Reza, Md. Esrafil, M. Abedin, Md. Abu Zubair, Md. Asaduzzaman Sikder, L. Bari
The misuse of antibiotics in poultry farming is a global issue.The focus of this study was the health risk assessment of consumers from the determination of ciprofloxacin (CIP), tetracycline (TC), and oxytetracycline (OTC) in broiler chicken in the raw, frozen, and boiled stages using solid-phase extraction, high-performance liquid chromatography, and ultraviolet detection (SPE-HPLC-UV).Chromatographic separation was achieved using 0.3% metaphosphoric acid and acetonitrile (1:10, v/v) for CIP at 280 nm and oxalic acid (0.01 M) and acetonitrile (1:1, v/v) for TC and OTC at 355 nm with different retention times. The method had an acceptable precision with good linearity, specificity, limit of detection, limit of quantification, accuracy, and stability.Among a total of 252 raw samples, approximately 68.25%, 25.4%, and 7.54% contained CIP, TC, and OTC, respectively. Out of the positive raw samples, CIP exceeded the maximum residual limit (MRL) in 3.6% muscle, 14.3% liver and 17.9% skin samples, whereas TC and OTC were below the MRLs. The residual concentrations of these antibiotics were almost unchanged in frozen samples. After boiling the chicken samples, the TC and OTC residues were reduced significantly compared to CIP. Although the concentrations of CIP in boiled samples were above the MRL set by the European Union, these did not exceed the hazard index 1.Based on these results, the exposure levels to antibiotics in broiler chicken meats may be considered to have a low risk for human health.
{"title":"Health risk assessment of ciprofloxacin, tetracycline, and oxytetracycline residues in raw, frozen, and boiled broiler chicken available in a local area of Bangladesh","authors":"Shaila Haque, Md. Yusuf Jamil, Md. Shahinul Haque Khan, Md. Sajib Al Reza, Md. Esrafil, M. Abedin, Md. Abu Zubair, Md. Asaduzzaman Sikder, L. Bari","doi":"10.3389/frabi.2024.1364946","DOIUrl":"https://doi.org/10.3389/frabi.2024.1364946","url":null,"abstract":"The misuse of antibiotics in poultry farming is a global issue.The focus of this study was the health risk assessment of consumers from the determination of ciprofloxacin (CIP), tetracycline (TC), and oxytetracycline (OTC) in broiler chicken in the raw, frozen, and boiled stages using solid-phase extraction, high-performance liquid chromatography, and ultraviolet detection (SPE-HPLC-UV).Chromatographic separation was achieved using 0.3% metaphosphoric acid and acetonitrile (1:10, v/v) for CIP at 280 nm and oxalic acid (0.01 M) and acetonitrile (1:1, v/v) for TC and OTC at 355 nm with different retention times. The method had an acceptable precision with good linearity, specificity, limit of detection, limit of quantification, accuracy, and stability.Among a total of 252 raw samples, approximately 68.25%, 25.4%, and 7.54% contained CIP, TC, and OTC, respectively. Out of the positive raw samples, CIP exceeded the maximum residual limit (MRL) in 3.6% muscle, 14.3% liver and 17.9% skin samples, whereas TC and OTC were below the MRLs. The residual concentrations of these antibiotics were almost unchanged in frozen samples. After boiling the chicken samples, the TC and OTC residues were reduced significantly compared to CIP. Although the concentrations of CIP in boiled samples were above the MRL set by the European Union, these did not exceed the hazard index 1.Based on these results, the exposure levels to antibiotics in broiler chicken meats may be considered to have a low risk for human health.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"193 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140746588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-02DOI: 10.3389/frabi.2024.1335654
I. Pala-Ozkok, Tugce Katipoglu-Yazan, T. Olmez-Hanci, Daniel Jonas, E. Ubay‐Cokgor, D. Orhon
The aim of this study was to reveal the microbial and kinetic impacts of acute and chronic exposure to one of the frequently administered antibiotics, i.e., sulfamethoxazole, on an activated sludge biomass. Respirometric analysis and model evaluation of the oxygen utilization rate profiles were the backbone of this study. The results showed that continuous exposure to sulfamethoxazole resulted in the inhibition of substrate storage and an increase in the endogenous decay rates by twofold, which was supported by analysis of the resistance genes. A mild inhibition on the growth and hydrolysis kinetics was also observed. Moreover, sulfamethoxazole had a binding impact with available organic carbon, resulting in a slightly less oxygen consumption. DNA sequencing and antibiotic resistance gene analyses showed that continuous exposure to sulfamethoxazole caused a change in the community structure at the species level. Resistant bacteria including Arthrobacter sp. and members of the Chitinophagaceae and Intrasporangiaceae families were found to have dominated the bacterial community. The impact of intermittent exposure was also investigated, and the results indicated a drop in the severity of the impact after 20 days of intermittence.
{"title":"Impact of acute and chronic exposure to sulfamethoxazole on the kinetics and microbial structure of an activated sludge community","authors":"I. Pala-Ozkok, Tugce Katipoglu-Yazan, T. Olmez-Hanci, Daniel Jonas, E. Ubay‐Cokgor, D. Orhon","doi":"10.3389/frabi.2024.1335654","DOIUrl":"https://doi.org/10.3389/frabi.2024.1335654","url":null,"abstract":"The aim of this study was to reveal the microbial and kinetic impacts of acute and chronic exposure to one of the frequently administered antibiotics, i.e., sulfamethoxazole, on an activated sludge biomass. Respirometric analysis and model evaluation of the oxygen utilization rate profiles were the backbone of this study. The results showed that continuous exposure to sulfamethoxazole resulted in the inhibition of substrate storage and an increase in the endogenous decay rates by twofold, which was supported by analysis of the resistance genes. A mild inhibition on the growth and hydrolysis kinetics was also observed. Moreover, sulfamethoxazole had a binding impact with available organic carbon, resulting in a slightly less oxygen consumption. DNA sequencing and antibiotic resistance gene analyses showed that continuous exposure to sulfamethoxazole caused a change in the community structure at the species level. Resistant bacteria including Arthrobacter sp. and members of the Chitinophagaceae and Intrasporangiaceae families were found to have dominated the bacterial community. The impact of intermittent exposure was also investigated, and the results indicated a drop in the severity of the impact after 20 days of intermittence.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"136 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140754531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-08eCollection Date: 2024-01-01DOI: 10.3389/frabi.2024.1380380
Alice Cappello, Ylenia Murgia, Daniele Roberto Giacobbe, Sara Mora, Roberta Gazzarata, Nicola Rosso, Mauro Giacomini, Matteo Bassetti
Antimicrobial resistance in bacteria has been associated with significant morbidity and mortality in hospitalized patients. In the era of big data and of the consequent frequent need for large study populations, manual collection of data for research studies on antimicrobial resistance and antibiotic use has become extremely time-consuming and sometimes impossible to be accomplished by overwhelmed healthcare personnel. In this review, we discuss relevant concepts pertaining to the automated extraction of antibiotic resistance and antibiotic prescription data from laboratory information systems and electronic health records to be used in clinical studies, starting from the currently available literature on the topic. Leveraging automatic extraction and standardization of antimicrobial resistance and antibiotic prescription data is an tremendous opportunity to improve the care of future patients with severe infections caused by multidrug-resistant organisms, and should not be missed.
{"title":"Automated extraction of standardized antibiotic resistance and prescription data from laboratory information systems and electronic health records: a narrative review.","authors":"Alice Cappello, Ylenia Murgia, Daniele Roberto Giacobbe, Sara Mora, Roberta Gazzarata, Nicola Rosso, Mauro Giacomini, Matteo Bassetti","doi":"10.3389/frabi.2024.1380380","DOIUrl":"10.3389/frabi.2024.1380380","url":null,"abstract":"<p><p>Antimicrobial resistance in bacteria has been associated with significant morbidity and mortality in hospitalized patients. In the era of big data and of the consequent frequent need for large study populations, manual collection of data for research studies on antimicrobial resistance and antibiotic use has become extremely time-consuming and sometimes impossible to be accomplished by overwhelmed healthcare personnel. In this review, we discuss relevant concepts pertaining to the automated extraction of antibiotic resistance and antibiotic prescription data from laboratory information systems and electronic health records to be used in clinical studies, starting from the currently available literature on the topic. Leveraging automatic extraction and standardization of antimicrobial resistance and antibiotic prescription data is an tremendous opportunity to improve the care of future patients with severe infections caused by multidrug-resistant organisms, and should not be missed.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"3 ","pages":"1380380"},"PeriodicalIF":0.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-27DOI: 10.3389/frabi.2024.1321368
Olivia S. K. Chan, W. Lam, Tint Naing, Dorothy Yuen Ting Cheong, Elaine Lee, Ben Cowling, Matthew Low
Clinicians need to prescribe antibiotics in a way that adequately treats infections, while simultaneously limiting the development of antibiotic resistance (ABR). Although there are abundant guidelines on how to best treat infections, there is less understanding of how treatment durations and antibiotic types influence the development of ABR. This study adopts a self-controlled case study (SCCS) method to relate antibiotic exposure time to subsequent changes in resistance patterns. This SCCS approach uses antibiotic exposure as a risk factor, and the development of ABR as an incidence rate ratio (IRR), which can be considered as the multiplicative change in risk for bacteria to become or maintain resistance.To investigate the IRR of extensive (more than 7 antibiotic classes), revert, persistent, and directed antibiotic resistance according to the duration and type of antibiotic exposures in Escherichia coli (E. coli).We use anonymized veterinary clinical data from dog and cat patients older than 6 months between 2015 and 2020. Patients were considered suitable cases if they received antibiotics and had a minimum of two urinary antibiograms within a 12-month period (the first prior to antibiotics exposure and the second from 1 week to 6 months after exposure). The first antibiogram is conducted before antibiotic exposure (case n=20).From 20 individuals and 42 paired antibiograms we found that the IRR = 2 for extensive drug resistance in patients who received short-course antibiotic treatment compared to longer treatments. In contrast, multi-drug resistance IRR = 2.6 for long-course compared to short-course antibiotic treatment. The ratio of E. coli isolates that reverted from resistant to sensitive was 5.4 times more likely in patients who received antibiotics for longer than 10 days.
{"title":"Examining pharmacoepidemiology of antibiotic use and resistance in first-line antibiotics: a self-controlled case series study of Escherichia coli in small companion animals","authors":"Olivia S. K. Chan, W. Lam, Tint Naing, Dorothy Yuen Ting Cheong, Elaine Lee, Ben Cowling, Matthew Low","doi":"10.3389/frabi.2024.1321368","DOIUrl":"https://doi.org/10.3389/frabi.2024.1321368","url":null,"abstract":"Clinicians need to prescribe antibiotics in a way that adequately treats infections, while simultaneously limiting the development of antibiotic resistance (ABR). Although there are abundant guidelines on how to best treat infections, there is less understanding of how treatment durations and antibiotic types influence the development of ABR. This study adopts a self-controlled case study (SCCS) method to relate antibiotic exposure time to subsequent changes in resistance patterns. This SCCS approach uses antibiotic exposure as a risk factor, and the development of ABR as an incidence rate ratio (IRR), which can be considered as the multiplicative change in risk for bacteria to become or maintain resistance.To investigate the IRR of extensive (more than 7 antibiotic classes), revert, persistent, and directed antibiotic resistance according to the duration and type of antibiotic exposures in Escherichia coli (E. coli).We use anonymized veterinary clinical data from dog and cat patients older than 6 months between 2015 and 2020. Patients were considered suitable cases if they received antibiotics and had a minimum of two urinary antibiograms within a 12-month period (the first prior to antibiotics exposure and the second from 1 week to 6 months after exposure). The first antibiogram is conducted before antibiotic exposure (case n=20).From 20 individuals and 42 paired antibiograms we found that the IRR = 2 for extensive drug resistance in patients who received short-course antibiotic treatment compared to longer treatments. In contrast, multi-drug resistance IRR = 2.6 for long-course compared to short-course antibiotic treatment. The ratio of E. coli isolates that reverted from resistant to sensitive was 5.4 times more likely in patients who received antibiotics for longer than 10 days.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"29 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140424604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-21DOI: 10.3389/frabi.2024.1374463
Márió Gajdács, Shazia Jamshed
{"title":"Editorial: Knowledge, attitude and practices of the public and healthcare-professionals towards sustainable use of antimicrobials: the intersection of pharmacology and social medicine","authors":"Márió Gajdács, Shazia Jamshed","doi":"10.3389/frabi.2024.1374463","DOIUrl":"https://doi.org/10.3389/frabi.2024.1374463","url":null,"abstract":"","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140445651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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