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Demonstration of phage inhibitory action against Clostridium perfringens LMG 11264 within a complex chicken cecal microbiota in vitro. 鸡盲肠菌群中噬菌体对产气荚膜梭菌LMG 11264的体外抑制作用。
Frontiers in antibiotics Pub Date : 2025-09-18 eCollection Date: 2025-01-01 DOI: 10.3389/frabi.2025.1599939
Maria Wiese, Eline S Klaassens, Volmar Hatt, Angelique Kreikamp, Mirna L Baak, Margreet Heerikhuisen, Jos M B M Van Der Vossen
{"title":"Demonstration of phage inhibitory action against <i>Clostridium perfringens</i> LMG 11264 within a complex chicken cecal microbiota <i>in vitro</i>.","authors":"Maria Wiese, Eline S Klaassens, Volmar Hatt, Angelique Kreikamp, Mirna L Baak, Margreet Heerikhuisen, Jos M B M Van Der Vossen","doi":"10.3389/frabi.2025.1599939","DOIUrl":"10.3389/frabi.2025.1599939","url":null,"abstract":"<p><strong>Introduction: </strong><i>Clostridium perfringens</i> strains may cause foodborne illness, and 95% of human infections are linked to the consumption of contaminated meat, including chicken products. In poultry, <i>C. perfringens</i> infection may cause necrotic enteritis, and infections are associated with high mortality rates partially due to antibiotic resistance, which hampers efficient treatment. <i>In-vitro</i> screening approaches of alternative treatment options, for instance, specific phages, represent a promising strategy for the selection of novel interventions to combat infections.</p><p><strong>Material and methods: </strong>In this study, we explored the application of a <i>C. perfringens</i> strain LMG 11264-specific phage #7 introduced at 10<sup>4</sup> pfu/mL to inhibit the growth of <i>C. perfringens</i> at 10<sup>6</sup> cfu/mL compared to two antibiotics (amoxicillin at 10 µg/mL and clindamycin at 10 µg/mL) within complex chicken cecal microbiota <i>in vitro.</i> Samples for gDNA isolation, qPCR, and metagenome sequencing were taken at the beginning and after 24 and 48 h of incubation.</p><p><strong>Results: </strong>The <i>C. perfringens</i> strain LMG 11264 proliferated within the untreated complex microbiota and reached levels of approximately 10<sup>8</sup> and 10<sup>9</sup> genome equivalents per mL after 24 and 48 h of incubation, respectively. The phage intervention with phage #7 inhibited the growth of <i>C. perfringens</i> LMG 11264 significantly; the inhibitory effects were similar to those exerted by the antibiotic intervention with amoxicillin and stronger than the inhibitory effects with clindamycin. In the absence of the <i>C. perfringens</i> challenge, we found a significant effect of amoxicillin (<i>p</i> = 0.040) or clindamycin (<i>p</i> = 0.000017) compared to the untreated control after 24 h of incubation, and the phage addition did not affect the alpha diversity expressed as Chao index significantly (<i>p</i> = 1). In addition, the endogenous <i>C. perfringens</i> in the chicken microbiota appeared insensitive to phage #7. The phage titer of phage #7 only increased in the presence of the inoculated <i>C. perfringens</i> strain LMG 11264. In conclusion, the i-screen model can be implemented to test the efficacy and specificity of phage therapy <i>in vitro.</i></p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"4 ","pages":"1599939"},"PeriodicalIF":0.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234199","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}
引用次数: 0
Zoonotic potential of ESBL-producing coliforms in pastorally managed ruminants with subclinical mastitis in Plateau State, Nigeria. 尼日利亚高原州畜牧管理的亚临床乳腺炎反刍动物中产生esbl大肠菌的人畜共患潜力
Frontiers in antibiotics Pub Date : 2025-09-15 eCollection Date: 2025-01-01 DOI: 10.3389/frabi.2025.1632264
Kenneth Nnamdi Anueyiagu, Ebere Roseann Agusi, Dennis Kabantiyok, Grace Mebi Ayanbimpe, Eugene Ifeanyichukwu Ikeh
{"title":"Zoonotic potential of ESBL-producing coliforms in pastorally managed ruminants with subclinical mastitis in Plateau State, Nigeria.","authors":"Kenneth Nnamdi Anueyiagu, Ebere Roseann Agusi, Dennis Kabantiyok, Grace Mebi Ayanbimpe, Eugene Ifeanyichukwu Ikeh","doi":"10.3389/frabi.2025.1632264","DOIUrl":"10.3389/frabi.2025.1632264","url":null,"abstract":"<p><strong>Background: </strong>Environmental coliform bacteria are frequently the cause of subclinical mastitis (SCM), a serious health issue in the dairy industry. Extended-spectrum β-lactamase (ESBL)-producing coliforms in livestock are a serious public health concern, particularly in environments where people and animals coexist. With an emphasis on their zoonotic and One Health implications, this study sought to evaluate the incidence of SCM and the occurrence of ESBL-producing coliforms in ruminants in Plateau State, Nigeria.</p><p><strong>Methods: </strong>The California Mastitis Test (CMT) was used to screen 287 milk samples that were taken from cows, ewes, and does. Standard microbiological methods were used to identify the bacterial isolates from CMT-positive samples. The presence of resistance genes (<i>bla</i> <sub>TEM</sub> and <i>bla</i> <sub>CTX-M</sub>) was ascertained by PCR, and ESBL production was confirmed phenotypically. Phylogenetic analysis showed genetic diversity and possible horizontal gene transfer among isolates.</p><p><strong>Results: </strong>Out of 287 milk samples, 79 (27.5%) had subclinical mastitis through the CMT, with a higher prevalence recorded in does 18(22.8%) while ewes and cows recorded 23(29.1%), and 38(48.1%) respectively. Of the 79 CMT-positive samples, the following isolates were identified: <i>Citrobacter freundii</i> (6.3%), <i>Klebsiella pneumoniae</i> (21.6%), <i>K. oxytoca</i> (2.5%), <i>K. aerogenes</i> (6.3%), and <i>E. coli</i>, being the most prevalent in cows (71%). Through PCR, 46 isolates expressed two important ESBL genes, <i>bla</i> <sub>TEM</sub> and <i>bla</i> <sub>CTX-M.</sub></p><p><strong>Conclusion: </strong>A possible zoonotic reservoir for antibiotic resistance in Nigeria is highlighted by the increased frequency of ESBL-producing coliforms in ruminants with SCM. These results highlight the necessity of implementing integrated One Health initiatives, such as public education, surveillance, and antimicrobial stewardship, in order to reduce the risk of resistant pathogen transmission from animals to people.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"4 ","pages":"1632264"},"PeriodicalIF":0.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202012","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}
引用次数: 0
An evaluation of antibiotic options for the treatment of biothreat pathogens. 评估治疗生物威胁病原体的抗生素选择。
Frontiers in antibiotics Pub Date : 2025-08-14 eCollection Date: 2025-01-01 DOI: 10.3389/frabi.2025.1611588
J Matthew Meinig, Michelle Nelson, Christopher K Cote, Stevan R Emmett, Sarah V Harding
{"title":"An evaluation of antibiotic options for the treatment of biothreat pathogens.","authors":"J Matthew Meinig, Michelle Nelson, Christopher K Cote, Stevan R Emmett, Sarah V Harding","doi":"10.3389/frabi.2025.1611588","DOIUrl":"10.3389/frabi.2025.1611588","url":null,"abstract":"<p><p>The development of medical countermeasures against pathogens of biodefense concern remains critical to protecting military and public health. This review compares data detailing antibacterial activity and efficacy for a selection of antibiotics evaluated against potential bacterial biothreat pathogens. The human safety and tolerability of these formulations were also considered. This review includes finafloxacin, levofloxacin, delafloxacin, omadacycline, gepotidacin, tebipenem and sulopenem. The selection criteria of these antibiotics were 1) the availability of an oral formulation, 2) the regulatory status (licensed by a regulatory authority or in an advanced stage of development) and 3) the availability of publicly available information on the biodefence pathogens of concern. We hope to highlight approved or advanced clinical candidates that have significant and unique potential in the biodefense space which may be deployed to protect both the public and warfighter against these bacterial infections.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"4 ","pages":"1611588"},"PeriodicalIF":0.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980967","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}
引用次数: 0
Assessment of antibiotic utilization patterns in an Indian Level-1 Trauma Center: a pilot study exploring days of antibiotic spectrum coverage and defined daily doses using WHO AWaRe classification trends. 评估印度一级创伤中心的抗生素使用模式:一项利用世卫组织AWaRe分类趋势探索抗生素谱覆盖天数和确定日剂量的试点研究。
Frontiers in antibiotics Pub Date : 2025-07-15 eCollection Date: 2025-01-01 DOI: 10.3389/frabi.2025.1578217
M Nizam Ahmed, Arpan Kumar Thakur, Smriti Srivastava, Aparna Ningombam, Madhavi Kirti, Sushma Sagar, Keshav Goyal, Subodh Kumar, Ashish Bindra, Gyaninder Pal Singh, Navdeep Sokhal, Richa Aggarwal, Vijay Sharma, Samarth Mittal, Kamran Farooque, Purva Mathur
{"title":"Assessment of antibiotic utilization patterns in an Indian Level-1 Trauma Center: a pilot study exploring days of antibiotic spectrum coverage and defined daily doses using WHO AWaRe classification trends.","authors":"M Nizam Ahmed, Arpan Kumar Thakur, Smriti Srivastava, Aparna Ningombam, Madhavi Kirti, Sushma Sagar, Keshav Goyal, Subodh Kumar, Ashish Bindra, Gyaninder Pal Singh, Navdeep Sokhal, Richa Aggarwal, Vijay Sharma, Samarth Mittal, Kamran Farooque, Purva Mathur","doi":"10.3389/frabi.2025.1578217","DOIUrl":"10.3389/frabi.2025.1578217","url":null,"abstract":"<p><strong>Background: </strong>Rising antimicrobial resistance (AMR) necessitates innovative metrics, such as days of antibiotic spectrum coverage (DASC), to optimize antibiotic stewardship. This study evaluated antibiotic use in an Indian trauma center using DASC, defined daily doses (DDD), and the World Health Organization (WHO) Access, Watch, Reserve (AWaRe) classification.</p><p><strong>Methods: </strong>This retrospective cohort study analyzed data from 1,812 adult inpatients (mean age: 35 years; 70% male; 80% with polytrauma) admitted to a 250-bed Level-1 Trauma Center at the All India Institute of Medical Sciences (AIIMS), India, from August to October 2022. We measured days of therapy (DOT), DDD, and DASC for 46 antibiotics across 12 pathogens [e.g., methicillin-susceptible <i>Staphylococcus aureus</i> (MSSA), carbapenem-resistant <i>Enterobacteriaceae</i>]. DASC scores were developed through expert consensus and local antibiogram data, and validated using Pearson's correlation with DOT (R = 0.43, p < 0.1) and DDD (R = 0.21). Differences in antibiotic usage between the ICU and ward were analyzed using a t-test in R software.</p><p><strong>Results: </strong>Total antibiotic consumption was 81,064.6 g (3,142 DDD/1,000 patient-days). The Watch group antibiotics dominated usage (37%, 16,018.6 g), resulting in a low Access-to-Watch ratio (0.47). ICU settings showed higher DDD values (326 vs. 193/1,000 patient-days, p < 0.05) and DASC/DOT ratios (mean: 3; 95% CI: 2.73-4.01). Piperacillin-tazobactam accounted for the largest share of the Watch category use (5,952.9 g). DASC values (mean 4401.5, 95% CI: 3592-5211.1) showed a moderate correlation with DOT (R = 0.43, p < 0.1), offering spectrum-specific insights.</p><p><strong>Conclusions: </strong>Excessive use of the Watch group antibiotics contributes significantly to AMR. However, DASC's novel, spectrum-focused approach offers a transformative tool for antibiotic stewardship, supporting targeted de-escalation and improved benchmarking. These findings underscore the urgent need for policy reforms to enforce adherence to the WHO AWaRe classification in Indian centers, potentially reducing AMR-related mortality (30% higher with resistant infections). Integrating DASC into global Antimicrobial stewardship (AMS) programs may redefine antibiotic prescribing practices and help mitigate the AMR crisis.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"4 ","pages":"1578217"},"PeriodicalIF":0.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12304517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746349","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}
引用次数: 0
National antibiotic consumption for human use in Chad (2017-2021): a descriptive cross-sectional study. 乍得人用抗生素全国消费量(2017-2021年):一项描述性横断面研究。
Frontiers in antibiotics Pub Date : 2025-07-11 eCollection Date: 2025-01-01 DOI: 10.3389/frabi.2025.1612557
Zongo R Frank Edgard, Kadidjia Bakari Traoré, Colette Ngabéré, Martine Yoyammel, Abatcha Oumar Kadai, John Eyong Efobi, Mathieu Hota, Didi Lamireou, Badawi Haroun Mahamat, Hamit Mahamat Alio, Jacques L Tamuzi, Patrick D M C Katoto, Charles S Wiysonge, Blanche-Philomene Melanga Anya
{"title":"National antibiotic consumption for human use in Chad (2017-2021): a descriptive cross-sectional study.","authors":"Zongo R Frank Edgard, Kadidjia Bakari Traoré, Colette Ngabéré, Martine Yoyammel, Abatcha Oumar Kadai, John Eyong Efobi, Mathieu Hota, Didi Lamireou, Badawi Haroun Mahamat, Hamit Mahamat Alio, Jacques L Tamuzi, Patrick D M C Katoto, Charles S Wiysonge, Blanche-Philomene Melanga Anya","doi":"10.3389/frabi.2025.1612557","DOIUrl":"10.3389/frabi.2025.1612557","url":null,"abstract":"<p><strong>Background: </strong>Antibiotic resistance (ABR) to commonly used antibiotics is significant in sub-Saharan Africa (SSA). In SSA, Chad has one of the highest antimicrobial resistance (AMR) rates. The link between ABR and antibiotic consumption (ABC) is well-established. However, no ABC-related studies have been conducted in Chad recently. The purpose of this study is to examine the trajectory of ABC in Chad from 2017 to 2021, using the World Health Organization's (WHO) Access, Watch, and Reserve (AWaRe) antibiotic classification.</p><p><strong>Methods: </strong>A descriptive retrospective study was conducted in N'Djamena, using antibiotic import and distribution data collected from the General Directorate of Pharmacy and four wholesale distributors of medicines. The defined daily doses (DDDs) and the mean relative change (MRC) were used to compute the results. Results were presented in terms of tables and graphs. The results were compared to the WHO's guidelines for ABC use via the AWaRe categorization.</p><p><strong>Results: </strong>Between 2017 and 2021, an average ABC of 2.5 doses per inhabitant per year was observed, peaking in 2020 at 5.3 doses per inhabitant. In terms of DDD, the ten most commonly consumed antibiotics during the time, in descending order, were amoxicillin, ampicillin, sulfamethoxazole/trimethoprim, doxycycline, ciprofloxacin, phenoxymethyl-penicillin, erythromycin, ceftriaxone, azithromycin, and gentamicin. However, the MRC analysis detected an increase in benzathine benzyl penicillin, benzylpenicillin, ampicillin, amoxicillin+clavulanic acid, flucloxacillin, ceftriaxone, cefixime, cefpodoxime and cefalexin, cotrimoxazole, ciprofloxacin, levofloxacin, norfloxacin, ofloxacin, and azithromycin. Controversially, amoxicillin, cefotaxime, doxycycline, erythromycin, and moxifloxacin had a lower MRC from 2017 to 2021. Although 90% of the ABC are from the \"Access\" group, the \"Watch\" group has increased over time.</p><p><strong>Conclusions: </strong>Our findings indicated a significant ABC in the Chadian population from 2017 to 2021, which may elucidate the country's elevated ABR. On average, 90% of ABC were categorized in the \"Access\" group, although utilization of the Watch group increased over time. This requires the prompt implementation of the monitoring system for ABC at all tiers in Chad.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"4 ","pages":"1612557"},"PeriodicalIF":0.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12290472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735784","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}
引用次数: 0
Temporal dynamics of antimicrobial resistance gene abundances in chicken manure and anaerobic digestate. 鸡粪和厌氧消化液中抗微生物基因丰度的时间动态。
Frontiers in antibiotics Pub Date : 2025-06-27 eCollection Date: 2025-01-01 DOI: 10.3389/frabi.2025.1612886
Aleksandra Atanasova, Thomas Amon, Uwe Roesler, Anika Friese, Roswitha Merle, Tina Kabelitz
{"title":"Temporal dynamics of antimicrobial resistance gene abundances in chicken manure and anaerobic digestate.","authors":"Aleksandra Atanasova, Thomas Amon, Uwe Roesler, Anika Friese, Roswitha Merle, Tina Kabelitz","doi":"10.3389/frabi.2025.1612886","DOIUrl":"10.3389/frabi.2025.1612886","url":null,"abstract":"<p><strong>Introduction: </strong>Antimicrobial resistance (AMR) can spread in microorganisms through the transfer of antimicrobial resistance genes (ARGs). Livestock husbandry is one of the pathways for AMR emergence and transmission. Chicken manure contains valuable nutrients for agricultural field fertilization and can be used as input material for biogas production by anaerobic digestion (AD). However, usually, chicken manure also contains quite high levels of ARGs. In this study, we investigated the presence and temporal dynamics of ARGs against different antibiotic classes in chicken manure and anaerobic digestate as a source of AMR spread.</p><p><strong>Methods: </strong>To get an overview of the ARG profiles, we quantified the abundances of 374 ARGs by high-throughput (HT)-PCR. We studied eight selected ARGs (<i>tetA</i>, <i>tetX</i>, <i>sul1</i>, <i>sul2</i>, <i>lnuF</i>, <i>emrD</i>, <i>aadA</i>, and <i>tnpA</i>) using qPCR in chicken manure from different flocks and animal ages and in digestate from different AD time points.</p><p><strong>Results: </strong>Chicken manure showed higher amounts of ARGs compared to digestate, which was characterized by a higher ARG diversity. We observed that the effect of chicken age differed between the flocks. ARG abundances in digestate from different time points and different treatment conditions did not exhibit major changes.</p><p><strong>Conclusion: </strong>The flocks' variability had no relevant effect on ARG abundances in chicken manure, likely due to similar growth conditions. However, manure ARG content increased with the age of the chickens. In our experimental batch setup, AD was more effective in reducing AMR microorganisms than reducing ARGs. Further investigations on process optimization or the application of pre-treatment methods could enhance ARG reduction. Notably, pre-mixing chicken manure with material from a biogas plant prior to processing resulted in a lower ARG load compared to untreated chicken manure.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"4 ","pages":"1612886"},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12245806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627890","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}
引用次数: 0
Synergistic effects of Pandanus fascicularis extracts and azithromycin: in vitro and in silico antimicrobial investigation against MDR clinical strains. 束状豆提取物与阿奇霉素协同作用:体外和室内对耐多药临床菌株的抗菌研究。
Frontiers in antibiotics Pub Date : 2025-05-29 eCollection Date: 2025-01-01 DOI: 10.3389/frabi.2025.1552382
Mst Hajera Khatun, Md Rashedul Islam, Shikha Khatun, Amro Ahmed Zalah, Md Hadisur Rahman Rony, Mst Munira Khatun, Emad Essa A Wasili, Jaytirmoy Barmon, Saad Ahmed Sami, Abdulrahman Hadi Masmali, Ishtiaq Qadri
{"title":"Synergistic effects of <i>Pandanus fascicularis</i> extracts and azithromycin: <i>in vitro</i> and <i>in silico</i> antimicrobial investigation against MDR clinical strains.","authors":"Mst Hajera Khatun, Md Rashedul Islam, Shikha Khatun, Amro Ahmed Zalah, Md Hadisur Rahman Rony, Mst Munira Khatun, Emad Essa A Wasili, Jaytirmoy Barmon, Saad Ahmed Sami, Abdulrahman Hadi Masmali, Ishtiaq Qadri","doi":"10.3389/frabi.2025.1552382","DOIUrl":"10.3389/frabi.2025.1552382","url":null,"abstract":"<p><strong>Background: </strong>Antibiotic-resistant bacteria are becoming a significant global concern. To combat the spread of resistance or reverse multidrug resistance, developing novel antimicrobials and/or resistance modulators is essential. This study aimed to evaluate the synergistic effects of the methanolic extract of <i>Pandanus fascicularis</i> fruits (MEPFF) in combination with azithromycin against multidrug-resistant bacteria.</p><p><strong>Methods: </strong>Phytochemical analysis along with the determination of total phenolic content (TPC), total flavonoid content (TFC), and total antioxidant capacity (TAC) of MEPFF, was performed using standard procedure. The extract's DPPH free radical scavenging activity was assessed to evaluate its potential antioxidant activity. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of MEPFF against <i>Staphylococcus aureus</i>, <i>Bacillus cereus</i>, <i>Escherichia coli</i>, and <i>Pseudomonas aeruginosa</i> were determined, followed by an analysis of the synergistic effect with azithromycin, as well as the activity of azithromycin alone. Subsequently, the drug-likeness, antibacterial activity, and toxicological properties were analyzed using in silico tools.</p><p><strong>Results: </strong>The quantitative investigation found terpenoids, flavonoids, tannins, phenolics, saponins, cardiac glycosides, and alkaloids in MEPFF. The TFC, TPC, and TAC of MEPFF were found at 183 ± 9.54 mg QE, 248.33 ± 11.06 mg GAE, and 95.33 ± 8.33 mg AAE/gm extract. The extract showed significant antioxidant activity in the DPPH experiment, with an IC50 value of 12.13±0.53 µg/ml. Azithromycin and the extract together have far greater antibacterial action against all four bacterial strains. The minimal inhibitory concentration (MIC) is 3.67 ± 1.15 to 5.83 ± 0.76 mg/mL, while the minimum bactericidal concentration (MBC) is 4.33 ± 1.26 to 7.33 ± 1.04 mg/mL. In silico studies revealed that pandamarilactone-1, nonpandamarilactone-B, and thiamine had the best docking energy (-9.9, -8.9, and -8.5 kcal/mol), suggesting most active compounds against MPh-II protein.</p><p><strong>Conclusion: </strong>The extract enhances antibiotic therapy and suggests that the aforesaid synergistic drug-herb combinations may treat MDR bacterial infections.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"4 ","pages":"1552382"},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287433","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}
引用次数: 0
Inclusion of patient-centered, non-microbiological endpoints and biomarkers in tuberculosis drug trials. 在结核病药物试验中纳入以患者为中心的非微生物终点和生物标志物。
Frontiers in antibiotics Pub Date : 2025-05-22 eCollection Date: 2025-01-01 DOI: 10.3389/frabi.2025.1570989
Andrew R DiNardo, Wilbert Sabiiti, Stephen H Gillespie, Sophia B Georghiou, Norbert Heinrich, Norbert Hittel, Sami Taghlabi, Danna Carrero Longlax, Mikashmi Kohli, Ursula Panzner, Collins Musia, Christoph Lange, Anca Vasiliu, Rob J W Arts, Anna M Mandalakas, Morten Ruhwald, Lieven J Stuyver, Reinout van Crevel
{"title":"Inclusion of patient-centered, non-microbiological endpoints and biomarkers in tuberculosis drug trials.","authors":"Andrew R DiNardo, Wilbert Sabiiti, Stephen H Gillespie, Sophia B Georghiou, Norbert Heinrich, Norbert Hittel, Sami Taghlabi, Danna Carrero Longlax, Mikashmi Kohli, Ursula Panzner, Collins Musia, Christoph Lange, Anca Vasiliu, Rob J W Arts, Anna M Mandalakas, Morten Ruhwald, Lieven J Stuyver, Reinout van Crevel","doi":"10.3389/frabi.2025.1570989","DOIUrl":"10.3389/frabi.2025.1570989","url":null,"abstract":"<p><p>Tuberculosis drug trials are primarily designed to identify antibiotic regimens with the strongest potency to kill <i>Mycobacterium tuberculosis</i>. However, microbiologic cure is not synonymous with improved health and recovery. Beyond antimicrobial efficacy, parameters such as morbidity and mortality related to lung function, cardiovascular health, and cancer should be prioritized. This narrative review emphasizes the critical need to emphasize clinical outcomes as much, if not more, than microbiological endpoints. We examine the underlying pathophysiological mechanisms and determinants of non-microbiological outcomes in tuberculosis, providing a synthesis of current knowledge. While there is growing evidence for some biomarkers to risk stratify TB patients for risk of all-cause mortality, relapse, or lung damage, no evidence was found on TB-associated cancer or cardiovascular disease. In addition to monitoring microbiologic outcomes, clinical trials and treatment cohorts need to capture patient-centered health dimensions more broadly. Finally, we highlight key research gaps and opportunities to evaluate non-microbiological biomarkers, aiming to improve patient monitoring and enable stratified approaches to tuberculosis management.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"4 ","pages":"1570989"},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236026","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}
引用次数: 0
The burden, risk factors, and antimicrobial susceptibility pattern associated with extended-spectrum beta-lactamase-producing E. coli and K. pneumoniae carriage among neonates and their surroundings at a referral hospital in the Moshi municipality. 莫希市一家转诊医院新生儿及其周围环境中产生广谱β -内酰胺酶的大肠杆菌和肺炎克雷伯菌携带的负担、危险因素和抗菌药物敏感性模式
Frontiers in antibiotics Pub Date : 2025-05-21 eCollection Date: 2025-01-01 DOI: 10.3389/frabi.2025.1556842
Happyness J Mshana, Dorottya Kovacs, Florida Muro, Ruth Zadoks, Katarina Oravcova, Louise Matthews, Blandina T Mmbaga
{"title":"The burden, risk factors, and antimicrobial susceptibility pattern associated with extended-spectrum beta-lactamase-producing <i>E. coli</i> and <i>K. pneumoniae</i> carriage among neonates and their surroundings at a referral hospital in the Moshi municipality.","authors":"Happyness J Mshana, Dorottya Kovacs, Florida Muro, Ruth Zadoks, Katarina Oravcova, Louise Matthews, Blandina T Mmbaga","doi":"10.3389/frabi.2025.1556842","DOIUrl":"10.3389/frabi.2025.1556842","url":null,"abstract":"<p><strong>Introduction: </strong>Infections are a major driver of broad-spectrum antibiotic use. This wide use of antibiotics contributes to the emergence of antimicrobial resistance globally that poses a threat to human and animal health. Infections continue to be a major cause of death among pregnant women and neonates. Therefore, this study aimed to assess the burden of extended-spectrum beta-lactamase (ESBL)-producing <i>E. coli</i> and <i>K. pneumoniae</i> carriage among neonates and their surroundings admitted to a referral hospital in Northeast Tanzania.</p><p><strong>Methodology: </strong>The burden of ESBL-producing <i>E. coli</i> and <i>K. pneumoniae</i> in a neonatal ward was assessed by screening neonates' rectums, maternal and healthcare workers' hands, and neonatal cots. Isolates were cultured, identified, and tested for antimicrobial resistance, while generalized linear models identified risk factors for carriage.</p><p><strong>Results: </strong>A total of 437 neonates were screened for ESBL-producing <i>E. coli</i> and <i>K. pneumoniae</i>, with 235 (54%) being male. In addition, 77 maternal hand swabs, 118 neonatal cots, and 45 healthcare workers' hand swabs were collected. ESBL-producing <i>K. pneumoniae</i> was isolated from 198 neonates (45%), and <i>E. coli</i> from 96 (23%). Additionally, 5% of maternal hands and 22% of neonatal cots were contaminated with these resistant bacteria. Overall ampicillin resistance was frequent in ESBL-producing <i>E. coli</i> and ESBL <i>K. pneumoniae</i> neonatal colonization (n=261,100%), as was resistance to trimethoprim-sulfamethoxazole (<i>n</i> = 233,89%), gentamicin (<i>n</i> = 169, 66%), and tetracycline (<i>n</i> = 140,54%). Only three (1%) of the ESBL-producing <i>E. coli</i> and ESBL <i>K. pneumoniae</i> isolates were resistant to meropenem. Risk factors significantly associated with carriage of either ESBL-producing <i>E. coli</i> or <i>K. pneumoniae</i> were being born in an admission room [odds ratio (OR)=1.95, confidence interval (CI)=1.31-3.13, p=0.006] and delivery mode, with vaginal delivery associated with a reduced risk of carriage (OR=0.57, CI=0.35-0.92, p=0.023).</p><p><strong>Conclusion: </strong>The study reveals a high burden of ESBL-producing <i>K. pneumoniae</i> and <i>E. coli</i> in neonates and their environment, with frequent resistance to ampicillin and gentamicin. Hospital admission and cesarean delivery increase the risk of carriage, while vaginal delivery lowers it. Active screening upon admission and advanced diagnostic methods can help reduce transmission and guide effective antimicrobial treatment.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"4 ","pages":"1556842"},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12134566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227849","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}
引用次数: 0
Quantification of bactericidal activity using the PATHFAST TB LAM Ag assay during the first 14 days of pulmonary tuberculosis treatment. 在肺结核治疗的头14天,使用PATHFAST TB LAM Ag测定法定量杀菌活性。
Frontiers in antibiotics Pub Date : 2025-05-15 eCollection Date: 2025-01-01 DOI: 10.3389/frabi.2025.1574688
Ayumi Akinaga, Andreas H Diacon, Remous Ocloo, Atsushi Yanagida, Naofumi Yoda, Masanori Kawasaki, Yongge Liu
{"title":"Quantification of bactericidal activity using the PATHFAST TB LAM Ag assay during the first 14 days of pulmonary tuberculosis treatment.","authors":"Ayumi Akinaga, Andreas H Diacon, Remous Ocloo, Atsushi Yanagida, Naofumi Yoda, Masanori Kawasaki, Yongge Liu","doi":"10.3389/frabi.2025.1574688","DOIUrl":"10.3389/frabi.2025.1574688","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis (TB) remains a global health challenge. Culture-free, rapid, and quantitative biomarkers to monitor treatment response are critical to accelerate development of better TB treatments. The PATHFAST TB LAM Ag assay (PATHFAST-LAM), a desktop chemiluminescent enzyme immunoassay that measures mycobacterial lipoarabinomannan (LAM) in sputum within 1 hour, is a promising candidate for this purpose. This study aimed to assess whether the PATHFAST-LAM can serve as a rapid, reliable biomarker for monitoring early treatment response in pulmonary TB.</p><p><strong>Methods: </strong>We conducted a retrospective longitudinal repository study using stored sputum samples from 14-day early bactericidal activity trials involving 75 pulmonary TB patients who received one of five different regimens. The results were compared with those from the TB LAM ELISA \"Otsuka\" (LAM-ELISA), which was previously shown to measure early bactericidal activity but takes more than 5 hours to obtain results, and conventional culture-based methods.</p><p><strong>Results: </strong>The LAM concentrations in both raw and decontaminated sputum showed strong correlations between the PATHFAST-LAM and the LAM-ELISA, with Spearman's correlation coefficients of 0.975 (95% CI: 0.971 - 0.979) and 0.987 (95% CI: 0.984 - 0.989), respectively. LAM concentrations in raw and decontaminated sputum by the PATHFAST-LAM were also highly correlated with a Spearman coefficient of 0.957 (95% CI: 0.950 - 0.964). Importantly, the LAM concentrations by the PATHFAST-LAM correlated with bacterial loads determined by culture-based methods in all five treatment arms (Spearman's coefficients: 0.723 - 0.947). Furthermore, the change in LAM levels over the treatment period mirrored the changes in bacterial load. Additionally, culture-based methods often result in missing data due to contamination: in our study, we observed a missing data rate of 9.6% (62/649) on quantifying CFU counts and 4.2% (27/649) on obtaining a valid MGIT TTD, while we obtained a valid LAM value with the PATHFAST-LAM (0/634 in raw samples and 0/637 in decontaminated samples).</p><p><strong>Conclusion: </strong>Our findings suggest that the PATHFAST-LAM can quantify bactericidal activity in the first 14 days of treatment with a quick turnaround time. The test's utility to monitor conversion from positive to negative and to predict relapse-free cure compared to culture-based methods should be determined in longer trials.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"4 ","pages":"1574688"},"PeriodicalIF":0.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12120838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180488","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}
引用次数: 0
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