Pub Date : 2025-12-12DOI: 10.3390/antibiotics14121259
Mohammed Zahedul Islam Nizami, Iris Xiaoxue Yin, John Yun Niu, Ollie Yiru Yu, Chun Hung Chu
Background: The widespread use of antibiotics in dentistry has become a significant driver of the global rise in antibiotic resistance, posing serious risks to both oral and overall health. Objectives: This study aims to review antibiotic use in dentistry, elucidates the mechanisms of resistance development, identifies contributing factors, and discusses strategies to mitigate this growing global health threat. Methods: This narrative review examines current patterns of antibiotic prescribing in dentistry and evaluates evidence showing that antibiotics, although essential for preventing and managing odontogenic infections, are often prescribed unnecessarily or inappropriately. Results: The analysis highlights the growing resistance of key oral pathogens such as Streptococcus spp., Enterococcus faecalis, and Porphyromonas gingivalis, which increasingly limits the effectiveness of conventional treatments. Factors contributing to this trend include inconsistent adherence to clinical guidelines, patient pressure, and insufficient awareness of antibiotics stewardship among dental professionals. To address these challenges, the review emphasizes the importance of evidence-based prescription, strengthened stewardship programs, and the development of alternative therapies, including host-modulating agents and bacteriophage applications. Ongoing education and professional development are equally vital to enhance clinical judgment and promote responsible prescribing habits. Conclusions: Overcoming antibiotic resistance in dentistry requires coordinated effort among clinicians, researchers, educators, and policymakers. Expanding surveillance, enforcing stewardship-driven policies, and supporting innovation in therapeutic research are key to reducing antibiotic misuse and preserving their effectiveness. Through collective commitment and informed practice, the dental profession can play a crucial role in protecting antibiotic efficacy and promoting sustainable, high-quality patient care.
{"title":"Antibiotic Resistance in Dentistry: A Review.","authors":"Mohammed Zahedul Islam Nizami, Iris Xiaoxue Yin, John Yun Niu, Ollie Yiru Yu, Chun Hung Chu","doi":"10.3390/antibiotics14121259","DOIUrl":"10.3390/antibiotics14121259","url":null,"abstract":"<p><p><b>Background:</b> The widespread use of antibiotics in dentistry has become a significant driver of the global rise in antibiotic resistance, posing serious risks to both oral and overall health. <b>Objectives:</b> This study aims to review antibiotic use in dentistry, elucidates the mechanisms of resistance development, identifies contributing factors, and discusses strategies to mitigate this growing global health threat. <b>Methods:</b> This narrative review examines current patterns of antibiotic prescribing in dentistry and evaluates evidence showing that antibiotics, although essential for preventing and managing odontogenic infections, are often prescribed unnecessarily or inappropriately. <b>Results:</b> The analysis highlights the growing resistance of key oral pathogens such as <i>Streptococcus</i> spp., <i>Enterococcus faecalis</i>, and <i>Porphyromonas gingivalis</i>, which increasingly limits the effectiveness of conventional treatments. Factors contributing to this trend include inconsistent adherence to clinical guidelines, patient pressure, and insufficient awareness of antibiotics stewardship among dental professionals. To address these challenges, the review emphasizes the importance of evidence-based prescription, strengthened stewardship programs, and the development of alternative therapies, including host-modulating agents and bacteriophage applications. Ongoing education and professional development are equally vital to enhance clinical judgment and promote responsible prescribing habits. <b>Conclusions:</b> Overcoming antibiotic resistance in dentistry requires coordinated effort among clinicians, researchers, educators, and policymakers. Expanding surveillance, enforcing stewardship-driven policies, and supporting innovation in therapeutic research are key to reducing antibiotic misuse and preserving their effectiveness. Through collective commitment and informed practice, the dental profession can play a crucial role in protecting antibiotic efficacy and promoting sustainable, high-quality patient care.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 12","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12729796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145859198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-12DOI: 10.3390/antibiotics14121256
Jee Young Sohn, Chang Seok Bang, A In Choi, Jeong-Gyu Choi, Eun Jeong Gong
Background/Objectives: Helicobacter pylori infection remains a significant health concern, as increasing antimicrobial resistance compromises the efficacy of eradication. Understanding regional antimicrobial resistance profiles is crucial for optimizing eradication strategies. In this study, we aimed to evaluate the antimicrobial susceptibility patterns and identify the factors influencing H. pylori culture success. Methods: In this prospective study, 697 gastric tissue samples were collected from consecutive patients who underwent upper endoscopy between November 2023 and May 2025. Tissue samples obtained by forceps biopsy or recovered from rapid urease test kits were cultured for H. pylori. Antimicrobial susceptibility testing was performed using the agar dilution method; factors associated with successful culture were analyzed using logistic regression. Results: Among 488 patients with H. pylori infection, culture and antimicrobial susceptibility testing were successful in 387 (79.3%). The overall antimicrobial resistance rates were 17.8%, 27.1%, 29.5%, 0.3%, and 32.8% for amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin, respectively. Notably, 27.6% (107/387) of the isolates were resistant to two or more antibiotics. Using multivariate analysis, the use of fresh biopsy tissue (odds ratio [OR]: 1.646, 95% confidence interval [CI]: 1.046-2.591, p = 0.031), transport interval (OR: 0.911, 95% CI: 0.853-0.973, p = 0.005), and presence of prior eradication therapy (OR: 0.318, 95% CI: 0.156-0.648, p = 0.002) were identified as significant predictors of culture success. Conclusions: The high rate of clarithromycin resistance underscores the need for susceptibility-guided eradication strategies in this region. Optimizing sample handling, particularly by minimizing transport time and using fresh biopsy tissue, may improve culture yields.
背景/目的:幽门螺杆菌感染仍然是一个重要的健康问题,因为不断增加的抗菌素耐药性损害了根除的效果。了解区域抗菌素耐药概况对于优化根除策略至关重要。在这项研究中,我们旨在评估抗菌药物的敏感性模式,并确定影响幽门螺杆菌培养成功的因素。方法:在这项前瞻性研究中,从2023年11月至2025年5月连续接受上胃镜检查的患者中收集697份胃组织样本。用镊子活检获得的组织样本或从快速脲酶测试试剂盒中恢复的组织样本培养幽门螺杆菌。采用琼脂稀释法进行药敏试验;采用逻辑回归分析与培养成功相关的因素。结果:488例幽门螺旋杆菌感染患者中,培养及药敏试验成功387例(79.3%)。阿莫西林、克拉霉素、甲硝唑、四环素和左氧氟沙星的总体耐药率分别为17.8%、27.1%、29.5%、0.3%和32.8%。值得注意的是,27.6%(107/387)的分离株对两种或两种以上抗生素耐药。通过多因素分析,使用新鲜活检组织(优势比[OR]: 1.646, 95%可信区间[CI]: 1.046-2.591, p = 0.031)、运输间隔(OR: 0.911, 95% CI: 0.853-0.973, p = 0.005)和既往根除治疗(OR: 0.318, 95% CI: 0.156-0.648, p = 0.002)被确定为培养成功的重要预测因素。结论:该地区克拉霉素耐药率较高,需要采取以药敏为导向的根除策略。优化样品处理,特别是通过减少运输时间和使用新鲜活检组织,可以提高培养产量。
{"title":"Antimicrobial Resistance Patterns and Determinants of <i>Helicobacter pylori</i> Culture Success: A Prospective Study.","authors":"Jee Young Sohn, Chang Seok Bang, A In Choi, Jeong-Gyu Choi, Eun Jeong Gong","doi":"10.3390/antibiotics14121256","DOIUrl":"10.3390/antibiotics14121256","url":null,"abstract":"<p><p><b>Background/Objectives</b>: <i>Helicobacter pylori</i> infection remains a significant health concern, as increasing antimicrobial resistance compromises the efficacy of eradication. Understanding regional antimicrobial resistance profiles is crucial for optimizing eradication strategies. In this study, we aimed to evaluate the antimicrobial susceptibility patterns and identify the factors influencing <i>H. pylori</i> culture success. <b>Methods</b>: In this prospective study, 697 gastric tissue samples were collected from consecutive patients who underwent upper endoscopy between November 2023 and May 2025. Tissue samples obtained by forceps biopsy or recovered from rapid urease test kits were cultured for <i>H. pylori</i>. Antimicrobial susceptibility testing was performed using the agar dilution method; factors associated with successful culture were analyzed using logistic regression. <b>Results</b>: Among 488 patients with <i>H. pylori</i> infection, culture and antimicrobial susceptibility testing were successful in 387 (79.3%). The overall antimicrobial resistance rates were 17.8%, 27.1%, 29.5%, 0.3%, and 32.8% for amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin, respectively. Notably, 27.6% (107/387) of the isolates were resistant to two or more antibiotics. Using multivariate analysis, the use of fresh biopsy tissue (odds ratio [OR]: 1.646, 95% confidence interval [CI]: 1.046-2.591, <i>p</i> = 0.031), transport interval (OR: 0.911, 95% CI: 0.853-0.973, <i>p</i> = 0.005), and presence of prior eradication therapy (OR: 0.318, 95% CI: 0.156-0.648, <i>p</i> = 0.002) were identified as significant predictors of culture success. <b>Conclusions</b>: The high rate of clarithromycin resistance underscores the need for susceptibility-guided eradication strategies in this region. Optimizing sample handling, particularly by minimizing transport time and using fresh biopsy tissue, may improve culture yields.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 12","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12730122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145859225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bloodstream infections (BSIs) pose a significant global health challenge, particularly due to the increasing prevalence of antimicrobial resistance (AMR). Timely and accurate identification of pathogens and resistance determinants is critical for guiding appropriate therapy and improving patient outcomes. Traditional culture-based diagnostics are limited by prolonged turnaround times and reduced sensitivity, especially in culture-negative or polymicrobial infections. This review systematically examined current and emerging sequencing technologies for AMR detection in BSIs, including whole-genome sequencing (WGS), targeted next-generation sequencing (tNGS), metagenomic next-generation sequencing (mNGS), and long-read sequencing platforms (Oxford Nanopore, PacBio). We compared their clinical performance using key metrics such as diagnostic sensitivity, turnaround time, and cost, highlighting contexts in which each technology is most effective. For example, tNGS can achieve the rapid detection of known resistance genes within 8-24 h, while WGS provides comprehensive genome-wide resistance profiling over 24-48 h. mNGS offers broader detection, including rare or unexpected pathogens, although at higher cost and longer processing times. Our analysis identifies specific strengths and limitations of each approach, supporting the use of context-specific strategies, such as combining rapid targeted sequencing for common pathogens with broader metagenomic approaches for complex cases, to improve diagnostic yield and guide antimicrobial therapy. Quantitative comparisons indicate that sequencing technologies can complement conventional methods, particularly in cases where culture-based approaches fail. In conclusion, sequencing-based diagnostics offer measurable improvements in sensitivity and speed over traditional methods for AMR detection in BSIs. Future work should focus on optimizing workflows, integrating sequencing data into clinical decision-making, and validating approaches in prospective studies.
{"title":"Comparative Evaluation of Sequencing Technologies for Detecting Antimicrobial Resistance in Bloodstream Infections.","authors":"Myrto Papamentzelopoulou, Georgia Vrioni, Vassiliki Pitiriga","doi":"10.3390/antibiotics14121257","DOIUrl":"10.3390/antibiotics14121257","url":null,"abstract":"<p><p>Bloodstream infections (BSIs) pose a significant global health challenge, particularly due to the increasing prevalence of antimicrobial resistance (AMR). Timely and accurate identification of pathogens and resistance determinants is critical for guiding appropriate therapy and improving patient outcomes. Traditional culture-based diagnostics are limited by prolonged turnaround times and reduced sensitivity, especially in culture-negative or polymicrobial infections. This review systematically examined current and emerging sequencing technologies for AMR detection in BSIs, including whole-genome sequencing (WGS), targeted next-generation sequencing (tNGS), metagenomic next-generation sequencing (mNGS), and long-read sequencing platforms (Oxford Nanopore, PacBio). We compared their clinical performance using key metrics such as diagnostic sensitivity, turnaround time, and cost, highlighting contexts in which each technology is most effective. For example, tNGS can achieve the rapid detection of known resistance genes within 8-24 h, while WGS provides comprehensive genome-wide resistance profiling over 24-48 h. mNGS offers broader detection, including rare or unexpected pathogens, although at higher cost and longer processing times. Our analysis identifies specific strengths and limitations of each approach, supporting the use of context-specific strategies, such as combining rapid targeted sequencing for common pathogens with broader metagenomic approaches for complex cases, to improve diagnostic yield and guide antimicrobial therapy. Quantitative comparisons indicate that sequencing technologies can complement conventional methods, particularly in cases where culture-based approaches fail. In conclusion, sequencing-based diagnostics offer measurable improvements in sensitivity and speed over traditional methods for AMR detection in BSIs. Future work should focus on optimizing workflows, integrating sequencing data into clinical decision-making, and validating approaches in prospective studies.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 12","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12729976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145858978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.3390/antibiotics14121252
Young Wook Cho, Jung Min Moon, Hyeong Han Lee, Jiyoung Kim, Chang Hwan Choi, Kang-Moon Lee, Young-Seok Cho
Background/Objectives: Guidelines recommend combination therapy with oral vancomycin and intravenous (IV) metronidazole for fulminant Clostridioides difficile infection (CDI). Although patients with severe CDI are often managed with combination therapy, evidence supporting this practice remains limited. This study was performed to compare the clinical outcomes of vancomycin monotherapy versus combination therapy in patients with severe CDI. Methods: We conducted a multicenter, retrospective, observational cohort study including adult patients with severe CDI who received oral vancomycin between January 2017 and May 2021. Patients were classified as receiving combination therapy if IV metronidazole was administered for at least 72 h within 48 h of initiating oral vancomycin; otherwise, they were classified as receiving vancomycin monotherapy. The primary outcome was a composite of inpatient all-cause death or colectomy within 60 days after CDI diagnosis. The secondary outcomes were the clinical cure rate, CDI recurrence rate, time to discharge after CDI diagnosis, and duration of ICU admission. Results: In total, 215 patients were included, with 100 (46.5%) receiving combination therapy. There were no significant differences in in-hospital mortality or colectomy between the monotherapy and combination therapy groups (25.2% vs. 26.0%, p = 1.00). Recurrence rates (19.1% vs. 16.8%, p = 0.81), total length of stay (31.0 vs. 23.0 days, p = 0.16), and ICU stay duration (35.0 vs. 32.0 days, p = 0.89) were also similar. However, the clinical cure rate was significantly higher in the monotherapy group than in the combination therapy group (79.1% vs. 65.0%, p = 0.03). Conclusions: Combination therapy with oral vancomycin and IV metronidazole was not associated with improved clinical outcomes in patients with severe CDI. Prospective randomized studies are needed to clarify optimal management strategies for severe CDI.
背景/目的:指南推荐口服万古霉素和静脉注射甲硝唑联合治疗暴发性艰难梭菌感染(CDI)。尽管严重CDI患者通常采用联合治疗,但支持这种做法的证据仍然有限。本研究旨在比较万古霉素单药治疗与联合治疗对重症CDI患者的临床疗效。方法:我们进行了一项多中心、回顾性、观察性队列研究,纳入了2017年1月至2021年5月期间接受口服万古霉素治疗的严重CDI成年患者。如果在开始口服万古霉素的48小时内静脉注射甲硝唑至少72小时,则患者被分类为接受联合治疗;否则,他们被分类为接受万古霉素单药治疗。主要结局是CDI诊断后60天内住院患者全因死亡或结肠切除术的综合结果。次要观察指标为临床治愈率、CDI复发率、CDI诊断后出院时间、ICU住院时间。结果:共纳入215例患者,其中100例(46.5%)接受联合治疗。单药组和联合治疗组在住院死亡率和结肠切除术方面无显著差异(25.2% vs 26.0%, p = 1.00)。复发率(19.1%比16.8%,p = 0.81)、总住院时间(31.0比23.0天,p = 0.16)和ICU住院时间(35.0比32.0天,p = 0.89)也相似。但单药组临床治愈率明显高于联合治疗组(79.1% vs. 65.0%, p = 0.03)。结论:口服万古霉素和静脉注射甲硝唑联合治疗与改善重症CDI患者的临床结果无关。需要前瞻性随机研究来明确重症CDI的最佳管理策略。
{"title":"Combination Therapy with Oral Vancomycin Plus Intravenous Metronidazole Is Not Superior to Oral Vancomycin Alone for the Treatment of Severe <i>Clostridioides difficile</i> Infection: A KASID Multicenter Study.","authors":"Young Wook Cho, Jung Min Moon, Hyeong Han Lee, Jiyoung Kim, Chang Hwan Choi, Kang-Moon Lee, Young-Seok Cho","doi":"10.3390/antibiotics14121252","DOIUrl":"10.3390/antibiotics14121252","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Guidelines recommend combination therapy with oral vancomycin and intravenous (IV) metronidazole for fulminant <i>Clostridioides difficile</i> infection (CDI). Although patients with severe CDI are often managed with combination therapy, evidence supporting this practice remains limited. This study was performed to compare the clinical outcomes of vancomycin monotherapy versus combination therapy in patients with severe CDI. <b>Methods</b>: We conducted a multicenter, retrospective, observational cohort study including adult patients with severe CDI who received oral vancomycin between January 2017 and May 2021. Patients were classified as receiving combination therapy if IV metronidazole was administered for at least 72 h within 48 h of initiating oral vancomycin; otherwise, they were classified as receiving vancomycin monotherapy. The primary outcome was a composite of inpatient all-cause death or colectomy within 60 days after CDI diagnosis. The secondary outcomes were the clinical cure rate, CDI recurrence rate, time to discharge after CDI diagnosis, and duration of ICU admission. <b>Results</b>: In total, 215 patients were included, with 100 (46.5%) receiving combination therapy. There were no significant differences in in-hospital mortality or colectomy between the monotherapy and combination therapy groups (25.2% vs. 26.0%, <i>p</i> = 1.00). Recurrence rates (19.1% vs. 16.8%, <i>p</i> = 0.81), total length of stay (31.0 vs. 23.0 days, <i>p</i> = 0.16), and ICU stay duration (35.0 vs. 32.0 days, <i>p</i> = 0.89) were also similar. However, the clinical cure rate was significantly higher in the monotherapy group than in the combination therapy group (79.1% vs. 65.0%, <i>p</i> = 0.03). <b>Conclusions</b>: Combination therapy with oral vancomycin and IV metronidazole was not associated with improved clinical outcomes in patients with severe CDI. Prospective randomized studies are needed to clarify optimal management strategies for severe CDI.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 12","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12729652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145859020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.3390/antibiotics14121253
Pedro Marín, Orhan Corum, Duygu Durna Corum, Elena Badillo, María Teresa Yuste, Onder Yildirim, Ertugrul Terzi, Ruby C Gonzales, Dan M Arriesgado, Victor R Navarro, Kamil Uney
Background/Objectives: The aim of this study was to determine the plasma and muscle pharmacokinetics of ceftriaxone (25 mg/kg) in tilapia after different administration routes. Methods: Two hundred and sixteen fish maintained at 30 ± 1.5 °C were divided equally into three treatment groups: intravascular (IV), intraperitoneal (IP), and intramuscular (IM). Ceftriaxone concentrations were quantified using high-performance liquid chromatography, and pharmacokinetic parameters were calculated by non-compartmental analysis. Results: The plasma total body clearance, volume of distribution at steady state, and elimination half-life (t1/2λz) were 0.22 L/h/kg, 0.85 L/kg, and 5.27 h, respectively. The t1/2λz values were comparable among the IV, IP, and IM injection groups. The peak plasma concentration was 37.71 ± 3.12 µg/mL and 40.51 ± 2.77 µg/mL following IP and IM injection, respectively. The bioavailability was 67.04% for IP and 101.48% for IM. The peak muscle concentration was 9.49 ± 0.75 µg/g for IV, 5.71 ± 0.85 µg/g for IP, and 12.24 ± 2.41 µg/g for IM injection. The AUC0-∞muscle/AUC0-∞plasma ratio was 0.23, 0.18, and 0.30 for the IV, IP, and IM groups, respectively. The AUCmuscle/AUCplasma indicates the ratio of drug penetration into the muscle, and a value less than 1 indicates that ceftriaxone penetrates into muscle tissue at a low ratio. Conclusions: These results indicate that ceftriaxone is well absorbed after IP and IM injections and passes into muscle tissue at a low tissue penetration. Ceftriaxone can be administered via IP and IM injection in Nile tilapia; nevertheless, its therapeutic efficacy requires evaluation.
{"title":"Plasma and Muscle Pharmacokinetics of Ceftriaxone in Nile Tilapia (<i>Oreochromis niloticus</i>) After Different Administration Routes.","authors":"Pedro Marín, Orhan Corum, Duygu Durna Corum, Elena Badillo, María Teresa Yuste, Onder Yildirim, Ertugrul Terzi, Ruby C Gonzales, Dan M Arriesgado, Victor R Navarro, Kamil Uney","doi":"10.3390/antibiotics14121253","DOIUrl":"10.3390/antibiotics14121253","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The aim of this study was to determine the plasma and muscle pharmacokinetics of ceftriaxone (25 mg/kg) in tilapia after different administration routes. <b>Methods</b>: Two hundred and sixteen fish maintained at 30 ± 1.5 °C were divided equally into three treatment groups: intravascular (IV), intraperitoneal (IP), and intramuscular (IM). Ceftriaxone concentrations were quantified using high-performance liquid chromatography, and pharmacokinetic parameters were calculated by non-compartmental analysis. <b>Results</b>: The plasma total body clearance, volume of distribution at steady state, and elimination half-life (t<sub>1/2λz</sub>) were 0.22 L/h/kg, 0.85 L/kg, and 5.27 h, respectively. The t<sub>1/2λz</sub> values were comparable among the IV, IP, and IM injection groups. The peak plasma concentration was 37.71 ± 3.12 µg/mL and 40.51 ± 2.77 µg/mL following IP and IM injection, respectively. The bioavailability was 67.04% for IP and 101.48% for IM. The peak muscle concentration was 9.49 ± 0.75 µg/g for IV, 5.71 ± 0.85 µg/g for IP, and 12.24 ± 2.41 µg/g for IM injection. The AUC<sub>0-∞muscle</sub>/AUC<sub>0-∞plasma</sub> ratio was 0.23, 0.18, and 0.30 for the IV, IP, and IM groups, respectively. The AUC<sub>muscle</sub>/AUC<sub>plasma</sub> indicates the ratio of drug penetration into the muscle, and a value less than 1 indicates that ceftriaxone penetrates into muscle tissue at a low ratio. <b>Conclusions</b>: These results indicate that ceftriaxone is well absorbed after IP and IM injections and passes into muscle tissue at a low tissue penetration. Ceftriaxone can be administered via IP and IM injection in Nile tilapia; nevertheless, its therapeutic efficacy requires evaluation.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 12","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12729600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145859302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The spread of multidrug-resistant bacteria around the world is rising, and new antibiotics are urgently needed to address the drug resistance crisis. Natural products have become a focal point in the research and development of antibacterial drugs, owing to their structural diversity and biological activity. Kaempferol, in particular, exhibits a range of biological properties, including antioxidant, antibacterial, and antitumor activities, and holds potential for application across various domains. This review aims to provide a comprehensive overview of the extraction, biosynthesis, and antibacterial activity of kaempferol, as well as to elucidate its antibacterial mechanisms. In addition, we also reviewed the synergistic combination of kaempferol with antibiotics, such as the combination of kaempferol with colistin or penicillin, which significantly improved their therapeutic effect. Finally, the preparation of kaempferol nanoparticles and their applications in antibacterial treatments were discussed.
{"title":"Advances in Kaempferol: Extraction, Biosynthesis, and Application with Antibacterial Agents.","authors":"Xiaojuan Wei, Weiwei Wang, Rongbin Hu, Xun Gao, Bing Li, Yubin Bai, Jiyu Zhang","doi":"10.3390/antibiotics14121254","DOIUrl":"10.3390/antibiotics14121254","url":null,"abstract":"<p><p>The spread of multidrug-resistant bacteria around the world is rising, and new antibiotics are urgently needed to address the drug resistance crisis. Natural products have become a focal point in the research and development of antibacterial drugs, owing to their structural diversity and biological activity. Kaempferol, in particular, exhibits a range of biological properties, including antioxidant, antibacterial, and antitumor activities, and holds potential for application across various domains. This review aims to provide a comprehensive overview of the extraction, biosynthesis, and antibacterial activity of kaempferol, as well as to elucidate its antibacterial mechanisms. In addition, we also reviewed the synergistic combination of kaempferol with antibiotics, such as the combination of kaempferol with colistin or penicillin, which significantly improved their therapeutic effect. Finally, the preparation of kaempferol nanoparticles and their applications in antibacterial treatments were discussed.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 12","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12729929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145859207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.3390/antibiotics14121251
Sara Cannella, Luca Pipitò, Martina Piazza, Domenico Graceffa, Rita Immordino, Roberta Virruso, Giovanni Maurizio Giammanco, Antonio Cascio, Celestino Bonura
Background: Rapid antimicrobial susceptibility testing (RAST) allows early detection of resistance directly from positive blood cultures, potentially improving outcomes in bloodstream infections (BSIs). We evaluated the performance of EUCAST RAST for Gram-negative ESKAPEEc pathogens and characterized carbapenemase genes in carbapenem-resistant Klebsiella pneumoniae (CRKP). Methods: A total of 354 positive blood cultures were screened, including 51 monomicrobial Gram-negative ESKAPEEc isolates. RAST results at 4, 6, 8, and 16-20 h were compared with standard antimicrobial susceptibility testing (AST) obtained using the BD Phoenix™ system. Categorical agreement (CA) and error frequency were calculated. Multiplex PCR and Sanger sequencing were performed on 15 CRKP isolates to identify carbapenemase genes and allelic variants. Results: 51 Gram-negative ESKAPEEc isolates met the inclusion criteria for RAST (15 E. coli, 19 K. pneumoniae, 11 A. baumannii, and 6 P. aeruginosa). Overall performance varied markedly by species and antibiotic. E. coli showed frequent unreadable or ATU zones at early timepoints and wide CA variability (50-100%), with high very major error (VME) rates for AMP, TZP, and CAZ, particularly at 6-8 h. K. pneumoniae displayed consistently high CA (mostly 100%) for carbapenems, CAZ, and TZP. A. baumannii demonstrated excellent agreement (100% for most agents), except for GEN at 6-8 h. P. aeruginosa could be evaluated only at 16-20 h, showing high CA for AMK, CAZ, and CIP; lower CA for MEM (83%); non-calculable CA for IMI due to universal ATU readings; and a CA value of 0% for TZP due to the predominance of the ATU results. VMEs ranged from 0% to 26.1% across species and reading times, but carbapenems did not generate VMEs. Molecular analysis revealed blaKPC in 66.7%, blaNDM in 46.7%, and blaOXA-48 in 33.3% of isolates, with co-occurrence in several strains. Sequencing identified blaKPC-2 and blaNDM-1 as the predominant variants, with one isolate harboring blaNDM-5. Conclusions: EUCAST RAST markedly accelerates susceptibility reporting from positive blood cultures, but its accuracy is species- and time-dependent. Performance was excellent for K. pneumoniae (including CRKP) and A. baumannii and acceptable for P. aeruginosa at 16-20 h. In contrast, E. coli showed frequent ATU results at early timepoints and high ME/VME rates, making readings before 8 h unreliable for clinical decisions. Overall, RAST can effectively support rapid antimicrobial stewardship when species-specific limitations are recognized, and early-timepoint results are interpreted with caution.
{"title":"Evaluation of EUCAST Rapid Antimicrobial Susceptibility Testing for Gram-Negative ESKAPEEc Pathogens in Blood Cultures, with a Focus on Carbapenemase-Producing <i>Klebsiella pneumoniae</i> in a University Hospital in Palermo, Italy.","authors":"Sara Cannella, Luca Pipitò, Martina Piazza, Domenico Graceffa, Rita Immordino, Roberta Virruso, Giovanni Maurizio Giammanco, Antonio Cascio, Celestino Bonura","doi":"10.3390/antibiotics14121251","DOIUrl":"10.3390/antibiotics14121251","url":null,"abstract":"<p><p><b>Background</b>: Rapid antimicrobial susceptibility testing (RAST) allows early detection of resistance directly from positive blood cultures, potentially improving outcomes in bloodstream infections (BSIs). We evaluated the performance of EUCAST RAST for Gram-negative ESKAPEEc pathogens and characterized carbapenemase genes in carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP). <b>Methods</b>: A total of 354 positive blood cultures were screened, including 51 monomicrobial Gram-negative ESKAPEEc isolates. RAST results at 4, 6, 8, and 16-20 h were compared with standard antimicrobial susceptibility testing (AST) obtained using the BD Phoenix™ system. Categorical agreement (CA) and error frequency were calculated. Multiplex PCR and Sanger sequencing were performed on 15 CRKP isolates to identify carbapenemase genes and allelic variants. <b>Results</b>: 51 Gram-negative ESKAPEEc isolates met the inclusion criteria for RAST (15 <i>E. coli</i>, 19 <i>K. pneumoniae</i>, 11 <i>A. baumannii</i>, and 6 <i>P. aeruginosa</i>). Overall performance varied markedly by species and antibiotic. <i>E. coli</i> showed frequent unreadable or ATU zones at early timepoints and wide CA variability (50-100%), with high very major error (VME) rates for AMP, TZP, and CAZ, particularly at 6-8 h. <i>K. pneumoniae</i> displayed consistently high CA (mostly 100%) for carbapenems, CAZ, and TZP. <i>A. baumannii</i> demonstrated excellent agreement (100% for most agents), except for GEN at 6-8 h. <i>P. aeruginosa</i> could be evaluated only at 16-20 h, showing high CA for AMK, CAZ, and CIP; lower CA for MEM (83%); non-calculable CA for IMI due to universal ATU readings; and a CA value of 0% for TZP due to the predominance of the ATU results. VMEs ranged from 0% to 26.1% across species and reading times, but carbapenems did not generate VMEs. Molecular analysis revealed <i>bla<sub>KPC</sub></i> in 66.7%, <i>bla<sub>NDM</sub></i> in 46.7%, and <i>bla<sub>OXA-48</sub></i> in 33.3% of isolates, with co-occurrence in several strains. Sequencing identified <i>bla<sub>KPC-2</sub></i> and <i>bla<sub>NDM-1</sub></i> as the predominant variants, with one isolate harboring <i>bla<sub>NDM-5</sub></i>. <b>Conclusions</b>: EUCAST RAST markedly accelerates susceptibility reporting from positive blood cultures, but its accuracy is species- and time-dependent. Performance was excellent for <i>K. pneumoniae</i> (including CRKP) and <i>A. baumannii</i> and acceptable for <i>P. aeruginosa</i> at 16-20 h. In contrast, <i>E. coli</i> showed frequent ATU results at early timepoints and high ME/VME rates, making readings before 8 h unreliable for clinical decisions. Overall, RAST can effectively support rapid antimicrobial stewardship when species-specific limitations are recognized, and early-timepoint results are interpreted with caution.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 12","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12729303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145859151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-10DOI: 10.3390/antibiotics14121249
Enrico Baraldi, Håkan Hanberger, Sofia Wagrell
Background/Objectives: Antibiotic shortages are a growing problem which harms patient safety, increases healthcare costs, and accelerates antibiotic resistance. Based on the example of Sweden, the paper aims to illustrate and discuss how an organized collaboration platform can devise several policy interventions against shortages of antibiotics for human use. Methods: We describe how the multi-sectoral collaboration Platinea (Platform for Innovation of Existing Antibiotics) first identified, structured, and prioritized the causes of antibiotic shortages, and then identified and prioritized a set of policy solutions matching these causes. The specific methods applied include expert elicitation, interactive workshops, focus groups, and multi-criteria decision processes. Results: After an overview of about 60 causes of antibiotic shortages, we relate them to 10 prioritized solutions including, e.g., increased inventories, central coordination, integrated IT systems, increased unit prices, yearly fixed payments, and Nordic collaboration in purchasing and production. Conclusions: We propose a process with six steps to devise policy solutions by involving a multi-sectoral stakeholder group: open brainstorming of the problem's causes, framing them into a clear structure, selecting and prioritizing key causes, matching causes and solutions, and devising prioritization mechanisms about emerging solutions. This approach can be applied to other national contexts and similar policy issues.
{"title":"From 60 Causes to 10 Solutions Against Antibiotics Shortages in Sweden: Platinea's Approach to Developing Policy Interventions.","authors":"Enrico Baraldi, Håkan Hanberger, Sofia Wagrell","doi":"10.3390/antibiotics14121249","DOIUrl":"10.3390/antibiotics14121249","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Antibiotic shortages are a growing problem which harms patient safety, increases healthcare costs, and accelerates antibiotic resistance. Based on the example of Sweden, the paper aims to illustrate and discuss how an organized collaboration platform can devise several policy interventions against shortages of antibiotics for human use. <b>Methods</b>: We describe how the multi-sectoral collaboration Platinea (Platform for Innovation of Existing Antibiotics) first identified, structured, and prioritized the causes of antibiotic shortages, and then identified and prioritized a set of policy solutions matching these causes. The specific methods applied include expert elicitation, interactive workshops, focus groups, and multi-criteria decision processes. <b>Results</b>: After an overview of about 60 causes of antibiotic shortages, we relate them to 10 prioritized solutions including, e.g., increased inventories, central coordination, integrated IT systems, increased unit prices, yearly fixed payments, and Nordic collaboration in purchasing and production. <b>Conclusions</b>: We propose a process with six steps to devise policy solutions by involving a multi-sectoral stakeholder group: open brainstorming of the problem's causes, framing them into a clear structure, selecting and prioritizing key causes, matching causes and solutions, and devising prioritization mechanisms about emerging solutions. This approach can be applied to other national contexts and similar policy issues.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 12","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12730113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145859001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-10DOI: 10.3390/antibiotics14121248
Mariam Abdulkadieva, Darya Slonova, Veronika Litvinenko, Nataliia Antonova, Elena Mazunina, Konstantin Sobyanin, Tatiana Guseva, Olga Parshina, Pavel Domnin, Vladislav Poloskov, Vladimir Guschin, Daria Vasina, Elena Sysolyatina, Alexander Gintsburg
Objectives: The study aimed to evaluate the antibacterial and wound-healing potential of the engineered lysin GRC-ML07 in a mouse model of full-thickness wounds infected with multidrug-resistant Pseudomonas aeruginosa under immunosuppression. Methods: Male BALB/c mice (22-24 g) were immunocompromised with cyclophosphamide. Three days later, full-thickness excisional wounds were created and infected with P. aeruginosa (107 cells/wound). The lysin GRC-ML07 incapsulated into an alginate gel was applied topically to the wound area twice a day for four days after infection. Wound swabs for microbiological assays and scab tissues for cytokine and cellular profiling were collected on days 4 and 7. Histological samples were taken on days 4, 7, 14, and 21. Results: Lysin GRC-ML07 induced bacterial lysis accompanied by low activation of TLR2, TLR4, or TLR7/8 signaling pathways and pro-inflammatory cytokine production in vitro. Its application in vivo resulted in decreased levels of GM-CSF, IL-1β, IL-6, IL-17A, and TNF-α in the wound, accompanied by a 46% increase in neutrophil counts on day 4 compared to control and placebo (alginate gel) groups. By day 7, lysin treatment reduced bacterial load by 2 log, decreased neutrophil counts in wounds, and led a transition of the wounds to the granulation and epithelialization phase with scab desquamation. Conclusions: It was first shown that engineered lysin GRC-ML07 exhibits not only antibacterial, but pronounced pro-healing effects in immunocompromised mice, promoting resolution of inflammation and transition to the granulation/epithelialization phase.
{"title":"Wound-Healing Potential of Engineered Lysin GRC-ML07 in <i>Pseudomonas aeruginosa</i> Infected Wounds in Immunocompromised Mice.","authors":"Mariam Abdulkadieva, Darya Slonova, Veronika Litvinenko, Nataliia Antonova, Elena Mazunina, Konstantin Sobyanin, Tatiana Guseva, Olga Parshina, Pavel Domnin, Vladislav Poloskov, Vladimir Guschin, Daria Vasina, Elena Sysolyatina, Alexander Gintsburg","doi":"10.3390/antibiotics14121248","DOIUrl":"10.3390/antibiotics14121248","url":null,"abstract":"<p><p><b>Objectives:</b> The study aimed to evaluate the antibacterial and wound-healing potential of the engineered lysin GRC-ML07 in a mouse model of full-thickness wounds infected with multidrug-resistant <i>Pseudomonas aeruginosa</i> under immunosuppression. <b>Methods:</b> Male BALB/c mice (22-24 g) were immunocompromised with cyclophosphamide. Three days later, full-thickness excisional wounds were created and infected with <i>P. aeruginosa</i> (10<sup>7</sup> cells/wound). The lysin GRC-ML07 incapsulated into an alginate gel was applied topically to the wound area twice a day for four days after infection. Wound swabs for microbiological assays and scab tissues for cytokine and cellular profiling were collected on days 4 and 7. Histological samples were taken on days 4, 7, 14, and 21. <b>Results:</b> Lysin GRC-ML07 induced bacterial lysis accompanied by low activation of TLR2, TLR4, or TLR7/8 signaling pathways and pro-inflammatory cytokine production <i>in vitro</i>. Its application <i>in vivo</i> resulted in decreased levels of GM-CSF, IL-1β, IL-6, IL-17A, and TNF-α in the wound, accompanied by a 46% increase in neutrophil counts on day 4 compared to control and placebo (alginate gel) groups. By day 7, lysin treatment reduced bacterial load by 2 log, decreased neutrophil counts in wounds, and led a transition of the wounds to the granulation and epithelialization phase with scab desquamation. <b>Conclusions:</b> It was first shown that engineered lysin GRC-ML07 exhibits not only antibacterial, but pronounced pro-healing effects in immunocompromised mice, promoting resolution of inflammation and transition to the granulation/epithelialization phase.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 12","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12729281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145859339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-10DOI: 10.3390/antibiotics14121246
Francesca Piras, Giuliana Siddi, Enrico Pietro Luigi De Santis, Christian Scarano
Wild boars, widely distributed across natural, agricultural, and urban landscapes, represent an ideal sentinel species for monitoring the emergence and spread of antimicrobial resistance (AMR) at the human-wildlife-livestock interface within the One Health framework. This review summarizes current knowledge on the prevalence, diversity, AMR, and epidemiological significance of major enteric pathogens isolated from wild boars in the European Union, with particular attention to their potential role in AMR dissemination. Numerous studies have reported variable prevalence rates for Salmonella spp., Yersinia enterocolitica, Shiga toxin-producing Escherichia coli (STEC), and Campylobacter spp. High prevalence rates has been observed in fecal samples-35% for Salmonella, 27% for Y. enterocolitica and STEC, and 66% for Campylobacter-highlighting the role of wild boars as carriers and the associated risk of carcass contamination during slaughter. Tonsils represent a key niche for Y. enterocolitica, with prevalence reaching 35%. Several studies have identified resistance to antimicrobials classified by the World Health Organization as critically important or high priority for human medicine, including fluoroquinolone-resistant non-typhoidal Salmonella spp. and third-generation cephalosporin-resistant Y. enterocolitica, raising notable public health concerns. Despite increasing interest, most available studies remain descriptive and geographically limited, providing limited insight into AMR acquisition and transmission pathways in wild boars. New approaches-such as resistome analyses and epidemiological cut-off values-offer added value to distinguish wild-type from acquired-resistant strains and to better understand AMR dissemination dynamics. Integrating wildlife into One Health surveillance systems is essential to capture the full complexity of AMR spread.
{"title":"Enteric Pathogens in Wild Boars Across the European Union: Prevalence and Antimicrobial Resistance Within a One Health Framework.","authors":"Francesca Piras, Giuliana Siddi, Enrico Pietro Luigi De Santis, Christian Scarano","doi":"10.3390/antibiotics14121246","DOIUrl":"10.3390/antibiotics14121246","url":null,"abstract":"<p><p>Wild boars, widely distributed across natural, agricultural, and urban landscapes, represent an ideal sentinel species for monitoring the emergence and spread of antimicrobial resistance (AMR) at the human-wildlife-livestock interface within the One Health framework. This review summarizes current knowledge on the prevalence, diversity, AMR, and epidemiological significance of major enteric pathogens isolated from wild boars in the European Union, with particular attention to their potential role in AMR dissemination. Numerous studies have reported variable prevalence rates for <i>Salmonella</i> spp., <i>Yersinia enterocolitica</i>, Shiga toxin-producing <i>Escherichia coli</i> (STEC), and <i>Campylobacter</i> spp. High prevalence rates has been observed in fecal samples-35% for <i>Salmonella</i>, 27% for <i>Y. enterocolitica</i> and STEC, and 66% for <i>Campylobacter</i>-highlighting the role of wild boars as carriers and the associated risk of carcass contamination during slaughter. Tonsils represent a key niche for <i>Y. enterocolitica</i>, with prevalence reaching 35%. Several studies have identified resistance to antimicrobials classified by the World Health Organization as critically important or high priority for human medicine, including fluoroquinolone-resistant non-typhoidal <i>Salmonella</i> spp. and third-generation cephalosporin-resistant <i>Y. enterocolitica</i>, raising notable public health concerns. Despite increasing interest, most available studies remain descriptive and geographically limited, providing limited insight into AMR acquisition and transmission pathways in wild boars. New approaches-such as resistome analyses and epidemiological cut-off values-offer added value to distinguish wild-type from acquired-resistant strains and to better understand AMR dissemination dynamics. Integrating wildlife into One Health surveillance systems is essential to capture the full complexity of AMR spread.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"14 12","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12729840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145859098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}