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Antibiotic Resistance in Dentistry: A Review. 牙科抗生素耐药性研究进展。
IF 4.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-12-12 DOI: 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.

背景:抗生素在牙科中的广泛使用已成为全球抗生素耐药性上升的重要驱动因素,对口腔和整体健康构成严重风险。目的:本研究旨在回顾抗生素在牙科中的使用,阐明耐药性发展的机制,确定影响因素,并讨论减轻这一日益严重的全球健康威胁的策略。方法:这篇叙述性综述审查了目前牙科抗生素处方的模式,并评估了表明抗生素虽然对预防和管理牙源性感染至关重要,但经常被不必要或不适当地开处方的证据。结果:该分析强调了主要口腔病原体如链球菌、粪肠球菌和牙龈卟啉单胞菌的耐药性日益增强,这越来越限制了常规治疗的有效性。导致这一趋势的因素包括不遵守临床指南、患者压力以及牙科专业人员对抗生素管理的认识不足。为了应对这些挑战,该综述强调了循证处方、加强管理计划和开发替代疗法(包括宿主调节剂和噬菌体应用)的重要性。持续的教育和专业发展对于提高临床判断和促进负责任的处方习惯同样至关重要。结论:克服牙科抗生素耐药性需要临床医生、研究人员、教育工作者和政策制定者之间的协调努力。扩大监测、执行管理驱动的政策和支持治疗研究创新是减少抗生素滥用和保持其有效性的关键。通过集体承诺和知情实践,牙科专业可以在保护抗生素疗效和促进可持续的高质量患者护理方面发挥关键作用。
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引用次数: 0
Antimicrobial Resistance Patterns and Determinants of Helicobacter pylori Culture Success: A Prospective Study. 幽门螺杆菌培养成功的耐药模式和决定因素:一项前瞻性研究。
IF 4.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-12-12 DOI: 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。
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引用次数: 0
Comparative Evaluation of Sequencing Technologies for Detecting Antimicrobial Resistance in Bloodstream Infections. 检测血液感染抗菌素耐药性的测序技术比较评价。
IF 4.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-12-12 DOI: 10.3390/antibiotics14121257
Myrto Papamentzelopoulou, Georgia Vrioni, Vassiliki Pitiriga

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.

血液感染(bsi)构成了一个重大的全球健康挑战,特别是由于抗菌素耐药性(AMR)日益普遍。及时准确地识别病原体和耐药决定因素对于指导适当治疗和改善患者预后至关重要。传统的基于培养的诊断受到周转时间长和灵敏度降低的限制,特别是在培养阴性或多微生物感染时。本综述系统地研究了目前和新兴的bsi中AMR检测的测序技术,包括全基因组测序(WGS)、靶向下一代测序(tNGS)、宏基因组下一代测序(mNGS)和长读测序平台(Oxford Nanopore, PacBio)。我们使用诊断灵敏度、周转时间和成本等关键指标比较了它们的临床表现,突出了每种技术最有效的环境。例如,tNGS可以在8-24小时内实现对已知抗性基因的快速检测,而WGS可以在24-48小时内提供全面的全基因组抗性分析,mNGS可以提供更广泛的检测,包括罕见或意想不到的病原体,尽管成本更高,处理时间更长。我们的分析确定了每种方法的特定优势和局限性,支持使用针对具体情况的策略,例如将针对常见病原体的快速靶向测序与针对复杂病例的更广泛的宏基因组方法相结合,以提高诊断率并指导抗菌药物治疗。定量比较表明,测序技术可以补充传统方法,特别是在基于培养的方法失败的情况下。总之,与传统的bsi AMR检测方法相比,基于测序的诊断方法在灵敏度和速度方面提供了可测量的改进。未来的工作应侧重于优化工作流程,将测序数据整合到临床决策中,并在前瞻性研究中验证方法。
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引用次数: 0
Combination Therapy with Oral Vancomycin Plus Intravenous Metronidazole Is Not Superior to Oral Vancomycin Alone for the Treatment of Severe Clostridioides difficile Infection: A KASID Multicenter Study. 口服万古霉素联合静脉注射甲硝唑治疗重症艰难梭菌感染并不优于口服万古霉素:一项KASID多中心研究
IF 4.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-12-11 DOI: 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}
引用次数: 0
Plasma and Muscle Pharmacokinetics of Ceftriaxone in Nile Tilapia (Oreochromis niloticus) After Different Administration Routes. 不同给药途径对头孢曲松在尼罗罗非鱼体内血浆和肌肉药动学的影响
IF 4.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-12-11 DOI: 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.

背景/目的:研究头孢曲松(25 mg/kg)在罗非鱼体内不同给药方式的血浆和肌肉药动学。方法:保持在30±1.5°C下的216条鱼平均分为血管内注射(IV)、腹腔注射(IP)和肌肉注射(IM)三组。采用高效液相色谱法定量头孢曲松浓度,采用非区室分析计算药动学参数。结果:血浆总清除率为0.22 L/h/kg,稳态分布容积为0.85 L/kg,消除半衰期(t1/2λz)为5.27 h。静脉注射组、IP注射组和IM注射组的t1/2λz值具有可比性。注射IP和IM后血药浓度峰值分别为37.71±3.12µg/mL和40.51±2.77µg/mL。生物利用度分别为67.04%和101.48%。静脉注射组肌肉浓度峰值为9.49±0.75µg/g, IP组为5.71±0.85µg/g, IM组为12.24±2.41µg/g。IV组、IP组和IM组AUC0-∞肌/AUC0-∞血浆比值分别为0.23、0.18和0.30。AUCmuscle/AUCplasma表示药物进入肌肉的比例,小于1表示头孢曲松进入肌肉组织的比例较低。结论:头孢曲松经IP和IM注射后吸收良好,并以较低的组织渗透进入肌肉组织。头孢曲松可通过尼罗罗非鱼的IP和IM注射给药;然而,其治疗效果有待评估。
{"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}
引用次数: 0
Advances in Kaempferol: Extraction, Biosynthesis, and Application with Antibacterial Agents. 山奈酚的提取、生物合成及其抗菌应用研究进展。
IF 4.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-12-11 DOI: 10.3390/antibiotics14121254
Xiaojuan Wei, Weiwei Wang, Rongbin Hu, Xun Gao, Bing Li, Yubin Bai, Jiyu Zhang

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.

耐多药细菌在世界各地的传播正在上升,迫切需要新的抗生素来解决耐药危机。天然产物因其结构的多样性和生物活性而成为抗菌药物研究和开发的热点。特别是山奈酚,具有一系列的生物学特性,包括抗氧化、抗菌和抗肿瘤活性,在各个领域都有应用潜力。本文综述了山奈酚的提取、生物合成、抑菌活性等方面的研究进展,并对其抑菌机制进行了初步探讨。此外,我们还综述了山奈酚与抗生素的增效联合,如山奈酚与粘菌素或青霉素联合使用,显著提高了治疗效果。最后讨论了山奈酚纳米颗粒的制备及其在抗菌方面的应用。
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引用次数: 0
Evaluation of EUCAST Rapid Antimicrobial Susceptibility Testing for Gram-Negative ESKAPEEc Pathogens in Blood Cultures, with a Focus on Carbapenemase-Producing Klebsiella pneumoniae in a University Hospital in Palermo, Italy. 意大利巴勒莫某大学医院EUCAST快速药敏试验对革兰氏阴性ESKAPEEc血培养病原菌的评价,重点是产碳青霉烯酶肺炎克雷伯菌。
IF 4.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-12-11 DOI: 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.

背景:快速抗菌药物敏感性试验(RAST)可以直接从阳性血液培养中早期发现耐药性,可能改善血流感染(bsi)的结局。我们评估了EUCAST RAST对革兰氏阴性ESKAPEEc病原体的性能,并鉴定了碳青霉烯耐药肺炎克雷伯菌(CRKP)的碳青霉烯酶基因。方法:筛选354例阳性血培养,其中革兰氏阴性ESKAPEEc单菌51株。将4、6、8和16-20 h的RAST结果与使用BD Phoenix™系统获得的标准抗菌药敏试验(AST)结果进行比较。计算了分类一致性(CA)和错误率。对15株CRKP分离株进行多重PCR和Sanger测序,鉴定碳青霉烯酶基因和等位基因变异。结果:51株革兰氏阴性ESKAPEEc符合RAST的纳入标准(大肠杆菌15株,肺炎克雷伯菌19株,鲍曼假杆菌11株,铜绿假单胞菌6株)。整体表现因菌种和抗生素而有显著差异。大肠杆菌在早期时间点显示出频繁的不可读区或ATU区,CA变化率很宽(50-100%),AMP、TZP和CAZ的非常严重错误(VME)率很高,特别是在6-8小时。肺炎凯布菌对碳青霉烯类、CAZ和TZP的CA一直很高(几乎100%)。鲍曼假单胞菌表现出极好的一致性(100%),除了GEN在6-8小时。铜绿假单胞菌只能在16-20小时进行评估,显示出AMK, CAZ和CIP的高CA;MEM的CA较低(83%);由于通用ATU读数,IMI的CA无法计算;由于ATU结果的优势,TZP的CA值为0%。不同物种和阅读时间的vme范围为0%至26.1%,但碳青霉烯类不产生vme。分子分析显示blaKPC阳性率为66.7%,blaNDM阳性率为46.7%,blaOXA-48阳性率为33.3%,且多株共出现。测序确定blaKPC-2和blaNDM-1为主要变体,其中一株含有blaNDM-5。结论:EUCAST - RAST显著加快了阳性血培养的敏感性报告,但其准确性与物种和时间有关。肺炎克雷伯菌(包括CRKP)和鲍曼假单胞菌在16-20小时的表现非常好,铜绿假单胞菌在16-20小时也可以接受。相比之下,大肠杆菌在早期时间点显示频繁的ATU结果和高ME/VME率,使得8小时前的读数对临床决策不可靠。总的来说,当认识到物种特异性限制时,RAST可以有效地支持快速抗菌药物管理,并且对早期时间点结果进行谨慎解释。
{"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}
引用次数: 0
From 60 Causes to 10 Solutions Against Antibiotics Shortages in Sweden: Platinea's Approach to Developing Policy Interventions. 从瑞典抗生素短缺的60个原因到10个解决方案:Platinea制定政策干预措施的方法。
IF 4.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-12-10 DOI: 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.

背景/目的:抗生素短缺是一个日益严重的问题,它危害患者安全,增加医疗保健费用,并加速抗生素耐药性。基于瑞典的例子,本文旨在说明和讨论一个有组织的协作平台如何能够设计若干政策干预措施,以应对人类使用抗生素的短缺。方法:我们描述了多部门合作Platinea(现有抗生素创新平台)如何首先确定、构建和优先考虑抗生素短缺的原因,然后确定和优先考虑一套与这些原因相匹配的政策解决方案。应用的具体方法包括专家启发、互动研讨会、焦点小组和多标准决策过程。结果:在概述了大约60种抗生素短缺的原因后,我们将其与10种优先解决方案联系起来,包括增加库存,中央协调,集成IT系统,提高单价,每年固定付款以及北欧采购和生产合作。结论:我们提出了一个包含六个步骤的流程,通过一个多部门利益相关者团体的参与来制定政策解决方案:对问题的原因进行公开的头脑风暴,将它们构建成一个清晰的结构,选择和优先考虑关键原因,匹配原因和解决方案,并为新兴解决方案设计优先考虑机制。这一方法可适用于其他国家情况和类似的政策问题。
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引用次数: 0
Wound-Healing Potential of Engineered Lysin GRC-ML07 in Pseudomonas aeruginosa Infected Wounds in Immunocompromised Mice. 工程溶酶GRC-ML07在免疫功能低下小鼠铜绿假单胞菌感染伤口中的伤口愈合潜力
IF 4.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-12-10 DOI: 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.

目的:研究工程化溶酶GRC-ML07在免疫抑制下耐多药铜绿假单胞菌全层创面感染小鼠模型中的抗菌和创面愈合潜力。方法:雄性BALB/c小鼠(22 ~ 24 g)经环磷酰胺免疫抑制。3天后,建立全层切除创面并感染铜绿假单胞菌(107个细胞/创面)。将溶酶GRC-ML07包封于海藻酸盐凝胶中,每日2次局部涂抹于创面,持续4天。在第4天和第7天收集伤口拭子进行微生物学分析,收集痂组织进行细胞因子和细胞谱分析。于第4、7、14、21天取组织学标本。结果:Lysin GRC-ML07诱导细菌裂解,并伴有TLR2、TLR4或TLR7/8信号通路的低激活和促炎细胞因子的体外产生。其在体内的应用导致伤口中GM-CSF、IL-1β、IL-6、IL-17A和TNF-α水平降低,与对照组和安慰剂(海藻酸盐凝胶)组相比,第4天中性粒细胞计数增加46%。到第7天,溶素治疗减少了2 log细菌负荷,减少了伤口中性粒细胞计数,导致伤口过渡到肉芽和上皮化阶段,并伴有痂脱屑。结论:研究首次表明,工程溶酶GRC-ML07不仅具有抗菌作用,而且在免疫功能低下的小鼠中具有明显的促愈合作用,促进炎症的消退和向肉芽/上皮化阶段的过渡。
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引用次数: 0
Enteric Pathogens in Wild Boars Across the European Union: Prevalence and Antimicrobial Resistance Within a One Health Framework. 在整个欧盟野猪肠道病原体:流行和抗菌素耐药性在一个健康框架内。
IF 4.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-12-10 DOI: 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.

野猪广泛分布在自然、农业和城市景观中,是在“同一个健康”框架下监测人类-野生动物-牲畜界面抗菌素耐药性(AMR)出现和传播的理想哨点物种。本文综述了目前在欧盟从野猪中分离的主要肠道病原体的患病率、多样性、抗菌素耐药性和流行病学意义方面的知识,特别关注了它们在抗菌素耐药性传播中的潜在作用。大量研究报告了沙门氏菌、小肠结肠炎耶尔森菌、产志贺毒素大肠杆菌(STEC)和弯曲杆菌的不同流行率。在粪便样本中观察到较高的流行率——沙门氏菌35%,小肠结肠炎耶尔森菌和STEC 27%,弯曲杆菌66%——突出了野猪作为携带者的作用以及屠宰过程中胴体污染的相关风险。扁桃体是小肠结肠炎耶夫氏菌的一个关键菌基,患病率达到35%。几项研究已经确定了对被世界卫生组织列为人类医学极其重要或高度优先事项的抗菌素的耐药性,包括氟喹诺酮耐药非伤寒沙门氏菌和第三代头孢菌素耐药小肠结肠炎耶夫氏菌,引起了显著的公共卫生关切。尽管越来越多的人对抗菌素耐药性感兴趣,但大多数现有的研究仍然是描述性的,地理位置有限,对野猪抗菌素耐药性的获取和传播途径提供的见解有限。抗性组分析和流行病学临界值等新方法为区分野生型和获得性耐药菌株以及更好地了解抗菌素耐药性传播动态提供了附加价值。将野生动物纳入“同一个健康”监测系统对于全面掌握抗菌素耐药性传播的复杂性至关重要。
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引用次数: 0
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