International Journal of Antimicrobial Agents最新文献

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International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-01 DOI: 10.1016/j.ijantimicag.2025.107444
{"title":"International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page","authors":"","doi":"10.1016/j.ijantimicag.2025.107444","DOIUrl":"10.1016/j.ijantimicag.2025.107444","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 2","pages":"Article 107444"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143193218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In vitro antimicrobial activity of six novel β-lactam and β-lactamase inhibitor combinations and cefiderocol against NDM-producing Enterobacterales in China 6种新型β-内酰胺和β-内酰胺酶抑制剂组合及头孢地罗对产ndm肠杆菌的体外抗菌活性研究。
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-01 DOI: 10.1016/j.ijantimicag.2024.107407
Xinmeng Liu , Ziyao Li , Feilong Zhang , Xinrui Yang , Zichen Lei , Chen Li , Yongli Wu , Jiankang Zhao , Yulin Zhang , Yanning Hu , FangFang Shen , Pingbang Wang , Junwen Yang , Yulei Liu , Huihui Shi , Binghuai Lu
{"title":"In vitro antimicrobial activity of six novel β-lactam and β-lactamase inhibitor combinations and cefiderocol against NDM-producing Enterobacterales in China","authors":"Xinmeng Liu ,&nbsp;Ziyao Li ,&nbsp;Feilong Zhang ,&nbsp;Xinrui Yang ,&nbsp;Zichen Lei ,&nbsp;Chen Li ,&nbsp;Yongli Wu ,&nbsp;Jiankang Zhao ,&nbsp;Yulin Zhang ,&nbsp;Yanning Hu ,&nbsp;FangFang Shen ,&nbsp;Pingbang Wang ,&nbsp;Junwen Yang ,&nbsp;Yulei Liu ,&nbsp;Huihui Shi ,&nbsp;Binghuai Lu","doi":"10.1016/j.ijantimicag.2024.107407","DOIUrl":"10.1016/j.ijantimicag.2024.107407","url":null,"abstract":"<div><h3>Introduction</h3><div>To date, the global prevalence of New Delhi metallo-<em>β</em>-lactamase (NDM) in carbapenem-resistant <em>Enterobacterales</em> (CRE) has been of concern, which is not inhibited by classical <em>β</em>-lactamase inhibitors (BLIs). In this study, we investigated the newly developed antimicrobial agents or inhibitors against NDM-producing <em>Enterobacterales</em> (NPEs).</div></div><div><h3>Methods</h3><div>The <em>in vitro</em> activities of cefiderocol, cefepime/taniborbactam, meropenem/taniborbactam, cefepime/zidebactam, meropenem/nacubactam, aztreonam/nacubactam and aztreonam/avibactam were analyzed in 204 NPE strains collected in China. The potential resistance mechanisms were identified by whole genome sequencing.</div></div><div><h3>Results</h3><div>Of 204 NPE strains, 18.1% (37/204) were resistant to cefiderocol, in which <em>cirA</em> deleterious alteration, PBP3 insertion and NDM production were taken as potential resistance mechanisms; 28.9% (59/204) were resistant to cefepime/zidebactam, involving <em>K. pneumoniae</em> with <em>ompK35</em> deleterious alteration; 22.5% (46/204) were resistant to cefepime/taniborbactam, in which YRIN or YRIK inserted in PBP3 and altered <em>ompC</em> are more frequently detected in the resistant <em>E. coli</em> isolates; 27.9% (57/204) were resistant to meropenem/taniborbactam. Aztreonam/avibactam and aztreonam/nacubactam exhibited excellent activity against NPE. However, meropenem/nacubactam had the lowest activity, with only 49.0% (100/204) of all isolates having MICs of &lt;4/4 mg/L.</div></div><div><h3>Conclusions</h3><div>Aztreonam/avibactam and aztreonam/nacubactam showed the highest activity against NPE. The potential resistance mechanisms of novel antimicrobial agents against NPE should be under active surveillance.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 2","pages":"Article 107407"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Individualized antimicrobial therapy using antibiotic combination testing and therapeutic drug monitoring to treat carbapenem-resistant Acintobacter baumannii infection 应用抗生素联合检测和治疗药物监测个体化抗菌治疗耐碳青霉烯鲍曼不动杆菌感染。
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-01 DOI: 10.1016/j.ijantimicag.2024.107410
Nathalie Grace Sy Chua , Kelvin Kau-Kiat Goh , Tze Peng Lim , Sarah Silin Tang , Winnie Lee , Candice Yuen Yue Chan , Andrea Layhoon Kwa
{"title":"Individualized antimicrobial therapy using antibiotic combination testing and therapeutic drug monitoring to treat carbapenem-resistant Acintobacter baumannii infection","authors":"Nathalie Grace Sy Chua ,&nbsp;Kelvin Kau-Kiat Goh ,&nbsp;Tze Peng Lim ,&nbsp;Sarah Silin Tang ,&nbsp;Winnie Lee ,&nbsp;Candice Yuen Yue Chan ,&nbsp;Andrea Layhoon Kwa","doi":"10.1016/j.ijantimicag.2024.107410","DOIUrl":"10.1016/j.ijantimicag.2024.107410","url":null,"abstract":"<div><div>Treatment of multidrug resistant infections is challenging due to limited therapeutic options. To maximise treatment success of such infections, our infectious disease-trained pharmacists employ a two-pronged approach, using both <em>in vitro</em> antibiotic combination testing and therapeutic drug monitoring, to individualise antibiotic combination regimens for our patients, akin to precision medicine. This approach ensures that the most optimal antibiotic combination and dosing regimens are prescribed for our patients with multidrug resistant infection, to ensure adequate antibiotic exposure and maximal clinical efficacy. We describe the implementation of such 2-pronged approach in two of our patients infected with extensively drug-resistant <em>Acinetobacter baumannii</em> infections. Doses higher than manufacturer-approved regimens were administered. Both cases achieved treatment success with no adverse effects.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 2","pages":"Article 107410"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Aerosolized plus intravenous polymyxin B in comparison to intravenous polymyxin B alone for the management of HAP caused by carbapenem-resistant gram-negative bacteria: A prospective multicenter cohort study 雾化加静脉注射多粘菌素B与单独静脉注射多粘菌素B治疗碳青霉烯耐药革兰氏阴性菌引起的HAP的比较:一项前瞻性多中心队列研究
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-01 DOI: 10.1016/j.ijantimicag.2024.107427
Jingjing Zhang , Linyun Du , Qindong Shi , Xinyu Li , Jianying Li , Enxia Dong , Hao Guo , Xiaoling Zhang , Yanli Hou , Xuting Jin , Jiamei Li , Xiaochuang Wang , Gang Wang
{"title":"Aerosolized plus intravenous polymyxin B in comparison to intravenous polymyxin B alone for the management of HAP caused by carbapenem-resistant gram-negative bacteria: A prospective multicenter cohort study","authors":"Jingjing Zhang ,&nbsp;Linyun Du ,&nbsp;Qindong Shi ,&nbsp;Xinyu Li ,&nbsp;Jianying Li ,&nbsp;Enxia Dong ,&nbsp;Hao Guo ,&nbsp;Xiaoling Zhang ,&nbsp;Yanli Hou ,&nbsp;Xuting Jin ,&nbsp;Jiamei Li ,&nbsp;Xiaochuang Wang ,&nbsp;Gang Wang","doi":"10.1016/j.ijantimicag.2024.107427","DOIUrl":"10.1016/j.ijantimicag.2024.107427","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to evaluate the clinical effectiveness of combined aerosolized (AER) and intravenous (IV) polymyxin B in managing patients with hospital-acquired pneumonia (HAP) caused by carbapenem-resistant gram-negative organism (CRO).</div></div><div><h3>Methods</h3><div>This multicenter prospective cohort study was conducted across six intensive care units in municipal and above-municipal hospitals in Shaanxi, China, from January 1, 2021 to December 31, 2022. Patients with CRO pneumonia were categorized into the intravenous group (IV polymyxin B alone) and the combination group (AER plus IV polymyxin B). Primary outcomes included ICU mortality, 28-day mortality and bacterial clearance, while secondary outcomes included the duration of mechanical ventilation and length of ICU stay.</div></div><div><h3>Results</h3><div>A total of 64 patients were included in the study, with 29 receiving AER plus IV polymyxin B and 35 receiving IV polymyxin B alone. On the seventh day of treatment, the combination group showed a significant reduction in the APACHE II score (17.86 ± 5.03 vs. 19.17 ± 11.02, <em>P</em> = 0.041) and procalcitonin levels (1.27 ± 0.20 vs. 3.18 ± 0.69, <em>P</em> &lt; 0.001) compared to the intravenous group. Additionally, the combination group exhibited a higher bacterial eradication rate (62.1% vs. 42.9%), lower ICU mortality (27.6% vs. 37.1%), shorter duration of mechanical ventilation (371.39 ± 68.97 h vs. 563.94 ± 100.25 h), and reduced ICU stay (34.41 ± 17.87 d vs. 35.03 ± 21.66 d), although the differences were not statistically significant.</div></div><div><h3>Conclusions</h3><div>In patients with CRO pneumonia, combination therapy resulted in significant reductions in APACHE II scores and procalcitonin, but did not lead to statistically significant improvements in clinical outcomes, compared to IV polymyxin B alone.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 2","pages":"Article 107427"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914514","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
Comparison of population pharmacokinetic modeling and machine learning approaches for predicting voriconazole trough concentrations in critically ill patients 危重病人群体药代动力学模型与机器学习方法预测伏立康唑谷浓度的比较。
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-01 DOI: 10.1016/j.ijantimicag.2024.107424
Yinxuan Huang , Yang Zhou , Dongdong Liu , Zhi Chen , Dongmei Meng , Jundong Tan , Yujiang Luo , Shouning Zhou , Xiaobi Qiu , Yuwen He , Li Wei , Xuan Zhou , Wenying Chen , Xiaoqing Liu , Hui Xie
{"title":"Comparison of population pharmacokinetic modeling and machine learning approaches for predicting voriconazole trough concentrations in critically ill patients","authors":"Yinxuan Huang ,&nbsp;Yang Zhou ,&nbsp;Dongdong Liu ,&nbsp;Zhi Chen ,&nbsp;Dongmei Meng ,&nbsp;Jundong Tan ,&nbsp;Yujiang Luo ,&nbsp;Shouning Zhou ,&nbsp;Xiaobi Qiu ,&nbsp;Yuwen He ,&nbsp;Li Wei ,&nbsp;Xuan Zhou ,&nbsp;Wenying Chen ,&nbsp;Xiaoqing Liu ,&nbsp;Hui Xie","doi":"10.1016/j.ijantimicag.2024.107424","DOIUrl":"10.1016/j.ijantimicag.2024.107424","url":null,"abstract":"<div><h3>Background</h3><div>Despite the widespread use of voriconazole in antifungal treatment, its high pharmacokinetic and pharmacodynamic variability may lead to suboptimal efficacy, especially in intensive care unit (ICU) patients. Machine learning (ML), an artificial intelligence modeling approach, is increasingly being applied to personalized medicine. The effectiveness of ML models for predicting voriconazole blood concentrations in ICU patients, compared to traditional population pharmacokinetics (popPK) models, has been uncertain until now. This study aims to identify the most effective modeling strategy for voriconazole.</div></div><div><h3>Methods</h3><div>We developed six ML models using 244 concentrations from 62 patients in our previous popPK dataset. Another additional dataset, consisting of 282 trough concentrations from 177 patients, was used to externally evaluate both ML models and five other published popPK models, utilizing prediction-based diagnostics, simulation-based diagnostics, and Bayesian forecasting.</div></div><div><h3>Results</h3><div>The XGBoost model exhibited superior predictive performance among the six ML models, achieving an R<sup>2</sup> of 0.73. Its performance metrics (RMSE%: 127.21 %, median absolute prediction error: 29.65 %, median prediction error: 9.82 %, F20: 34.04 %, F30: 50.71 %) outperformed those of the best popPK model (RMSE%: 152.41 %, median absolute prediction error: 44.75 %, median prediction error: −0.99 %, F20: 23.40 %, F30: 36.88 %), suggesting greater accuracy and precision in predicting pharmacokinetics.</div></div><div><h3>Conclusions</h3><div>Both ML and popPK models can be utilized for individualized voriconazole therapy. Our comparative study provides insights into the most effective methods for modeling and predicting voriconazole concentrations.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 2","pages":"Article 107424"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multiple mechanisms mediate aztreonam-avibactam resistance in Klebsiella pneumoniae: Driven by KPC-2 and OmpK36 mutations 多种机制介导肺炎克雷伯菌对氨曲南-阿维巴坦的耐药:由KPC-2和OmpK36突变驱动
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-01 DOI: 10.1016/j.ijantimicag.2024.107425
Xinli Xiang , Jingchun Kong , Jia Zhang , Xiaotuan Zhang , Changrui Qian , Tieli Zhou , Yao Sun
{"title":"Multiple mechanisms mediate aztreonam-avibactam resistance in Klebsiella pneumoniae: Driven by KPC-2 and OmpK36 mutations","authors":"Xinli Xiang ,&nbsp;Jingchun Kong ,&nbsp;Jia Zhang ,&nbsp;Xiaotuan Zhang ,&nbsp;Changrui Qian ,&nbsp;Tieli Zhou ,&nbsp;Yao Sun","doi":"10.1016/j.ijantimicag.2024.107425","DOIUrl":"10.1016/j.ijantimicag.2024.107425","url":null,"abstract":"<div><div>Aztreonam-avibactam (ATM-AVI) is a promising β-lactam/β-lactamase inhibitor combination with an antimicrobial spectrum covering serine carbapenemase– or metallo-β-lactamase–producing Enterobacterales. Although ATM-AVI has not been widely used in clinical practice, resistance to it in <em>Escherichia coli</em> has been widely reported. In this study, we investigated an ATM-AVI-resistant <em>Klebsiella pneumoniae</em> strain, designated as 1705R, derived from <em>K. pneumoniae</em> ATCC BAA-1705 by induction, with a minimal inhibitory concentration of 128 µg/mL. The 1705R strain contained two copies of the <em>bla</em><sub>KPC-2</sub> variant, which encodes for a <em>K. pneumoniae</em> carbapenemase (KPC) variant with a Ser109Pro substitution, as well as a premature termination in OmpK36 and OmpK35 porins. This KPC variant decreased susceptibility to ATM-AVI by four-fold and demonstrated a reduced affinity for ATM and AVI in molecular docking analysis. In porin-deficient strains harbouring this KPC variant, ATM-AVI susceptibility was further diminished, exhibiting a 32-fold reduction. Whole-genome sequencing revealed that the transposition of Tn<em>4401</em> carrying <em>bla</em><sub>KPC</sub> from the IncFIB/FIIK plasmid into the ColRNAI plasmid produced a second copy of <em>bla</em><sub>KPC</sub>. Quantitative polymerase chain reaction revealed that the copy number of <em>bla</em><sub>KPC</sub> and its carrier plasmid increased, which significantly up-regulated their mRNA expression. Overexpression of the AcrAB-TolC efflux pump may also be associated with high levels of ATM-AVI resistance. Furthermore, collateral susceptibility and costs of growth and biofilm formation developed after the acquisition of ATM-AVI resistance. This study demonstrates that multiple molecular mechanisms collectively contribute to ATM-AVI resistance in <em>K. pneumoniae</em> 1705R strain, which may represent a mode of resistance to ATM-AVI.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 2","pages":"Article 107425"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Assessment of actual renal function in critically ill patients with severe infections: Moving towards a personalized approach 重症感染的危重患者实际肾功能评估:走向个性化方法。
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-01 DOI: 10.1016/j.ijantimicag.2024.107417
Alessandra Oliva , Lorenzo Volpicelli , Antonietta Gigante
{"title":"Assessment of actual renal function in critically ill patients with severe infections: Moving towards a personalized approach","authors":"Alessandra Oliva ,&nbsp;Lorenzo Volpicelli ,&nbsp;Antonietta Gigante","doi":"10.1016/j.ijantimicag.2024.107417","DOIUrl":"10.1016/j.ijantimicag.2024.107417","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 2","pages":"Article 107417"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Replacing rifampicin with minocycline increases the activity of the treatment regimen for Mycobacterium avium complex pulmonary disease in a dynamic hollow-fibre system 用米诺环素代替利福平增加了动态中空纤维系统中鸟分枝杆菌复杂肺部疾病治疗方案的活性。
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-01 DOI: 10.1016/j.ijantimicag.2024.107423
Jelmer Raaijmakers , Mike M. Ruth , Jodie A. Schildkraut , Erik van den Hombergh , Rob E. Aarnoutse , Elin M. Svensson , Heiman F.L. Wertheim , Wouter Hoefsloot , Jakko van Ingen
{"title":"Replacing rifampicin with minocycline increases the activity of the treatment regimen for Mycobacterium avium complex pulmonary disease in a dynamic hollow-fibre system","authors":"Jelmer Raaijmakers ,&nbsp;Mike M. Ruth ,&nbsp;Jodie A. Schildkraut ,&nbsp;Erik van den Hombergh ,&nbsp;Rob E. Aarnoutse ,&nbsp;Elin M. Svensson ,&nbsp;Heiman F.L. Wertheim ,&nbsp;Wouter Hoefsloot ,&nbsp;Jakko van Ingen","doi":"10.1016/j.ijantimicag.2024.107423","DOIUrl":"10.1016/j.ijantimicag.2024.107423","url":null,"abstract":"<div><h3>Objective</h3><div><em>Mycobacterium avium</em> complex bacteria cause chronic pulmonary disease (MAC-PD) in susceptible patients. The recommended treatment regimen (rifampicin, ethambutol and azithromycin) achieves 65% cure rates but with considerable toxicity and drug-drug interactions [<span><span>[2]</span></span>, <span><span>[3]</span></span>]. Minocycline proved active in monotherapy experiments using the hollow-fibre model [<span><span>4</span></span>]. We compared the efficacy of the recommended regimen with a minocycline, ethambutol and azithromycin regimen using this model.</div></div><div><h3>Methods</h3><div>Epithelial lining fluid pharmacokinetic (PK) profiles of the recommended regimen and minocycline, ethambutol, azithromycin regimen were simulated. THP-1 cells infected with <em>M. avium</em> ATCC 700898 were exposed to these regimens for 21 d. PK profiles were determined at d 0 and d 21. The pharmacodynamic effect was measured by determining bacterial densities at d 0, 3, 7, 14 and 21 for intra- and extracellular fractions. Emergence of macrolide-resistance was monitored by inoculating azithromycin-containing agar, MIC measurements and resistance mutation analysis.</div></div><div><h3>Results</h3><div>The minocycline-containing regimen exhibited a 1.5 log10 CFU/mL lower bacterial burden than the recommended regimen at d 7, though both regimens lost effectiveness over time. Treatment failure in both arms was not linked to the emergence macrolide-resistance. PK profiles simulated in the model matched those in MAC-PD patients.</div></div><div><h3>Conclusions</h3><div>Replacing rifampicin with minocycline increased the antimycobacterial activity of the MAC-PD treatment regimen in the hollow-fibre model, without jeopardizing the prevention of macrolide-resistance. This promising minocycline-containing regimen is a candidate for inclusion in clinical trials.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 2","pages":"Article 107423"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903160","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
Analysis of time-to-positivity data in tuberculosis treatment studies: Identifying a new limit of quantification 结核病治疗研究中阳性时间数据的分析:确定量化的新限制。
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-01 DOI: 10.1016/j.ijantimicag.2024.107404
Suzanne M. Dufault , Geraint R. Davies , Elin M. Svensson , Derek J. Sloan , Andrew D. McCallum , Anu Patel , Pieter Van Brantegem , Paolo Denti , Patrick P.J. Phillips
{"title":"Analysis of time-to-positivity data in tuberculosis treatment studies: Identifying a new limit of quantification","authors":"Suzanne M. Dufault ,&nbsp;Geraint R. Davies ,&nbsp;Elin M. Svensson ,&nbsp;Derek J. Sloan ,&nbsp;Andrew D. McCallum ,&nbsp;Anu Patel ,&nbsp;Pieter Van Brantegem ,&nbsp;Paolo Denti ,&nbsp;Patrick P.J. Phillips","doi":"10.1016/j.ijantimicag.2024.107404","DOIUrl":"10.1016/j.ijantimicag.2024.107404","url":null,"abstract":"<div><h3>Background</h3><div>The BACTEC Mycobacteria Growth Indicator Tube (MGIT) machine is the standard globally for detecting viable mycobacteria in patients’ sputum. Samples are observed for no longer than 42 days, at which point the sample is declared ‘negative’ for tuberculosis (TB). This time to detection of bacterial growth, referred to as time-to-positivity (TTP), is increasingly of interest, not solely as a diagnostic tool but also as a continuous biomarker wherein change in TTP can be used for comparing the bactericidal activity of different TB treatments. However, as a continuous measure, there are oddities in the distribution of TTP values observed, particularly at higher values.</div></div><div><h3>Methods</h3><div>We explored whether there is evidence to suggest setting an upper limit of quantification for modeling purposes (ULOQ<em><sub>M</sub></em>) lower than the diagnostic limit of detection (LOD) using data from several TB-PACTS randomized clinical trials and PanACEA MAMS-TB.</div></div><div><h3>Results</h3><div>Across all trials, less than 7.1% of weekly samples returned TTP measurements between 25 and 42 days. Further, the relative absolute prediction error (%) was highest in this range. When modelling with ULOQ<em><sub>M</sub></em>s of 25 and 30 days, estimator precision improved for 23 of 25 regimen-level slopes compared to models using the LOD. Discrimination between regimens based on Bayesian posteriors also improved.</div></div><div><h3>Conclusions</h3><div>Although TTP measurements between 25 days and the diagnostic LOD may be important for diagnostic purposes, TTP values in this range may not contribute meaningfully to its use as a quantitative measure, particularly when assessing treatment response, and may lead to underpowered clinical trials.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 2","pages":"Article 107404"},"PeriodicalIF":4.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800553","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
Prophylactic phage aerosols for nosocomial infection control in an extracorporeal membrane oxygenation unit: A 4-year prospective study of temporospatially designed phage cocktails 预防性噬菌体气雾剂用于体外膜氧合装置的医院感染控制:时空设计噬菌体鸡尾酒的4年前瞻性研究。
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-01 DOI: 10.1016/j.ijantimicag.2024.107413
Chun-Chieh Tseng , Li-Kuang Chen , Hsiu-Tzu Chu , Yi-Ting Chen , Hui-Li Jiang , Hui-Hua Yang , Chin-Cheng Chang , Sankhla Debangana , Lee-Mei Ponge , Min-Xiu Li , Ying-Hao Chin , Jui-Chih Chang
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