International Journal of Antimicrobial Agents最新文献

{"title":"Alexander (Alasdair) McIntosh Geddes: 1934–2024","authors":"","doi":"10.1016/j.ijantimicag.2024.107282","DOIUrl":"10.1016/j.ijantimicag.2024.107282","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0924857924002000/pdfft?md5=605c68a97c53eac74a68d504cf4278cd&pid=1-s2.0-S0924857924002000-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142048994","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}

{"title":"International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page","authors":"","doi":"10.1016/j.ijantimicag.2024.107307","DOIUrl":"10.1016/j.ijantimicag.2024.107307","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0924857924002231/pdfft?md5=807585f03302690ec9120f2eb877d49d&pid=1-s2.0-S0924857924002231-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142040720","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}

{"title":"Reduced mortality with antimicrobial stewardship guided by BioFire FilmArray Blood Culture Identification 2 panel in critically ill patients with bloodstream infection: A retrospective propensity score-matched study","authors":"","doi":"10.1016/j.ijantimicag.2024.107300","DOIUrl":"10.1016/j.ijantimicag.2024.107300","url":null,"abstract":"<div><h3>Objectives</h3><p>To investigate whether using the BioFire® FilmArray® Blood Culture Identification 2 panel (BCID2) leads to timely antimicrobial therapy and improves patient outcomes in critically ill patients with bloodstream infections (BSIs).</p></div><div><h3>Methods</h3><p>This retrospective observational study included patients with BSIs admitted to the intensive care unit from July 1, 2021, to August 31, 2023. Patients were divided into groups receiving appropriate or inappropriate antimicrobial therapy. Those receiving inappropriate therapy underwent adjustments using standard-of-care (SOC) testing or BCID2. Propensity score matching (PSM) was performed on the original cohort (Model 1) and a time-window bias-adjusted cohort (Model 2). Clinical impact of BCID2-guided antimicrobial adjustment was analysed in both models.</p></div><div><h3>Results</h3><p>A total of 181 patients received inappropriate antimicrobial therapy, with 33 undergoing BCID2 testing and 148 undergoing SOC testing. Following PSM and time-window bias adjustment, 66 patients were analysed in Model 1 and 46 patients in Model 2. BCID2 significantly reduced the median time to appropriate antimicrobial therapy (40.8 vs. 74.0 h in Model 1; 42.8 vs. 68.9 h in Model 2) and the day-28 mortality rate (27.8% vs. 77.1%, <em>P</em> &lt; 0.001 in Model 1; 23.5% vs. 58.6%, <em>P</em> = 0.021 in Model 2). In multivariate regression analysis, BCID2-guided antimicrobial adjustment was an independent prognostic factor for day-28 mortality (adjusted odds ratio [aOR] 0.07 in Model 1 and aOR 0.12 in Model 2).</p></div><div><h3>Conclusion</h3><p>BCID2-guided antimicrobial stewardship was associated with a shorter time to appropriate antimicrobial therapy and reduced day-28 mortality in critically ill patients with BSIs receiving inappropriate antimicrobial therapy.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035807","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}

{"title":"A physiologically based pharmacokinetic model of voriconazole in human CNS—Integrating time-dependent inhibition of CYP3A4, genetic polymorphisms of CYP2C19 and possible transporter mechanisms","authors":"","doi":"10.1016/j.ijantimicag.2024.107310","DOIUrl":"10.1016/j.ijantimicag.2024.107310","url":null,"abstract":"<div><h3>Objectives</h3><p>Voriconazole is a classical antifungal drug that is often used to treat CNS fungal infections due to its permeability through the BBB. However, its clinical use remains challenging because of its narrow therapeutic window and wide inter-individual variability. In this study, we proposed an optimised and validated PBPK model by integrating <em>in vitro, in vivo</em> and clinical data to simulate the distribution and PK process of voriconazole in the CNS, providing guidance for clinical individualised treatment.</p></div><div><h3>Methods</h3><p>The model structure was optimised and tissue-to-plasma partition coefficients were obtained through animal experiments. Using the allometric relationships, the distribution of voriconazole in the human CNS was predicted. The model integrated factors affecting inter-individual variation and drug interactions of voriconazole—polymorphisms in the CYP2C19 gene and auto-inhibition and then was validated using real clinical data.</p></div><div><h3>Results</h3><p>The overall AFE value showing model predicted differences was 1.1420 in the healthy population; and in the first prediction of plasma and CSF in actual clinical patients, 89.5% of the values were within the 2-fold error interval, indicating good predictive performance of the model. The bioavailability of voriconazole varied at different doses (39%-86%), and the optimised model conformed to this pattern (46%–83%).</p></div><div><h3>Conclusions</h3><p>Combined with the relevant pharmacodynamic indexes, the PBPK model provides a feasible way for precise medication in patients with CNS infection and improve the treatment effect and prognosis.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017335","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}

{"title":"Meta-analysis on safety of standard vs. prolonged infusion of beta-lactams","authors":"","doi":"10.1016/j.ijantimicag.2024.107309","DOIUrl":"10.1016/j.ijantimicag.2024.107309","url":null,"abstract":"<div><h3>Background</h3><p>Efficacy for prolonged infusion beta-lactam dosing schemes has been previously described, but there has been less focus on the safety of standard vs. prolonged infusion protocols of beta-lactams. This study explored differences in adverse drug reactions (ADRs) reported for beta-lactams between each of these infusion protocols.</p></div><div><h3>Methods</h3><p>A systematic review of MEDLINE literature databases via PubMed was conducted and references were reviewed. Articles were compiled and assessed with specific inclusion/exclusion criteria. We included randomised and nonrandomised, prospective, and retrospective cohort studies that reported adverse drug reactions (ADRs) due to either standard (30–60 mins) or prolonged (≥3 h) infusions of beta-lactam infusions. Total ADRs between strategies were analysed by infusion methodology. The most consistently reported ADRs were subject to meta-analysis across studies.</p></div><div><h3>Results</h3><p>12 studies met inclusion/exclusion criteria with data for 4163 patients. There was insufficient data to systematically analyse neurotoxicity or cytopenias. Seven studies reported on nephrotoxicity outcomes with no significant difference in event rates between standard (n = 434/2258,19.2%) vs. prolonged infusion (n = 266/1271, 20.9%) of beta-lactams (OR = 1.08, 95% CI [0.91, 1.29]). Six studies observed diarrhoea in a total of 759 patients with no significant difference in patients of standard (n = 18/399, 4.5%) vs. prolonged (n = 19/360, 5.3%) infusion of beta-lactams (OR = 1.14, 95% CI [0.59,2.20]).</p></div><div><h3>Conclusion</h3><p>Prolonged and standard infusion schemes for beta-lactams demonstrated similar adverse event rates. Future research should focus on improved standardisation of adverse effect definitions and a priori aim to study neurotoxicity and cytopenias. Consistent recording of ADRs and standardised definitions of these reactions will be paramount to further study of this subject.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017337","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}

{"title":"Host immunomodulation strategies to combat pandemic-associated antimicrobial-resistant secondary bacterial infections","authors":"","doi":"10.1016/j.ijantimicag.2024.107308","DOIUrl":"10.1016/j.ijantimicag.2024.107308","url":null,"abstract":"<div><p>The incidence of secondary bacterial infections has increased in recent decades owing to various viral pandemics. These infections further increase the morbidity and mortality rates associated with viral infections and remain a significant challenge in clinical practice. Intensive antibiotic therapy has mitigated the threat of such infections; however, overuse and misuse of antibiotics have resulted in poor outcomes, such as inducing the emergence of bacterial populations with antimicrobial resistance (AMR) and reducing the therapeutic options for this crisis. Several antibiotic substitutes have been suggested and employed; however, they have certain limitations and novel alternatives are urgently required. This review highlights host immunomodulation as a promising strategy against secondary bacterial infections to overcome AMR. The definition and risk factors of secondary bacterial infections, features and limitations of currently available therapeutic strategies, host immune responses, and future perspectives for treating such infections are discussed.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017336","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}

{"title":"Dual Therapy based on Co-formulated darunavir/ritonavir plus lamivudine for initial therapy of HIV infection: the ANDES randomized controlled trial.","authors":"M I Figueroa, O Sued, D Cecchini, M Sanchez, M J Rolón, G Lopardo, M Ceschel, G Miernes, M Destefano, P Patterson, A Gun, V Fink, Z Ortiz, P Cahn","doi":"10.1016/j.ijantimicag.2024.107301","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107301","url":null,"abstract":"<p><strong>Background: </strong>Tenofovir containing antiretroviral therapy regimens may bring long-term toxicity-related side effects. We aimed to assess the virological efficacy of co-formulated darunavir-ritonavir plus lamivudine compared to darunavir-ritonavir plus tenofovir and emtricitabine or lamivudine.</p><p><strong>Methods: </strong>The ANDES study was a 48-week, phase 4, randomized, open-label, non-inferiority trial in naïve adults living with HIV. Patients were randomized 1:1 to receive a daily oral regimen of either dual therapy based on a generic co-formulation of darunavir-ritonavir (800/100 mg) plus a generic lamivudine 300 mg pill, or triple therapy with darunavir-ritonavir plus tenofovir/emtricitabine (300/200 mg) or tenofovir/lamivudine (300/300 mg). The primary endpoint was the proportion of patients with a viral load of less than 50 copies/mL at week 48 in the intention-to-treat population. We used the FDA snapshot algorithm and a non-inferiority margin of -12%. Secondary objectives included safety analysis in the per-protocol population. This study is registered at ClinicalTrials.gov, NCT02770508.</p><p><strong>Results: </strong>Between November 2015 to October 31, 2020, 336 participants were randomly assigned either to the triple therapy arm (165) or the dual therapy arm (171). After 48 weeks, 153 patients in the triple therapy group (93%) and 155 patients in the double therapy group (91%) achieved virological suppression (difference -2·1%, 95%CI -7·0 to 2·9). Drug-related adverse events were more common in the triple therapy group (p=0·04). Two toxicity-related events led to discontinuation in each group.</p><p><strong>Interpretation: </strong>Co -formulated darunavir/ ritonavir plus lamivudine has shown non-inferiority and a safer toxicity profile compared to a standard-of-care triple regimen including tenofovir in treatment-naïve patients.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995710","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}

{"title":"Verapamil enhances the activity of Caspofungin against Cryptococcus neoformans， coinciding with inhibited Ca2+/CN pathway and damage to cell wall integrity","authors":"","doi":"10.1016/j.ijantimicag.2024.107303","DOIUrl":"10.1016/j.ijantimicag.2024.107303","url":null,"abstract":"<div><h3>Objectives</h3><p>Given the challenges posed by toxicity and drug resistance in the treatment of cryptococcal infections, we sought to explore the antifungal potential of verapamil (VER), a calcium channel blocker, against <em>Cryptococcus neoformans</em> (<em>C. neoformans</em>), and its potential synergy with antifungals, specifically caspofungin (CAS).</p></div><div><h3>Materials and Methods</h3><p><em>In vitro</em> and <em>in vivo</em> (<em>Galleria mellonella</em>) models were employed to assess VER's antifungal activity and its interaction with CAS. Mechanisms underlying the synergism were explored through analysis of cell wall integrity, membrane permeability, and gene expression related to the calcineurin pathway. Additionally, the influence of Ca²⁺ on chitin deacetylase activity was investigated.</p></div><div><h3>Results</h3><p>VER exhibited a pronounced antifungal effect on <em>C. neoformans</em> and synergized with CAS, enhancing antifungal efficacy in <em>Galleria mellonella</em>. VER reduced chitosan content and disrupted cell wall integrity, evidenced by melanin leakage and fluorescence staining. VER+CAS modified membrane permeability, triggering intracellular ROS accumulation and mitochondrial membrane potential alterations. VER mitigated CAS-induced calcium fluctuations and downregulated calcineurin pathway genes. Furthermore, it was found that the enzyme activity of chitin deacetylase of <em>C. neoformans</em> is significantly influenced by the presence of Ca²⁺, suggesting that the use of VER may affect this activity.</p></div><div><h3>Conclusions</h3><p>The synergistic antifungal effect of VER and CAS represents a promising therapeutic strategy for cryptococcal infections. The multifaceted mechanisms, including disruption of cell wall integrity and modulation of membrane permeability, and regulation of intracellular calcium signaling pathways, offer new insights into antifungal drug development.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995711","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}

{"title":"Predictive performance of multi-model approaches for model-informed precision dosing of piperacillin in critically ill patients","authors":"","doi":"10.1016/j.ijantimicag.2024.107305","DOIUrl":"10.1016/j.ijantimicag.2024.107305","url":null,"abstract":"<div><h3>Objectives</h3><p>Piperacillin (PIP)/tazobactam is a frequently prescribed antibiotic; however, over- or underdosing may contribute to toxicity, therapeutic failure, and development of antimicrobial resistance. An external evaluation of 24 published PIP-models demonstrated that model-informed precision dosing (MIPD) can enhance target attainment. Employing various candidate models, this study aimed to assess the predictive performance of different MIPD-approaches comparing (i) a single-model approach, (ii) a model selection algorithm (MSA) and (iii) a model averaging algorithm (MAA).</p></div><div><h3>Methods</h3><p>Precision, accuracy and expected target attainment, considering either initial (B1) or initial and secondary (B2) therapeutic drug monitoring (TDM)-samples per patient, were assessed in a multicentre dataset (561 patients, 11 German centres, 3654 TDM-samples).</p></div><div><h3>Results</h3><p>The results demonstrated a slight superiority in predictive performance using MAA in B1, regardless of the candidate models, compared to MSA and the best single models (MAA, MSA, best single models: inaccuracy ±3%, ±10%, ±8%; imprecision: &lt;25%, &lt;31%, &lt;28%; expected target attainment &gt;77%, &gt;71%, &gt;73%). The inclusion of a second TDM-sample notably improved precision and target attainment for all MIPD-approaches, particularly within the context of MSA and most of the single models. The expected target attainment is maximized (up to &gt;90%) when the TDM-sample is integrated within 24 h.</p></div><div><h3>Conclusions</h3><p>In conclusion, MAA streamlines MIPD by reducing the risk of selecting an inappropriate model for specific patients. Therefore, MIPD of PIP using MAA implicates further optimisation of antibiotic exposure in critically ill patients, by improving predictive performance with only one sample available for Bayesian forecasting, safety, and usability in clinical practice.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0924857924002218/pdfft?md5=d215d933dc422ceff04ee5a5d0e95ad5&pid=1-s2.0-S0924857924002218-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987813","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}

{"title":"Advancing Research and Development of Anti-infectives for Children: A Clinical Development Perspective.","authors":"Ann M Buchanan, Adrie Bekker, Hardik Chandasana, Ralph DeMasi, Zrinka Lulic, Terry Ernest, Cindy Brothers, Sherene Min, Theodore Ruel, Lionel K Tan","doi":"10.1016/j.ijantimicag.2024.107306","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107306","url":null,"abstract":"<p><p>The HIV treatment landscape for adults has progressed dramatically in recent decades; however, paediatric populations continue to experience delayed and limited access to effective and safe antiretroviral therapy options. Despite current incentive programs, formulation research and development and approved drug dosing for children have been limited, particularly for neonates (aged <4 weeks). Regulatory approval of drug formulations and dosing in children may lag behind adult approvals by years. Formulation and trial design adjustments complicate paediatric drug development, all of which are vital to accommodate for physiological differences, organ maturation, and rapid weight gain, which are most significant in the youngest children. To facilitate more rapid anti-infective drug development for paediatric populations, regulatory agencies provide guidelines that include extrapolating efficacy and safety data from relevant populations; using pharmacokinetic (PK) bridging and modelling to reduce sample sizes and limit the number of PK studies needed before efficacy analyses; and enrolling age- or weight-based cohorts in parallel rather than sequentially for clinical trials. Ensuring access to approved drugs poses an additional challenge, as uncertainty in demand leads to manufacturing and supply complexity with potentially higher costs that can be a barrier to uptake. Here we summarize challenges in drug development for children living with HIV, which are not unique to antiretrovirals. We aim to propose strategies for how model-based approaches and global partnerships can overcome some of these barriers to accelerate paediatric drug development, with particular reference to HIV, and how lessons learnt from HIV could be extended to other anti-infectives.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987910","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}