Drugs最新文献

{"title":"The Challenge of Treating Infections Caused by Metallo-β-Lactamase-Producing Gram-Negative Bacteria: A Narrative Review.","authors":"Carmen Hidalgo-Tenorio, German Bou, Antonio Oliver, Montserrat Rodríguez-Aguirregabiria, Miguel Salavert, Luis Martínez-Martínez","doi":"10.1007/s40265-024-02102-8","DOIUrl":"10.1007/s40265-024-02102-8","url":null,"abstract":"<p><p>Gram-negative multidrug-resistant (MDR) bacteria, including Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa, pose a significant challenge in clinical practice. Infections caused by metallo-β-lactamase (MBL)-producing Gram-negative organisms, in particular, require careful consideration due to their complexity and varied prevalence, given that the microbiological diagnosis of these pathogens is intricate and compounded by challenges in assessing the efficacy of anti-MBL antimicrobials. We discuss both established and new approaches in the treatment of MBL-producing Gram-negative infections, focusing on 3 strategies: colistin; the recently approved combination of aztreonam with avibactam (or with ceftazidime/avibactam); and cefiderocol. Despite its significant activity against various Gram-negative pathogens, the efficacy of colistin is limited by resistance mechanisms, while nephrotoxicity and acute renal injury call for careful dosing and monitoring in clinical practice. Aztreonam combined with avibactam (or with avibactam/ceftazidime if aztreonam plus avibactam is not available) exhibits potent activity against MBL-producing Gram-negative pathogens. Cefiderocol in monotherapy is effective against a wide range of multidrug-resistant organisms, including MBL producers, and favorable clinical outcomes have been observed in various clinical trials and case series. After examining scientific evidence in the management of infections caused by MBL-producing Gram-negative bacteria, we have developed a comprehensive clinical algorithm to guide therapeutic decision making. We recommend reserving colistin as a last-resort option for MDR Gram-negative infections. Cefiderocol and aztreonam/avibactam represent favorable options against MBL-producing pathogens. In the case of P. aeruginosa with MBL-producing enzymes and with difficult-to-treat resistance, cefiderocol is the preferred option. Further research is needed to optimize treatment strategies and minimize resistance.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1519-1539"},"PeriodicalIF":13.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Vorasidenib: First Approval.","authors":"Yvette N Lamb","doi":"10.1007/s40265-024-02127-z","DOIUrl":"10.1007/s40265-024-02127-z","url":null,"abstract":"","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1673"},"PeriodicalIF":13.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Difficult-to-Treat Axial Spondyloarthritis: A New Challenge.","authors":"Daniel Wendling","doi":"10.1007/s40265-024-02100-w","DOIUrl":"10.1007/s40265-024-02100-w","url":null,"abstract":"<p><p>Axial spondyloarthritis is a common form of chronic inflammatory rheumatic disease in adults, the treatment of which is based on non-pharmacological elements on the one hand, and pharmacological options on the other, such as non-steroidal anti-inflammatory drugs in the first line, followed by biological or targeted synthetic treatments. The therapeutic objective is remission or a low level of disease activity; if this objective is not achieved, the treatment is rotated or changed. Multiple changes is one factor illustrating the inability to achieve disease control and may lead to the notion of a difficult-to-treat disease (D2T). This requires a consensual definition including, beyond the number or therapeutic changes, the assessment of all the dimensions of the disease (objective signs of inflammation, residual pain, degenerative changes, psychosocial context). Recognising D2T patients will enable us to identify a particular population and the factors associated with this condition. When faced with a D2T disease, we need to analyse the causes of treatment failure and take into account the different components of the disease and the patient. In the absence of any prospect of new therapeutic targets in the short term for this disease, patient management may involve intensification of non-pharmacological means and evaluation of new therapeutic strategies such as combinations of targeted treatments.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1501-1508"},"PeriodicalIF":13.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2024 Recommendations on the Optimal Use of Lipid-Lowering Therapy in Established Atherosclerotic Cardiovascular Disease and Following Acute Coronary Syndromes: A Position Paper of the International Lipid Expert Panel (ILEP).","authors":"Maciej Banach, Željko Reiner, Stanisław Surma, Gani Bajraktari, Agata Bielecka-Dabrowa, Matjaz Bunc, Ibadete Bytyçi, Richard Ceska, Arrigo F G Cicero, Dariusz Dudek, Krzysztof Dyrbuś, Jan Fedacko, Zlatko Fras, Dan Gaita, Dov Gavish, Marek Gierlotka, Robert Gil, Ioanna Gouni-Berthold, Piotr Jankowski, Zoltán Járai, Jacek Jóźwiak, Niki Katsiki, Gustavs Latkovskis, Stefania Lucia Magda, Eduard Margetic, Roman Margoczy, Olena Mitchenko, Azra Durak-Nalbantic, Petr Ostadal, Gyorgy Paragh, Zaneta Petrulioniene, Francesco Paneni, Ivan Pećin, Daniel Pella, Arman Postadzhiyan, Anca Pantea Stoian, Matias Trbusic, Cristian Alexandru Udroiu, Margus Viigimaa, Dragos Vinereanu, Charalambos Vlachopoulos, Michal Vrablik, Dusko Vulic, Peter E Penson","doi":"10.1007/s40265-024-02105-5","DOIUrl":"10.1007/s40265-024-02105-5","url":null,"abstract":"<p><p>Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Fortunately, as much as two thirds of this disease's burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that, with respect to low-density lipoprotein cholesterol (LDL-C), \"lower is better for longer\", and recent data have strongly emphasised the need for also \"the earlier the better\". In addition to statins, which have been available for several decades, ezetimibe, bempedoic acid (also as fixed dose combinations), and modulators of proprotein convertase subtilisin/kexin type 9 (PCSK9 inhibitors and inclisiran) are additionally very effective approaches to LLT, especially for those at very high and extremely high cardiovascular risk. In real life, however, clinical practice goals are still not met in a substantial proportion of patients (even in 70%). However, with the options we have available, we should render lipid disorders a rare disease. In April 2021, the International Lipid Expert Panel (ILEP) published its first position paper on the optimal use of LLT in post-ACS patients, which complemented the existing guidelines on the management of lipids in patients following ACS, which defined a group of \"extremely high-risk\" individuals and outlined scenarios where upfront combination therapy should be considered to improve access and adherence to LLT and, consequently, the therapy's effectiveness. These updated recommendations build on the previous work, considering developments in the evidential underpinning of combination LLT, ongoing education on the role of lipid disorder therapy, and changes in the availability of lipid-lowering drugs. Our aim is to provide a guide to address this unmet clinical need, to provide clear practical advice, whilst acknowledging the need for patient-centred care, and accounting for often large differences in the availability of LLTs between countries.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1541-1577"},"PeriodicalIF":13.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgement to Referees.","authors":"","doi":"10.1007/s40265-024-02123-3","DOIUrl":"https://doi.org/10.1007/s40265-024-02123-3","url":null,"abstract":"","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Novel Pharmacotherapy Candidates for Cannabis Use Disorder: Uncovering Promising Agents on the Horizon by Mechanism of Action.","authors":"Myra Alayoubi, Brittany A Henry, Catherine M Cahill, Ziva D Cooper","doi":"10.1007/s40265-024-02098-1","DOIUrl":"10.1007/s40265-024-02098-1","url":null,"abstract":"<p><p>With rapid expansion of cannabis legalization worldwide, rates of cannabis use and cannabis use disorder (CUD) are increasing; the need for safe and effective medications to treat CUD is urgent. This narrative review evaluates evidence for promising pharmacotherapies to treat CUD from randomized, placebo-controlled trials. Pharmacotherapies for CUD are categorized based on compound targets (e.g., cannabinoid receptor 1 [CB1] agonists such as nabilone, serotonergic compounds such as bupropion, GABAergic compounds such as zolpidem) and outcomes are organized by predetermined withdrawal symptoms, cannabis craving, and cannabis relapse/use. Most promising pharmacotherapies for CUD are drugs that act on the endocannabinoid system and specifically at the CB1 receptor. Priority populations such as females, certain racial/ethnic groups, and age groups experience a different course of CUD progression, symptoms, and drug effects that are important to consider when evaluating outcomes related to CUD. Possible explanations for these disparities are explored, along with the clinical trials that explore these demographics in treating CUD with pharmacotherapies.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1395-1417"},"PeriodicalIF":13.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How Psychedelics Modulate Multiple Memory Mechanisms in Posttraumatic Stress Disorder.","authors":"Manoj K Doss, AnnaMarie DeMarco, Joseph E Dunsmoor, Josh M Cisler, Gregory A Fonzo, Charles B Nemeroff","doi":"10.1007/s40265-024-02106-4","DOIUrl":"10.1007/s40265-024-02106-4","url":null,"abstract":"<p><p>Posttraumatic stress disorder (PTSD) is a psychiatric disorder with defining abnormalities in memory, and psychedelics may be promising candidates for the treatment of PTSD given their effects on multiple memory systems. Most PTSD and psychedelic research has investigated memory with fear conditioning and extinction. While fruitful, conditioning and extinction provide a limited model of the complexity of PTSD and phenomenology of psychedelics, thereby limiting the refinement of therapies. In this review, we discuss abnormalities in fear conditioning and extinction in PTSD and review 25 studies testing psychedelics on these forms of memory. Perhaps the most reliable effect is that the acute effects of psychedelics can enhance extinction learning, which is impaired in PTSD. However, the post-acute effects may also enhance extinction learning, and the acute effects can also enhance fear conditioning. We then discuss abnormalities in episodic and semantic memory in PTSD and review current knowledge on how psychedelics impact these memory systems. Although PTSD and psychedelics acutely impair the formation of hippocampal-dependent episodic memories, psychedelics may acutely enhance cortical-dependent learning of semantic memories that could facilitate the integration of trauma memories and disrupt maladaptive beliefs. More research is needed on the acute effects of psychedelics on episodic memory consolidation, retrieval, and reconsolidation and post-acute effects of psychedelics on all phases of episodic memory. We conclude by discussing how targeting multiple memory mechanisms could improve upon the current psychedelic therapy paradigm for PTSD, thereby necessitating a greater emphasis on assessing diverse measures of memory in translational PTSD and psychedelic research.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1419-1443"},"PeriodicalIF":13.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Axatilimab: First Approval.","authors":"Susan J Keam","doi":"10.1007/s40265-024-02109-1","DOIUrl":"10.1007/s40265-024-02109-1","url":null,"abstract":"<p><p>Axatilimab (NIKTIMVO™; axatilimab-csfr), an anti-colony-stimulating Factor 1 Receptor (CSF-1R) humanized IgG4 (κ light chain) monoclonal antibody, is being developed by Incyte Corporation and Syndax Pharmaceuticals for the treatment of chronic graft-versus-host disease (cGVHD) and other indications, including idiopathic pulmonary fibrosis (IPF). In August 2024, axatilimab was approved in the USA for the treatment of cGVHD after failure of at least two prior lines of systemic therapy in adult and paediatric patients weighing at least 40 kg. Axatilimab was added to the NCCN guidelines for cGVHD in August 2024. This article summarizes the development milestones leading to this first approval of axatilimab for the treatment of cGVHD.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1475-1480"},"PeriodicalIF":13.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seladelpar: First Approval.","authors":"Sheridan M Hoy","doi":"10.1007/s40265-024-02114-4","DOIUrl":"10.1007/s40265-024-02114-4","url":null,"abstract":"<p><p>Seladelpar (LIVDELZI^®) is an oral delpar [i.e. a selective peroxisome proliferator-activated receptor (PPAR)δ agonist] being developed by Gilead Sciences for the treatment of primary biliary cholangitis (PBC). On 14 August 2024, based on a reduction in alkaline phosphatase (ALP), it received accelerated approval in the USA for the treatment of PBC in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory studies. A regulatory assessment for seladelpar for the treatment of PBC is underway in the EU and the UK. This article summarizes the milestones in the development of seladelpar leading to this first approval.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1487-1495"},"PeriodicalIF":13.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renin-Angiotensin-Aldosterone System Modulators in Adults with Hypertension: A Network Meta-Analysis of Randomized Controlled Trials.","authors":"Xiaoyan Yi, Shumin Yang, Jun Yang, Xiangjun Chen, Aipin Zhang, Qinglian Zeng, Wenjin Luo, Qifu Li, Jinbo Hu","doi":"10.1007/s40265-024-02092-7","DOIUrl":"10.1007/s40265-024-02092-7","url":null,"abstract":"<p><strong>Background: </strong>Although a range of renin-angiotensin-aldosterone system (RAAS) modulators are available for blood pressure lowering, the optimal choice within this class remains unclear. We aimed to compare the efficacy and safety of RAAS modulators in the adult hypertensive population.</p><p><strong>Methods: </strong>A systematic literature search was performed in PubMed, CENTRAL, and Embase. The primary efficacy outcome was all-cause mortality and the secondary efficacy outcome was cardiovascular mortality. Tolerability outcome was discontinuation due to adverse events. Safety outcomes included the occurrence of cough, dizziness, edema, hyperkalemia, and hypotension. Network meta-analyses were performed utilizing a random-effects model within a frequentist framework.</p><p><strong>Results: </strong>We finally identified 51 articles from 49 randomized controlled trials. When compared to placebo, mineralocorticoid receptor antagonists (MRAs) significantly reduced the risk of all-cause mortality (odds ratio (OR) 0.83; 95% confidence interval (CI) 0.74-0.92) and cardiovascular mortality (OR 0.79; 95% CI 0.68-0.93), while none of other RAAS modulators significantly lowered the risk of all-cause or cardiovascular mortality. Individual comparisons indicated that MRAs were associated with a significantly lower risk of all-cause mortality than the other RAAS modulators (reduction: 16% compared with angiotensin-converting enzyme inhibitors (ACEIs), 14% compared with angiotensin receptor blockers (ARBs), and 22% compared with direct renin inhibitors (DRIs)). No difference in discontinuation due to adverse events was found in a comparison of RAAS modulators with placebo. With regard to safety outcomes, ACEIs have a higher risk of cough (OR 4.68; 95% CI 1.61-13.60), ARBs have a higher risk of dizziness (OR 1.42; 95% CI 1.06-1.91), hypotension (OR 2.10; 95% CI 1.02-4.34), and hyperkalemia (OR 1.99; 95% CI 1.17-3.41), and MRAs had a higher risk of hyperkalemia (OR 2.68; 95% CI 1.99-3.62) when compared to placebo.</p><p><strong>Conclusions: </strong>MRAs were the only RAAS modulators with a survival benefit in adults with hypertension, although they carried a higher risk of hyperkalemia. Our data challenge current hypertension guidelines which recommend MRAs as fourth-line therapy, and suggest that MRAs should be prescribed earlier and more widely.</p><p><strong>Registration: </strong>PROSPERO identifier number CRD42023405714.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1445-1462"},"PeriodicalIF":13.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}