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Safety and efficacy of cefiderocol for off-label treatment indications: A systematic review. 用于标示外治疗适应症的头孢哌酮的安全性和有效性:系统综述。
Pub Date : 2022-07-01 Epub Date: 2022-06-04 DOI: 10.1002/phar.2704
Riyan Babidhan, Abigale Lewis, Cailin Atkins, Nicolas J Jozefczyk, Branden D Nemecek, Courtney A Montepara, Michael R Gionfriddo, David E Zimmerman, Jordan R Covvey, Anthony J Guarascio

Purpose: Cefiderocol is a siderophore cephalosporin recently approved by the United States Food and Drug Administration for the treatment of hospital- and ventilator-acquired bacterial pneumonia and complicated urinary tract infections. However, there is potential for cefiderocol utility for a variety of other infections. The purpose of this systematic review was to identify literature examining the safety and efficacy of cefiderocol for off-label indications.

Methods: The PRISMA guidelines were utilized for reporting. Databases searched included PubMed, Scopus, and Embase, from inception to September 2021. Manuscripts describing cefiderocol off-label use in clinical settings were included. Exclusion criteria were studies focused on labeled indications, animal studies, pharmacodynamic/pharmacokinetic studies, in vitro or laboratory studies, and manuscripts in languages other than English or Arabic. Each stage of review utilized two independent investigators, with conflicts resolved and critical appraisal performed. Data regarding presentation, clinical course, and infection characteristics were extracted and descriptively analyzed.

Results: The search identified a total of 985 records, narrowed to a final set of 27 studies. Among studies included were 18 (66.7%) case reports, 8 (29.6%) case series, and 1 (3.7%) phase 3 clinical trial. Cefiderocol was most frequently used off-label for bacteremia/sepsis with or without an identified source in 51 (67.1%) out of a total of 76 included patients. Among case series/reports with available data, 43 of 53 patients (81.1%) received combination antibiotic therapy. The most common pathogens identified included multi/extensively drug-resistant Pseudomonas aeruginosa and/or Acinetobacter baumannii. Various clinical end points were reported, while microbiological end points were reported in 18 (66.7%) studies. Cefiderocol-related side effects were uncommon and rarely use-limiting.

Conclusions: This systematic review depicts relative clinical effectiveness of off-label cefiderocol, most commonly for P. aeruginosa and A. baumannii infections as combination antibiotic therapy. Further study is needed to elucidate the safety and efficacy of cefiderocol across an expanded set of patients and indications.

目的:头孢羟氨苄是一种嗜苷头孢菌素,最近被美国食品和药物管理局批准用于治疗医院和呼吸机获得性细菌性肺炎以及复杂性尿路感染。不过,头孢羟氨苄还有可能用于治疗其他各种感染。本系统性综述的目的是找出研究头孢羟氨苄用于标签外适应症的安全性和有效性的文献:方法:采用 PRISMA 指南进行报告。检索的数据库包括 PubMed、Scopus 和 Embase,检索时间从开始到 2021 年 9 月。纳入了描述头孢羟氨苄在临床环境中标示外使用的稿件。排除标准包括侧重于标签适应症的研究、动物研究、药效学/药代动力学研究、体外或实验室研究,以及非英语或阿拉伯语的稿件。每个阶段的审查均由两名独立研究人员进行,并解决冲突和进行批判性评估。研究人员提取了有关发病情况、临床过程和感染特征的数据,并进行了描述性分析:搜索共发现了 985 条记录,最后筛选出 27 项研究。其中包括 18 项(66.7%)病例报告、8 项(29.6%)系列病例和 1 项(3.7%)3 期临床试验。在总共 76 例纳入研究的患者中,有 51 例(67.1%)患者在标示外使用头孢羟氨苄治疗菌血症/败血症,无论有无明确病源。在有数据的病例系列/报告中,53 名患者中有 43 名(81.1%)接受了联合抗生素治疗。最常见的病原体包括多重/广泛耐药的铜绿假单胞菌和/或鲍曼不动杆菌。有 18 项(66.7%)研究报告了各种临床终点,而微生物终点则有报告。与头孢羟氨苄相关的副作用并不常见,而且很少限制使用:本系统综述描述了标签外头孢羟氨苄的相对临床疗效,最常用于铜绿假单胞菌和鲍曼不动杆菌感染的联合抗生素治疗。需要进一步研究以阐明头孢羟氨苄在更多患者和适应症中的安全性和有效性。
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引用次数: 3
Poor tolerability of cystic fibrosis transmembrane conductance regulator modulator therapy in lung transplant recipients 肺移植受者囊性纤维化跨膜传导调节剂治疗耐受性差
Pub Date : 2022-06-11 DOI: 10.1002/phar.2710
C. Doligalski, C. McKinzie, Anita Yang, L. Lobo, R. Coakley
Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is a highly effective therapy for patients with cystic fibrosis (CF) with potential benefits in lung transplant recipients (LTRs) for extrapulmonary CF manifestations; however, tolerability and efficacy in this population are largely unknown. We report our experience with ELX/TEZ/IVA in LTRs for extrapulmonary complications of CF including tolerability, drug–drug interactions, and therapeutic benefit. All LTRs at a single center initiated on ELX/TEZ/IVA were reviewed. Adverse events and patient‐reported outcomes attributed to ELX/TEZ/IVA were documented. Pulmonary function, tacrolimus requirements in mg/kg/dl, body mass index (BMI), and reason for initiation were assessed at the initiation of ELX/TEZ/IVA, and at 12 months post‐initiation or at the time of discontinuation for those in whom therapy was discontinued. Thirteen LTRs were initiated on ELX/TEZ/IVA at a mean of 115 ± 92 months post‐transplant. All were initiated on ELX/TEZ/IVA for sinus or sinus and gastrointestinal CF manifestations. Five (38.4%) patients discontinued therapy due to declining pulmonary function (2/5, 40%), mood disturbances (2/5, 40%), or lack of benefit (1/5, 20%). Of the eight patients who remain on ELX/TEZ/IVA, four reported adverse effects and three LTRs temporarily held therapy. Six (46.2%) LTRs reported improvement in sinus symptoms, while four (30.7%) reported improved gastrointestinal symptoms. Weight declined in the cohort overall. Tacrolimus dose requirements decreased following initiation of ELX/TEZ/IVA therapy, with a 50% decline in dose requirements observed. In our experience, ELX/TEZ/IVA in LTRs is poorly tolerated with modest perceived extrapulmonary benefit and a significant effect on tacrolimus dose requirements. More data are needed to determine the benefits of ELX/TEZ/IVA therapy in LTRs.
elexaftor /tezacaftor/ivacaftor (ELX/TEZ/IVA)是一种治疗囊性纤维化(CF)患者的高效药物,对肺移植受者(lts)的肺外CF表现有潜在益处;然而,在这一人群中的耐受性和疗效在很大程度上是未知的。我们报告了ELX/TEZ/IVA治疗慢性纤维化肺外并发症的经验,包括耐受性、药物-药物相互作用和治疗效果。回顾了在ELX/TEZ/IVA启动的单一中心的所有ltr。记录了ELX/TEZ/IVA导致的不良事件和患者报告的结果。肺功能、他克莫司需氧量(mg/kg/dl)、体重指数(BMI)和开始治疗的原因在ELX/TEZ/IVA开始治疗时、开始治疗后12个月或停止治疗时进行评估。移植后平均115±92个月,13例ELX/TEZ/IVA启动ltr。所有患者均开始ELX/TEZ/IVA治疗鼻窦或鼻窦和胃肠道CF表现。5例(38.4%)患者因肺功能下降(2/ 5,40 %)、情绪障碍(2/ 5,40 %)或缺乏获益(1/ 5,20 %)而停止治疗。在继续使用ELX/TEZ/IVA的8名患者中,4名报告了不良反应,3名ltr暂时接受治疗。6名(46.2%)ltr报告鼻窦症状改善,4名(30.7%)ltr报告胃肠道症状改善。整个队列的体重都下降了。ELX/TEZ/IVA治疗开始后,他克莫司的剂量需求下降,剂量需求下降50%。根据我们的经验,ELX/TEZ/IVA在ltr中的耐受性较差,具有适度的肺外益处,对他克莫司剂量要求有显著影响。需要更多的数据来确定ELX/TEZ/IVA治疗ltr的益处。
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引用次数: 10
Reduced risk of NSAID‐Induced adverse events with concomitant use of misoprostol (MICRO study) 同时使用米索前列醇可降低非甾体抗炎药诱导不良事件的风险(MICRO研究)
Pub Date : 2022-06-05 DOI: 10.1002/phar.2708
M. Munger, S. Nelson, C. Teng, A. Cheung, B. Sauer
Non‐steroidal anti‐inflammatory drugs (NSAIDs) are one of the most frequently used medications for pain, even though they increase the risk for adverse cardiovascular events.
非甾体抗炎药(NSAIDs)是治疗疼痛最常用的药物之一,尽管它们会增加心血管不良事件的风险。
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引用次数: 2
Evaluating adherence to concomitant diabetes, hypertension, and hyperlipidemia treatments and intermediate outcomes among elderly patients using marginal structural modeling 使用边缘结构模型评估老年患者对合并糖尿病、高血压和高脂血症治疗的依从性和中期结果
Pub Date : 2022-05-25 DOI: 10.1002/phar.2705
R. Paranjpe, Michael L. Johnson, Hua Chen, K. Birtcher, O. Serna, A. Mohan, S. Abughosh
Medication adherence to concomitant oral antidiabetics, statins, and renin‐angiotensin system (RAS) antagonists (triple therapy) is vital to manage glycated hemoglobin (A1C) and low‐density lipoprotein cholesterol (LDL‐C) control among patients with comorbid diabetes, hyperlipidemia, and hypertension. The objective of the current study was to evaluate the association between adherence to concomitant triple therapy and A1C as well as LDL‐C outcomes, among elderly patients using marginal structural modeling.
同时服用口服降糖药、他汀类药物和肾素-血管紧张素系统(RAS)拮抗剂(三联疗法)对于控制糖尿病、高脂血症和高血压患者的糖化血红蛋白(A1C)和低密度脂蛋白胆固醇(LDL - C)至关重要。本研究的目的是利用边缘结构模型评估老年患者坚持三联治疗与A1C和LDL - C结局之间的关系。
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引用次数: 0
Association between glucagon‐like peptide‐1 receptor agonists and biliary‐related diseases in patients with type 2 diabetes: A nationwide cohort study 胰高血糖素样肽- 1受体激动剂与2型糖尿病患者胆道相关疾病的相关性:一项全国性队列研究
Pub Date : 2022-05-04 DOI: 10.1002/phar.2688
Yaa-Hui Dong, Jo-Hsuan Wu, Chia‐Hsuin Chang, Jou-Wei Lin, Li‐Chiu Wu, S. Toh
Clinical trials have suggested that glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) may be associated with a higher risk of biliary‐related diseases in patients with type 2 diabetes. Limited real‐world studies have examined the comparative biliary safety of GLP‐1RAs versus other antihyperglycemic drugs. We aimed to estimate the comparative risk of biliary‐related diseases between GLP‐1RAs and sodium glucose cotransporter 2 inhibitors (SGLT2is), which are indicated for patients with similar diabetes severity in Taiwan.
临床试验表明,胰高血糖素样肽- 1受体激动剂(GLP - 1RAs)可能与2型糖尿病患者胆道相关疾病的高风险相关。有限的真实世界研究已经比较了GLP - 1RAs与其他降糖药物的胆道安全性。我们的目的是评估GLP - 1RAs和葡萄糖共转运蛋白2钠抑制剂(SGLT2is)之间胆道相关疾病的比较风险,这两种药物适用于台湾糖尿病严重程度相似的患者。
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引用次数: 2
The safety of rapid infusion levetiracetam: A systematic review 快速输注左乙拉西坦的安全性:系统评价
Pub Date : 2022-05-02 DOI: 10.1002/phar.2687
Alexa Jense, Alyssa A. Douville, Ashley Weiss
Epilepsy is a common diagnosis and can quickly progress to status epilepticus which requires rapid treatment. Levetiracetam is a frequent treatment choice in these situations. The approved administration of intravenous levetiracetam is an infusion over 15 min. In recent years, studies have been published on faster infusion rates of levetiracetam. The objective of this review is to discuss the safety of levetiracetam as an intravenous push at a rate quicker than recommended. A literature search using PubMed, Cochrane Library, ClinicalTrials.gov, and Google Scholar resulted in 192 articles. Inclusion criteria consisted of English language, human studies, use of levetiracetam administered intravenously at a rate faster than 15 min, discussion of safety, and full‐text availability. After screening, nine articles remained for inclusion. Of the nine articles, one was a prospective, open‐label study, six were retrospective studies, and two were open‐label, randomized controlled trials. The most common rapid infusion speed was 5 min and doses ranged from 280 to 4500 mg. Some of these trials used undiluted levetiracetam and many reported that peripheral access was used for a portion or all of the administrations. There were few adverse effects, including specific adverse effects relating to medication concentration and speed of infusion, in all the studies. Administration of intravenous levetiracetam at a rate faster than recommended in the labeling information appears to be safe and tolerable and can be given via a peripheral line. Rapid infusion of levetiracetam is a beneficial method of administration in an acute care setting where patients need rapid attainment of therapeutic levels of antiepileptic medications. Additional research is needed to ensure that rapid administration of intravenous levetiracetam is as efficacious as the traditional dosing method.
癫痫是一种常见的诊断,可迅速发展为癫痫持续状态,需要快速治疗。在这些情况下,左乙拉西坦是常用的治疗选择。经批准的左乙拉西坦静脉输注时间超过15分钟。近年来,有研究发表了更快的左乙拉西坦输注速度。本综述的目的是讨论左乙拉西坦静脉推注速度快于推荐速度时的安全性。使用PubMed、Cochrane图书馆、ClinicalTrials.gov和Google Scholar进行文献检索,结果得出192篇文章。纳入标准包括英语语言、人体研究、左乙拉西坦静脉注射速度大于15分钟、安全性讨论和全文可得性。筛选后,仍有9篇文章有待纳入。在这9篇文章中,1篇是前瞻性、开放标签研究,6篇是回顾性研究,2篇是开放标签、随机对照试验。最常见的快速输注速度为5分钟,剂量范围为280至4500毫克。其中一些试验使用未稀释的左乙拉西坦,许多试验报告部分或全部给药使用外周通路。在所有的研究中,几乎没有不良反应,包括与药物浓度和输注速度有关的特异性不良反应。以比标签信息中推荐的更快的速度静脉给药左乙拉西坦似乎是安全且可耐受的,并且可以通过外周静脉输注。快速输注左乙拉西坦是一种有益的给药方法,在急性护理环境中,患者需要快速达到抗癫痫药物的治疗水平。需要进一步的研究来确保快速静脉给药左乙拉西坦与传统给药方法一样有效。
{"title":"The safety of rapid infusion levetiracetam: A systematic review","authors":"Alexa Jense, Alyssa A. Douville, Ashley Weiss","doi":"10.1002/phar.2687","DOIUrl":"https://doi.org/10.1002/phar.2687","url":null,"abstract":"Epilepsy is a common diagnosis and can quickly progress to status epilepticus which requires rapid treatment. Levetiracetam is a frequent treatment choice in these situations. The approved administration of intravenous levetiracetam is an infusion over 15 min. In recent years, studies have been published on faster infusion rates of levetiracetam. The objective of this review is to discuss the safety of levetiracetam as an intravenous push at a rate quicker than recommended. A literature search using PubMed, Cochrane Library, ClinicalTrials.gov, and Google Scholar resulted in 192 articles. Inclusion criteria consisted of English language, human studies, use of levetiracetam administered intravenously at a rate faster than 15 min, discussion of safety, and full‐text availability. After screening, nine articles remained for inclusion. Of the nine articles, one was a prospective, open‐label study, six were retrospective studies, and two were open‐label, randomized controlled trials. The most common rapid infusion speed was 5 min and doses ranged from 280 to 4500 mg. Some of these trials used undiluted levetiracetam and many reported that peripheral access was used for a portion or all of the administrations. There were few adverse effects, including specific adverse effects relating to medication concentration and speed of infusion, in all the studies. Administration of intravenous levetiracetam at a rate faster than recommended in the labeling information appears to be safe and tolerable and can be given via a peripheral line. Rapid infusion of levetiracetam is a beneficial method of administration in an acute care setting where patients need rapid attainment of therapeutic levels of antiepileptic medications. Additional research is needed to ensure that rapid administration of intravenous levetiracetam is as efficacious as the traditional dosing method.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84843723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Norepinephrine reuptake inhibitors and risk of antihypertensive treatment intensification and major adverse cardiovascular events in patients with stable hypertension and depression 去甲肾上腺素再摄取抑制剂与稳定期高血压合并抑郁症患者抗高血压强化治疗及主要心血管不良事件的风险
Pub Date : 2022-04-28 DOI: 10.1002/phar.2686
Raj Desai, Haesuk Park, Joshua D. Brown, Raj Mohandas, Steven M. Smith
To compare the risk of antihypertensive treatment intensification (TI) and major adverse cardiovascular events (MACE) with the initiation of serotonin norepinephrine reuptake inhibitors compared to selective serotonin reuptake inhibitors (SSRIs) in patients with stable hypertension and depression.
比较稳定型高血压和抑郁症患者开始使用5 -羟色胺去甲肾上腺素再摄取抑制剂与选择性5 -羟色胺再摄取抑制剂(SSRIs)时抗高血压强化治疗(TI)和主要不良心血管事件(MACE)的风险。
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引用次数: 1
Analysis of the frequency distribution of five single‐nucleotide polymorphisms of the MTRRgene in a Chinese pediatric population with acute lymphoblastic leukemia 中国儿童急性淋巴细胞白血病患者mtrr基因5个单核苷酸多态性的频率分布分析
Pub Date : 2022-04-17 DOI: 10.1002/phar.2685
Miao Li, Xiao-yan Kong, Shu‐Mei Wang
The objective of the present study was to examine the frequency distribution of five single‐nucleotide polymorphisms (SNPs; rs1801394 A>G, rs1532268 C>T, rs162036 A>G, rs10380 C>T, and rs9332 C>T) of the methionine synthase reductase (MTRR) gene, their effects on methotrexate (MTX) concentration, and the risk of relapse in a Chinese pediatric population with acute lymphoblastic leukemia (ALL).
本研究的目的是检查五种单核苷酸多态性(snp)的频率分布;rs1801394 A>G、rs1532268 C>T、rs162036 A>G、rs10380 C>T、rs9332 C>T)对中国急性淋巴细胞白血病(ALL)患儿甲硫氨酸合成酶还原酶(MTRR)基因的表达及其对甲氨蝶呤(MTX)浓度和复发风险的影响。
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引用次数: 1
Machine learning to predict vasopressin responsiveness in patients with septic shock 机器学习预测感染性休克患者的抗利尿激素反应性
Pub Date : 2022-04-15 DOI: 10.1002/phar.2683
Aileen Scheibner, K. Betthauser, A. Bewley, P. Juang, B. Lizza, S. Micek, P. Lyons
The objective of this study was to develop and externally validate a model to predict adjunctive vasopressin response in patients with septic shock being treated with norepinephrine for bedside use in the intensive care unit.
本研究的目的是开发并外部验证一个模型,以预测在重症监护室接受去甲肾上腺素床边使用的脓毒性休克患者的辅助抗利尿激素反应。
{"title":"Machine learning to predict vasopressin responsiveness in patients with septic shock","authors":"Aileen Scheibner, K. Betthauser, A. Bewley, P. Juang, B. Lizza, S. Micek, P. Lyons","doi":"10.1002/phar.2683","DOIUrl":"https://doi.org/10.1002/phar.2683","url":null,"abstract":"The objective of this study was to develop and externally validate a model to predict adjunctive vasopressin response in patients with septic shock being treated with norepinephrine for bedside use in the intensive care unit.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87470081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Impact of proton pump inhibitors on sustained virologic response in veterans treated with sofosbuvir/velpatasvir for chronic hepatitis C virus: A retrospective cohort study 质子泵抑制剂对接受索非布韦/维帕他韦治疗慢性丙型肝炎的退伍军人持续病毒学反应的影响:一项回顾性队列研究
Pub Date : 2022-04-09 DOI: 10.1002/phar.2682
Danielle M Rumph, C. Straley, Jenny L Kolberg, David A. Jacob
The objective of this study was to determine the clinical relationship between proton pump inhibitor (PPI) use and sustained virologic response (SVR) in patients treated with sofosbuvir/velpatasvir (SOF/VEL) for chronic hepatitis C virus (HCV) infection.
本研究的目的是确定质子泵抑制剂(PPI)的使用与索非布韦/维帕他韦(SOF/VEL)治疗慢性丙型肝炎病毒(HCV)感染患者持续病毒学反应(SVR)之间的临床关系。
{"title":"Impact of proton pump inhibitors on sustained virologic response in veterans treated with sofosbuvir/velpatasvir for chronic hepatitis C virus: A retrospective cohort study","authors":"Danielle M Rumph, C. Straley, Jenny L Kolberg, David A. Jacob","doi":"10.1002/phar.2682","DOIUrl":"https://doi.org/10.1002/phar.2682","url":null,"abstract":"The objective of this study was to determine the clinical relationship between proton pump inhibitor (PPI) use and sustained virologic response (SVR) in patients treated with sofosbuvir/velpatasvir (SOF/VEL) for chronic hepatitis C virus (HCV) infection.","PeriodicalId":19812,"journal":{"name":"Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73455176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
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