scholarly journals The African Green Monkey Model of Pneumonic Plague and US Food and Drug Administration Approval of Antimicrobials Under the Animal Rule

2020 ◽  
Vol 70 (Supplement_1) ◽  
pp. S51-S59
Author(s):  
Judith A Hewitt ◽  
Lynda L Lanning ◽  
Joseph L Campbell
Keyword(s):  
Drug Administration ◽  
Human Disease ◽  
Case Reports ◽  
Food And Drug Administration ◽  
Treatment Options ◽  
Lethal Dose ◽  
Additional Treatment ◽  
Primary Data ◽  
Pneumonic Plague ◽  
Multiple Drugs

Abstract Background Additional treatment options for pneumonic plague, the most severe form of infection by Yersinia pestis, are needed, as past US Food and Drug Administration (FDA) approvals were not based on clinical trials that meet today’s standards, and multiple drugs are sought to counter resistance or use in special populations. Due to the sporadic nature of outbreaks and the low number of pneumonic cases of disease, we sought FDA approval of antimicrobials for treatment under the Animal Efficacy Rule, where efficacy can be demonstrated in 1 or more well-characterized animal models that sufficiently represent human disease. Methods A model was developed in African green monkeys (AGMs) after challenge with a lethal dose of Y. pestis delivered as an aerosol, in 4 independent studies in 3 laboratories. The primary data points were bacteremia (daily), body temperature and heart rate (continuously monitored by telemetry), and survival. In antimicrobial efficacy studies, human-equivalent doses of gentamicin, ciprofloxacin, levofloxacin, and doxycycline were administered upon fever onset for 10 days. Results Disease in AGMs was similar to case reports of human disease. Fever was determined to be a reliable sign of disease and selected as a treatment trigger. Gentamicin was 60%–80% effective depending on the dose given to animals. Ciprofloxacin and levofloxacin were found to be >90% efficacious. These data were submitted to FDA and plague indications were approved. Doxycycline was less effective. Conclusions The AGM model of pneumonic plague is reproducible, well-characterized, and mimics human disease. It has been used to support plague indications for fluoroquinolones and to test the efficacy of additional antimicrobials.

Ginkgo biloba and vitamin E for Alzheimer's disease

2012 ◽  
Vol 1 (11) ◽  
pp. 283-284
Author(s):  
Chris Paxos
Keyword(s):  
United States ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vitamin E ◽  
Drug Administration ◽  
Ginkgo Biloba ◽  
Food And Drug Administration ◽  
Treatment Options ◽  
The United States ◽  
Additional Treatment

Alzheimer's disease affects an estimated 35 million people worldwide, with over 5 million affected in the United States. Few medications are currently approved by the Food and Drug Administration (FDA) for the treatment of Alzheimer's disease; subsequently, patients and caregivers often look for additional treatment options. This article reviews studies evaluating the use of Ginkgo biloba and vitamin E for the treatment of Alzheimer's disease.

scholarly journals Prolonged Use of Oritavancin for Vancomycin-Resistant Enterococcus faecium Prosthetic Valve Endocarditis

2015 ◽  
Vol 2 (4) ◽  
Author(s):  
Jennifer A. Johnson ◽  
Eoin R. Feeney ◽  
David W. Kubiak ◽  
G. Ralph Corey
Keyword(s):  
Prosthetic Valve ◽  
Case Reports ◽  
Treatment Options ◽  
Prosthetic Valve Endocarditis ◽  
Additional Treatment ◽  
High Dose ◽  
Vancomycin Resistant Enterococci ◽  
The Us ◽  
Vancomycin Resistant

Abstract Oritavancin is a novel lipoglycopeptide with activity against Gram-positive organisms including streptococci, methicillin-resistant Staphylococcus aureus, vancomycin-resistant S aureus (VRSA), and vancomycin-resistant enterococci (VRE) [1–3]. The US Food and Drug Administration approved oritavancin as a single intravenous dose of 1200 mg for the treatment of acute bacterial skin and skin structure infections on the basis of 2 clinical trials demonstrating noninferiority compared with vancomycin [4, 5]. There are limited options for treatment of serious VRE infections. Monotherapy with daptomycin or tigecycline or linezolid may be sufficient in some cases, but combination therapy is often indicated for severe or complicated infections such as endocarditis. Several antibiotic combinations have been used in isolated case reports with some efficacy, including the following: high-dose ampicillin with an aminoglycoside [6], ampicillin with ceftriaxone or imipenem [7, 8], high-dose daptomycin with ampicillin and gentamicin [9] or with gentamicin and rifampin [10], daptomycin with tigecycline [11, 12], quinupristin-dalfopristin with high-dose ampicillin [13] or doxycycline and rifampin [14], and linezolid with tigecycline [15]. The limited efficacy, limited susceptibility, and extensive toxicities with many of these agents and combinations present barriers to effective treatment. Additional treatment options for VRE endocarditis would be valuable. Although oritavancin has been shown to have in vitro activity against some isolates of VRE, clinical data are lacking. We describe the first use of a prolonged course of oritavancin in the treatment of a serious VRE infection, prosthetic valve endocarditis.

scholarly journals Drug-Associated Delirium Identified in The Food and Drug Administration Adverse Events Reporting System

2019 ◽  
pp. 1-7
Author(s):  
Adrian Wong ◽  
Angela Li ◽  
Kane Gill ◽  
Matthew P. Gray ◽  
Pamela L. Smithburger ◽  
...  
Keyword(s):  
Adverse Events ◽  
Drug Administration ◽  
Reporting System ◽  
Case Reports ◽  
Food And Drug Administration ◽  
Public Knowledge ◽  
Future Studies ◽  
The Public ◽  
Post Marketing Surveillance ◽  
Post Marketing

Introduction: Drug toxicity and polypharmacy are major risk factors for delirium, especially in older adult patients with underlying comorbidities. However, numerous case reports have described drugs with a lower suspicion of being deliriogenic. The objective of this study was to identify deliriogenic drugs in the Food and Drug Administration Adverse Events Reporting System (FAERS) to broaden the public knowledge and understanding. Study Design: Retrospective pharmacovigilance evaluation. Methods: FAERS reports from 2004 through 2015 were reviewed for delirium-associated terms, which were utilized to identify drugs most frequently reported to cause delirium. Drugs were categorized as: 1) known to be deliriogenic; 2) potentially deliriogenic; or 3) new potential to be deliriogenic. The 100 most frequently reported drugs were analyzed in reporting odds ratios (ROR). Results: Of the known deliriogenic drugs (n=32), paroxetine (ROR 4.1, CI 4.0-4.3), olanzapine (ROR 3.3, CI 3.2-3.4), and clozapine (ROR 2.9, CI 2.8-3.0) were most reported. Of the potentially deliriogenic drugs (n=54), duloxetine (ROR 3.2, CI 3.1-3.3), varenicline (ROR 3.1, CI 3.0-3.2), and gabapentin (ROR 2.9, CI 2.7-3.0) were most reported. Three drugs were considered to have new potential to be deliriogenic: heparin (ROR 1.5, CI 1.4-1.6), metformin (ROR 1.3, CI 1.3-1.4), and dalfampridine (ROR 1.1, CI 1.1-1.2). Conclusion: The majority of drugs were considered potentially deliriogenic. FAERS can provide post-marketing surveillance data to guide future studies on potentially deliriogenic drugs to guide management of causal agents.

Brodalumab for Treatment-Resistant Psoriasis: Case Reports and Safety Update

2020 ◽  
Vol 5 (3) ◽  
pp. 82-85
Author(s):  
Nicholas D. Brownstone ◽  
Vidhatha Reddy ◽  
Quinn Thibodeaux ◽  
Stephanie Chan ◽  
Bridget Myers ◽  
...  
Keyword(s):  
Causal Relationship ◽  
Drug Administration ◽  
Safety Profile ◽  
Case Reports ◽  
Food And Drug Administration ◽  
Black Box ◽  
Interleukin 17 ◽  
Treatment Resistant ◽  
Effective Agent ◽  
Increased Risk

Introduction: Brodalumab is an interleukin-17 receptor blocker that is effective for the treatment of psoriasis. However, due to a Food and Drug Administration black box warning on depression and suicide, many providers are hesitant to use this agent despite its efficacy. Methods: We present the cases of 2 brothers seen at our clinic with treatment-resistant psoriasis who were both successfully treated with brodalumab, despite failing 6 other biologics. We also review the safety profile of brodalumab regarding the currently available evidence on the increased risk of suicidality or depression in patients treated with brodalumab. Results: Both patients achieved completely clear skin and maintained clearance on brodalumab. Discussion: Brodalumab appears to be an effective agent in severe treatment-resistant cases of psoriasis. In addition, a causal relationship between increased risk of suicidality or depression and brodalumab use has not been established.

Docetaxel-induced cardiac-respiratory arrest in a patient with chronic atrial fibrillation

2017 ◽  
Vol 24 (7) ◽  
pp. 531-536 ◽  
Author(s):  
Mostaqul Huq ◽  
Tracie M Balvanz ◽  
Scott Mambourg
Keyword(s):  
Prostate Cancer ◽  
Atrial Fibrillation ◽  
Drug Administration ◽  
Case Reports ◽  
Food And Drug Administration ◽  
Chronic Atrial Fibrillation ◽  
Respiratory Arrest ◽  
Life Threatening ◽  
Cancer Types ◽  
Hispanic Male

Docetaxel has been approved by the Food and Drug Administration for the treatment of many cancer types, including breast cancer, head and neck cancer, lung cancer, and prostate cancer. Many severe to life-threatening side effects (Grades 3–5) of docetaxel have been reported in clinical trials, case reports, and Food and Drug Administration Adverse Events Reporting System. These include anaphylactic reactions, febrile neutropenia, fluid retention, acute respiratory distress, pleural effusion, pneumonia, and peripheral neuropathy. There were fewer cardiac toxicities reported for docetaxel as compared to paclitaxel, which were less severe. In this report, we present a clinical case of docetaxel-induced cardiac-respiratory arrest in a 62-year-old Hispanic male patient with stable chronic atrial fibrillation, who has been recently diagnosed with metastatic prostate cancer. The cardiac event developed within 15 min of docetaxel infusion during the second cycle of chemotherapy despite using recommended premedication with corticosteroids.

scholarly journals An Update on Eight “New” Antibiotics against Multidrug-Resistant Gram-Negative Bacteria

2021 ◽  
Vol 10 (5) ◽  
pp. 1068
Author(s):  
Erlangga Yusuf ◽  
Hannelore I. Bax ◽  
Nelianne J. Verkaik ◽  
Mireille van Westreenen
Keyword(s):  
Drug Administration ◽  
Food And Drug Administration ◽  
Treatment Options ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Beta Lactamases ◽  
New Antibiotics ◽  
Tract Infections ◽  
The U.S

Infections in the ICU are often caused by Gram-negative bacteria. When these microorganisms are resistant to third-generation cephalosporines (due to extended-spectrum (ESBL) or AmpC beta-lactamases) or to carbapenems (for example carbapenem producing Enterobacteriales (CPE)), the treatment options become limited. In the last six years, fortunately, there have been new antibiotics approved by the U.S. Food and Drug Administration (FDA) with predominant activities against Gram-negative bacteria. We aimed to review these antibiotics: plazomicin, eravacycline, temocillin, cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam, and imipenem/relebactam. Temocillin is an antibiotic that was only approved in Belgium and the UK several decades ago. We reviewed the in vitro activities of these new antibiotics, especially against ESBL and CPE microorganisms, potential side effects, and clinical studies in complicated urinary tract infections (cUTI), intra-abdominal infections (cIAI), and hospital-acquired pneumonia/ventilator-associatedpneumonia (HAP/VAP). All of these new antibiotics are active against ESBL, and almost all of them are active against CPE caused by KPC beta-lactamase, but only some of them are active against CPE due to MBL or OXA beta-lactamases. At present, all of these new antibiotics are approved by the U.S. Food and Drug Administration for cUTI (except eravacycline) and most of them for cIAI (eravacycline, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam) and for HAP or VAP (cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam).

scholarly journals The Interdisciplinary Stem Cell Institute’s Use of Food and Drug Administration-Expanded Access Guidelines to Provide Experimental Cell Therapy to Patients With Rare Serious Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Aisha Khan ◽  
Michael A. Bellio ◽  
Ivonne H. Schulman ◽  
Allan D. Levi ◽  
Bangon Longsomboon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Drug Administration ◽  
Food And Drug Administration ◽  
Treatment Options ◽  
Complex Congenital Heart Disease ◽  
Allogeneic Bone ◽  
Expanded Access ◽  
Cell Based Therapy ◽  
Cord Injury ◽  
Brain Stem Injury

The U.S. Food and Drug Administration (FDA) provides guidance for expanded access to experimental therapies, which in turn plays an important role in the Twenty-first Century Cures Act mandate to advance cell-based therapy. In cases of incurable diseases where there is a lack of alternative treatment options, many patients seek access to cell-based therapies for the possibility of treatment responses demonstrated in clinical trials. Here, we describe the use of the FDA’s expanded access to investigational new drug (IND) to address rare and emergency conditions that include stiff-person syndrome, spinal cord injury, traumatic brain stem injury, complex congenital heart disease, ischemic stroke, and peripheral nerve injury. We have administered both allogeneic bone marrow-derived mesenchymal stem cell (MSC) and autologous Schwann cell (SC) therapy to patients upon emergency request using Single Patient Expanded Access (SPEA) INDs approved by the FDA. In this report, we present our experience with 10 completed SPEA protocols.

scholarly journals Rationale and Design of the Targeted Agent and Profiling Utilization Registry Study

2018 ◽  
pp. 1-14 ◽  
Author(s):  
Pam K. Mangat ◽  
Susan Halabi ◽  
Suanna S. Bruinooge ◽  
Elizabeth Garrett-Mayer ◽  
Ajjai Alva ◽  
...  
Keyword(s):  
Advanced Cancer ◽  
Drug Administration ◽  
Case Reports ◽  
Food And Drug Administration ◽  
Objective Response ◽  
Tumor Board ◽  
Genomic Alteration ◽  
Primary Study ◽  
Tumor Type ◽  
Targeted Agent

Purpose Case reports and small prospective trials suggest that administering targeted therapies to patients with advanced cancer and an identified genomic target may be associated with clinical benefit. The Targeted Agent and Profiling Utilization Registry (TAPUR) study, a phase II prospective, nonrandomized, multibasket pragmatic clinical trial, aims to identify signals of drug activity when US Food and Drug Administration–approved drugs are matched to prespecified genomic targets in patients with advanced cancer, outside of approved indications. Methods Patients eligible to participate in TAPUR are age ≥ 12 years and have advanced measurable or evaluable solid tumors, multiple myeloma, or B-cell non-Hodgkin lymphoma. Eligible participants are matched to any of the 16 US Food and Drug Administration–approved study drugs based on protocol-specified genomic inclusion and exclusion criteria. Genomic profiling from any Clinical Laboratory Improvement Amendments–certified, College of American Pathologists–accredited laboratory is acceptable. The treating physician selects the treatment from the available study therapies or consults with the TAPUR Molecular Tumor Board. Participants are placed into multiple parallel cohorts defined by tumor type, genomic alteration, and drug. The primary study end point within each cohort is objective response or stable disease of at least 16 weeks duration. Secondary end points include safety, progression-free survival, and overall survival. Results More than 1,000 participants have thus far been registered, and more than 800 have been treated with a TAPUR study drug. Two study cohorts have permanently closed to enrollment because of lack of antitumor activity, and 12 have expanded to the second stage of enrollment after promising preliminary activity. Conclusion The TAPUR study will describe the efficacy and toxicity of the targeted drugs used outside of their approved indications when matched to a somatic genomic variant.

US Food and Drug Administration (FDA): Benefit-Risk Considerations for Cefiderocol (Fetroja®)

2020 ◽  
Author(s):  
Shabnam Naseer ◽  
Edward A Weinstein ◽  
Daniel B Rubin ◽  
Kalavati Suvarna ◽  
Xiaohui Wei ◽  
...  
Keyword(s):  
Drug Administration ◽  
Nosocomial Pneumonia ◽  
Food And Drug Administration ◽  
Treatment Options ◽  
Bloodstream Infections ◽  
Gram Negative Bacteria ◽  
Open Label ◽  
Double Blind ◽  
Gram Negative ◽  
Tract Infections

Abstract In November 2019, the Food and Drug Administration (FDA) approved cefiderocol for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis caused by susceptible gram-negative bacteria in adults with limited to no alternative treatment options based on a randomized, double-blind, noninferiority cUTI trial (APEKS-cUTI). In a randomized, open-label trial (CREDIBLE-CR) in patients with cUTI, nosocomial pneumonia, bloodstream infections, or sepsis due to carbapenem-resistant gram-negative bacteria, an increase in all-cause mortality was observed in patients treated with cefiderocol as compared to best available therapy. The cause of the increased mortality was not established, but some deaths were attributed to treatment failure. Preliminary data from a randomized, double-blind trial (APEKS-NP) in patients with nosocomial pneumonia due to carbapenem-susceptible gram-negative bacteria showed a similar rate of mortality as compared to meropenem. We describe the uncertainties and challenges in the interpretation of the CREDIBLE-CR trial and some benefit-risk considerations for the use of cefiderocol in clinical practice. Clinical Trials Registration NCT02714595.

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