Action and Resistance Mechanisms of Antibiotics: a Guide for Clinicians
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Chapter 12 Antimicrobial Therapy Antibiotics
Chapter 12 Antimicrobial Therapy Topics: • Ideal drug - Antimicrobial Therapy - Selective Toxicity • Terminology - Survey of Antimicrobial Drug • Antibiotics - Microbial Drug Resistance - Drug and Host Interaction An ideal antimicrobic: Chemotherapy is the use of any chemical - soluble in body fluids, agent in the treatment of disease. - selectively toxic , - nonallergenic, A chemotherapeutic agent or drug is any - reasonable half life (maintained at a chemical agent used in medical practice. constant therapeutic concentration) An antibiotic agent is usually considered to - unlikely to elicit resistance, be a chemical substance made by a - has a long shelf life, microorganism that can inhibit the growth or - reasonably priced. kill microorganisms. There is no ideal antimicrobic An antimicrobic or antimicrobial agent is Selective Toxicity - Drugs that specifically target a chemical substance similar to an microbial processes, and not the human host’s. antibiotic, but may be synthetic. Antibiotics Spectrum of antibiotics and targets • Naturally occurring antimicrobials – Metabolic products of bacteria and fungi – Reduce competition for nutrients and space • Bacteria – Streptomyces, Bacillus, • Molds – Penicillium, Cephalosporium * * 1 The mechanism of action for different 5 General Mechanisms of Action for antimicrobial drug targets in bacterial cells Antibiotics - Inhibition of Cell Wall Synthesis - Disruption of Cell Membrane Function - Inhibition of Protein Synthesis - Inhibition of Nucleic Acid Synthesis - Anti-metabolic activity Antibiotics -
CPT Fellowship Psychopharm Focus
Clinical Pharmacology and Toxicology Residency Program, McGill University One year Fellowship in Clinical Pharmacology and Toxicology: Psychopharmacology Focus Fellowship Director: Dr. Theodore Kolivakis, MD, FRCPC Program Director: Dr. Howard Margolese Location: MUHC (70-90%) JGH (10-20%) DH (10-20%) (% Depends on Selectives chosen based on interest of the Fellow) Number of Positions: 1 Length of Program: 1 year. The ‘academic’ year is July 1 to June 30, however ‘off-cycle’ candidates will also be considered Program General Information: The Clinical Pharmacology and Toxicology Fellowship: Psychopharmacology Focus is a one-year supervised training program open to qualified psychiatry residents who have completed their Psychiatry Postgraduate training and are eligible for practice in Canada. This fellowship program is based in the Clinical Psychopharmacology and Therapeutics Unit of the McGill University Health Centre (MUHC), Department of Psychiatry, McGill University, and is carried out in collaboration with a number of University hospitals and centers, namely the Clinical Toxicology Service of the MUHC, Alan Edwards Centre for Research on Pain at the MUHC, Internal Medicine at the MUHC or JGH (Hypertension clinic), Douglas Mental Health University Institute, and the Montreal Neurological Hospital and Institute; as well as the Department of Pharmacy of the MUHC. The objective of this program is to provide advanced training in clinical pharmacology and toxicology with a psychopharmacology focus to residents interested in gaining an expertise in the pharmacological treatment of their patients. Specifically they will learn best practices for 1. patients with complex medication regimes, 2. treatment resistant patients, 3. adverse drug reactions including iatrogenic ADR 4. consultation based care and practices After successfully completing the fellowship it is expected that fellows will become experts in the management of the most difficult psychiatric patients who are often those with significant other medical co-morbidities. -
Antibiotic Resistance: from the Bench to Patients
antibiotics Editorial Antibiotic Resistance: From the Bench to Patients Márió Gajdács 1,* and Fernando Albericio 2,3 1 Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Dóm tér 10., 6720 Szeged, Hungary 2 School of Chemistry, University of KwaZulu-Natal, Durban 4001, South Africa 3 Department of Organic Chemistry, University of Barcelona, CIBER-BBN, 08028 Barcelona, Spain * Correspondence: [email protected]; Tel.: +36-62-341-330 Received: 20 August 2019; Accepted: 26 August 2019; Published: 27 August 2019 The discovery and subsequent clinical introduction of antibiotics is one of the most important game-changers in the history of medicine [1]. These drugs have saved millions of lives from infections that would previously have been fatal, and later, they allowed for the introduction of surgical interventions, organ transplantation, care of premature infants, and cancer chemotherapy [2]. Nevertheless, the therapy of bacterial infections is becoming less and less straightforward due to the emergence of multidrug resistance (MDR) in these pathogens [3]. Direct consequences of antibiotic resistance include delays in the onset of the appropriate (effective) antimicrobial therapy, the need to use older, more toxic antibiotics (e.g., colistin) with a disadvantageous side-effect profile, longer hospital stays, and an increasing burden on the healthcare infrastructure; overall, a decrease in the quality-of-life (QoL) and an increase in the mortality rate of the affected patients [4,5]. To highlight the severity of the issue, several international declarations have been published to call governments around the globe to take action on antimicrobial resistance [6–9]. Since the 1980s, pharmaceutical companies have slowly turned away from antimicrobial research and towards the drug therapy of chronic non-communicable diseases [10,11]. -
Clinical Pharmacology 1: Phase 1 Studies and Early Drug Development
Clinical Pharmacology 1: Phase 1 Studies and Early Drug Development Gerlie Gieser, Ph.D. Office of Clinical Pharmacology, Div. IV Objectives • Outline the Phase 1 studies conducted to characterize the Clinical Pharmacology of a drug; describe important design elements of and the information gained from these studies. • List the Clinical Pharmacology characteristics of an Ideal Drug • Describe how the Clinical Pharmacology information from Phase 1 can help design Phase 2/3 trials • Discuss the timing of Clinical Pharmacology studies during drug development, and provide examples of how the information generated could impact the overall clinical development plan and product labeling. Phase 1 of Drug Development CLINICAL DEVELOPMENT RESEARCH PRE POST AND CLINICAL APPROVAL 1 DISCOVERY DEVELOPMENT 2 3 PHASE e e e s s s a a a h h h P P P Clinical Pharmacology Studies Initial IND (first in human) NDA/BLA SUBMISSION Phase 1 – studies designed mainly to investigate the safety/tolerability (if possible, identify MTD), pharmacokinetics and pharmacodynamics of an investigational drug in humans Clinical Pharmacology • Study of the Pharmacokinetics (PK) and Pharmacodynamics (PD) of the drug in humans – PK: what the body does to the drug (Absorption, Distribution, Metabolism, Excretion) – PD: what the drug does to the body • PK and PD profiles of the drug are influenced by physicochemical properties of the drug, product/formulation, administration route, patient’s intrinsic and extrinsic factors (e.g., organ dysfunction, diseases, concomitant medications, -
DESCRIPTION CLINICAL PHARMACOLOGY Mechanism Of
NDA 20-844/ Topamav Sprinkle Capsules Approved Labeling Text Version: 10/26/98 DESCRIPTION Topiramate is a sulfamate-substituted monosaccharide that is intended for use as an antiepileptic drug. TOPAMAX@ (topiramate capsules) Sprinkle Capsules are available as I5 mg, 25 mg and 50mg sprinkle capsules for oral administration as whole capsules or for opening and sprinkling onto soft food. Topiramate is a white crystalline powder with a bitter taste. Topiramate is most soluble in alkaline solutions containing sodium hydroxide or sodium phosphate and hawng a pH of 9 to IO. It is freely soluble in acetone, chloroform, dimethylsulfoxide, and ethanol. The solubility in water is 9.8 mg/mL. Its saturated solution has a pH of 6.3. Topiramate has the molecular formula C,,H,,NO,S and a molecular weight of 339.37. Topiramate is designated chemically as 2,3:4,5-Di-O-isopropylidene-~- D-fructopyranose sulfamate and has the following structural formula: H3C CH3 TOPAMAX” (topiramate capsules) Sprinkle Capsules contain topiramate coated beads in a hard gelatin capsule. The inactive ingredients are: sugar spheres (sucrose and starch), povidone, cellulose acetate, gelatin, silicone dioxide, sodium lauryl sulfate, titanium dioxide, and black pharmaceutical ink. CLINICAL PHARMACOLOGY Mechanism of Action: The precise mechanism by which topiramate exerts its antiseizure effect is unknown; however, electrophysiological and biochemical studies of the effects of topiramate on cultured neurons have revealed three properties that may contribute to topiramate’s antiepileptic efficacy. First, action potentials elicited repetitively by a sustained depolarization of the neurons are blocked by topiramate in a time-dependent manner, suggestive of a state-dependent sodium channel blocking action. -
IJBCP International Journal of Basic & Clinical Pharmacology Antibiotic
Print ISSN: 2319-2003 | Online ISSN: 2279-0780 IJBCP International Journal of Basic & Clinical Pharmacology DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20191567 Original Research Article Antibiotic sensitivity profile and resistance of microorganisms isolated from south Indian population, a hospital based study at Velappanchavady, Chennai, India Brethis C. S.1*, Mahender G.2, Thamizharasan S.1, Suresh Kumar K.3, Sudharson T.3 1Department of Pharmacology, A.C.S Medical College and ABSTRACT Hospital, Velappanchavadi, Chennai, Tamil Nadu, India Background: Increasing rates of antibiotic drug resistance has been noted in 2Department of Forensic recent times and this adversely affects the prognosis and outcomes of patients. Medicine and Toxicology, There is a greater need for local resistance prevalence data in order to guide District Hospital Gajwel, empirical prescription and to identify areas in which medical need for newer Telangana, India antimicrobial agents is greater. 3Department of Forensic Methods: A prospective hospital based observational study was carried out to Medicine and Toxicology, determine antibiotic sensitivity profile and resistance pattern of microorganisms. A.C.S Medical College and Samples were collected from urinary tract infections, while cultures from blood Hospital, Velappanchavadi, stream infections, sputum samples and Serology. Antibiotic susceptibility was Chennai, Tamil Nadu, India determined by the standard disc diffusion method. Data interpretation was based on CLSI, 2017 guidelines for antimicrobial susceptibility testing. Received: 14 April 2019 Results: The predominant isolates from the samples were, Staphylococcus Accepted: 19 April 2019 aureus (16.7%) 67, K. pneumoniae (11.5%) 46, E. coli (29.4%) 118, P. aeruginosa (6%) 24. Escherichia coli, the most common causative organism *Correspondence to: showed high resistance to commonly used drugs such as Ampicillin (60.1%) 71, Dr. -
Moving Beyond Single Gene-Drug Pairs in Clinical Pharmacogenomics Testing
Moving Beyond Single Gene-Drug Pairs in Clinical Pharmacogenomics Testing Yuan Ji, PhD, DABCP, FACMG Gwendolyn McMillin, PhD, DABCC Learning Objectives • Describe the strengths and limitations of pharmacogenomic testing. • List examples of single gene-drug associations with the strongest levels of evidence for clinical implementation. • Discuss cautions when considering the use of multi-gene drug associations to inform drug therapy decisions. 2 Disclosure • None 3 Outline • Singe gene-drug based pharmacogenomics (PGx) testing – An introduction – Evidence and examples – Considerations for developing and evaluating clinical PGx laboratory developed tests (LDTs) • Multi-gene PGx panels – Evidence and examples – PROs and CONs for utilizing PGx panels – Considerations for successful PGx implementation 4 Single Gene-Drug Based PGx Testing Yuan Ji, PhD, DABCP, FACMG Medical Director of Genomics and Genetics; PGx, ARUP Laboratories Associate Professor (Clinical) of Pathology, University of Utah Medications: Myths and Facts • are~30% peoplenot take“one at least-size one medication fits all” within a 30-day period • Most medications cause adverse drug events (ADEs) • Some medications like antibiotics may do more harm than good • CDC statistics: – ~ 200,000 ADEs-related ER visits in pediatric population (17 years or younger) – ~ 450,000 ADEs-related ER visits in older adults (65 years or older) – Medications, e.g., anticoagulant warfarin • Many ADEs are preventable by closely supervising of dosing, blood tests (therapeutic drug monitoring, TDM), -
Antimicrobial Resistance Benchmark 2020 Antimicrobial Resistance Benchmark 2020
First independent framework for assessing pharmaceutical company action Antimicrobial Resistance Benchmark 2020 Antimicrobial Resistance Benchmark 2020 ACKNOWLEDGEMENTS The Access to Medicine Foundation would like to thank the following people and organisations for their contributions to this report.1 FUNDERS The Antimicrobial Resistance Benchmark research programme is made possible with financial support from UK AID and the Dutch Ministry of Health, Welfare and Sport. Expert Review Committee Research Team Reviewers Hans Hogerzeil - Chair Gabrielle Breugelmans Christine Årdal Gregory Frank Fatema Rafiqi Karen Gallant Nina Grundmann Adrián Alonso Ruiz Hans Hogerzeil Magdalena Kettis Ruth Baron Hitesh Hurkchand Joakim Larsson Dulce Calçada Joakim Larsson Marc Mendelson Moska Hellamand Marc Mendelson Margareth Ndomondo-Sigonda Kevin Outterson Katarina Nedog Sarah Paulin (Observer) Editorial Team Andrew Singer Anna Massey Deirdre Cogan ACCESS TO MEDICINE FOUNDATION Rachel Jones The Access to Medicine Foundation is an independent Emma Ross non-profit organisation based in the Netherlands. It aims to advance access to medicine in low- and middle-income Additional contributors countries by stimulating and guiding the pharmaceutical Thomas Collin-Lefebvre industry to play a greater role in improving access to Alex Kong medicine. Nestor Papanikolaou Address Contact Naritaweg 227-A For more information about this publication, please contact 1043 CB, Amsterdam Jayasree K. Iyer, Executive Director The Netherlands [email protected] +31 (0) 20 215 35 35 www.amrbenchmark.org 1 This acknowledgement is not intended to imply that the individuals and institutions referred to above endorse About the cover: Young woman from the Antimicrobial Resistance Benchmark methodology, Brazil, where 40%-60% of infections are analyses or results. -
Clinical Pharmacology and Pharmacogenomics Fellowship Research Training
CCPP COMMITTEE ON CLINICAL PHARMACOLOGY AND PHARMACOGENOMICS Clinical Pharmacology and Pharmacogenomics Fellowship Research Training The Committee on Clinical Pharmacology and Pharmacogenomics at the University of Chicago, chaired by M. Eileen Dolan, PhD, is seeking motivated trainees for our clinical pharmacology and pharmacogenomics fellowship training program. Candidates should have a PhD, MD, PharmD/PhD or PharmD degree and have successfully completed a clinical residency. Ability to demonstrate a commitment to research, including but not limited to evidence provided by a record of prior publication is encouraged. This program is open to those interested in personalized medicine, pharmacogenomics, new drug development, clinical pharmacology, clinical trial design, genome wide association studies, genetics of drug abuse and/or overcoming drug resistance. Our two-year American Board of Clinical Pharmacology (ABCP) accredited program is a multidisciplinary, comprehensive and collaborative initiative that emphasizes individual creativity in the context of an encouraging environment. The two-year fellowship provides salary support/benefits for protected research time dedicated to research efforts along with support to attend meetings. Trainees will have the opportunity to tailor their work to emphasize clinical, translational or basic science research spending protected time devoted to their research efforts with the remainder dedicated to core curriculum and clinical activities (as applicable). After successful completion, trainees are eligible to become board certified in Clinical Pharmacology. General information at: http://ccpp.uchicago.edu/ or contact the programs’ educational manager, Michelle Domecki at [email protected]. Candidates who are U.S. citizens or permanent residents will be considered for support via an institutional training grant. The University of Chicago is an Equal Opportunity/Affirmative Action Employer. -
Antibiotic Resistance in Plant-Pathogenic Bacteria
PY56CH08-Sundin ARI 23 May 2018 12:16 Annual Review of Phytopathology Antibiotic Resistance in Plant-Pathogenic Bacteria George W. Sundin1 and Nian Wang2 1Department of Plant, Soil, and Microbial Sciences, Michigan State University, East Lansing, Michigan 48824, USA; email: [email protected] 2Citrus Research and Education Center, Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Lake Alfred, Florida 33850, USA Annu. Rev. Phytopathol. 2018. 56:8.1–8.20 Keywords The Annual Review of Phytopathology is online at kasugamycin, oxytetracycline, streptomycin, resistome phyto.annualreviews.org https://doi.org/10.1146/annurev-phyto-080417- Abstract 045946 Antibiotics have been used for the management of relatively few bacterial Copyright c 2018 by Annual Reviews. plant diseases and are largely restricted to high-value fruit crops because of Access provided by INSEAD on 06/01/18. For personal use only. All rights reserved the expense involved. Antibiotic resistance in plant-pathogenic bacteria has Annu. Rev. Phytopathol. 2018.56. Downloaded from www.annualreviews.org become a problem in pathosystems where these antibiotics have been used for many years. Where the genetic basis for resistance has been examined, antibiotic resistance in plant pathogens has most often evolved through the acquisition of a resistance determinant via horizontal gene transfer. For ex- ample, the strAB streptomycin-resistance genes occur in Erwinia amylovora, Pseudomonas syringae,andXanthomonas campestris, and these genes have pre- sumably been acquired from nonpathogenic epiphytic bacteria colocated on plant hosts under antibiotic selection. We currently lack knowledge of the effect of the microbiome of commensal organisms on the potential of plant pathogens to evolve antibiotic resistance. -
Challenges to Tackling Antimicrobial Resistance
Challenges to Tackling Antimicrobial Resistance Antimicrobial resistance (AMR) is a biological mechanism whereby a microorganism evolves over time to develop the ability to become resistant to antimicrobial therapies such as antibiotics. The drivers of and poten- tial solutions to AMR are complex, often spanning multiple sectors. The internationally recognized response to AMR advocates for a ‘One Health’ approach, which requires policies to be developed and implemented across human, animal, and environmental health. To date, misaligned economic incentives have slowed the development of novel antimicrobials and lim- ited efforts to reduce antimicrobial usage. However, the research which underpins the variety of policy options to tackle AMR is rapidly evolving across multiple disciplines such as human medicine, veterinary medicine, agricultural sciences, epidemiology, economics, sociology and psychology. By bringing together in one place the latest evidence and analysing the different facets of the complex problem of tackling AMR, this book offers an accessible summary for policy-makers, academics and students on the big questions around AMR policy. This title is also available as Open Access on Cambridge Core. Michael anderson is a Research Officer in Health Policy at the Department of Health Policy, London School of Economics and Political Science, and a Medical Doctor undertaking General Practice specialty training. Michele cecchini is a Senior Health Economist, Health Division, in the Directorate for Employment, Labour and Social Affairs, Organisation for Economic Co-operation and Development. elias Mossialos is Brian Abel-Smith Professor of Health Policy, Head of the Department of Health Policy at the London School of Economics and Political Science, and Co-Director of the European Observatory on Health Systems. -
Immediately Dangerous to Life Or Health (IDLH) Value Profile: Butane
Butane CAS® No. 106-97-8 DEPARTMENT OF HEALTH AND HUMAN SERVICES Center for Disease Control and Prevention National Institute of Occupational Safety and Health This page intentionally left blank. Immediately Dangerous to Life or Health (IDLH) Value Profile Butane [CAS® No. 106-97-8] H3C CH3 DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Institute for Occupational Safety and Health This document is in the public domain and may be freely copied or reprinted. Disclaimer Mention of any company or product does not constitute endorsement by the National Institute for Occupational Safety and Health (NIOSH). In addition, citations to websites external to NIOSH do not constitute NIOSH endorsement of the sponsoring organizations or their programs or products. Furthermore, NIOSH is not responsible for the content of these websites. Ordering Information To receive this document or information about other occupational safety and health topics, contact NIOSH: Telephone: 1-800-CDC-INFO (1-800-232-4636) TTY: 1-888-232-6348 E-mail: [email protected] or visit the NIOSH ebsite at: www.cdc.gov/niosh For a monthly update on news at NIOSH, subscribe to NIOSH eNews by visiting www.cdc.gov/niosh/eNews. Suggested Citation NIOSH [2016]. Immediately dangerous to life or health (IDLH) value profile: butane. By Dotson GS, Maier A, Parker A, Haber L. Cincinnati, OH: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupa- tional Safety and Health, DHHS (NIOSH) Publication 2016-174. DHHS (NIOSH) Publication No. 2016-174 September 2016 ii IDLH Value Profile for Butane Foreword Chemicals are a ubiquitous component of the modern workplace.