Structure of a Penicillin Binding Protein Complexed with a Cephalosporin-Peptidoglycan Mimic M.A
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Antimicrobial Stewardship Guidance
Antimicrobial Stewardship Guidance Federal Bureau of Prisons Clinical Practice Guidelines March 2013 Clinical guidelines are made available to the public for informational purposes only. The Federal Bureau of Prisons (BOP) does not warrant these guidelines for any other purpose, and assumes no responsibility for any injury or damage resulting from the reliance thereof. Proper medical practice necessitates that all cases are evaluated on an individual basis and that treatment decisions are patient-specific. Consult the BOP Clinical Practice Guidelines Web page to determine the date of the most recent update to this document: http://www.bop.gov/news/medresources.jsp Federal Bureau of Prisons Antimicrobial Stewardship Guidance Clinical Practice Guidelines March 2013 Table of Contents 1. Purpose ............................................................................................................................................. 3 2. Introduction ...................................................................................................................................... 3 3. Antimicrobial Stewardship in the BOP............................................................................................ 4 4. General Guidance for Diagnosis and Identifying Infection ............................................................. 5 Diagnosis of Specific Infections ........................................................................................................ 6 Upper Respiratory Infections (not otherwise specified) .............................................................................. -
New Β-Lactamase Inhibitor Combinations: Options for Treatment; Challenges for Testing
MEDICAL/SCIENTIFIC AffAIRS BULLETIN New β-lactamase Inhibitor Combinations: Options for Treatment; Challenges for Testing Background The β-lactam class of antimicrobial agents has played a crucial role in the treatment of infectious diseases since the discovery of penicillin, but β–lactamases (enzymes produced by the bacteria that can hydrolyze the β-lactam core of the antibiotic) have provided an ever expanding threat to their successful use. Over a thousand β-lactamases have been described. They can be divided into classes based on their molecular structure (Classes A, B, C and D) or their function (e.g., penicillinase, oxacillinase, extended-spectrum activity, or carbapenemase activity).1 While the first approach to addressing the problem ofβ -lactamases was to develop β-lactamase stable β-lactam antibiotics, such as extended-spectrum cephalosporins, another strategy that has emerged is to combine existing β-lactam antibiotics with β-lactamase inhibitors. Key β-lactam/β-lactamase inhibitor combinations that have been used widely for over a decade include amoxicillin/clavulanic acid, ampicillin/sulbactam, and pipercillin/tazobactam. The continued use of β-lactams has been threatened by the emergence and spread of extended-spectrum β-lactamases (ESBLs) and more recently by carbapenemases. The global spread of carbapenemase-producing organisms (CPOs) including Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii, limits the use of all β-lactam agents, including extended-spectrum cephalosporins (e.g., cefotaxime, ceftriaxone, and ceftazidime) and the carbapenems (doripenem, ertapenem, imipenem, and meropenem). This has led to international concern and calls to action, including encouraging the development of new antimicrobial agents, enhancing infection prevention, and strengthening surveillance systems. -
Penicillin Allergy Guidance Document
Penicillin Allergy Guidance Document Key Points Background Careful evaluation of antibiotic allergy and prior tolerance history is essential to providing optimal treatment The true incidence of penicillin hypersensitivity amongst patients in the United States is less than 1% Alterations in antibiotic prescribing due to reported penicillin allergy has been shown to result in higher costs, increased risk of antibiotic resistance, and worse patient outcomes Cross-reactivity between truly penicillin allergic patients and later generation cephalosporins and/or carbapenems is rare Evaluation of Penicillin Allergy Obtain a detailed history of allergic reaction Classify the type and severity of the reaction paying particular attention to any IgE-mediated reactions (e.g., anaphylaxis, hives, angioedema, etc.) (Table 1) Evaluate prior tolerance of beta-lactam antibiotics utilizing patient interview or the electronic medical record Recommendations for Challenging Penicillin Allergic Patients See Figure 1 Follow-Up Document tolerance or intolerance in the patient’s allergy history Consider referring to allergy clinic for skin testing Created July 2017 by Macey Wolfe, PharmD; John Schoen, PharmD, BCPS; Scott Bergman, PharmD, BCPS; Sara May, MD; and Trevor Van Schooneveld, MD, FACP Disclaimer: This resource is intended for non-commercial educational and quality improvement purposes. Outside entities may utilize for these purposes, but must acknowledge the source. The guidance is intended to assist practitioners in managing a clinical situation but is not mandatory. The interprofessional group of authors have made considerable efforts to ensure the information upon which they are based is accurate and up to date. Any treatments have some inherent risk. Recommendations are meant to improve quality of patient care yet should not replace clinical judgment. -
Management of Penicillin and Beta-Lactam Allergy
Management of Penicillin and Beta-Lactam Allergy (NB Provincial Health Authorities Anti-Infective Stewardship Committee, September 2017) Key Points • Beta-lactams are generally safe; allergic and adverse drug reactions are over diagnosed and over reported • Nonpruritic, nonurticarial rashes occur in up to 10% of patients receiving penicillins. These rashes are usually not allergic and are not a contraindication to the use of a different beta-lactam • The frequently cited risk of 8 to 10% cross-reactivity between penicillins and cephalosporins is an overestimate based on studies from the 1970’s that are now considered flawed • Expect new intolerances (i.e. any allergy or adverse reaction reported in a drug allergy field) to be reported after 0.5 to 4% of all antimicrobial courses depending on the gender and specific antimicrobial. Expect a higher incidence of new intolerances in patients with three or more prior medication intolerances1 • For type-1 immediate hypersensitivity reactions (IgE-mediated), cross-reactivity among penicillins (table 1) is expected due to similar core structure and/or major/minor antigenic determinants, use not recommended without desensitization • For type-1 immediate hypersensitivity reactions, cross-reactivity between penicillins (table 1) and cephalosporins is due to similarities in the side chains; risk of cross-reactivity will only be significant between penicillins and cephalosporins with similar side chains • Only type-1 immediate hypersensitivity to a penicillin manifesting as anaphylaxis, bronchospasm, -
Cephalosporin Administration to Patients with a History of Penicillin Allergy Adverse Reactions to Drugs, Biologicals and Latex Committee
Work group report May, 2009 Cephalosporin Administration to Patients with a History of Penicillin Allergy Adverse Reactions to Drugs, Biologicals and Latex Committee Work Group Members : Roland Solensky, MD FAAAAI, Chair Aleena Banerji, MD Gordon R. Bloomberg, MD FAAAAI Marianna C. Castells, MD PhD FAAAAI Paul J. Dowling, MD George R. Green, MD FAAAAI Eric M. Macy, MD FAAAAI Myngoc T. Nguyen, MD FAAAAI Antonino G. Romano, MD PhD Fanny Silviu-Dan, MD FAAAAI Clifford M. Tepper, MD FAAAAI INTRODUCTION Penicillins and cephalosporins share a common beta-lactam ring structure, and hence the potential for IgE-mediated allergic cross-reactivity. Allergic cross-reactivity between penicillins and cephalosporins potentially may also occur due to presence of identical or similar R-group side chains, in which case IgE is directed against the side chain, rather the core beta-lactam structure. This work group report will address the administration of cephalosporins in patients with a history of penicillin allergy. First, published data will be reviewed regarding 1) cephalosporin challenges of patients with a history of penicillin allergy (without preceding skin testing or in vitro testing), and 2) cephalosporin challenges of patients proven to have a type I allergy to penicillins (via positive penicillin skin test, in vitro test or challenge). Secondly, 1 2/9/2011 recommendations on cephalosporin administration to patients with a history of penicillin allergy will be presented. Unless specifically noted, the term ‘penicillin allergy’ will be used to indicate an allergy to one or more of the penicillin-class antibiotics, not just to penicillin itself. The following discussion includes references, in certain clinical situations, to performing cephalosporin graded challenges in patients with a history of penicillin allergy. -
Cephalosporins Can Be Prescribed Safely for Penicillin-Allergic Patients ▲
JFP_0206_AE_Pichichero.Final 1/23/06 1:26 PM Page 106 APPLIED EVIDENCE New research findings that are changing clinical practice Michael E. Pichichero, MD University of Rochester Cephalosporins can be Medical Center, Rochester, NY prescribed safely for penicillin-allergic patients Practice recommendations an allergic reaction to cephalosporins, ■ The widely quoted cross-allergy risk compared with the incidence of a primary of 10% between penicillin and (and unrelated) cephalosporin allergy. cephalosporins is a myth (A). Most people produce IgG and IgM antibodies in response to exposure to ■ Cephalothin, cephalexin, cefadroxil, penicillin1 that may cross-react with and cefazolin confer an increased risk cephalosporin antigens.2 The presence of of allergic reaction among patients these antibodies does not predict allergic, with penicillin allergy (B). IgE cross-sensitivity to a cephalosporin. ■ Cefprozil, cefuroxime, cefpodoxime, Even penicillin skin testing is generally not ceftazidime, and ceftriaxone do not predictive of cephalosporin allergy.3 increase risk of an allergic reaction (B). Reliably predicting cross-reactivity ndoubtedly you have patients who A comprehensive review of the evidence say they are allergic to penicillin shows that the attributable risk of a cross- U but have difficulty recalling details reactive allergic reaction varies and is of the reactions they experienced. To be strongest when the chemical side chain of safe, we often label these patients as peni- the specific cephalosporin is similar to that cillin-allergic without further questioning of penicillin or amoxicillin. and withhold not only penicillins but Administration of cephalothin, cepha- cephalosporins due to concerns about lexin, cefadroxil, and cefazolin in penicillin- potential cross-reactivity and resultant IgE- allergic patients is associated with a mediated, type I reactions. -
Emergence of Third-Generation Cephalosporin-Resistant Morganella Morganii in a Captive Breeding Dolphin in South Korea
animals Brief Report Emergence of Third-Generation Cephalosporin-Resistant Morganella morganii in a Captive Breeding Dolphin in South Korea 1,2, 3, 3 1 1 Seon Young Park y , Kyunglee Lee y, Yuna Cho , Se Ra Lim , Hyemin Kwon , Jee Eun Han 4,* and Ji Hyung Kim 1,* 1 Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea; [email protected] (S.Y.P.); [email protected] (S.R.L.); [email protected] (H.K.) 2 Division of Animal and Dairy Sciences, College of Agriculture and Life Science, Chungnam National University, Daejeon 34134, Korea 3 Cetacean Research Institute, National Institute of Fisheries Science, Ulsan 44780, Korea; [email protected] (K.L.); tnvlfl[email protected] (Y.C.) 4 Laboratory of Aquatic Biomedicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea * Correspondence: [email protected] (J.E.H.); [email protected] (J.H.K.) These authors equally contributed to this work. y Received: 9 July 2020; Accepted: 28 October 2020; Published: 6 November 2020 Simple Summary: The emergence of antimicrobial resistance (AMR) has become an important consideration in animal health, including marine mammals, and several potential zoonotic AMR bacterial strains have been isolated from wild cetacean species. Although the emergence of AMR bacteria can be assumed to be much more plausible in captive than in free-ranging cetaceans owing to their frequent contact with humans and antibiotic treatments, the spread and its impacts of AMR bacteria in captive animals have not been adequately investigated yet. Here in this study, we present evidence on the presence of multidrug-resistant potential zoonotic bacteria which caused fatal infection in a captive dolphin bred at a dolphinarium in South Korea. -
Β-Lactam/Β-Lactamase Inhibitors for the Treatment of Infections Caused by Extended-Spectrum Β-Lactamase (ESBL)-Producing Enterobacteriaceae
β-lactam/β-lactamase Inhibitors for the Treatment of Infections Caused by Extended-Spectrum β-Lactamase (ESBL)-producing Enterobacteriaceae Alireza FakhriRavari, Pharm.D. PGY-2 Pharmacotherapy Resident Controversies in Clinical Therapeutics University of the Incarnate Word Feik School of Pharmacy San Antonio, Texas November 13, 2015 Learning Objectives At the completion of this activity, the participant will be able to: 1. Describe different classes of β-lactamases produced by gram-negative bacteria. 2. Identify β-lactamase inhibitors and their spectrum of inhibition of β-lactamases. 3. Evaluate the evidence for use of β-lactam/β-lactamase inhibitors compared to carbapenems for treatment of ESBL infections. β-lactam/β-lactamase inhibitors for the treatment of infections caused by ESBL-producing Enterobacteriaceae 1 1. A Brief History of the Universe A. Timeline: 1940s a. β-lactams and β-lactamases i. Sir Alexander Fleming discovered penicillin from Penicillium notatum (now Penicillium chrysogenum) in 1928.1,2 ii. Chain, Florey, et al isolated penicillin in 1940, leading to its commercial production.3 iii. First β-lactamase was described as a penicillinase in Escherichia coli in 1940.4 iv. Giuseppe Brotzu discovered cephalosporin C from the mold Cephalosporin acremonium (now Acremonium chrysogenum) in 1945, but cephalosporins were not clinically used for another 2 decades.2,5 b. What are β-lactamases? i. β-lactamases are enzymes that hydrolyze the amide bond of the β-lactam ring, thereby inactivating them.6 Figure 1: Mechanism of action of β-lactamases ii. β-lactamase production is the principal mechanism by which gram-negative bacteria resist β-lactam antibiotics.6 iii. -
Non-Penicillin Beta-Lactam Drugs: a CGMP Framework for Preventing Cross- Contamination
Guidance for Industry Non-Penicillin Beta-Lactam Drugs: A CGMP Framework for Preventing Cross- Contamination U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) April 2013 Current Good Manufacturing Practices (CGMPs) Guidance for Industry Non-Penicillin Beta-Lactam Drugs: A CGMP Framework for Preventing Cross- Contamination Additional copies are available from: Office of Communications Division of Drug Information, WO51, Room 2201 Center for Drug Evaluation and Research Food and Drug Administration 10903 New Hampshire Ave. Silver Spring, MD 20993-0002 Phone: 301-796-3400; Fax: 301-847-8714 [email protected] http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) April 2013 Current Good Manufacturing Practices (CGMP) Contains Nonbinding Recommendations TABLE OF CONTENTS I. INTRODUCTION....................................................................................................................1 II. BACKGROUND ......................................................................................................................2 III. RECOMMENDATIONS.........................................................................................................7 i Contains Nonbinding Recommendations Guidance for Industry1 Non-Penicillin Beta-Lactam Drugs: A CGMP Framework for Preventing Cross-Contamination This guidance -
Antibiotic Resistance Threats in the United States, 2019
ANTIBIOTIC RESISTANCE THREATS IN THE UNITED STATES 2019 Revised Dec. 2019 This report is dedicated to the 48,700 families who lose a loved one each year to antibiotic resistance or Clostridioides difficile, and the countless healthcare providers, public health experts, innovators, and others who are fighting back with everything they have. Antibiotic Resistance Threats in the United States, 2019 (2019 AR Threats Report) is a publication of the Antibiotic Resistance Coordination and Strategy Unit within the Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention. Suggested citation: CDC. Antibiotic Resistance Threats in the United States, 2019. Atlanta, GA: U.S. Department of Health and Human Services, CDC; 2019. Available online: The full 2019 AR Threats Report, including methods and appendices, is available online at www.cdc.gov/DrugResistance/Biggest-Threats.html. DOI: http://dx.doi.org/10.15620/cdc:82532. ii U.S. Centers for Disease Control and Prevention Contents FOREWORD .............................................................................................................................................V EXECUTIVE SUMMARY ........................................................................................................................ VII SECTION 1: THE THREAT OF ANTIBIOTIC RESISTANCE ....................................................................1 Introduction .................................................................................................................................................................3 -
Cephalosporins
Case Histories of Significant Medical Advances: Cephalosporins Amar Bhidé Srikant Datar Katherine Stebbins Working Paper 20-133 Case Histories of Significant Medical Advances: Cephalosporins Amar Bhidé Harvard Business School Srikant Datar Harvard Business School Katherine Stebbins Harvard Business School Working Paper 20-133 Copyright © 2020 by Amar Bhidé, Srikant Datar, and Katherine Stebbins. Working papers are in draft form. This working paper is distributed for purposes of comment and discussion only. It may not be reproduced without permission of the copyright holder. Copies of working papers are available from the author. Funding for this research was provided in part by Harvard Business School. Case Histories of Significant Medical Advances Cephalosporins Amar Bhidé, Harvard Business School Srikant Datar, Harvard Business School Katherine Stebbins, Harvard Business School Abstract: Our case history describes the development of three generations of cephalosporins – antibiotics that have significantly reduced hospital infections. Specifically, we chronicle how: 1) Early (pre-cephalosporin) antibiotics were developed in the first half of the 20th century. 2) Drug companies developed first-generation cephalosporins in the 1960s using foundational discoveries made by researchers in Italy and the UK in the 1940s and 1950s. 3) Continued modifications of cephalosporin molecules resulted in second and third generation of the drugs in the 1970s and 1980s. Note: Cephalosporins, like the others in this series of case-histories, are included in a list compiled by Victor Fuchs and Harold Sox (2001) of technologies produced (or significantly advanced) between 1975 and 2000 that internists in the United States said had had a major impact on patient care. The case histories focus on advances in the 20th century (i.e. -
Beta-Lactam Antibiotics - Cephalosporins
Beta-lactam antibiotics - Cephalosporins Targets - PBP’s Activity - Cidal - growing organisms (like the penicillins) Principles of action - Affinity for PBP’s Permeability properties Stability to bacterial enzymes 1 Cephalosporins Development - Giuseppe Brodtzu - Sardinian sewage Cephalosporin C - Cephalothin No meningeal penetration Failed in meningococcal meningitis Painful to give IM Advantages Cephalosporin nucleus - resistant to Staphylococcal penicillinase Cephalosporin nucleus - more readily modified Development of C’sporins Generations - in response to clinical needs First generation - Cephalothin (not used) Cefazolin oral - Cephalexin, cefaclor Activity - Broad spectrum: Gram positive Streptococci, S. aureus Gram negative - E.coli, Klebsiella No activity against Enterococci - different PBP’s 2 Second generation C’sporins Cefuroxime Cefoxitin Cefotetan 70’s - Beta-lactamase’s recognized (H. influenzae) Anaerobic infections Cefoxitin - Methoxy group - conferred beta-lactamase stability Induction of chromosomal beta-lactamases Bacteroides fragilis - enteric anaerobes Cefuroxime - Respiratory tract infections - community acquired 3 Kinetics of c’sporin binding Affinity for receptor - PBP Permeability characteristics of the porin Beta-lactamase production - within periplasmic space 4 Third generation C’sporins 80’s - Intensive care - nosocomial infections Multi-Resistant Gram negative organisms Chromosomal beta-lactamase - C’sporinase Inducible Plasmid mediated enzymes - mutants with both Penicillinase and C’sporinase activity Permeability