DOCSLIB.ORG

Tetracycline Antibiotics and Resistance

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Tetracycline Antibiotics and Resistance Downloaded from http://perspectivesinmedicine.cshlp.org/ on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Tetracycline Antibiotics and Resistance Trudy H. Grossman Tetraphase Pharmaceuticals, Watertown, Massachusetts 02472 Correspondence: [email protected] Tetracyclines possess many properties considered ideal for antibiotic drugs, including activ- ity against Gram-positive and -negative pathogens, proven clinical safety, acceptable toler- ability, and the availability of intravenous (IV) and oral formulations for most members of the class. As with all antibiotic classes, the antimicrobial activities of tetracyclines are subject to both class-specific and intrinsic antibiotic-resistance mechanisms. Since the discovery of the first tetracyclines more than 60 years ago, ongoing optimization of the core scaffold has produced tetracyclines in clinical use and development that are capable of thwarting many of these resistance mechanisms. New chemistry approaches have enabled the creation of synthetic derivatives with improved in vitro potency and in vivo efficacy, ensuring that the full potential of the class can be explored for use against current and emerging multidrug- resistant (MDR) pathogens, including carbapenem-resistant Enterobacteriaceae, MDR Aci- netobacter species, and Pseudomonas aeruginosa. etracycline antibiotics are well known for rivatives with improved antibacterial potency, Ttheir broad spectrum of activity, spanning a spectrum, resistance coverage, solubility, and/ wide range of Gram-positive and -negative bac- or oral bioavailability (methacycline, rolitetra- teria, spirochetes, obligate intracellular bacteria, cycline, lymecycline, doxycycline, and minocy- as well as protozoan parasites. The first tetracy- cline) (Jarolmen et al. 1970; Cunha et al. 1982; clines were natural products derived from the Nelson and Levy 2011). Several of these “legacy” fermentations of actinomycetes. Chlortetracy- tetracyclines remain in clinical use for the treat- cline, produced by Streptomyces aureofaciens, ment of uncomplicated respiratory, urogenital, and marketed as Aureomycin, was first reported gastrointestinal, and other rare and serious in- www.perspectivesinmedicine.org by Benjamin Duggar at Lederle Laboratories in fections; however, the dissemination of tetracy- 1948 and approved forclinical use that sameyear cline-resistant mechanisms has narrowed their (Duggar 1948). Soon after, Pfizer (New York) utility, limiting use to only infections with con- scientists isolated oxytetracycline, approved by firmed susceptibility (Fig. 1). the U.S. Food and Drug Administration (FDA) After a long pause in the advancement of the in 1950 and marketed as Terramycin (Finlayet al. tetracycline class, renewed interest in optimiza- 1950). Other tetracyclines that followed over tion of tetracyclines during the late 1980s led the next two decades were also natural products to the discovery of semisynthetic derivatives produced by streptomycetes (tetracycline, de- with improved potency against difficult-to-treat methylchlortetracycline) or semisynthetic de- emerging multidrug-resistant (MDR) Gram- Editors: Lynn L. Silver and Karen Bush Additional Perspectives on Antibiotics and Antibiotic Resistance available at www.perspectivesinmedicine.org Copyright # 2016 Cold Spring Harbor Laboratory Press; all rights reserved; doi: 10.1101/cshperspect.a025387 Cite this article as Cold Spring Harb Perspect Med 2016;6:a025387 1 Downloaded from http://perspectivesinmedicine.cshlp.org/ on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press T.H. Grossman H C CH H3C CH H C CH CH 3 3 3 3 3 CI 3 N CH3 OH N CH3 N HO H H HO H H 7 HO H H OH OH 3 OH 8 6 5 4 D C B A 9 NH2 NH2 1 2 NH2 10 11 12 O O O OH O HO H O O OH O HO H O O OH O HO H O O Chlortetracycline (Aureomycin, 1948) Oxytetracycline (Terramycin, 1951) Tetracycline (Teracyn, 1953) H C CH H C CH CI CH 3 N 3 CH 3 N 3 H HO 3 H H OH H OH H NH2 NN O O OH O HO H O O OH O HO H O O Demethylchlortetracycline (Declomycin, 1957) Rolitetracycline (Reverin, 1958) H C CH H C CH CH 3 N 3 O CI CH 3 N 3 HO 3 H H HO 3 H H OH N H N H OH 2 OH H NH NOH O O OH O HO H O O OH O HO H O O Limecycline (Tetralysal, 1961) Clomocycline (Megaclor, 1963) H H H3C CH H3C CH H C CH H C CH OH N 3 CH OH N 3 3 N 3 3 N 3 H 3 H H H OH H H OH OH NH2 NH2 NH2 O O O OH O HO H O O OH O HO H O O OH O HO H O O Methacycline (Rondomycin, 1965) Doxycycline (Vibramycin, 1967) Minocycline (Minocin, 1972) H C CH 3 3 H3C CH3 H C CH H C CH N N 3 N 3 3 N 3 H H H H OH OH O CH H H C 3 H H C N NH 3 N 3 N 2 NH2 H3C H3C H O O CH3 OH O HO H O O OH O HO H O O Tigecycline (Tygacil, 2005) Omadacycline (in phase-three trials) H C CH F 3 N 3 H H OH www.perspectivesinmedicine.org O N NH N 2 H O OH O HO H O O Eravacycline (in phase-three trials) Figure 1. Chemical structures of clinically used tetracyclines and development candidates. Tetracycline structures are labeled with generic names; trade names and year of discovery are indicated within parentheses. The core structure rings (A–D) and carbons (1–12) are labeled in the chemical structure of tetracycline using the convention for tetracycline carbon numbering and ring letter assignments. negative and -positive pathogens, including bac- 2005 (Sum and Petersen 1999; Zhanel et al. teria with tetracycline-specific resistance mech- 2004). Tigecycline continues to be an important anisms. Tigecycline, a semisynthetic parenteral treatment option for serious infections caused glycylcycline, was discovered in 1993 by scien- by pathogens resistant to other antibiotic class- tists at Lederle (which later became Wyeth, es. In recent years, two new tetracyclines have New York), and introduced into clinical use in entered clinical development: omadacycline, a 2 Cite this article as Cold Spring Harb Perspect Med 2016;6:a025387 Downloaded from http://perspectivesinmedicine.cshlp.org/ on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Tetracyclines and Resistance semisynthetic aminomethylcycline derivative of ribosomal subunit, arresting translation by ste- minocycline discovered at Paratek Pharmaceu- rically interfering with the docking of amino- ticals (Boston, MA) (Draper et al. 2014), and acyl-transfer RNA (tRNA) during elongation eravacycline, a fully synthetic fluorocycline dis- (Maxwell 1967; Brodersen et al. 2000; Pioletti covered at Tetraphase Pharmaceuticals (Water- et al. 2001). Tetracyclines are usually considered town, MA) (Clark et al. 2012; Xiao et al. 2012). bacteriostatic antibiotics; however, organism- In addition to efficacy against MDR infections, and isolate-specific bactericidal activity in vitro an important feature of these two new antibiot- has been described (Norcia et al. 1999; Petersen ics is their oral formulations. This review will et al. 2007; Bantar et al. 2008; Noviello et al. focus on recent developments in the under- 2008), and, recently, the bactericidal activity of standing of tetracycline-resistance mechanisms tigecycline against E. coli and K. pneumoniae in and their potential impact on the clinical utility a mouse model suggests that in vitro bacterici- of tetracycline-class antibiotics. dal assessments may not necessarily predict in vivo outcomes (Tessier and Nicolau 2013). The mechanism of tetracycline uptake has MECHANISM, UPTAKE, AND been reviewed by Nikaido and Thanassi (1993). TETRACYCLINE-SPECIFIC RESISTANCE Briefly, in Gram-negative cells such as E. coli, In recent surveillance studies, the prevalence of tetracycline passively diffuses through the outer tetracycline resistance in selected European membrane porins OmpF and OmpC (Morti- countries was found to be 66.9% and 44.9% mer and Piddock 1993; Thanassi et al. 1995), for extended-spectrum b-lactamase (ESBL)- most likely as a Mg2þ chelate, and this is con- producing Escherichia coli and Klebsiella species sistent with the finding that outer membrane (spp.), respectively (Jones et al. 2014), and glob- porin mutants show decreased susceptibility to al tetracycline-resistance percentages were 8.7% tetracyclines (Pugsley and Schnaitman 1978). and 24.3% for methicillin-resistant Staphylo- Accumulation of tetracycline in the periplasm coccus aureus (MRSA) and Streptococcus pneu- is driven by the Donnan potential across the moniae, respectively (Mendes et al. 2015). outer membrane. The dissociation of tetracy- Resistance to tetracyclines is usually attributed cline from Mg2þ enables the weakly lipophilic, to one or more of the following: the acquisition uncharged form to diffuse through the inner of mobile genetic elements carrying tetracy- membrane to the cytoplasm where it may cline-specific resistance genes, mutations within be complexed with magnesium and reach its the ribosomal binding site, and/orchromosom- ribosomal target. Uptake into the cytoplasm is al mutations leading to increased expression of partially energy dependent, involving passive www.perspectivesinmedicine.org intrinsic resistance mechanisms. Three general diffusion, proton motive force, and phosphate class-specific mechanisms have been well de- bond hydrolysis (McMurry and Levy 1978; scribed: efflux, ribosomal protection, and enzy- Smith and Chopra 1984; Yamaguchi et al. matic inactivation of tetracycline drugs. As there 1991). are several recent reviews on the topics of tetra- cycline-specific resistance determinants and Ribosomal Interactions their prevalence in clinical and environmental settings (Roberts 2005, 2011; Jones et al. 2008; Crystallographic studies with the Thermus ther- Thaker et al. 2010), only a limited
Load more

Recommended publications
  • The Role of Nanobiosensors in Therapeutic Drug Monitoring
    Journal of Personalized Medicine Review Personalized Medicine for Antibiotics: The Role of Nanobiosensors in Therapeutic Drug Monitoring Vivian Garzón 1, Rosa-Helena Bustos 2 and Daniel G. Pinacho 2,* 1 PhD Biosciences Program, Universidad de La Sabana, Chía 140013, Colombia; [email protected] 2 Therapeutical Evidence Group, Clinical Pharmacology, Universidad de La Sabana, Chía 140013, Colombia; [email protected] * Correspondence: [email protected]; Tel.: +57-1-8615555 (ext. 23309) Received: 21 August 2020; Accepted: 7 September 2020; Published: 25 September 2020 Abstract: Due to the high bacterial resistance to antibiotics (AB), it has become necessary to adjust the dose aimed at personalized medicine by means of therapeutic drug monitoring (TDM). TDM is a fundamental tool for measuring the concentration of drugs that have a limited or highly toxic dose in different body fluids, such as blood, plasma, serum, and urine, among others. Using different techniques that allow for the pharmacokinetic (PK) and pharmacodynamic (PD) analysis of the drug, TDM can reduce the risks inherent in treatment. Among these techniques, nanotechnology focused on biosensors, which are relevant due to their versatility, sensitivity, specificity, and low cost. They provide results in real time, using an element for biological recognition coupled to a signal transducer. This review describes recent advances in the quantification of AB using biosensors with a focus on TDM as a fundamental aspect of personalized medicine. Keywords: biosensors; therapeutic drug monitoring (TDM), antibiotic; personalized medicine 1. Introduction The discovery of antibiotics (AB) ushered in a new era of progress in controlling bacterial infections in human health, agriculture, and livestock [1] However, the use of AB has been challenged due to the appearance of multi-resistant bacteria (MDR), which have increased significantly in recent years due to AB mismanagement and have become a global public health problem [2].
    [Show full text]
  • Technical Information
    Technical Information Antibiotic Assay Medium No.1 (Seed Agar) Product Code : DM1003 Application: - Antibiotic Assay Medium No.1 (Seed Agar) is used in the microbiological assay of beta-lactam and other antibiotics. Composition** Ingredients Gms / Litre Peptic digest of animal tissue (Peptone) 6.000 or detecting faecal coliforms drinking in water waste water, seawater and foods samples by MPN Method. Casein enzymic hydrolysate 4.000 Yeast extract 3.000 Beef extract 1.500 Dextrose 1.000 Agar 15.000 Final pH (at 25°C) 6.6±0.2 **Formula adjusted, standardized to suit performance parameters Principle & Interpretation The potency of an antibiotic can be determined by chemical, physical and biological methods. An assay is performed to determine the ability of an antibiotic to kill or inhibit the growth of living microorganisms. Biological tests offer the most convenient m eans of performing an assay (1), since a reduction in the antimicrobial activity of a specific antibiotic reveals changes that is not usually displayed by chemical methods (2). Antibacterial susceptibility testing may be performed by either dilution (turbidimetric) or diffusion methods. The choice o f methodology is based on many factors, including ease of performance, flexibility and use of automated or semi-automated devices for both identification and susceptibility testing (3). Grove and Randall have elucidated antibiotic assays and media in their comprehensive treatise on antibiotic assays (4). Antibiotic Assay Medium No.1 is used in the microbiological assay of ß-lactam and other antibiotics. These media are prepared according to the specifications detailed in various pharmacopoeias (2-6) and by the FDA (7).
    [Show full text]
  • Omadacycline (PTK796)
    Poster C1-609 Novartis Institutes for BioMedical Research, Inc. Omadacycline (PTK796) Mechanism of Action Studies by Using In Vitro Protein Synthesis 4560 Horton Street Session 87 Emeryville, CA 94608 Phone: 510-923-2057, Fax: 510-923-5550 Inhibition Assay and Molecular Modeling Email: [email protected] A. RUZIN, S. MULLIN, P. PETRONE, L. WHITEHEAD and P. A. BRADFORD − Novartis Institutes for BioMedical Research, Cambridge, MA Figure 1. Structures of molecules used in this study. Computational Chemistry • In comparison with tetracycline (Figure 3A), additional C. Omadacycline predicted binding pose using Cresset B. Omadacycline interaction map. ABSTRACT favorable molecular interactions are made in the C1054/G1053 alignment to tetracycline. N N N N The Thermus thermophilus X-ray solution of tetracycline within ADE966 GUA 966 H2N H H H H H H HO HO the 30S subunit (accession code 1HNW) was used for generating binding area with the additional tertiary-amine-containing N N O O O O CYT1054 H P O HO H H P N Background H H CYT1195 OH H N N H N side-chains of both omadacycline and tygecycline. H OHOH O 2 2 N the modeling hypotheses. The ConQuest small molecule X-ray H N N O N N 2 Omadacylcine (OMC) is a novel aminomethylcycline anti- OH OH H URA OH O 1196 O O OH O OH O O OH O OH O O OH O OH database for ligand three dimensional atomic structures was also • Omadacycline has a secondary amine functionality capable of N N bacterial compound. The structural similarity between OMC and H H H O used in the preparation of ligand structures.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 9,662.400 B2 Smith Et Al
    USOO9662400B2 (12) United States Patent (10) Patent No.: US 9,662.400 B2 Smith et al. (45) Date of Patent: *May 30, 2017 (54) METHODS FOR PRODUCING A (2013.01); C08B 37/003 (2013.01); C08L 5/08 BODEGRADABLE CHITOSAN (2013.01); A6 IK 38/00 (2013.01); A61 L COMPOSITION AND USES THEREOF 2300/404 (2013.01) (58) Field of Classification Search (71) Applicant: University of Memphis Research CPC ...... A61K 47/36; A61K 31/00; A61K 9/7007; Foundation, Memphis, TN (US) A61K 9/0024; A61 L 15/28: A61L 27/20; A61L 27/58: A61L 31/042; C08B 37/003 (72) Inventors: James Keaton Smith, Memphis, TN USPC ................................ 514/23, 40, 777; 536/20 (US); Ashley C. Parker, Memphis, TN See application file for complete search history. (US); Jessica A. Jennings, Memphis, (56) References Cited TN (US); Benjamin T. Reves, Memphis, TN (US); Warren O. U.S. PATENT DOCUMENTS Haggard, Bartlett, TN (US) 4,895,724. A * 1/1990 Cardinal .............. A61K9/0024 424,278.1 (73) Assignee: The University of Memphis Research 5,541,233 A 7/1996 Roenigk Foundation, Memphis, TN (US) 5,958,443 A 9/1999 Viegas et al. 6,699,287 B2 3/2004 Son et al. (*) Notice: Subject to any disclaimer, the term of this 6,989,157 B2 1/2006 Gillis et al. patent is extended or adjusted under 35 7,371.403 B2 5/2008 McCarthy et al. 2003, OO15825 A1 1/2003 Sugie et al. U.S.C. 154(b) by 0 days. 2003/0206958 A1 11/2003 Cattaneo et al.
    [Show full text]
  • Antibiotic Assay Medium No. 3 (Assay Broth) Is Used for Microbiological Assay of Antibiotics. M042
    HiMedia Laboratories Technical Data Antibiotic Assay Medium No. 3 (Assay Broth) is used for M042 microbiological assay of antibiotics. Antibiotic Assay Medium No. 3 (Assay Broth) is used for microbiological assay of antibiotics. Composition** Ingredients Gms / Litre Peptic digest of animal tissue (Peptone) 5.000 Beef extract 1.500 Yeast extract 1.500 Dextrose 1.000 Sodium chloride 3.500 Dipotassium phosphate 3.680 Potassium dihydrogen phosphate 1.320 Final pH ( at 25°C) 7.0±0.2 **Formula adjusted, standardized to suit performance parameters Directions Suspend 17.5 grams in 1000 ml distilled water. Heat if necessary to dissolve the medium completely. Sterilize by autoclaving at 15 lbs pressure (121°C) for 15 minutes. Advice:Recommended for the Microbiological assay of Amikacin, Bacitracin, Capreomycin, Chlortetracycline,Chloramphenicol,Cycloserine,Demeclocycline,Dihydrostreptomycin, Doxycycline, Gentamicin, Gramicidin, Kanamycin, Methacycline, Neomycin, Novobiocin, Oxytetracycline, Rolitetracycline, Streptomycin, Tetracycline, Tobramycin, Trolendomycin and Tylosin according to official methods . Principle And Interpretation Antibiotic Assay Medium is used in the performance of antibiotic assays. Grove and Randall have elucidated those antibiotic assays and media in their comprehensive treatise on antibiotic assays (1). Antibiotic Assay Medium No. 3 (Assay Broth) is used in the microbiological assay of different antibiotics in pharmaceutical and food products by the turbidimetric method. Ripperre et al reported that turbidimetric methods for determining the potency of antibiotics are inherently more accurate and more precise than agar diffusion procedures (2). Turbidimetric antibiotic assay is based on the change or inhibition of growth of a test microorganims in a liquid medium containing a uniform concentration of an antibiotic. After incubation of the test organism in the working dilutions of the antibiotics, the amount of growth is determined by measuring the light transmittance using spectrophotometer.
    [Show full text]
  • Linezolid - Tigecycline
    Linezolid - Tigecycline Paul M. Tulkens, MD, PhD Cellular and Molecular Pharmacology Louvain Drug Research Institute Catholic University of Louvain, Brussels, Belgium With the support of Wallonie-Bruxelles-International 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 1 Dong-A pharmaceuticals and tedizolid: step #1 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 2 Mode of action: • Protein synthesis inhibition: LZD binds to the 23S portion of the ribosomal 50S subunit (the centre of peptidyl transferase activity) → no initial complex 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 3 RNA interaction Karen L. Leach et al, Molecular Cell (2007) 26,393-402 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 4 Spectrum of activity No useful activity against other Gram-negative organisms because of constitutive efflux ! 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 5 Registered clinical indications Linezolid is often used off-label (endocarditis, osteomyelitis, ….) in pace of vancomycin 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 6 Linzezolid: mechanism of resistance 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 7 Can linzolid induce resistance ? 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 8 Linzolid can induce resistance… Locke et al. Antimicrob Agent Chemother 2009;53:5265-5274. 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 9 Linezolid pharmacokinetics 12-11-2015 WBI - HUP Cooperation - Bach Mai Hospital 10 Linezolid human pharmacokinetics Oral therapeutic doses (600mg linezolid q12h for 21 days) Linezolid Tedizolid MIC 90 MIC90 Muñoz et al. ECCMID 2010; P1594 Flanagan SD, et al. Pharmacotherapy 2014;34(3):240–250.
    [Show full text]
  • Environmental Risk Assessment of Antibiotics: Investigations Into Cyanobacteria Interspecies Sensitivities and Establishing Appropriate Protection Limits
    Environmental Risk Assessment of Antibiotics: Investigations into Cyanobacteria Interspecies Sensitivities and Establishing Appropriate Protection Limits Submitted by Gareth Curtis Le Page to the University of Exeter as a thesis for the degree of Doctor of Philosophy in Biological Sciences In December 2018 This thesis is available for Library use on the understanding that it is copyright material and that no quotation from the thesis may be published without proper acknowledgement I certify that all material in this thesis which is not my own work has been identified and that no material has previously been submitted and approved for the award of a degree by this or any other University. Signature: …………………………………………………………...(Gareth Le Page) 1 Abstract Antibiotics have been described as a ‘wonder drug’ that have transformed medicine since their discovery at the beginning of the 20th century and are used globally in safeguarding human and animal health. Environmental risk assessment (ERA) aims to ensure their environmental safety by setting protection limits that seek to prevent adverse effects upon populations and ecosystem function. In the case of antibiotics however, there is concern that ERA may not be fully protective of bacterial populations. This thesis examines the ERA of antibiotics and highlights that protection limits may in some cases be under-protective or over-protective for bacteria populations (including cyanobacteria), depending on the antibiotic mode of action and the species on which the protection limit is based. The first section of the thesis contains a systematic review including a meta-analysis of all publically available aquatic ecotoxicity data. The results illustrate that generally bacteria are the most sensitive taxa to antibiotics compared with eukaryotes but that interspecies variability in sensitivity among bacteria can range by up to five orders of magnitude.
    [Show full text]
  • 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.
    [Show full text]
  • Structural Basis for Potent Inhibitory Activity of the Antibiotic Tigecycline During Protein Synthesis
    Structural basis for potent inhibitory activity of the antibiotic tigecycline during protein synthesis Lasse Jennera,b,1, Agata L. Starostac,1, Daniel S. Terryd,e, Aleksandra Mikolajkac, Liudmila Filonavaa,b,f, Marat Yusupova,b, Scott C. Blanchardd, Daniel N. Wilsonc,g,2, and Gulnara Yusupovaa,b,2 aInstitut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale U964, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7104, 67404 Illkirch, France; bUniversité de Strasbourg, F-67084 Strasbourg, France; cGene Center and Department for Biochemistry, University of Munich, 81377 Munich, Germany; dDepartment of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY 10065; eTri-Institutional Training Program in Computational Biology and Medicine, New York, NY 10065; fMax Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany; and gCenter for Integrated Protein Science Munich, University of Munich, 81377 Munich, Germany Edited by Rachel Green, Johns Hopkins University, Baltimore, MD, and approved January 17, 2013 (received for review September 28, 2012) + Here we present an X-ray crystallography structure of the clinically C1054 via a coordinated Mg2 ion (Fig. 1 D and E), as reported relevant tigecycline antibiotic bound to the 70S ribosome. Our previously for tetracycline (2). In addition, ring A of tigecycline + structural and biochemical analysis indicate that the enhanced coordinates a second Mg2 ion to facilitate an indirect interaction potency of tigecycline results from a stacking interaction with with the phosphate-backbone of G966 in h31 (Fig. 1 C–E). We also nucleobase C1054 within the decoding site of the ribosome.
    [Show full text]
  • Blepharitis Last Revised in October 2015
    Menu Sign in (https://accounts.nice.org.uk/signin) Search... Blepharitis Last revised in October 2015 Changes Back to top Last revised in October 2015 October 2015 — reviewed. A literature search was conducted in October 2015 to identify evidence­ based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. No changes to clinical recommendations have been made. Previous changes Back to top September 2012 — reviewed. A literature search was conducted in September 2012 to identify evidence­based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. No changes to clinical recommendations have been made. April 2011 — minor update. Change to recommendation regarding need for additional contraception during or after a course of tetracycline ­ additional contraception is no longer required when using antibiotics that are not enzyme inducers with combined hormonal methods for durations of 3 weeks or less [FSRH, 2011 (/blepharitis#!references/­315093)]. Issued in June 2011. March 2011 — topic structure revised to ensure consistency across CKS topics — no changes to clinical recommendations have been made. September 2010 — minor update. Hydromoor® (hypromellose 0.3% preservative­free single dose eye drops) have been included. Issued in September 2010. March 2010 — minor update. Lubri­Tears® eye ointment has been discontinued. Prescription removed. Issued in March 2010. December 2007 to May 2008 — converted from CKS guidance to CKS topic structure. The evidence­ base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence. The clinical scenario structure has been reviewed.
    [Show full text]
  • Tigecycline: a Igecycline
    Molecules of the Millennium Tigecycline: A novel glycylcycline antibioticantibiotic Tetracycline antibiotics were first isolated at Lederle to occur.[5] Tigecycline is also active against organisms that Laboratories in 1945 and represented a significant display efflux-based resistance, which may be because of the advancement in the treatment of many infections. However, inability of the glycylcyclines to induce tetracycline efflux due to an increased incidence of resistance among various proteins, or because the efflux protein cannot export bacteria, the use of tetracyclines has been relegated to second tigecycline.[6] and third-line categories for most clinical indications. The two The binding site of tigecycline on the ribosome is common major mechanisms of resistance include tetracycline efflux to tetracyclines, but tigecycline binds 5-fold more strongly to and ribosomal protection, where tetracycline is prevented from the ribosome than tetracyclines and this enhanced binding is, binding to the ribosome. Research to find tetracycline probably, responsible for overcoming the ribosomal protection analogues, that circumvented these resistance mechanisms, mechanisms of tetracycline resistance.[5] The action of has led to the development of a novel group of drugs called tigecycline is bacteriostatic in nature, which is likely due to its glycylcyclines, the most promising compound being the 9-tert­ reversible interaction with the ribosome.[5] Its efficacy suggests butyl glycyclamido derivative of minocycline-tigecycline (GAR­ that traditional thinking about using bacteriostatic drugs in 936). treating serious infections needs to be revised.[7] Chemistry Antimicrobial activity The nucleus consists of four linear fused tetracyclic rings In vitro antibacterial activity of tigecycline has been and there is the addition of N, N-dimethylglycylamido (DMG) assessed against clinical isolates as a part of ongoing TEST group at C-9 position of minocycline.[1] initiative (Tigecycline Evaluation Surveillance Trial).
    [Show full text]
  • Clinical Policy: Amikacin (Arikayce) Reference Number: CP.PHAR.401 Initial Approval Criteria A
    Title: Q1 2019 PDL Changes The following list of recommended Preferred Drug List (PDL) changes were reviewed and approved by the MHS Pharmacy & Therapeutics (P&T) Committee on January 16th, 2019. Table 1: Summary PDL Changes – Effective 3/1/2019 Drug Action Notes: Galafold Add to PDL with A. Fabry Disease (must meet all): PA 1. Diagnosis of Fabry disease; (Migalastat HCl) 2. Prescribed by or in consultation with a clinical geneticist; 3. Age ≥ 18 years; 4. Presence of at least one amenable GLA variant (mutation), as confirmed by one of the following resources (a, b, or c): a. Galafold Prescribing Information brochure (package insert; Section 12, Table 2); b. Amicus Fabry GLA Gene Variant Search Tool:; c. Amicus Medical Information 5. Galafold is not prescribed concurrently with Fabrazyme; 6. Dose does not exceed 123 mg (1 capsule) every other day. Delstrigo Add to PDL with Trial of Symfi for treatment naïve members. ST (Doravirine- Lamivudine- Tenofovir DF) New Drug Specific PA Criteria: Full Medical Necessity Crieria Posted at: https://www.mhsindiana.com/providers/resources/clinical-payment-policies.html Clinical Policy: Amikacin (Arikayce) Reference Number: CP.PHAR.401 Initial Approval Criteria A. Mycobacterium Avium Complex (MAC) (must meet all): 1. Diagnosis of MAC; 2. Prescribed by or in consultation with an infectious disease specialist or pulmonologist; 3. Age ≥ 18 years; 4. Failure, as evidenced by positive sputum culture, of at least a 6-month trial of a multidrug background regimen therapy at up to maximally indicated doses (see Appendix B), unless contraindicated or clinically significant adverse effects are experienced; 5.
    [Show full text]