DOCSLIB.ORG

Antibiotics and Translation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Antibiotics and Translation Dissertation zur Erlangung des Doktorgrades der Fakultät fur Chemie und Pharmazie der Ludwig-Maximilians-Universität München Antibiotics and translation Overcoming emerging bacterial resistance to old and new antimicrobials Agata Lucyna Starosta aus Rzeszow, Polen 2011 Erklärung Diese Dissertation wurde im Sinne von § 13 Abs. 3 bzw. 4 der Promotionsordnung vom 29. Januar 1998 (in der Fassung der Sechsten Änderungssatzung von 16. August 2010) von Herrn Prof. Dr. Roland Beckmann betreut. Ehrenwörtliche Versicherung Diese Dissertation wurde selbstständig, ohne unerlaubte Hilfe erarbeitet. München, am 24.11.2011 Agata Lucyna Starosta Dissertation eingereicht am 24.11.2011 1. Gutachter: Herr Prof. Dr. Roland Beckmann 2. Gutachter: Herr Prof. Dr. Klaus Förstemann Mündliche Prüfung am 31.01.2012 2 Agata L. Starosta List of contents List of contents Acknowledgements .................................................................................................................................. 5 List of original publications .................................................................................................................... 6 Contribution report ................................................................................................................................. 8 Abbreviations ........................................................................................................................................ 10 Summary ................................................................................................................................................ 11 1 Introduction ........................................................................................................................................ 12 1.1 Traditional antibiotics .................................................................................................................. 13 1.1.1 Introduction to antibiotics .................................................................................................... 13 1.1.2 Targets for antibiotic action ................................................................................................. 14 1.1.2.1 Inhibition of cell wall synthesis ..................................................................................... 14 1.1.2.2 Inhibition of DNA replication ........................................................................................ 16 1.1.2.3 Inhibition of RNA synthesis ........................................................................................... 16 1.1.2.4 Inhibition of protein synthesis ....................................................................................... 16 1.1.3 Protein synthesis ................................................................................................................... 17 1.1.3.1 Inhibitors of the small ribosomal subunit .................................................................. 22 1.1.3.2 Inhibitors of the large ribosomal subunit ................................................................... 23 1.1.3.2.1 Inhibitors of the peptidyl-transferase center ...................................................... 23 1.1.3.2.2 Inhibitors of the progressing nascent polypeptide chain .................................... 24 1.1.3.2.3 Inhibitors of the GTPase-associated center (GAC) ............................................ 24 1.1.4 Mechanism of cell death induced by bactericidal antibiotics .............................................. 25 1.2 Antibiotics used in these studies .................................................................................................. 27 1.2.1 Hygromycin A ....................................................................................................................... 27 1.2.2 Macrolides ............................................................................................................................ 29 1.2.3 Thiopeptides ......................................................................................................................... 31 1.2.4 Orthosomycins ...................................................................................................................... 34 1.2.5 Fusidic acid .......................................................................................................................... 35 1.3 Alternative antimicrobials targeting virulence ............................................................................ 36 1.3.1 Definition of virulence .......................................................................................................... 36 1.3.2 Colonization ......................................................................................................................... 36 1.3.3 Biofilm .................................................................................................................................. 36 1.3.4 Quorum sensing .................................................................................................................... 37 3 Agata L. Starosta List of contents 1.3.5 Motility ................................................................................................................................. 37 1.3.6 Secretion systems .................................................................................................................. 37 1.3.7 Elongation factor P .............................................................................................................. 38 2 Objectives of these studies .................................................................................................................. 41 3 Cumulative thesis ............................................................................................................................... 43 3.1 Hygromycin A ............................................................................................................................. 43 3.1.1 Paper 1 .................................................................................................................................. 43 3.1.2 Paper 2 .................................................................................................................................. 43 3.2 Macrolides ................................................................................................................................... 47 3.2.1 Paper 3 .................................................................................................................................. 47 3.2.2 Paper 4 .................................................................................................................................. 47 3.3 Thiopeptides ................................................................................................................................ 50 3.3.1 Paper 5 .................................................................................................................................. 50 3.3.2 Paper 6 .................................................................................................................................. 50 3.4 Orthosomycins ............................................................................................................................. 52 3.5 Fusidic acid.................................................................................................................................. 53 3.5.1 Paper 7 .................................................................................................................................. 53 3.6 Elongation factor P ...................................................................................................................... 54 3.6.1 Paper 8 .................................................................................................................................. 54 4 Conclusions ........................................................................................................................................ 58 5 References .......................................................................................................................................... 59 4 Agata L. Starosta Ackowledgements Acknowledgements This would not be possible without the support of many people that I had a pleasure of meeting during my PhD studies. First of all I would like to thank Dr. Daniel Wilson for giving me an opportunity to work in his group in the Gene Center . I am grateful for the trust and support I received from him during all those years. I appreciate each and every advice, discussion, criticism and praise I ever received from him. That was a lesson I will never forget. I would like to thank Prof. Roland Beckmann for all the expertise, good advices and support as well as for providing us with a great scientific environment without which this work could not happen. I am grateful to all our collaborators for having fruitful time collecting all the data: to Prof. B. Cooperman for great work on thiopeptides; Prof. A. Bogdanov for macrolide story; Prof. K. Reynolds for hygromycin A studies; Prof. C. Spahn for first and hopefuly not the last Nature paper; Prof. G. Dinos for hosting me in Greece and support in experiments; and last but not least, to Prof. J. Remme for great work on EF-P. I would also like to thank people, whom I had a pleasure to have conducted the experiments with: Aleksandra Mikolajka, Alexandra Dönhöfer, Viktorija Karpenko, Gemma Atkinson and Vidya Dhote. Special thanks to Lauri
Load more

Recommended publications
  • Micromonospora: an Important Microbe for Biomedicine and Potentially for Biocontrol and Biofuels
    ARTICLE IN PRESS Soil Biology & Biochemistry xxx (2009) 1e7 Contents lists available at ScienceDirect Soil Biology & Biochemistry journal homepage: www.elsevier.com/locate/soilbio Review Micromonospora: An important microbe for biomedicine and potentially for biocontrol and biofuels Ann M. Hirsch a,b,*, Maria Valdés c a Department of Molecular, Cell and Developmental Biology, University of California, 405 Hilgard Avenue, Los Angeles, CA 90095-1606, USA b Molecular Biology Institute, University of California, 405 Hilgard Avenue, Los Angeles, CA 90095-1606, USA c Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, I. P. N., Plan de Ayala y Carpio, 11340, Mexico article info abstract Article history: Micromonospora species have long been recognized as important sources of antibiotics and also for their Received 2 September 2009 unusual spores. However, their involvement in plant-microbe associations is poorly understood although Received in revised form several studies demonstrate that Micromonospora species function in biocontrol, plant growth promo- 17 November 2009 tion, root ecology, and in the breakdown of plant cell wall material. Our knowledge of this generally Accepted 20 November 2009 understudied group of actinomycetes has been greatly advanced by the increasing number of reports of Available online xxx their associations with plants, by the deployment of DNA cloning and molecular systematics techniques, and by the recent application of whole genome sequencing. Efforts to annotate the genomes of several Keywords: Actinomycetes Micromonospora species are underway. This information will greatly augment our knowledge of these Biocontrol versatile microorganisms. Hydrolytic enzymes Ó 2009 Elsevier Ltd. All rights reserved. Secondary metabolites 1. Introduction species also produce anti-tumor antibiotics (lomaiviticins A and B, tetrocarcin A, LL-E33288 complex, etc.) and anthracycline antibi- Although the genus Micromonospora has long been recognized otics.
    [Show full text]
  • Natural Thiopeptides As a Privileged Scaffold for Drug Discovery and Therapeutic Development
    – MEDICINAL Medicinal Chemistry Research (2019) 28:1063 1098 CHEMISTRY https://doi.org/10.1007/s00044-019-02361-1 RESEARCH REVIEW ARTICLE Natural thiopeptides as a privileged scaffold for drug discovery and therapeutic development 1 1 1 1 1 Xiaoqi Shen ● Muhammad Mustafa ● Yanyang Chen ● Yingying Cao ● Jiangtao Gao Received: 6 November 2018 / Accepted: 16 May 2019 / Published online: 29 May 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Since the start of the 21st century, antibiotic drug discovery and development from natural products has experienced a certain renaissance. Currently, basic scientific research in chemistry and biology of natural products has finally borne fruit for natural product-derived antibiotics drug discovery. A batch of new antibiotic scaffolds were approved for commercial use, including oxazolidinones (linezolid, 2000), lipopeptides (daptomycin, 2003), and mutilins (retapamulin, 2007). Here, we reviewed the thiazolyl peptides (thiopeptides), an ever-expanding family of antibiotics produced by Gram-positive bacteria that have attracted the interest of many research groups thanks to their novel chemical structures and outstanding biological profiles. All members of this family of natural products share their central azole substituted nitrogen-containing six-membered ring and are fi 1234567890();,: 1234567890();,: classi ed into different series. Most of the thiopeptides show nanomolar potencies for a variety of Gram-positive bacterial strains, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and penicillin-resistant Streptococcus pneumonia (PRSP). They also show other interesting properties such as antiplasmodial and anticancer activities. The chemistry and biology of thiopeptides has gathered the attention of many research groups, who have carried out many efforts towards the study of their structure, biological function, and biosynthetic origin.
    [Show full text]
  • FDA-Approved Drugs with Potent in Vitro Antiviral Activity Against Severe Acute Respiratory Syndrome Coronavirus 2
    pharmaceuticals Article FDA-Approved Drugs with Potent In Vitro Antiviral Activity against Severe Acute Respiratory Syndrome Coronavirus 2 1, , 1, 2 1 Ahmed Mostafa * y , Ahmed Kandeil y , Yaseen A. M. M. Elshaier , Omnia Kutkat , Yassmin Moatasim 1, Adel A. Rashad 3 , Mahmoud Shehata 1 , Mokhtar R. Gomaa 1, Noura Mahrous 1, Sara H. Mahmoud 1, Mohamed GabAllah 1, Hisham Abbas 4 , Ahmed El Taweel 1, Ahmed E. Kayed 1, Mina Nabil Kamel 1, Mohamed El Sayes 1, Dina B. Mahmoud 5 , Rabeh El-Shesheny 1 , Ghazi Kayali 6,7,* and Mohamed A. Ali 1,* 1 Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; [email protected] (A.K.); [email protected] (O.K.); [email protected] (Y.M.); [email protected] (M.S.); [email protected] (M.R.G.); [email protected] (N.M.); [email protected] (S.H.M.); [email protected] (M.G.); [email protected] (A.E.T.); [email protected] (A.E.K.); [email protected] (M.N.K.); [email protected] (M.E.S.); [email protected] (R.E.-S.) 2 Organic & Medicinal Chemistry Department, Faculty of Pharmacy, University of Sadat City, Menoufia 32897, Egypt; [email protected] 3 Department of Biochemistry & Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USA; [email protected] 4 Department of Microbiology and Immunology, Zagazig University, Zagazig 44519, Egypt; [email protected] 5 Pharmaceutics Department, National Organization for Drug Control and Research, Giza 12654, Egypt; [email protected] 6 Department of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas, Houston, TX 77030, USA 7 Human Link, Baabda 1109, Lebanon * Correspondence: [email protected] (A.M.); [email protected] (G.K.); [email protected] (M.A.A.) Contributed equally to this work.
    [Show full text]
  • Identification of Antibiotics for Use in Selection of the Chytrid Fungi Batrachochytrium
    bioRxiv preprint doi: https://doi.org/10.1101/2020.07.02.184721; this version posted July 2, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Identification of antibiotics for use in selection of the chytrid fungi Batrachochytrium 2 dendrobatidis and Batrachochytrium salamandrivorans 3 4 5 Kristyn A. Robinson, Mallory Dunn, Shane P. Hussey, Lillian K. Fritz-Laylin* 6 7 8 The University of Massachusetts Amherst, Department of Biology, Amherst, MA 01003 9 *Correspondence: [email protected] 10 11 12 ABSTRACT 13 14 Global amphibian populations are being decimated by chytridiomycosis, a deadly skin infection 15 caused by the fungal pathogens Batrachochytrium dendrobatidis (Bd) and B. salamandrivorans 16 (Bsal). Although ongoing efforts are attempting to limit the spread of these infections, targeted 17 treatments are necessary to manage the disease. Currently, no tools for genetic manipulation 18 are available to identify and test specific drug targets in these fungi. To facilitate the 19 development of genetic tools in Bd and Bsal, we have tested five commonly used antibiotics 20 with available resistance genes: Hygromycin, Blasticidin, Puromycin, Zeocin, and Neomycin. 21 We have identified effective concentrations of each for selection in both liquid culture and on 22 solid media. These concentrations are within the range of concentrations used for selecting 23 genetically modified cells from a variety of other eukaryotic species. 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.07.02.184721; this version posted July 2, 2020.
    [Show full text]
  • Microbiological Profile of Telithromycin, the First Ketolide Antimicrobial
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE Paperprovided by 48Elsevier Disc - Publisher Connector Microbiological profile of telithromycin, the first ketolide antimicrobial D. Felmingham GR Micro Ltd, London, UK ABSTRACT Telithromycin, the first of the ketolide antimicrobials, has been specifically designed to provide potent activity against common and atypical/intracellular or cell-associated respiratory pathogens, including those that are resistant to b-lactams and/or macrolide±lincosamide±streptograminB (MLSB) antimicrobials. Against Gram- positive cocci, telithromycin possesses more potent activity in vitro and in vivo than the macrolides clarithromycin and azithromycin. It retains its activity against erm-(MLSB)ormef-mediated macrolide-resistant Streptococcus pneumoniae and Streptococcus pyogenes and against Staphylococcus aureus resistant to macrolides through inducible MLSB mechanisms. Telithromycin also possesses high activity against the Gram-negative pathogens Haemophilus influenzae and Moraxella catarrhalis, regardless of b-lactamase production. In vitro, it shows similar activity to azithromycin against H. influenzae, while in vivo its activity against H. influenzae is higher than that of azithromycin. Telithromycin's spectrum of activity also extends to the atypical, intracellular and cell-associated pathogens Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae. In vitro, telithromycin does not induce MLSB resistance and it shows low potential to select for resistance or cross-resistance to other antimicrobials. These characteristics indicate that telithromycin will have an important clinical role in the Ahed empirical treatment of community-acquired respiratory tract infections. Bhed Clin Microbiol Infect 2001: 7 (Supplement 3): 2±10 Ched Dhed Ref marker Fig marker these agents. Resistance to penicillin, particularly among S.
    [Show full text]
  • Tetracycline and Sulfonamide Antibiotics in Soils: Presence, Fate and Environmental Risks
    processes Review Tetracycline and Sulfonamide Antibiotics in Soils: Presence, Fate and Environmental Risks Manuel Conde-Cid 1, Avelino Núñez-Delgado 2 , María José Fernández-Sanjurjo 2 , Esperanza Álvarez-Rodríguez 2, David Fernández-Calviño 1,* and Manuel Arias-Estévez 1 1 Soil Science and Agricultural Chemistry, Faculty Sciences, University Vigo, 32004 Ourense, Spain; [email protected] (M.C.-C.); [email protected] (M.A.-E.) 2 Department Soil Science and Agricultural Chemistry, Engineering Polytechnic School, University Santiago de Compostela, 27002 Lugo, Spain; [email protected] (A.N.-D.); [email protected] (M.J.F.-S.); [email protected] (E.Á.-R.) * Correspondence: [email protected] Received: 30 October 2020; Accepted: 13 November 2020; Published: 17 November 2020 Abstract: Veterinary antibiotics are widely used worldwide to treat and prevent infectious diseases, as well as (in countries where allowed) to promote growth and improve feeding efficiency of food-producing animals in livestock activities. Among the different antibiotic classes, tetracyclines and sulfonamides are two of the most used for veterinary proposals. Due to the fact that these compounds are poorly absorbed in the gut of animals, a significant proportion (up to ~90%) of them are excreted unchanged, thus reaching the environment mainly through the application of manures and slurries as fertilizers in agricultural fields. Once in the soil, antibiotics are subjected to a series of physicochemical and biological processes, which depend both on the antibiotic nature and soil characteristics. Adsorption/desorption to soil particles and degradation are the main processes that will affect the persistence, bioavailability, and environmental fate of these pollutants, thus determining their potential impacts and risks on human and ecological health.
    [Show full text]
  • Double Stage Activity in Aminoglycoside Antibiotics
    VOL.53 NO. 10, OCT.2000 THE JOURNAL OF ANTIBIOTICS pp.1168 - 1174 Double Stage Activity in Aminoglycoside Antibiotics Kunimoto Hotta, Atsuko Sunada, Yoko Ikeda1" and Shinichi Kondo1" National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan f Institute of Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan (Received for publication July 5, 2000) Fourteen different aminoglycoside antibiotics (AGs) were challenged with aminoglycoside acetyltransferases (AACs) of actinomycete origin in order to examine their 'double stage activity' that is arbitrarily defined as antibiotic activity retainable after enzymatic modification. In kanamycin (KM)-group AGs tested [KM, dibekacin (DKB), amikacin and arbekacin (ABK)], ABKretained activity after acetylations by AAC(3), AAC(2') and AAC(6'). DKBalso retained a weak activity after acetylation by AAC(2'). In gentamicin (GM)-group AGs tested [GM, micronomicin, sisomicin (SISO), netilmicin (NTL) and isepamicin], GM, SISO and NTL retained activites after acetylation by AAC(2'). In neomycin (NM)-group AGs tested [ribostamycin, NM,paromomycin], NMretained activity after acetylation by AAC(6') and AAC(2'). None of astromicin (ASTM)-group AGs tested (ASTMand istamycin B) retained activity after acetylation by AAC(2') and AAC(6'). The activities of acetylated ABK derivatives by AAC(3) and AAC(2') were distinctively high, compared to the others. Streptomyces lividans TK21containing the cloned aac genes were markedly sensitive to AGs that retained activities after acetylation, indicating the substantial effect of 'double stage activity'. Aminoglycoside (AG) antibiotics are generally resistant bacteria was developed by introducing (S)-4- inactivated by acetylation, phosphorylation and adenylyl- amino-2-hydroxybutyryl (AHB) side chain at 1-NH2 of ation due to AG acetyltransferases (AACs), AG KM.
    [Show full text]
  • Sexually Transmitted Diseases Treatment Options
    Sexually transmitted disease (STD) treatment options PREFERRED & ALTERNATIVE OPTIONS Many clinical partners are operating in a limited capacity during the COVID-19 pandemic. Below are preferred (in clinic or other location where injections can be given) and alternative (when only oral medicines are available 1) treatments for STDs. Syndrome Preferred Treatments Alternative Treatments Follow-up Male urethritis syndrome Ceftriaxone 250mg intramuscular (IM) x 1 PLUS Men who have sex with men (MSM) and transgender women2: Patients should be counseled to azithromycin 1g PO x 1 Cefixime 800 mg PO x 1 PLUS doxycycline 100 mg PO BID x 7 days be tested for STDs once clinical Presumptively treating: care is resumed in the local If azithromycin is not available: doxycycline 100 Men who have sex with women only: gonorrhea clinics. Clients who have been mg PO BID for 7 days (except in pregnancy3) Cefixime 800mg PO x 1 PLUS azithromycin 1g PO x 1 referred for oral treatment If cephalosporin allergy5 is reported, gentamicin If cefixime is unavailable, substitute cefpodoxime 400mg PO q12h should return for 240mg IM x 1 PLUS azithromycin 2g PO x 1 x 2 for cefixime in above regimens4 comprehensive testing and screening and linked to services If oral cephalosporin not available or history of cephalosporin at that time. allergy5: azithromycin 2g PO x 1 If azithromycin is not available: doxycycline 100 mg PO BID for 7 days (except in pregnancy3) Patients should be advised to abstain from sex for 7 days Treatment typically guided by examination and For presumptive therapy when examination and laboratory following completion of Vaginal discharge syndrome treatment.
    [Show full text]
  • Antibiotic Use Guidelines for Companion Animal Practice (2Nd Edition) Iii
    ii Antibiotic Use Guidelines for Companion Animal Practice (2nd edition) iii Antibiotic Use Guidelines for Companion Animal Practice, 2nd edition Publisher: Companion Animal Group, Danish Veterinary Association, Peter Bangs Vej 30, 2000 Frederiksberg Authors of the guidelines: Lisbeth Rem Jessen (University of Copenhagen) Peter Damborg (University of Copenhagen) Anette Spohr (Evidensia Faxe Animal Hospital) Sandra Goericke-Pesch (University of Veterinary Medicine, Hannover) Rebecca Langhorn (University of Copenhagen) Geoffrey Houser (University of Copenhagen) Jakob Willesen (University of Copenhagen) Mette Schjærff (University of Copenhagen) Thomas Eriksen (University of Copenhagen) Tina Møller Sørensen (University of Copenhagen) Vibeke Frøkjær Jensen (DTU-VET) Flemming Obling (Greve) Luca Guardabassi (University of Copenhagen) Reproduction of extracts from these guidelines is only permitted in accordance with the agreement between the Ministry of Education and Copy-Dan. Danish copyright law restricts all other use without written permission of the publisher. Exception is granted for short excerpts for review purposes. iv Foreword The first edition of the Antibiotic Use Guidelines for Companion Animal Practice was published in autumn of 2012. The aim of the guidelines was to prevent increased antibiotic resistance. A questionnaire circulated to Danish veterinarians in 2015 (Jessen et al., DVT 10, 2016) indicated that the guidelines were well received, and particularly that active users had followed the recommendations. Despite a positive reception and the results of this survey, the actual quantity of antibiotics used is probably a better indicator of the effect of the first guidelines. Chapter two of these updated guidelines therefore details the pattern of developments in antibiotic use, as reported in DANMAP 2016 (www.danmap.org).
    [Show full text]
  • Yeast Glycosylation Mutants Are Sensitive to Aminoglycosides
    Proc. Natl. Acad. Sci. USA Vol. 92, pp. 1287-1291, February 1995 Cell Biology Yeast glycosylation mutants are sensitive to aminoglycosides NETA DEAN Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, NY 11794-5215 Communicated by William J. Lennarz, State University of New York Stony Brook, NY, September 30, 1994 (received for review July 13, 1994) ABSTRACT Aminoglycosides are a therapeutically im- tants and their genetic analyses will be described elsewhere.) portant class of antibiotics that inhibit bacterial protein syn- Surprisingly, two mutants were isolated that are defective in very thesis and a number of viral and eukaryotic functions by early steps of glycosylation that take place in or before the blocking RNA-protein interactions. Vanadate-resistant Sac- endoplasmic reticulum (ER). The isolation of mutants with de- charomyces cerevisiae mutants with defects in Golgi-specific fects in early steps in the glycosylation pathway suggested that glycosylation processes exhibit growth sensitivity to hygro- hygromycin B sensitivity is not due to defects in Golgi-specific mycin B, an aminoglycoside [Ballou, L., Hitzeman, R. A., functions. To understand how a molecule that binds to RNA Lewis, M. S. & Ballou, C. E. (1991) Proc. Nall. Acad. Sci. USA impinges upon glycosylation within the secretory pathway, I ex- 88,3209-3212]. Here, evidence is presented that glycosylation amined the effect of aminoglycosides on the growth character- is, in and of itself, a key factor mediating aminoglycoside istics ofyeast glycosylation mutants. In the present work, I report sensitivity in yeast. Examination ofmutants with a wide range the results of experiments that demonstrate that aminoglycoside of glycosylation abnormalities reveals that all are sensitive to hypersensitivity is due, at least in part, to defects in glycosylation.
    [Show full text]
  • Antibiotic Resistance and Typing of the Methicillin-Resistant Staphylococcus Aureus Clones in Kuwait Hospitals, 2016–2017 Samar S
    Boswihi et al. BMC Microbiology (2020) 20:314 https://doi.org/10.1186/s12866-020-02009-w RESEARCH ARTICLE Open Access Antibiotic resistance and typing of the methicillin-resistant Staphylococcus aureus clones in Kuwait hospitals, 2016–2017 Samar S. Boswihi, Edet E. Udo* and Wadha AlFouzan Abstract Background: Methicillin-resistant Staphylococcus aureus (MRSA) belong to diverse genetic backgrounds that differ in antibiotic resistance. Knowledge of the local clonal composition of MRSA strains is important for patients’ management and for designing effective control and eradication methods. The aim of this study was to compare the antibiotic resistance patterns and genotypic characteristics of MRSA isolates obtained in public hospitals in Kuwait in 2016 and 2017 for changes in their resistance patterns and clonal composition. Methods: A total of 4726 MRSA isolates obtained in 2016–2017 from clinical specimens in Kuwait public hospitals were characterized using antibiogram, SCCmec typing, spa typing and DNA microarray. Results: The isolates expressed resistance to fusidic acid (52.9%), kanamycin (41.6%), gentamicin (32.5%) and erythromycin (36.2%). The prevalence of high-level mupirocin resistance decreased from 3.7% in 2016 to 2.4% in 2017, while the proportion of resistance to other antibiotics remained relatively stable. A total of 382 spa types were detected with eight spa types, t688 (N = 547), t304 (N = 428), t860 (N = 394), t127 (N = 306), t044 (N = 230), t311 (N = 243), t223 (N = 184) and t002 (N = 181) constituting 53.1% of the MRSA isolates in 2016–2017. Of the 3004 MRSA isolates obtained in 2016 (N = 1327) and 2017 (N = 1677) selected for DNA microarray analysis, 26 clonal complexes (CCs) were identified.
    [Show full text]
  • Topical Antibiotics for Impetigo: a Review of the Clinical Effectiveness and Guidelines
    CADTH RAPID RESPONSE REPORT: SUMMARY WITH CRITICAL APPRAISAL Topical Antibiotics for Impetigo: A Review of the Clinical Effectiveness and Guidelines Service Line: Rapid Response Service Version: 1.0 Publication Date: February 21, 2017 Report Length: 23 Pages Authors: Rob Edge, Charlene Argáez Cite As: Topical antibiotics for impetigo: a review of the clinical effectiveness and guidelines. Ottawa: CADTH; 2017 Feb. (CADTH rapid response report: summary with critical appraisal). ISSN: 1922-8147 (online) Disclaimer: The information in this document is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services. While care has been taken to ensure that the information prepared by CADTH in this document is accurate, complete, and up-to-date as at the applicable date the material was first published by CADTH, CADTH does not make any guarantees to that effect. CADTH does not guarantee and is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing this document.
    [Show full text]