DOCSLIB.ORG

Gemifloxacin; a Distinctive Quinolone Or a By-Passer Jamal Wadi Al Ramahi M.D

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Gemifloxacin; a Distinctive Quinolone Or a By-Passer Jamal Wadi Al Ramahi M.D Gemifloxacin;Gemifloxacin; AA DistinctiveDistinctive QuinoloneQuinolone oror aa ByBy--passerpasser Jamal Wadi Al Ramahi M.D. http://www.infectiologie.org.tn Schema • Quinolones • Epidemiology of Resistance • Quinolones Differences in Resistant bugs • Mechanism of Quinolones Resistance and the Difference among Them. • PK/PD and MPC • Quinolones and Gemifloxacin in Clinical Syndromes http://www.infectiologie.org.tn Classification of quinolone antimicrobials First generation Third generation (b) – Nalidixic acid – Sparfloxacin – Cinoxacin – Gatifloxacin – Grepafloxacin Second generation – Norfloxacin Fourth generation (c) – Ciprofloxacin (a) – Trovafloxacin – Lomefloxacin – Moxifloxacin – Ofloxacin – Gemifloxacin – Levofloxacin a MosMostt potent agent against Pseudomonas aeruginosa. b More potent against Streptococcus pneumoniae and anaerobes, compared with earlier agents. c Most potent against S. pneumoniae and anaerobes. Vincent Andriole CID 2005:41, S114 (Suppl 2) http://www.infectiologie.org.tn Bacterial Pathogens Involved in Respiratory Infections Lower Respiratory: Streptococcus pneumoniae Haemophilus influenzae Moraxella catarrhalis Staphylococcus aureus http://www.infectiologie.org.tn Major Bacterial Pathogens Associated With AECB Haemophilus influenzae Moraxella catarrhalis Streptococcus pneumoniae ‐‐‐ 10‐15 % Staphylococcus aureus Pseudomonas aeruginosa 20% Haemophilus parainfluenzae Enterobacteriaceae Mycoplasma pneumoniae 10% Chlamydia pneumoniae Adel Obaji and Sanjay Sethi. Drugs And Aging 2001;18 5 http://www.infectiologie.org.tn Haemophilus influenzae and -lactamases (started after 1972) Before 1972, Penicillin and Ampicillin MICs of 0.25-0.5 mg/l. MIC90 changed from 1mg/dl to 32 mg/dl in -lactamases positive ones. IN a decade: Amoxicillin susceptibility dropped from 84% to 53.5% Cefuroxime susceptibility has dropped from 94 to 76% Cefixime susceptibility remains 100%, MIC90 of 0.1mg/dl Jan Verhoef, International Journal of Antimicrobial agents 21 (2003) 501‐509 6 http://www.infectiologie.org.tn Prevalence of β-Lactamase Positive Haemophilus influenzae Percentages in Red Isolate Numbers in Black 13/38 30/111 25/98 94/386 3/30 3/93 6/133 7/100 Alexander Network Website, www.alexandernetwork.com http://www.infectiologie.org.tn H. influenzae Resistance TRUST 7 (2003) NN == 12121212 Agent MIC90 (μg/mL) %S %I %R Ceftriaxone ≤0.015 100 – – Amox/clav 2 99.9 – 0.1 Cefuroxime 2 *76-99.8 0.1 0.1 Ampicillin >8 *53.5-70.7 0.1 29.2 Azithromycin 2 99.8 – – TMP-SMX >4 77.3 4.5 18.2 *Cefixime 0.01 100 0 0 TRUST = Tracking Resistance in the United States Today MIC90 = minimum inhibitory concentration required to inhibit 90% of isolates; S = susceptible; I = intermediate; R = resistant. Daniel F. Sahm PhD Clinical Cornerstone Volume 2003 Suppl 3 • 2003 Blondeau, Missaghi; Expert Opinion on Pharmacotherapy, May 2004, Vol. 5, No. 5, 1117‐1152. http://www.infectiologie.org.tn •*Jan Verhoef, International Journal of Antimicrobial agents 21 (2003) 501‐509 Moraxella catarrhalis Resistance TRUST 7 (2003) N = 817 Agent MIC90 (μg/mL) Ceftriaxone 1 Amoxicillin/clavulanate 0.25 Cefuroxime 2 Ampicillin 8 Azithromycin 0.03 TMP-SMX 0.25 TRUST = Tracking Resistance in the United States Today MIC90 = minimum inhibitory concentration required to inhibit 90% of isolates Daniel F. Sahm PhD Clinical Cornerstone Volume 2003 Suppl 3 • 2003 Blondeau, Missaghi: Expert Opinion on Pharmacotherapy, May 2004, Vol. 5, No. 5, 1117‐ http://www.infectiologie.org.tn 1152 Selected Quinolones MIC90 Selected Quinolones Against Isolates of H. MIC 90 Against Isolates influenzae of M. catarrhalis g/ml) g/ml) μ μ ( ( 90 90 MIC MIC Gemifloxacin (N=8523) Gemifloxacin ( N=874) Ciprofloxacin (N= 8523) Ciprofloxacin ( N= 874) Levofloxacin (N = 5651) Levofloxacin (N = 421) Gatifloxacin (N= 2764) Gatifloxacin (N= 250) Moxifloxacin (N= 2764) Moxifloxacin (N= 250) Alexander Project 1998‐2000 http://www.infectiologie.org.tn S. Pneumoniae;Resistant toPenicillin Isolates Resistant and Intermediate to Pen icill 19 Intermediat10 e to12 Pen14 icill16 in %18 2 4 6 8 0 1 98 6‐ 87 1 98 7‐ 88 Trust us N =33,499 1 98 8‐ 89 1 98 9‐ 90 1 99 1‐ 92 1 99 4‐ 95 1 99 6‐ 97 1 99 7‐ 98 1 99 8‐ 99 *Clinical Infectious Diseases 2009; 48. e23 – *Clinical Clinical Infectious Dis 1 99 9‐ 00 2 00 0‐ 01 12.7 21.5 % eases 2004;39:S142–50 19 9 * * 9‐ % 00 20 04 * ‐ * 05 Y Y 17.9 14.6 e e N a a r r = 1647 % % e33 http://www.infectiologie.org.tn S. pneumoniae: Prevalence of Penicillin-Resistant Strains Turkey 24% 1% Lebanon Kuwait 59% 9% 66% 0% UAE 71% 6% Tunisia Tunisia Egypt Jordan 32% 18% 94% 0% 47% 0% Saudi Arabia 38% 13% Penicillin-intermediate (MIC 0.12 – 1 µg/ml) Penicillin-resistant (MIC 2µg/ml) Clin Microbiol Infect. 2004;10 Suppl 3:111, Abs No P507. http://www.infectiologie.org.tn Worldwide Rates of macrolide and penicillin resistance in Streptococcus pneumoniae from PROTEKT US PPenicillinenicillin resistance (Pen R) is defined as MIC ≥2 mg/L Erythromycin resistance (Ery R) is defined as MIC ≥ 1mg/L Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin, for 2002–2003. Antimicrobial‐Resistant Pneumococci •CID 2005:41 (Suppl 4) •S229 http://www.infectiologie.org.tn TRUST US MDR, Streptococcus pneumoniae 1 6 1 13.5 4 12.2 1 12.2 ) 2 11 % 1 ( 0 8 es 6.2 at 6 ol 4 s I 2 0 1997‐1998 1998‐1999 1999‐2000 2000‐2001 Resistant to 3 antimicrobial classes, (most commonly penicillin, trimethoprim-sulfamethoxazole, and macrolides) Dr. Adolf W. Karchmer, Harvard Medical School, Beth Israel Deaconess Medical Center Clinical Infectious Diseases 2004; 39:S142–50; by the Infectious Diseases Society of America http://www.infectiologie.org.tn Selected Quinolones MIC90 Against Isolates of Streptococcus pneumoniae g/ml) g/ml) μ μ ( ( 90 90 MIC MIC Numbers below Antimicrobials denotes tested isolates Alexander Project 1998‐2000 http://www.infectiologie.org.tn Activity of Various Antibiotics Against Ciprofloxacin- Susceptible Pneumococcal strains with Different Susceptibility Patterns to Penicillin Antibiotic Penicillin- Penicillin- Penicillin- susceptible intermediate resistant MIC90 (µg/ml) (n=64) (n=68) (n=75) Gemifloxacin 0.03 0.06 0.06 Ciprofloxacin 2 2 4 Levofloxacin 2 2 2 Clarithromycin 0.03/0.06 0.03/32.0 2.0/>128.0 Amoxicillin 0.06 1 4 Cefuroxime 0.25 2 16 Azithromycin 0.5 >128 >128 Adopted from Todd A. Davies et al, Antimicrobial Agents and Chemotherapy, February 2000, p. 304‐310, Vol. 44, No. 2 http://www.infectiologie.org.tn Activity of Various Quinolones Against 28 Ciprofloxacin-Resistant Pneumococcal Strains Fluoroquinolone Range of MIC MIC 50 MIC90 (µg/ml) (µg/ml) (µg/ml) Gemifloxacin 0.03-1 0.25 0.5 Ciprofloxacin 8-32 16 >32 Levofloxacin 4 ->32 16 >32 Sparfloxacin 0.25-32 8 16 Grepafolxacin 0.5-16 4 8 Trovafloxacin 0.25 1 4 From; Davies et al. Antimicro Agents Chemother. 2000;44:304‐310 http://www.infectiologie.org.tn Comparative activities of fluoroquinolones against levofloxacin-susceptible and levofloxacin-resistant S. pneumoniae clinical isolates AAC, Nov. 2000, p. 2962–2968 http://www.infectiologie.org.tn Fluoroquinolone Resistance! TRUST, and PROTEKT US Surveillance Data Among Canadian isolates of S. pneumoniae CipCiprofloxacinrofloxacin Levofloxacin Levofloxacin Gatifloxacin Moxifloxacin GemiGemifloxacinfloxacin 1.8%, 0.7% 1.8%, 0.7% 0.6% 0.3% 0.1 Ciprofloxacin‐R, Levofloxacin‐S, S. pneumoniae may have first‐step mutations reducing fluoroquinolone susceptibility. Dr. Adolf W. Karchmer, Clinical Infectious Diseases 2004; 39:S142–50 M. R. Jacobs et al, Journal of Antimicrobial Chemotherapy; 2003, 52, 229-246 http://www.infectiologie.org.tn Patterns & Mechanisms of Resistance, Respiratory Anti-Infective Agents • β‐Lactamases like Penicillins and Cephalosporins in Haemophilus influenzae and Moraxella catarrhalis • Protein Binding Proteins, (PBP) like in Streptococcus pneumoniae • Efflux and Methylation like in MKLSB in Streptococcus pneumoniae http://www.infectiologie.org.tn Patterns & Mechanisms of Resistance, Respiratory Anti-Infective Agents: Quinolones Resistance in S. pneumoniae . Enzyme Modification like in Quinolones, mutations in the genes encoding the target enzymes . parC, par E, encodes the A subunit of DNA topoisomerase IV. gyrA, encodes the A subunit of DNA gyrase (topoisomerase II). Combined parC and gyrA . First‐step mutations in parC occur fairly frequently(～1/107 ) . Once the S. pneumoniae has a first‐step parC mutation, the acquisition of increased fluoroquinolone resistance is dependent on a second‐step mutation in gyrA. •Also mutations in parE and gyrB have been reported, but to a lesser extent. •Resistance can also be mediated by active efflux, although its role in contributing to resistance to the newer FQ is unclear http://www.infectiologie.org.tn The Evolution of Resistance to Quinolones MIC‐3M MIC‐2M 4 –8 X MIC‐1M 4 –8 X MIC‐WT 4 –8 X Each step in the evolution represents a spontaneous mutation that diminishes quinolone susceptibility 4‐8 fold. Thus the MIC of the quinolone used to select mutants from the wild type (WT) is 4‐8 fold diminished for successive first‐step (1M), second‐step (2M), and third‐step (3M) mutants. Resistance among the Quinolones x CID 2001:32 (Suppl 1) http://www.infectiologie.org.tn The Evolution of Resistance to Quinolones Cross-resistance Among the Quinolones MIC‐3M Drug A MIC‐2M 256 MIC‐3M MIC‐1M 64 MIC‐2M 64 4.0 16 2g/ml MIC‐WT MIC‐1M 1.0 1.0 Drug B MIC‐WT 1.0 0.25 If both quinolones achieve a concentration of 2 µg/mL at the site of infection, the 8‐fold rule would predict that quinolone B would provide the most effective therapy and be less likely to select for resistance because achievable concentrations exceed the MIC for the wild‐type and first‐step mutants. Resistance among the Quinolones x CID 2001:32 (Suppl 1) http://www.infectiologie.org.tn The Evolution of Resistance to Quinolones Dichotomous resistance among the quinolones MIC‐3M Drug A MIC‐2M MIC‐1M MIC‐2M MIC‐3M MIC‐WT MIC‐1M Drug B A as selected by quinolone A is shown (left), with each successive mutation causing diminished susceptibility to quinolone A.
Load more

Recommended publications
  • Dead Bugs Don't Mutate: Susceptibility Issues in the Emergence of Bacterial Resistance
    PERSPECTIVES Dead Bugs Don’t Mutate: Susceptibility Issues in the Emergence of Bacterial Resistance Charles W. Stratton*1 The global emergence of antibacterial resistance among and macrolides (the antibacterial agents used most frequently common and atypical respiratory pathogens in the last decade for pneumococcal infections) have become prevalent through- necessitates the strategic application of antibacterial agents. out the world. Indeed, rates of S. pneumoniae resistance to The use of bactericidal rather than bacteriostatic agents as penicillin now exceed 40% in many regions, and a high pro- first-line therapy is recommended because the eradication of portion of these strains are also resistant to macrolides. More- microorganisms serves to curtail, although not avoid, the devel- over, the trend is growing rapidly. Whereas 10.4% of all S. opment of bacterial resistance. Bactericidal activity is achieved with specific classes of antimicrobial agents as well as by com- pneumoniae isolates were resistant to penicillin and 16.5% bination therapy. Newer classes of antibacterial agents, such resistant to macrolides in 1996, these proportions rose to as the fluoroquinolones and certain members of the macrolide/ 14.1% and 21.9%, respectively, in 1997 (9). A more recent lincosamine/streptogramin class have increased bactericidal susceptibility study conducted in 2000–2001 showed that activity compared with traditional agents. More recently, the 51.5% of all S. pneumoniae isolates were resistant to penicillin ketolides (novel, semisynthetic, erythromycin-A derivatives) and 30.0% to macrolides (10). have demonstrated potent bactericidal activity against key res- The urgent need to curtail proliferation of antibacterial- piratory pathogens, including Streptococcus pneumoniae, Hae- resistant bacteria has refocused attention on the proper use of mophilus influenzae, Chlamydia pneumoniae, and Moraxella antibacterial agents.
    [Show full text]
  • Fluoroquinolones in the Management of Acute Lower Respiratory Infection
    Thorax 2000;55:83–85 83 Occasional review Thorax: first published as 10.1136/thorax.55.1.83 on 1 January 2000. Downloaded from The next generation: fluoroquinolones in the management of acute lower respiratory infection in adults Peter J Moss, Roger G Finch Lower respiratory tract infections (LRTI) are ing for up to 40% of isolates in Spain19 and 33% the leading infectious cause of death in most in the United States.20 In England and Wales developed countries; community acquired the prevalence is lower; in the first quarter of pneumonia (CAP) and acute exacerbations of 1999 6.5% of blood/cerebrospinal fluid isolates chronic bronchitis (AECB) are responsible for were reported to the Public Health Laboratory the bulk of the adult morbidity. Until recently Service as showing intermediate sensitivity or quinolone antibiotics were not recommended resistance (D Livermore, personal communi- for the routine treatment of these infections.1–3 cation). Pneumococcal resistance to penicillin Neither ciprofloxacin nor ofloxacin have ad- is not specifically linked to quinolone resist- equate activity against Streptococcus pneumoniae ance and, in general, penicillin resistant in vitro, and life threatening invasive pneumo- pneumococci are sensitive to the newer coccal disease has been reported in patients fluoroquinolones.11 21 treated for respiratory tract infections with Resistance to ciprofloxacin develops rela- these drugs.4–6 The development of new fluoro- tively easily in both S pneumoniae and H influ- quinolone agents with increased activity enzae, requiring only a single mutation in the against Gram positive organisms, combined parC gene.22 23 Other quinolones such as with concerns about increasing microbial sparfloxacin and clinafloxacin require two resistance to â-lactam agents, has prompted a mutations in the parC and gyrA genes.11 23 re-evaluation of the use of quinolones in LRTI.
    [Show full text]
  • Gatifloxacin for Treating Enteric Fever Submission to the 18Th Expert
    Gatifloxacin for enteric fever Gatifloxacin for treating enteric fever Submission to the 18th Expert Committee on the Selection and Use of Essential Medicines 1 Gatifloxacin for enteric fever Table of contents Gatifloxacin for treating enteric fever....................................................................................... 1 Submission to the 18th Expert Committee on the Selection and Use of Essential Medicines . 1 1 Summary statement of the proposal for inclusion........................................................... 4 1.1 Rationale for this submission................................................................................... 4 2 Focal point in WHO submitting the application ............................................................... 4 3 Organizations consulted and supporting the application ................................................ 5 4 International Nonproprietary Name (INN, generic name) of the medicine..................... 5 5 Formulation proposed for inclusion ................................................................................. 5 5.1 Prospective formulation improvements.................................................................. 6 6 International availability................................................................................................... 6 6.1 Patent status ............................................................................................................ 6 6.2 Production...............................................................................................................
    [Show full text]
  • Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set
    MTC eHealth DSI [eHDSI v2.2.2-OR] eHealth DSI – Master Value Set Catalogue Responsible : eHDSI Solution Provider PublishDate : Wed Nov 08 16:16:10 CET 2017 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 1 of 490 MTC Table of Contents epSOSActiveIngredient 4 epSOSAdministrativeGender 148 epSOSAdverseEventType 149 epSOSAllergenNoDrugs 150 epSOSBloodGroup 155 epSOSBloodPressure 156 epSOSCodeNoMedication 157 epSOSCodeProb 158 epSOSConfidentiality 159 epSOSCountry 160 epSOSDisplayLabel 167 epSOSDocumentCode 170 epSOSDoseForm 171 epSOSHealthcareProfessionalRoles 184 epSOSIllnessesandDisorders 186 epSOSLanguage 448 epSOSMedicalDevices 458 epSOSNullFavor 461 epSOSPackage 462 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 2 of 490 MTC epSOSPersonalRelationship 464 epSOSPregnancyInformation 466 epSOSProcedures 467 epSOSReactionAllergy 470 epSOSResolutionOutcome 472 epSOSRoleClass 473 epSOSRouteofAdministration 474 epSOSSections 477 epSOSSeverity 478 epSOSSocialHistory 479 epSOSStatusCode 480 epSOSSubstitutionCode 481 epSOSTelecomAddress 482 epSOSTimingEvent 483 epSOSUnits 484 epSOSUnknownInformation 487 epSOSVaccine 488 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 3 of 490 MTC epSOSActiveIngredient epSOSActiveIngredient Value Set ID 1.3.6.1.4.1.12559.11.10.1.3.1.42.24 TRANSLATIONS Code System ID Code System Version Concept Code Description (FSN) 2.16.840.1.113883.6.73 2017-01 A ALIMENTARY TRACT AND METABOLISM 2.16.840.1.113883.6.73 2017-01
    [Show full text]
  • Grepafloxacin Susceptibility Against Penicillin Resistant
    Invasive Streptococcus pneumoniae in Canada 2011: Study of Antimicrobial Resistance and Serotypes Alyssa Golden Department of Clinical Microbiology, Health Sciences Centre, and Faculty of Medicine, University of Manitoba Correspondence: Alyssa Golden c/o Dr. G.G. Zhanel Department of Clinical Microbiology Health Sciences Centre MS673 - 820 Sherbrook Street Winnipeg, Manitoba R3A 1R9 CANADA Phone: (204) 787-4902 Fax: (204) 787-4699 email: [email protected] Introduction Infections caused by Streptococcus pneumoniae are of critical concern, as respiratory and invasive isolates are commonly resistant to many drug classes, including penicillins. They are also frequently multi-drug resistant (simultaneous resistance to e3 structurally unrelated classes). A conjugate vaccine Prevnar® (PCV-7: 4, 6B, 9V, 14, 18C, 19F, 23F) has been used in Canada to great effect, reducing the number of invasive S. pneumoniae infections observed in children. However, S. pneumoniae serotypes that are not related to the vaccine are rising in Canada. For this reason, a new vaccine, PCV- 13 (PCV-7 + 1, 3, 5, 6A, 7F and 19A), was recently released in Canada to combat the rise of non-vaccine serotypes, especially 19A. This vaccination allows for broader coverage of S. pneumoniae serotypes. The purpose of my summer research project was to study invasive S. pneumoniae in Canada (2011) and assess their serotypes and antimicrobial resistance. Hypotheses PCV-13 will provide greater coverage of S. pneumoniae isolates than PCV-7. With the continued use of these conjugated vaccines, a greater proportion of non- vaccine serotypes will circulate in Canada. These serotypes will also be antimicrobial resistant. Methods Isolates tested were obtained from all geographic regions of Canada during the 2011 year.
    [Show full text]
  • WHO Report on Surveillance of Antibiotic Consumption: 2016-2018 Early Implementation ISBN 978-92-4-151488-0 © World Health Organization 2018 Some Rights Reserved
    WHO Report on Surveillance of Antibiotic Consumption 2016-2018 Early implementation WHO Report on Surveillance of Antibiotic Consumption 2016 - 2018 Early implementation WHO report on surveillance of antibiotic consumption: 2016-2018 early implementation ISBN 978-92-4-151488-0 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution- NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons. org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non- commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. WHO report on surveillance of antibiotic consumption: 2016-2018 early implementation. Geneva: World Health Organization; 2018. Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • The Role of the Immune Response in the Effectiveness of Antibiotic Treatment for Antibiotic Susceptible and Antibiotic Resistant Bacteria
    The role of the immune response in the effectiveness of antibiotic treatment for antibiotic susceptible and antibiotic resistant bacteria. by Olachi Nnediogo Anuforom A thesis submitted to the University of Birmingham for the degree of Doctor of Philosophy. Institute of Microbiology and Infection, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham. May, 2015. University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. Abstract The increasing spread of antimicrobial resistant bacteria and the decline in the development of novel antibiotics have incited exploration of other avenues for antimicrobial therapy. One option is the use of antibiotics that enhance beneficial aspects of the host’s defences to infection. This study explores the influence of antibiotics on the innate immune response to bacteria. The aims were to investigate antibiotic effects on bacterial viability, innate immune cells (neutrophils and macrophages) in response to bacteria and interactions between bacteria and the host. Five exemplar antibiotics; ciprofloxacin, tetracycline, ceftriaxone, azithromycin and streptomycin at maximum serum concentration (Cmax) and minimum inhibitory concentrations (MIC) were tested. These five antibiotics were chosen as they are commonly used to treat infections and represent different classes of drug.
    [Show full text]
  • The Grohe Method and Quinolone Antibiotics
    The Grohe method and quinolone antibiotics Antibiotics are medicines that are used to treat bacterial for modern fluoroquinolones. The Grohe process and the infections. They contain active ingredients belonging to var- synthesis of ciprofloxacin sparked Bayer AG’s extensive ious substance classes, with modern fluoroquinolones one research on fluoroquinolones and the global competition of the most important and an indispensable part of both that produced additional potent antibiotics. human and veterinary medicine. It is largely thanks to Klaus Grohe – the “father of Bayer quinolones” – that this entirely In chemical terms, the antibiotics referred to for simplicity synthetic class of antibiotics now plays such a vital role for as quinolones are derived from 1,4-dihydro-4-oxo-3-quin- medical practitioners. From 1965 to 1997, Grohe worked oline carboxylic acid (1) substituted in position 1. as a chemist, carrying out basic research at Bayer AG’s Fluoroquinolones possess a fluorine atom in position 6. In main research laboratory (WHL) in Leverkusen. During this addition, ciprofloxacin (2) has a cyclopropyl group in posi- period, in 1975, he developed the Grohe process – a new tion 1 and also a piperazine group in position 7 (Figure A). multi-stage synthesis method for quinolones. It was this This substituent pattern plays a key role in its excellent achievement that first enabled him to synthesize active an- antibacterial efficacy. tibacterial substances such as ciprofloxacin – the prototype O 5 O 4 3 6 COOH F COOH 7 2 N N N 8 1 H N R (1) (2) Figure A: Basic structure of quinolone (1) (R = various substituents) and ciprofloxacin (2) Quinolones owe their antibacterial efficacy to their inhibition This unique mode of action also makes fluoroquinolones of essential bacterial enzymes – DNA gyrase (topoisomer- highly effective against a large number of pathogenic ase II) and topoisomerase IV.
    [Show full text]
  • Customs Tariff - Schedule
    CUSTOMS TARIFF - SCHEDULE 99 - i Chapter 99 SPECIAL CLASSIFICATION PROVISIONS - COMMERCIAL Notes. 1. The provisions of this Chapter are not subject to the rule of specificity in General Interpretative Rule 3 (a). 2. Goods which may be classified under the provisions of Chapter 99, if also eligible for classification under the provisions of Chapter 98, shall be classified in Chapter 98. 3. Goods may be classified under a tariff item in this Chapter and be entitled to the Most-Favoured-Nation Tariff or a preferential tariff rate of customs duty under this Chapter that applies to those goods according to the tariff treatment applicable to their country of origin only after classification under a tariff item in Chapters 1 to 97 has been determined and the conditions of any Chapter 99 provision and any applicable regulations or orders in relation thereto have been met. 4. The words and expressions used in this Chapter have the same meaning as in Chapters 1 to 97. Issued January 1, 2019 99 - 1 CUSTOMS TARIFF - SCHEDULE Tariff Unit of MFN Applicable SS Description of Goods Item Meas. Tariff Preferential Tariffs 9901.00.00 Articles and materials for use in the manufacture or repair of the Free CCCT, LDCT, GPT, UST, following to be employed in commercial fishing or the commercial MT, MUST, CIAT, CT, harvesting of marine plants: CRT, IT, NT, SLT, PT, COLT, JT, PAT, HNT, Artificial bait; KRT, CEUT, UAT, CPTPT: Free Carapace measures; Cordage, fishing lines (including marlines), rope and twine, of a circumference not exceeding 38 mm; Devices for keeping nets open; Fish hooks; Fishing nets and netting; Jiggers; Line floats; Lobster traps; Lures; Marker buoys of any material excluding wood; Net floats; Scallop drag nets; Spat collectors and collector holders; Swivels.
    [Show full text]
  • European Surveillance of Healthcare-Associated Infections in Intensive Care Units
    TECHNICAL DOCUMENT European surveillance of healthcare-associated infections in intensive care units HAI-Net ICU protocol Protocol version 1.02 www.ecdc.europa.eu ECDC TECHNICAL DOCUMENT European surveillance of healthcare- associated infections in intensive care units HAI-Net ICU protocol, version 1.02 This technical document of the European Centre for Disease Prevention and Control (ECDC) was coordinated by Carl Suetens. In accordance with the Staff Regulations for Officials and Conditions of Employment of Other Servants of the European Union and the ECDC Independence Policy, ECDC staff members shall not, in the performance of their duties, deal with a matter in which, directly or indirectly, they have any personal interest such as to impair their independence. This is version 1.02 of the HAI-Net ICU protocol. Differences between versions 1.01 (December 2010) and 1.02 are purely editorial. Suggested citation: European Centre for Disease Prevention and Control. European surveillance of healthcare- associated infections in intensive care units – HAI-Net ICU protocol, version 1.02. Stockholm: ECDC; 2015. Stockholm, March 2015 ISBN 978-92-9193-627-4 doi 10.2900/371526 Catalogue number TQ-04-15-186-EN-N © European Centre for Disease Prevention and Control, 2015 Reproduction is authorised, provided the source is acknowledged. TECHNICAL DOCUMENT HAI-Net ICU protocol, version 1.02 Table of contents Abbreviations ...............................................................................................................................................
    [Show full text]
  • Alphabetical Listing of ATC Drugs & Codes
    Alphabetical Listing of ATC drugs & codes. Introduction This file is an alphabetical listing of ATC codes as supplied to us in November 1999. It is supplied free as a service to those who care about good medicine use by mSupply support. To get an overview of the ATC system, use the “ATC categories.pdf” document also alvailable from www.msupply.org.nz Thanks to the WHO collaborating centre for Drug Statistics & Methodology, Norway, for supplying the raw data. I have intentionally supplied these files as PDFs so that they are not quite so easily manipulated and redistributed. I am told there is no copyright on the files, but it still seems polite to ask before using other people’s work, so please contact <[email protected]> for permission before asking us for text files. mSupply support also distributes mSupply software for inventory control, which has an inbuilt system for reporting on medicine usage using the ATC system You can download a full working version from www.msupply.org.nz Craig Drown, mSupply Support <[email protected]> April 2000 A (2-benzhydryloxyethyl)diethyl-methylammonium iodide A03AB16 0.3 g O 2-(4-chlorphenoxy)-ethanol D01AE06 4-dimethylaminophenol V03AB27 Abciximab B01AC13 25 mg P Absorbable gelatin sponge B02BC01 Acadesine C01EB13 Acamprosate V03AA03 2 g O Acarbose A10BF01 0.3 g O Acebutolol C07AB04 0.4 g O,P Acebutolol and thiazides C07BB04 Aceclidine S01EB08 Aceclidine, combinations S01EB58 Aceclofenac M01AB16 0.2 g O Acefylline piperazine R03DA09 Acemetacin M01AB11 Acenocoumarol B01AA07 5 mg O Acepromazine N05AA04
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]