DOCSLIB.ORG

Focus on Oritavancin and New Ketolides and Quinolones

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Focus on Oritavancin and New Ketolides and Quinolones Annals of Medicine, 2014; Early Online: 1–18 © 2014 Informa UK, Ltd. ISSN 0785-3890 print/ISSN 1365-2060 online DOI: 10.3109/07853890.2014.935470 REVIEW ARTICLE Renaissance of antibiotics against difficult infections: Focus on oritavancin and new ketolides and quinolones Françoise Van Bambeke Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium Lipoglycopeptide, ketolide, and quinolone antibiotics are currently Key messages in clinical development, with specific advantages over available molecules within their respective classes. The lipoglycopeptide • New antibiotics in the classes of lipoglycopeptides, ketolides, oritavancin is bactericidal against MRSA, vancomycin-resistant and quinolones are in the late stages of clinical development, enterococci, and multiresistant Streptococcus pneumoniae, and mainly for the treatment of acute bacterial infections of skin proved effective and safe for the treatment of acute bacterial and skin structures and/or of the respiratory tract. skin and skin structure infection (ABSSSI) upon administration • These molecules mainly address the problem of resistance of a single 1200 mg dose (two completed phase III trials). The in Gram-positive bacteria; their dose has been rationally ketolide solithromycin (two phase III studies recruiting for established based on pharmacokinetic/pharmacodynamic community-acquired pneumonia) shows a profile of activity concepts in order to optimize the chance of therapeutic similar to that of telithromycin, but in vitro data suggest a lower success while at the same time avoiding the risk of selection risk of hepatotoxicity, visual disturbance, and aggravation of of resistance. myasthenia gravis due to reduced affinity for nicotinic receptors. • They all presented a satisfactory safety profile in clinical trials, Among quinolones, finafloxacin and delafloxacin share the which should be further documented upon administration unique property of an improved activity in acidic environments to larger patient populations. For personal use only. (found in many infection sites). Finafloxacin (phase II completed; activity profile similar to that of ciprofloxacin) is evaluated for complicated urinary tract and Helicobacter pylori infections. The other quinolones (directed towards Gram-positive or the ‘Innovative Medicine Initiative’ (http://www.imi.europa. pathogens) show improved activity on MRSA and multiresistant eu/) from the European Union. At this stage, a series of mole- S. pneumoniae compared to current molecules. They are in cules are in the late stages of clinical development (2,3), many of clinical evaluation for ABSSSI (avarofloxacin (phase II completed), them being essentially new molecules in existing classes, which nemonoxacin and delafloxacin (ongoing phase III)), respiratory display, however, better properties in terms of intrinsic activity, tract infections (zabofloxacin and nemonoxacin (ongoing reduced susceptibility to resistance mechanisms, and improved phase III)), or gonorrhea (delafloxacin). pharmacokinetic or safety profiles. This paper will focus on Key words: Avarofloxacin, delafloxacin, EDP-322, finafloxacin, those families that count molecules in phase III of clinical de- oritavancin, nemonoxacin, solithromycin, zabofloxacin velopment, namely lipoglycopeptides (oritavancin), ketolides (solithromycin), and quinolones (nemonoxacin; delafloxacin). It will explain the prevailing rationale in the development of these antibiotics and examine their current pharmacological Ann Med Downloaded from informahealthcare.com by Centre de Biostatistique et Documentation Medicale on 07/24/14 Since the beginning of this century, only 14 new antibiotics have been approved for use in human medicine (Table I). Still- profile based on available clinical data. unmet needs include mainly the so-called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneu- moniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Lipoglycopeptides: focus on oritavancin Enterobacter spp.), which remain difficult to treat because they Lipoglycopeptides are a subclass within the glycopeptide anti- have accumulated resistance mechanisms to most of the antibi- biotics, which all possess a lipophilic tail attached to the amino otics available so far. Global initiatives have been raised to try sugar substituting the cyclic heptapeptide core. Teicoplanin, stimulating research and investment in the field of antibiotic introduced in the clinics in Europe in 1988, is a natural represen- development, like the ‘10 x ‘20 Initiative’ (1) from the Infectious tative of this subclass. More recently, semi-synthetic derivatives Disease Society of America (http://www.idsociety.org/10x20/) were produced, among which telavancin has been on the market Correspondence: Françoise Van Bambeke, Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, Avenue Mounier 73, B1.73.05, 1200 Brussels, Belgium. E-mail: [email protected] (Received 27 April 2014; accepted 11 June 2014) 2 F. Van Bambeke Table I. Antibiotics approved by the FDA and the EMA since 2000. Date of approval Molecule Antibiotic class FDA EMA Linezolid oxazolidinone April 2000 (decentralized procedure; ∼ 2001) cefditoren pivoxil b-lactam August 2001 (available in specific countries) Ertapenem b-lactam November 2001 April 2004 Gemifloxacin fluoroquinolone April 2003 Not available Daptomycin lipopeptide September 2003 January 2006 Telithromycin ketolide April 2004 July 2007 Tigecycline glycylcycline 2005 April 2006 Retapamulin pleuromutilin April 2007 May 2007 Doripenem b-lactam October 2007 July 2008 Telavancin lipoglycopeptide September 2009 September 2009 Ceftaroline b-lactam November 2010 August 2012 Fidaxomicin fluoroquinolone May 2011 December 2011 Dalbavancin lipoglycopeptide May 2014 Not yet approved Tedizolid oxazolidinone June 2014 Not yet approved since 2009, dalbavancin has been approved by the FDA in May resistance is associated with higher risk of therapeutic failure 2014, and oritavancin is in the late phase of development. (13). The prevalence of these strains is controversial because of The rationale for the development of these drugs was to cope the difficulty to detect them correctly. with vancomycin resistance, which spread in enterococci mainly In this context, early work from Eli Lilly demonstrated that in the USA at the end of the 1980s. chloroeremomycin, which differs from vancomycin by the ste- Vancomycin’s mode of action consists in an inhibition of reochemistry of the sugar substituting the ring 4 amino-acid the late stages of peptidoglycan synthesis (4, and references and by the presence of an additional L-4-epi-vancosamine, cited herein). The cyclic heptapeptide core of the molecule displayed enhanced activity, including against vancomycin- establishes non-covalent interactions with the D-alanyl-D- resistant strains, possibly due to dimerization facilitating a alanine termini of the pentapeptide moiety of lipid II. The co-operative binding to the target (14). In parallel, deriva- resulting steric hindrance around these termini prevents the tives of vancomycin substituted by an alkyl side chain on their access of enzymes that are needed for cross-linking peptido- vancosamine sugar showed also enhanced activity on resis- glycan precursors via transglycosylation and transpeptidation tant strains (15). Combining these two features, oritavancin reactions. As a result, vancomycin is slowly bactericidal, with (initially LY333328; Eli Lilly, Indianapolis, IN, USA) was first a spectrum of activity limited to Gram-positive bacteria, be- described in 1996 (16) as the chlorobiphenylmethyl side chain cause its large size prevents it from crossing the outer mem- analog of chloroeremomycin (Figure 1). As compared to van- brane of Gram-negative bacteria. Two resistance mechanisms comycin, this antibiotic shows higher intrinsic activity (lower For personal use only. have emerged over the years (4, and references cited herein). MICs) (Table II) against susceptible Gram-positive organisms, The first one, mainly found in enterococci, consists in the -ac as well as against staphylococci displaying the VISA phenotype quisition of genes allowing for the synthesis of alternative cell or even against VRE (vancomycin-resisitant enterococci) or wall precursors ending in D-alanyl-D-lactate or in D-alanyl- VRSA (vancomycin-resistant S. aureus) (17,18). This can be D-serine, which show a reduced affinity for vancomycin. At explained by a dual mode of action (see for review 19), which the present time, the prevalence of this resistance mechanism combines an inhibition of transpeptidase and transglycosylase in enterococci collected from infection sites culminates in the activity with an alteration of membrane integrity (20) caused USA, reaching 14% (E. faecalis) to 88% (E. faecium) (5) versus by the anchoring of the lipophilic side chain in the bilayer (21). about 10% in Europe but with huge variations among coun- Importantly also, this novel mode of action confers to orita- tries (6), 15% in Latin America (7), 2% (E. faecalis) to 18% (E. vancin a rapid and intense bactericidal character, as well as a faecium) in Canada (8), and, quite surprisingly, low levels of maintained activity on slow-growing bacteria or on biofilms resistance ( 5%) in Asia (9). Worryingly, a few cases of gene (22). Among the other remarkable features of this molecule, transfer to multidrug-resistant MRSA (methicillin-resistant
Load more

Recommended publications
  • Effects of Probenecid and Cimetidine on the Pharmacokinetics of Nemonoxacin Open Access to Scientific and Medical Research Doi
    Journal name: Drug Design, Development and Therapy Article Designation: Original Research Year: 2016 Volume: 10 Drug Design, Development and Therapy Dovepress Running head verso: Zhang et al Running head recto: Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin open access to scientific and medical research doi: http://dx.doi.org/10.2147/DDDT.S95934 Open Access Full Text Article ORIGINAL RESEARCH Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in healthy Chinese volunteers Yi-fan Zhang1 Purpose: To investigate the effects of probenecid and cimetidine on the pharmacokinetics of Xiao-jian Dai1 nemonoxacin in humans. Yong Yang1 Methods: Two independent, open-label, randomized, crossover studies were conducted in Xiao-yan Chen1 24 (12 per study) healthy Chinese volunteers. In Study 1, each volunteer received a single oral Ting Wang2 dose of 500 mg of nemonoxacin alone or with 1.5 g of probenecid divided into three doses within Yun-biao Tang3 25 hours. In Study 2, each volunteer received a single oral dose of 500 mg of nemonoxacin alone or with multiple doses of cimetidine (400 mg thrice daily for 7 days). The plasma and urine Cheng-yuan Tsai4 nemonoxacin concentrations were determined using validated liquid chromatography–tandem Li-wen Chang4 mass spectrometry methods. Yu-ting Chang4 Results: Coadministration of nemonoxacin with probenecid reduced the renal clearance (CL ) 1 r Da-fang Zhong of nemonoxacin by 22.6%, and increased the area under the plasma concentration–time curve 1State Key Laboratory of Drug from time 0 to infinity (AUC0–∞) by 26.2%. Coadministration of nemonoxacin with cimetidine Research, Shanghai Institute of reduced the CL of nemonoxacin by 13.3% and increased AUC by 9.4%.
    [Show full text]
  • Paper I and II)
    Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1335 Constraints on up-regulation of drug efflux in the evolution of ciprofloxacin resistance LISA PRASKI ALZRIGAT ACTA UNIVERSITATIS UPSALIENSIS ISSN 1651-6206 ISBN 978-91-554-9923-5 UPPSALA urn:nbn:se:uu:diva-320580 2017 Dissertation presented at Uppsala University to be publicly examined in B22, BMC, Husargatan 3, Uppsala, Friday, 9 June 2017 at 09:00 for the degree of Doctor of Philosophy (Faculty of Medicine). The examination will be conducted in English. Faculty examiner: Professor Fernando Baquero (Departamento de Microbiología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain). Abstract Praski Alzrigat, L. 2017. Constraints on up-regulation of drug efflux in the evolution of ciprofloxacin resistance. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1335. 48 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-554-9923-5. The crucial role of antibiotics in modern medicine, in curing infections and enabling advanced medical procedures, is being threatened by the increasing frequency of resistant bacteria. Better understanding of the forces selecting resistance mutations could help develop strategies to optimize the use of antibiotics and slow the spread of resistance. Resistance to ciprofloxacin, a clinically important antibiotic, almost always involves target mutations in DNA gyrase and Topoisomerase IV. Because ciprofloxacin is a substrate of the AcrAB-TolC efflux pump, mutations causing pump up-regulation are also common. Studying the role of efflux pump-regulatory mutations in the development of ciprofloxacin resistance, we found a strong bias against gene-inactivating mutations in marR and acrR in clinical isolates.
    [Show full text]
  • NEW ANTIBACTERIAL DRUGS Drug Pipeline for Gram-Positive Bacteria
    NEW ANTIBACTERIAL DRUGS Drug pipeline for Gram-positive bacteria Françoise Van Bambeke, PharmD, PhD Paul M. Tulkens, MD, PhD Pharmacologie cellulaire et moléculaire Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium http://www.facm.ucl.ac.be Based largely on presentations given at the 24th and 25th European Congress of Clinical Microbiology and Infectious Diseases and the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy 22/05/2015 Gause Institute for New Antibiotics: the anti-Gram positive pipeline 1 Disclosures Research grants for work on investigational compounds discussed in this presentation from • Cempra Pharmaceuticals • Cerexa • GSK • Melinta therapeutics • The Medicine Company • MerLion Pharmaceuticals • Theravance • Trius 22/05/2015 Gause Institute for New Antibiotics: the anti-Gram positive pipeline 2 Belgium 22/05/2015 Gause Institute for New Antibiotics: the anti-Gram positive pipeline 3 Belgium 10 millions inhabitants … 10 Nobel prizes (10/850) • Peace - Institute of International Law, Ghent (1904) - Auguste Beernaert (1909) - Henri Lafontaine (1913) - Father Dominique Pire (1958) • Literature - Maurice Maeterlinck, Ghent (1911) • Medicine - Jules Bordet, Brussels (1919) - Corneille Heymans, Ghent (1938) - Christian de Duve, Louvain (1974) - Albert Claude, Brussels (1974) • Chemistry - Ilya Prigogyne, Brussels (1977) - Physics - François Englert, Brussels (2013) 22/05/2015 Gause Institute for New Antibiotics: the anti-Gram positive pipeline 4 The Catholic University of Louvain in brief (1 of 4) • originally founded in 1425 in the city of Louvain (in French and English; known as Leuven in Flemish) 22/05/2015 Gause Institute for New Antibiotics: the anti-Gram positive pipeline 5 The Catholic University of Louvain in brief (2 of 4) • It was one of the major University of the so-called "Low Countries" in the 1500 – 1800 period, with famous scholars and discoverers (Vesalius for anatomy, Erasmus for philosophy, …).
    [Show full text]
  • Antimicrobial Pipeline and Drug Development
    Antimicrobial Pipeline and Drug Development Alasdair MacGowan Bristol Centre for Antimicrobial Research & Evaluation North Bristol NHS Trust & University of Bristol BRISTOL UK Topics: - Background - The present situation - Drugs recently approved and in late development - Future issues - Conclusions Background: Not enough new antibacterials or companies active in the therapeutic area FDA Approvals of new antibacterials 1983-2015 (Boucher et al, 2013, updated FDA website) Years Antibacterial approved 1983-1987 16 1988-1992 14 1993-1997 10 1998-2002 6 2003-2007 5 2008-2012 2 2013-2015 6 (ceftazidime+avibactam; dalbavancin; oritavancin; tedizolid; telavancin; Ceftolozane+tazobactam) Active corporate antibacterial programmes: 1940 - onwards (Kinch et al, 2014) Year Active programme 1940 1 1950 4 1960 9 1970 22 1980 26 1990 29 2000 31 2010 12 2013 9 Why are there so few drugs and companies? Few novel modes of action Increasing regulatory demands (manufacture, safety, efficacy) Trial designs (superiority vs non-inferiority) Infection control interventions Highly saturated market High generic competition Conservative prescribers Short course therapy Cost containment Antimicrobial resistance - Means less attractive commercially than other therapeutic areas Drug development takes a long time (Paul et al, 2010; Rex, 2015) Discovery 72 leads 3 Pre-clinical 36 candidates 10 years Clinical trials Phase 1 18 6 Phase 2 6 Phase 3 3 7 years Regulator review/approval 1-2 Start now and you may have approval by 2025-2030 Determinants impacting
    [Show full text]
  • WO 2018/048944 Al 15 March 2018 (15.03.2018) W !P O PCT
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/048944 Al 15 March 2018 (15.03.2018) W !P O PCT (51) International Patent Classification: A61K38/1 7 (2006.01) C07K 14/575 (2006.01) A61P 3/00 (2006.01) A61K 38/22 (2006.01) (21) International Application Number: PCT/US2017/050334 (22) International Filing Date: 06 September 2017 (06.09.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/383,957 06 September 2016 (06.09.2016) US (71) Applicant: LA JOLLA PHARMCEUTICAL COMPA¬ NY [US/US]; 10182 Telesis Court, 6th Floor, San Diego, CA 92121 (US). (72) Inventors: TD3MARSH, George; 45 Tintern Lane, Porto- la Valley, CA 94028 (US). CHAWLA, Lakhmir; 10586 Abalone Landing Ter, San Diego, CA 92 130 (US). = (74) Agent: HALSTEAD, David, P. et al; Foley Hoag LLP, = 155 Seaport Boulevard, Boston, MA 02210-2600 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, = AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, = CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, = DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, = HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, = KR, KW,KZ, LA, LC, LK, LR, LS, LU, LY,MA, MD, ME, = MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, = OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, = SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, ≡ TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
    [Show full text]
  • Summary Report on Antimicrobials Dispensed in Public Hospitals
    Summary Report on Antimicrobials Dispensed in Public Hospitals Year 2014 - 2016 Infection Control Branch Centre for Health Protection Department of Health October 2019 (Version as at 08 October 2019) Summary Report on Antimicrobial Dispensed CONTENTS in Public Hospitals (2014 - 2016) Contents Executive Summary i 1 Introduction 1 2 Background 1 2.1 Healthcare system of Hong Kong ......................... 2 3 Data Sources and Methodology 2 3.1 Data sources .................................... 2 3.2 Methodology ................................... 3 3.3 Antimicrobial names ............................... 4 4 Results 5 4.1 Overall annual dispensed quantities and percentage changes in all HA services . 5 4.1.1 Five most dispensed antimicrobial groups in all HA services . 5 4.1.2 Ten most dispensed antimicrobials in all HA services . 6 4.2 Overall annual dispensed quantities and percentage changes in HA non-inpatient service ....................................... 8 4.2.1 Five most dispensed antimicrobial groups in HA non-inpatient service . 10 4.2.2 Ten most dispensed antimicrobials in HA non-inpatient service . 10 4.2.3 Antimicrobial dispensed in HA non-inpatient service, stratified by service type ................................ 11 4.3 Overall annual dispensed quantities and percentage changes in HA inpatient service ....................................... 12 4.3.1 Five most dispensed antimicrobial groups in HA inpatient service . 13 4.3.2 Ten most dispensed antimicrobials in HA inpatient service . 14 4.3.3 Ten most dispensed antimicrobials in HA inpatient service, stratified by specialty ................................. 15 4.4 Overall annual dispensed quantities and percentage change of locally-important broad-spectrum antimicrobials in all HA services . 16 4.4.1 Locally-important broad-spectrum antimicrobial dispensed in HA inpatient service, stratified by specialty .
    [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]
  • Visão De Futuro Para Produção De Antibióticos: Tendências De Pesquisa, Desenvolvimento E Inovação
    UNIVERSIDADE FEDERAL DO RIO DE JANEIRO CRISTINA D’URSO DE SOUZA MENDES SANTOS VISÃO DE FUTURO PARA PRODUÇÃO DE ANTIBIÓTICOS: TENDÊNCIAS DE PESQUISA, DESENVOLVIMENTO E INOVAÇÃO Rio de Janeiro EQ/UFRJ 2014 CRISTINA D ’U RSO DE SOUZA MENDES SANTOS VISÃO DE FUTURO PARA A PRODUÇÃO DE ANTIBIÓTICOS: TENDÊNCIAS DE PESQUISA, DESENVOLVIMENTO E INOVAÇÃO Tese de Doutorado apresentada ao Programa de Pós-Graduação em Tecnologia de Processos Químicos e Bioquímicos, Escola de Química, Universidade Federal do Rio de Janeiro, como requisito parcial à obtenção do título de Doutor em Ciências, D.Sc. Orientadora: Profa. Adelaide Maria de Souza Antunes, D.Sc. Rio de Janeiro 2014 Santos, Cristina d’Urso de Souza Mendes. Visão de futuro para produção de antibióticos: tendências de pesquisa, desenvolvimento e inovação / Cristina d’Urso de Souza Mendes Santos. - Rio de Janeiro, 2014. 216 f.: il.; 29,7 cm. Tese (Doutorado em Ciências) – Universidade Federal do Rio de Janeiro, Escola de Química, Programa de Pós-Graduação em Tecnologia de Processos Químicos e Bioquímicos, Rio de Janeiro, 2014. Orientadora: Adelaide Maria de Souza Antunes. 1. Antibióticos. 2. P&D na Indústria Farmacêutica. 3. Prospecção Tecnológica. 4. Patentes. I. Antunes, Adelaide Maria de Souza. II. Universidade Federal do Rio de Janeiro. Escola de Química. III. Visão de futuro para a produção de antibióticos: tendências de pesquisa, desenvolvimento e inovação. iv v Dedico esta tese à minha mãe querida e amada, que está no céu comemorando esta vitória, que é mais dela do que minha. Dedico também à minha filhinha Malu que sem entender foi a minha maior motivação para concluir esta tese.
    [Show full text]
  • In-Vitro Activity of Nemonoxacin Against Streptococcus Pneumoniae and Haemophilus Influenzae
    EV0440 IN-VITRO ACTIVITY OF NEMONOXACIN AGAINST STREPTOCOCCUS PNEUMONIAE AND HAEMOPHILUS INFLUENZAE 1* 1 1 1 2 2 Kozlov R.S. , Dekhnich A.V. , Sukhorukova M.V. , Edelstein M.V. , Chernavin A.V. , Samsonov M.Y. 1 Institute of Antimicrobial Chemotherapy, Smolensk, RU; 2 “R-Pharm”, Moscow, RU * E-mail: [email protected] 27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), 22 - 25 April 2017, Vienna, Austria Table 1. Results of susceptibility testing of S.pneumoniae (n=200) Table 2. MIC distributions for S.pneumoniae (n=200) Background S(%) I(%) R(%) % of strains tested with MIC, mg/l Antimicrobial MIC MIC Antimicrobial 50 90 EUCAST CLSI EUCAST CLSI EUCAST CLSI 0.004 0.008 0.015 0.03 0.06 0.125 0.25 0.5 1 2 4 8 16 32 64 128 256 Amoxicillin 0.03 2 NA 95.5 NA 1.5 NA 3.0 Amoxicillin 61.0 4.5 4.0 4.5 3.0 12.5 6.0 1.5 3.0 Nemonoxacin is a new non-fluorinated quinolone Azithromycin 27.0 34.0 0.5 2.0 0.5 3.5 3.5 2.0 0.5 0.5 1.0 25.0 Azithromycin 0.06 128 63.5 64.0 0.5 3.5 36.0 32.5 Cefixime 7.5 38.5 16.0 7.5 3.5 4.0 4.5 6.0 3.0 3.5 3.0 2.0 1.0 antimicrobial agent in the late stage of clinical NA NA NA NA NA NA Cefixime 0.25 16 Ceftaroline 8.0 49.0 8.5 5.5 5.5 12.0 9.5 1.5 0.5 development.
    [Show full text]
  • A Mini Review on the Study of New Broad-Spectrum Antimicrobial Fluoroquinolone JNJ-Q2
    Avens Publishing Group Inviting Innovations Open Access Case Study J Chem Applications June 2014 Volume 1 Issue 1 © All rights are reserved by Mohammad Asif AvensJournal Publishing of Group InviChemistryting Innovations & A Mini Review on the Study Applications Mohammad Asif* of New Broad-Spectrum Department of Pharmacy, GRD (PG) Institute of Management & Technology, Dehradun, (Uttarakhand), 248009, India Address for Correspondence Antimicrobial Fluoroquinolone Mohammad Asif, Department of Pharmacy, GRD (PG) Institute of Management & Technology, Dehradun, Uttarakhand, 248009, India, E-mail: [email protected] JNJ-Q2 Copyright: © 2014 Asif M. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Keywords: Antimicrobial; Anticancer; Fluoroquinolone; New drug; Submission: 03 April 2014 JNJ-Q2 Accepted: 29 May 2014 Abstract Published: 04 June 2014 The prokaryotic type II topoisomerases (DNA gyrase and topoisomerase IV) and the eukaryotic type II topoisomerases represent quinolones are distinguished from the antibacterial quinolones [7,8] the cellular targets for quinolone antibacterial and anticancer agents. Both enzymes effort the selectively shift from an antibacterial and are preferentially target the different prokaryotic and eukaryotic to an antitumor activity. In the search for potential molecule in the type II topoisomerases [9] (Figure 1). quinolones series, some of quinolone analogs displayed antibacterial and cytotoxic activities. The newly developed quinolone JNJ-Q2 is Generations of Quinolones a broad-spectrum fluoroquinolone, has activity against pathogenic bacteria but its anticancer activity is still disclosed. The studies The quinolones are divided into generations based on their demonstrated that quinolone series changes the biological profile antibacterial spectrum.
    [Show full text]
  • Newer Antibiotics: Need for More Studies in Neonates and Children Jeeson C Unni
    ANTIMICROBIALS Newer Antibiotics: Need for More Studies in Neonates and Children Jeeson C Unni ABSTRACT This article reviews few trials assessing the use of newer antibiotics in the neonates and children. Published data show that more studies are conducted in the adult population (50 times) when compared to children with respect to the testing of newer antibiotics. The figures are approximately 177 and 580 times more as compared to neonatal and preterm babies, respectively. Although there is paucity of data in the pediatric domain, carbavance (meropenem + vaborbactam) and solithromycin deserve special mention, as they are currently being used in pediatric clinical trials. Keywords: New antibiotics, Pediatric population, Resistance. Pediatric Infectious Disease (2019): 10.5005/jp-journals-10081-1212 INTRODUCTION IAP Drug Formulary, Aster Medcity, Kochi, Kerala, India Ninety-one years after the invention of penicillin, a silent epidemic Corresponding Author: Jeeson C Unni, IAP Drug Formulary, Aster of antibiotic resistance is emerging. There is a dearth of new Medcity, Kochi, Kerala, India, Phone: +91 9847245207, e-mail: antibiotics to fall back upon. Newly approved antibiotics tend to [email protected] be reserved as a last line of defense against multidrug-resistant How to cite this article: Unni JC. Newer Antibiotics: Need for More (MDR) infections, thus minimizing its sales value. Drugs on which Studies in Neonates and Children. Pediatr Inf Dis 2019;1(4):164–168. millions are spent on research and development (R&D) sometimes, Source of support: Nil therefore, do not see the light of day. This is a major deterrent for Conflict of interest: None investment in R&D by pharmaceuticals, which has resulted in a bleak future for development of new antibiotic molecules.
    [Show full text]
  • Antibiotics Currently in Global Clinical Development Note: This Data Visualization Was Updated in September 2018 with New Data
    A data table from Sept 2018 Antibiotics Currently in Global Clinical Development Note: This data visualization was updated in September 2018 with new data. As of June 2018, approximately 42 new antibiotics with the potential to treat serious bacterial infections are in clinical development. The success rate for clinical drug development is low; historical data show that, generally, only 1 in 5 infectious disease products that enter human testing (phase 1 clinical trials) will be approved for patients.* Below is a snapshot of the current antibiotic pipeline, based on publicly available information and informed by external experts. Please note that this resource focuses exclusively on small molecule products that act systemically (drugs that work throughout the body), contain at least one component not previously approved, and have the potential to treat serious or life-threatening infections.1 In September 2017, the antibiotics pipeline was expanded to include products in development globally. Because this resource is updated periodically, footnote numbers may not be sequential. Please contact [email protected] with additions or updates. Expected Expected activity activity against against CDC Development Drug name Company Drug class Target resistant Gram- urgent or WHO Potential indication(s)?5 phase2 negative ESKAPE critical threat pathogens?3 pathogen?4 Approved for: Complicated urinary tract Melinta infections including pyelonephritis; other Vabomere β-lactam (carbapenem) Approved Aug. 30, Therapeutics Inc. potential indications: complicated (meropenem + + β-lactamase inhibitor PBP, β-lactamase Yes Yes (CRE) 2017 (U.S. FDA) (formerly The intra-abdominal infections, hospital- vaborbactam) (cyclic boronate)11,13 Medicines Co.) acquired bacterial pneumonia/ventilator- associated bacterial pneumonia Approved for: Complicated urinary tract infections including acute pyelonephritis; Zemdri Approved June 26, 30S subunit of other potential indications: hospital- Achaogen Inc.
    [Show full text]