DOCSLIB.ORG

Identification and Antimicrobial Susceptibility Profiles of Nocardia

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Identification and Antimicrobial Susceptibility Profiles of Nocardia www.nature.com/scientificreports OPEN Identifcation and antimicrobial susceptibility profles of Nocardia species clinically isolated in Japan Masahiro Toyokawa 1,2,4*, Noboru Ohana2, Akiko Ueda3, Minako Imai4, Daiki Tanno2,4, Mutsuko Honda4, Yukiko Takano4, Kazutaka Ohashi4, Kyoichi Saito2 & Hiroki Shimura2,4 The aims of the present study were to profle the antimicrobial susceptibility patterns of a diverse range of Nocardia species isolated in Japan, and to determine the ability of matrix-assisted laser desorption ionization-time of fight mass spectrometry (MALDI-TOF MS) for species/complex identifcation. Identifcation of 153 clinical isolates was performed by full-length 16S rRNA gene sequencing as a reference method to evaluate the usefulness of MALDI-TOF MS identifcation. Antimicrobial susceptibility testing (AST) for 14 antibiotics was performed using the broth microdilution method against 146 of the isolates. Among the total 153 clinical isolates, Nocardia farcinica complex (25%) was the most common species, followed by Nocardia cyriacigeorgica (18%), Nocardia brasiliensis (9%), Nocardia nova (8%), and Nocardia otitidiscaviarum (7%). Among 150 isolates identifed to the species/complex level by 16S rRNA gene sequencing, MALDI-TOF MS with the use of a supplemental Nocardia library (JMLD library ver.ML01) correctly identifed 97.3% (n = 146) to the species/complex level and 1.3% (n = 2) to the genus level. Among the 146 Nocardia isolates that underwent AST, the susceptibilities were 100% to linezolid, 96% to amikacin, 94% to trimethoprim- sulfamethoxazole, and 76% to imipenem. None of the trimethoprim-sulfamethoxazole-resistant isolates carried either plasmid-mediated sulfonamide-resistant genes (sul1, sul2) or trimethoprim- resistant genes (dfrA). Nocardia species are ubiquitous environmental organisms that can cause local or disseminated infection in humans. Te lung is the most common primary site of infection, and central nervous system infection is ofen encountered through hematogenous dissemination from a pulmonary focus, particularly in immunocompro- mised hosts1. Prompt diagnosis and appropriate treatment of nocardiosis are required, because it is a fatal infection2. Trimethoprim-sulfamethoxazole (TMP-SMX) is the frst-line agent for initial therapy for nocardiosis3, thus accurate determination of the susceptibility to TMP-SMX in clinical isolates is crucial. Conville et al. reported that the standard broth microdilution method for TMP-SMX may cause false resistance because of difculties in end-point interpretation, and they recommend performing a confrmation test via sulfsoxazole disk difusion testing 4. Unfortunately we are unable to purchase sulfsoxazole disks in Japan; therefore there is no reliable data concerning Nocardia isolates resistant to TMP-SMX in Japan. On the other hands, identifcation of clinical isolates to the species/complex level is important, because Nocardia species difer in clinical spectrum and susceptibility patterns5–7. Gene sequencing such as 16S rRNA gene is currently used for the identifcation of Nocardia species; however, recently, matrix-assisted laser desorption ionization-time of fight mass spectrometry (MALDI-TOF MS)-based identifcation has been identifed as a rapid, easy and reliable method 8,9. Te aims of the present study were to profle the antimicrobial susceptibility patterns of a diverse range of Nocardia species isolated from clinical specimens in Japan, and to determine the utility of MALDI-TOF MS for the routine identifcation of Nocardia species. Materials and methods Bacterial isolates and identifcation. A total of 153 clinical isolates of Nocardia species recovered from patients in 25 microbiology laboratories in Japan were studied. Te isolates were cultured from respiratory tract specimens (n = 90), skin and sof tissue (n = 14), blood (n = 5), deep abscess (n = 6), pleural efusion (n = 1), ascitic 1Preparing section for New Faculty of Medical Science, Fukushima Medical University, 1 Hikariga-oka, Fukushima City 960-1295, Japan. 2Department of Laboratory Medicine, Fukushima Medical University, Fukushima, Japan. 3Laboratory for Clinical Investigation, Osaka University Hospital, Osaka, Japan. 4Department of Clinical Laboratory Medicine, Fukushima Medical University Hospital, Fukushima, Japan. *email: [email protected] Scientifc Reports | (2021) 11:16742 | https://doi.org/10.1038/s41598-021-95870-2 1 Vol.:(0123456789) www.nature.com/scientificreports/ fuid (n = 1), synovial fuid (n = 1), others (n = 5) and unknown (n = 30). Identifcation of Nocardia species was based on Gram stain, colonial morphology and molecular technique. All isolates were identifed by full-length 16S rRNA gene sequencing, for which the universal primers 8UA (5′-AGA GTT TGATCMTGG CTC AG-3′) and 1485B (5′-ACG GGC GGT GTG TRC-3′) were used, as described previously10. We performed sequencing analysis using a GenBank BLAST search and EzBioCloud (https:// www. ezbio cloud. net/ ident ify/ result? id= 5ef99 cb3c3 9ad46 1094e 9aa3). Previously established criteria for identifcation of Nocardia isolates to the species or complex level were followed11,12. MALDI-TOF MS identifcation. All Nocardia species isolates were analyzed using a Microfex LT bench top mass spectrometer (Bruker Daltonics, Germany). MALDI Biotyper 3.1 sofware (Bruker Daltonics, MALDI Biotyper reference library version 8.0.0.0) was applied with the use of a supplemental Nocardia library (JMLD library ver.ML01, containing 114 Main Spectras for 46 Nocardia species) provided by BCKK MALDINOMICS (Beckman Coulter Japan, Tokyo, Japan). Te isolates were cultivated on 5% sheep blood agar plates at 35℃, and tested at 18 and 48 h, an early stage of growth8. Samples were prepared as previously described (on-plate extrac- tion)8. Protein extraction was also performed using the formic acid/ethanol method according to the Bruker Daltonics’ protocol for any isolate failed to be identifed by on-plate extraction. A spectral score of ≥ 2.00 was considered identifcation to the species level, a score of 1.700–1.999 indicated identifcation at the genus level, and a score of < 1.70 was considered unreliable identifcation. Complex level identifcation was performed on some Nocardia species according to Conville’s criteria11. Nocardia asteroides ATCC 23206, Nocardia brasiliensis ATCC 23238, Nocardia farcinica ATCC 23157, and Nocardia otitidiscaviarum ATCC 23240 were used as the quality control strains. Antimicrobial susceptibility testing (AST). AST was performed using the broth microdilution method with frozen panels (Eiken Chemical, Tokyo, Japan), according to the Clinical and Laboratory Standards Institute (CLSI) M24-A2 guidelines13 against 146 clinical isolates. In brief, a heavy organism suspension was prepared in a small volume of sterile saline with 7–10 3-mm glass beads and was vortexed vigorously. Clumps were allowed to settle for 15 min, and the supernatant was adjusted to a 0.5 McFarland standard using a calibrated neph- elometer. For frozen panel inoculation, the adjusted 0.5 McFarland suspension was diluted 30-fold with sterile saline and 10 µl of the diluted solution was dispensed into each well of the panel. Te panels were incubated at 35℃ for 72 h until moderate growth was observed in the growth control wells. For TMP-SMX, the MICs were determined as the wells corresponding to 80% inhibition of growth compared to the controls. Te MICs were determined for TMP-SMX, amikacin, tobramycin, cefriaxone, imipenem, minocycline, linezolid, ciprofoxa- cin, moxifoxacin, clarithromycin, cefotaxime (100 isolates only), meropenem (100 isolates only), tigecycline (100 isolates only), and arbekacin (100 isolates only), and interpreted as recommended by CLSI. Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853 and Enterococcus faecalis ATCC 29212 were used as the quality control strains. For confrmation of TMP-SMX resistance, disk difusion testing with a 250-μg sulfsoxazole disk (Hardy Diagnostics, CA, USA)4 was performed in all 21 TMP-SMX-resistant isolates determined by AST (MIC ≥ 4/76 μg/ ml). Moreovere, re-analysis of the broth microdilution method using panels with diferent lots and inoculum colony count were also performed. For this analysis, Nocardia nova ATCC BAA-2227 and Escherichia coli ATCC 25922 were used as the quality control strains. Detection of plasmid-mediated TMP-SMX-resistant genes. Te plasmid-mediated sulfonamide- resistant genes (sul1, sul2)14 and trimethoprim-resistant gene (dfrA)15 were detected by PCR in 21 TMP-SMX- resistant isolates, determined by AST (MIC ≥ 4/76 μg/ml) (see Table S1 for the primer sequence and Figure S1 for a gel electrophoresis image of positive controls in the supplemental material). Te present study was conducted in accordance with the ethical guidelines of the Ministry of Health, Labor and Welfare of Japan. No ethical committee approvals or informed consent were needed for this study. Conference presentation. A part of this study was presented at the 27th European Congress of Clinical Microbiology and Infectious Diseases, 22 to 25 April 2017, Vienna, Austria [abstr. #316]. Results Identifcation of clinical isolates by full-length 16S rRNA gene sequencing. Among the 153 clin- ical isolates, 150 were identifed to the species/complex level, including 24 diferent species/complexes, and the remaining three isolates were identifed to the genus level (Table 1). Nocardia farcinica complex (n = 39; 25%) was the most common species, followed by Nocardia cyriacigeorgica (n = 27; 18%), Nocardia brasiliensis (n =
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]