DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2015/0328244 A1 Eagle Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) Patent Application Publication (10) Pub. No.: US 2015/0328244 A1 Eagle Et Al US 2015 0328244A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2015/0328244 A1 Eagle et al. (43) Pub. Date: Nov. 19, 2015 (54) METHODS FOR TREATING PULMONARY A6II 45/06 (2006.01) NON-TUBERCULOUS MYCOBACTERIAL A 6LX 9/27 (2006.01) INFECTIONS (52) U.S. Cl. CPC ............. A6 IK3I/7036 (2013.01); A61K 9/127 (71) Applicant: Insmed Incorporated, Bridgewater, NJ (2013.01); A61 K9/0078 (2013.01); A61 K (US) 45/06 (2013.01) (72) Inventors: Gina Eagle, Morristown, NJ (US); Renu (57) ABSTRACT Gupta, Moorestown, NJ (US) Provided herein are methods for treating a pulmonary infec (21) Appl. No.: 14/713,926 tion in a patient in need thereof, for example, a nontubercu lous mycobacterial pulmonary infection for at least one treat (22) Filed: May 15, 2015 ment cycle. The method comprises administering to the lungs of the patient a pharmaceutical composition comprising a Related U.S. Application Data liposomal complexed aminoglycoside comprising a lipid (60) Provisional application No. 61/993,439, filed on May component comprising electrically neutral lipids and an ami 15, 2014, provisional application No. 62/042,126, noglycoside. Administration comprises aerosolizing the filed on Aug. 26, 2014, provisional application No. pharmaceutical composition to provide an aerosolized phar 62/048,068, filed on Sep. 9, 2014, provisional applica maceutical composition comprising a mixture of free ami tion No. 62/056.296, filed on Sep. 26, 2014. noglycoside and liposomal complexed aminoglycoside, and administering the aerosolized pharmaceutical composition Publication Classification via a nebulizer to the lungs of the patient. The methods pro vided herein result in a change from baseline on the semi (51) Int. C. quantitative scale for mycobacterial culture for a treated A6 IK3I/7036 (2006.01) patient, and/or NTM culture conversion to negative during or A6 IK9/00 (2006.01) after the administration period. Patent Application Publication Nov. 19, 2015 Sheet 1 of 9 US 2015/0328244 A1 Patent Application Publication ?àn?ejua333Sg?y *-----------------------------------------------------------------; |paueauos; (06=u)pºz?udopue?|68=u+1L?u Patent Application Publication Nov. 19, 2015 Sheet 3 of 9 US 2015/0328244 A1 f CO Y ra r 'em Patent Application Publication Nov. 19, 2015 Sheet 5 of 9 US 2015/0328244 A1 & S Åpnis **** ::::::::::::::::::::::::$$$$$ :38,388 to tissues Patent Application Publication US 2015/0328244 A1 Y: - : -------------------------------------------------------------------&r^$333s?ºº?ºg Patent Application Publication Nov. 19, 2015 Sheet 7 of 9 US 2015/0328244 A1 --------------------------------- s 33 esp (; 33ue Jea/ Patent Application Publication Nov. 19, 2015 Sheet 8 of 9 US 2015/0328244 A1 i ; {5,3333 is ga}EA Saeetu) payeAA 33; esp afue lee?, 33ties : 83183 ueeA Patent Application Publication Nov. 19, 2015 Sheet 9 of 9 US 2015/0328244 A1 US 2015/0328244 A1 Nov. 19, 2015 METHODS FOR TREATING PULMONARY 0008. In one embodiment, the NTM infection is a pulmo NON-TUBERCULOUS MYCOBACTERIAL nary NTM infection selected from an M. avium, M. avium INFECTIONS subsp. hominissuis (MAH), M. abscessus, M. chelonae, M. bolletii, M. kansasii, M. ulcerans, M. avium, M. avium com plex (MAC) (M. avium and M. intracellulare), M. Con CROSS REFERENCE TO RELATED spicuum, M. kansasii, M. peregrinum, M. immunogenium, M. APPLICATIONS xenopi, M. marinum, M. malmoense, M. marinum, M. muco 0001. This application claims priority from U.S. Provi genicum, M. nonchromogenicum, M. Scrofulaceum, M. simiae, M. Smegmatis, M. Szulgai, M. terrae, M. terrae com sional Application Ser. Nos. 61/993,439, filed May 15, 2014: plex, M. haemophilum, M.genavense, M. gordonae, M. ulcer 62/042,126, filed Aug. 26, 2014; 62/048,068, filed Sep. 9, ans, M. fortuitum, M. fortuitum complex (M. fortuitum and M. 2014; and 62/056.296, filed Sep. 26, 2014, the disclosures of chelonae) infection or a combination thereof. In a further each of which are incorporated by reference in their entireties embodiment, the NTM infection is an M. avium complex for all purposes. (MAC) (M. avium and M. intracellulare) infection. In one embodiment, the NTM infection is a pulmonary recalcitrant BACKGROUND OF THE INVENTION NTM infection. 0009. In one embodiment, the composition comprising the 0002 Certain technologies suitable for administration by liposomal complexed aminoglycoside is a dispersion (e.g., a inhalation employ liposomes and lipid complexes Supply a liposomal solution or Suspension). The liposomal portion of prolonged therapeutic effect of drug in the lung. These tech the composition comprises a lipid component that includes nologies also provide the drug with Sustained activities, and electrically neutral lipids. In a further embodiment, the elec the ability to target and enhance the uptake of the drug into trically neutral lipids comprise a phosphatidylcholine and a sites of disease. sterol (e.g., dipalmitoylphosphatidylcholine and cholesterol). 0003. Inhalation delivery of liposomes is complicated by In a further embodiment, the aminoglycoside is amikacin or a their sensitivity to shear-induced stress during nebulization, pharmaceutically acceptable salt thereof. In even a further which can lead to change in physical characteristics (e.g., embodiment, the aminoglycoside is amikacin Sulfate. entrapment, size). However, as long as the changes in char 0010. In one embodiment, the method for treating or pro acteristics are reproducible and meet acceptability criteria, viding prophylaxis against an NTM infection comprises they need not be prohibitive to pharmaceutical development. administering an aerosolized pharmaceutical composition to 0004 Pulmonary infection with non-tuberculous myco the lungs of the patient in need thereof; wherein the aero bacterium (NTM) in the susceptible host can lead to poten solized pharmaceutical composition comprises a mixture of tially severe morbidity and even mortality among those free aminoglycoside and liposomal complexed aminoglyco affected. As infection rates are rising, pulmonary nontuber side, and the lipid component of the liposome consists of electrically neutral lipids. In a further embodiment, the elec culous mycobacterial disease (PNTM) represents an emerg trically neutral lipids comprise a phosphatidylcholine and a ing public health concern in the United States. NTM are sterol (e.g., dipalmitoylphosphatidylcholine and cholesterol). ubiquitous in the environment. Over 80% of pulmonary NTM In a further embodiment, the aminoglycoside is amikacin or a (PNTM) infections in the US are due to Mycobacterium pharmaceutically acceptable salt thereof. In even a further avium complex (MAC). In addition, M. Kansasii, M. absces embodiment, the aminoglycoside is amikacin Sulfate. sus, and M. fortuitum are regularly isolated. 0011. The methods provided herein result in a change 0005. The prevalence of pulmonary NTM infections in the from baseline on the semi-quantitative scale for mycobacte United States has more than doubled in the last 15 years. The rial culture for a treated patient, and/or NTM culture conver ATS/IDSA PNTM reported 2-year period prevalence of pull sion to negative during or after the administration period. For monary NTM infections is 8.6/100,000 persons. The preva example, in one embodiment, the method provided herein lence of pulmonary NTM infections increases with age with results in the patient having an NTM culture conversion to 20.4/100,000 in those at least 50 years of age and is especially negative after an administration period. prevalent in females (median age: 66 years; female: 59%). 0012. In one embodiment, the aminoglycoside or pharma 0006. In the susceptible individual, pulmonary NTM ceutically acceptable salt thereof is amikacin, apramycin, infections can be serious or life threatening. Available thera arbekacin, astromicin, capreomycin, dibekacin, framycetin, pies may be poorly tolerated, and may have significant gentamicin, hygromycin B, isepamicin, kanamycin, neomy adverse events. The present invention addresses this and other cin, netilmicin, paromomycin, rhodestreptomycin, ribosta needs by providing methods for treating pulmonary NTM mycin, Sisomicin, spectinomycin, Streptomycin, tobramycin, infections in patients in need thereof. Verdamicin, a pharmaceutically acceptable salt thereof, or a combination thereof. In even a further embodiment, the ami SUMMARY OF THE INVENTION noglycoside is amikacin. In another embodiment, the ami noglycoside is selected from an aminoglycoside set forth in 0007. The present invention, in one aspect, provides meth Table 1, below, a pharmaceutically acceptable salt thereof, or ods for treating or providing prophylaxis against a nontuber a combination thereof. culous mycobacterial (NTM) infection (pulmonary infection caused or due to one or more nontuberculous mycobacteria), TABLE 1 via inhalation administration of an effective amount of a composition comprising a liposomal complexed aminogly Aminoglycosides for use with the present invention coside, or a pharmaceutically acceptable salt thereof, to a AC4437 dibekacin K-4619 Sisomicin patient in need thereof. The patient in need of treatment, in amikacin dactimicin isepamicin rhodestreptomycin one embodiment, is a cystic fibrosis patient, a bronchiectasis apramycin etimicin KA-5685 sorbistin patient, suffers from asthma or suffers from chronic obstruc arbekacin framycetin kanamycin spectinomycin tive pulmonary disorder (COPD). US 2015/0328244 A1 Nov. 19, 2015 TABLE 1-continued a further embodiment, the amikacin is amikacin Sulfate.
Load more

Recommended publications
  • Pharmaceutical Applications Notebook
    Pharmaceutical Applications Notebook Antibiotics Table of Contents Index of Analytes .......................................................................................................................................................................3 Introduction to Pharmaceuticals ................................................................................................................................................4 UltiMate 3000 UHPLC+ Systems .............................................................................................................................................5 IC and RFIC Systems ................................................................................................................................................................6 MS Instruments .........................................................................................................................................................................7 Chromeleon 7 Chromatography Data System Software ..........................................................................................................8 Process Analytical Systems and Software ................................................................................................................................9 Automated Sample Preparation ..............................................................................................................................................10 Analysis of Antibiotics ...........................................................................................................................................................11
    [Show full text]
  • G Genito Urinary System and Sex Hormones
    WHO/EMP/RHT/TSN/2018.2 © 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. Learning clinical pharmacology with the use of INNs and their stems. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.2). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data. CIP data are available at http://apps.who.int/iris. Sales, rights and licensing. To purchase WHO publications, see http://apps.who.int/bookorders. To submit requests for commercial use and queries on rights and licensing, see http://www.who.int/about/licensing.
    [Show full text]
  • P147-Bioorgchem-Kanamycin Nucleotidyltransferase-1999.Pdf
    Bioorganic Chemistry 27, 395±408 (1999) Article ID bioo.1999.1144, available online at http://www.idealibrary.com on Kinetic Mechanism of Kanamycin Nucleotidyltransferase from Staphylococcus aureus1 Misty Chen-Goodspeed,* Janeen L. Vanhooke,² Hazel M. Holden,² and Frank M. Raushel*,2 *Department of Chemistry, Texas A&M University, College Station, Texas 77843; and ²Department of Biochemistry, Institute for Enzyme Research, University of Wisconsin, Madison, Wisconsin 53705 Received December 16, 1998 Kanamycin nucleotidyltransferase (KNTase) catalyzes the transfer of the adenyl group from MgATP to either the 4Ј or 4Љ-hydroxyl group of aminoglycoside antibiotics. The steady state kinetic parameters of the enzymatic reaction have been measured by initial velocity, product, and dead-end inhibition techniques. The kinetic mechanism is ordered where the antibiotic binds prior to MgATP and the modified antibiotic is the last product to be released. The effects of altering the relative solvent viscosity are consistent with the release of the products as the rate-limiting step. The pH profiles for Vmax and V/KATP show that a single ionizable group with apK of ϳ8.9 must be protonated for catalysis. The V/K profile for kanamycin as a function of pH is bell-shaped and indicates that one group must be protonated with a pK value of 8.5, while another group must be unprotonated with a pK value of 6.6. An analysis of the kinetic constants for 10 different aminoglycoside antibiotics and 5 nucleotide triphosphates indicates very little difference in the rate of catalysis or substrate binding among these substrates. ᭧ 1999 Academic Press Key Words: kanamycin nucleotidyltransferase; antibiotic modification.
    [Show full text]
  • Computational Antibiotics Book
    Andrew V DeLong, Jared C Harris, Brittany S Larcart, Chandler B Massey, Chelsie D Northcutt, Somuayiro N Nwokike, Oscar A Otieno, Harsh M Patel, Mehulkumar P Patel, Pratik Pravin Patel, Eugene I Rowell, Brandon M Rush, Marc-Edwin G Saint-Louis, Amy M Vardeman, Felicia N Woods, Giso Abadi, Thomas J. Manning Computational Antibiotics Valdosta State University is located in South Georgia. Computational Antibiotics Index • Computational Details and Website Access (p. 8) • Acknowledgements (p. 9) • Dedications (p. 11) • Antibiotic Historical Introduction (p. 13) Introduction to Antibiotic groups • Penicillin’s (p. 21) • Carbapenems (p. 22) • Oxazolidines (p. 23) • Rifamycin (p. 24) • Lincosamides (p. 25) • Quinolones (p. 26) • Polypeptides antibiotics (p. 27) • Glycopeptide Antibiotics (p. 28) • Sulfonamides (p. 29) • Lipoglycopeptides (p. 30) • First Generation Cephalosporins (p. 31) • Cephalosporin Third Generation (p. 32) • Fourth-Generation Cephalosporins (p. 33) • Fifth Generation Cephalosporin’s (p. 34) • Tetracycline antibiotics (p. 35) Computational Antibiotics Antibiotics Covered (in alphabetical order) Amikacin (p. 36) Cefempidone (p. 98) Ceftizoxime (p. 159) Amoxicillin (p. 38) Cefepime (p. 100) Ceftobiprole (p. 161) Ampicillin (p. 40) Cefetamet (p. 102) Ceftoxide (p. 163) Arsphenamine (p. 42) Cefetrizole (p. 104) Ceftriaxone (p. 165) Azithromycin (p.44) Cefivitril (p. 106) Cefuracetime (p. 167) Aziocillin (p. 46) Cefixime (p. 108) Cefuroxime (p. 169) Aztreonam (p.48) Cefmatilen ( p. 110) Cefuzonam (p. 171) Bacampicillin (p. 50) Cefmetazole (p. 112) Cefalexin (p. 173) Bacitracin (p. 52) Cefodizime (p. 114) Chloramphenicol (p.175) Balofloxacin (p. 54) Cefonicid (p. 116) Cilastatin (p. 177) Carbenicillin (p. 56) Cefoperazone (p. 118) Ciprofloxacin (p. 179) Cefacetrile (p. 58) Cefoselis (p. 120) Clarithromycin (p. 181) Cefaclor (p.
    [Show full text]
  • W O 2015/175939 A1 19 November 2015 (19.11.2015) W I PO I P C T
    (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 W O 2015/175939 A1 19 November 2015 (19.11.2015) W I PO I P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated,for every A61K 9/127 (2006.01) A01N 43/04 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (21) International Application Number: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, PCT/US2015/03 1079 DO, DZ, EC, EE, EG, ES, Fl, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, 15 May 2015 (15.05.2015) KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (25) Filing Language: English PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (26) Publication Language: English 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. (30) Priority Data: 61/993,439 15 May 2014 (15.05.2014) US (84) Designated States (unless otherwise indicated,for every 62/042,126 26 August 2014 (26.08.2014) US kind of regional protection available): ARIPO (BW, GH, 62/048,068 9 September 2014 (09.09.2014) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 62/056,296 26 September 2014 (26.09.2014) US TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (71) Applicant: INSMED INCORPORATED [US/US]; 10 DK, EE, ES, Fl, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, Finderne Avenue, Building N'10, Bridgewater, NJ 08807- LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, 3365 (US).
    [Show full text]
  • EMA/CVMP/158366/2019 Committee for Medicinal Products for Veterinary Use
    Ref. Ares(2019)6843167 - 05/11/2019 31 October 2019 EMA/CVMP/158366/2019 Committee for Medicinal Products for Veterinary Use Advice on implementing measures under Article 37(4) of Regulation (EU) 2019/6 on veterinary medicinal products – Criteria for the designation of antimicrobials to be reserved for treatment of certain infections in humans Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union © European Medicines Agency, 2019. Reproduction is authorised provided the source is acknowledged. Introduction On 6 February 2019, the European Commission sent a request to the European Medicines Agency (EMA) for a report on the criteria for the designation of antimicrobials to be reserved for the treatment of certain infections in humans in order to preserve the efficacy of those antimicrobials. The Agency was requested to provide a report by 31 October 2019 containing recommendations to the Commission as to which criteria should be used to determine those antimicrobials to be reserved for treatment of certain infections in humans (this is also referred to as ‘criteria for designating antimicrobials for human use’, ‘restricting antimicrobials to human use’, or ‘reserved for human use only’). The Committee for Medicinal Products for Veterinary Use (CVMP) formed an expert group to prepare the scientific report. The group was composed of seven experts selected from the European network of experts, on the basis of recommendations from the national competent authorities, one expert nominated from European Food Safety Authority (EFSA), one expert nominated by European Centre for Disease Prevention and Control (ECDC), one expert with expertise on human infectious diseases, and two Agency staff members with expertise on development of antimicrobial resistance .
    [Show full text]
  • Anew Drug Design Strategy in the Liht of Molecular Hybridization Concept
    www.ijcrt.org © 2020 IJCRT | Volume 8, Issue 12 December 2020 | ISSN: 2320-2882 “Drug Design strategy and chemical process maximization in the light of Molecular Hybridization Concept.” Subhasis Basu, Ph D Registration No: VB 1198 of 2018-2019. Department Of Chemistry, Visva-Bharati University A Draft Thesis is submitted for the partial fulfilment of PhD in Chemistry Thesis/Degree proceeding. DECLARATION I Certify that a. The Work contained in this thesis is original and has been done by me under the guidance of my supervisor. b. The work has not been submitted to any other Institute for any degree or diploma. c. I have followed the guidelines provided by the Institute in preparing the thesis. d. I have conformed to the norms and guidelines given in the Ethical Code of Conduct of the Institute. e. Whenever I have used materials (data, theoretical analysis, figures and text) from other sources, I have given due credit to them by citing them in the text of the thesis and giving their details in the references. Further, I have taken permission from the copyright owners of the sources, whenever necessary. IJCRT2012039 International Journal of Creative Research Thoughts (IJCRT) www.ijcrt.org 284 www.ijcrt.org © 2020 IJCRT | Volume 8, Issue 12 December 2020 | ISSN: 2320-2882 f. Whenever I have quoted written materials from other sources I have put them under quotation marks and given due credit to the sources by citing them and giving required details in the references. (Subhasis Basu) ACKNOWLEDGEMENT This preface is to extend an appreciation to all those individuals who with their generous co- operation guided us in every aspect to make this design and drawing successful.
    [Show full text]
  • THALMUUNTURUS009732370B2 (12 ) United States Patent (10 ) Patent No
    THALMUUNTURUS009732370B2 (12 ) United States Patent (10 ) Patent No. : US 9 , 732 , 370 B2 Jagesar ( 45 ) Date of Patent: Aug. 15, 2017 ( 54 ) METHOD FOR THE DETERMINATION OF ( 58 ) Field of Classification Search THE PRESENCE OF AN ANTIBIOTIC IN A None FLUID See application file for complete search history. (71 ) Applicant: DSM IP ASSETS B . V ., Heerlen (NL ) ( 56 ) References Cited ( 72 ) Inventor : Dhiredj Chandre Jagesar , Echt (NL ) U . S . PATENT DOCUMENTS 2007/ 0092929 A1* 4 / 2007 Dekker .. .. .. C12Q 1/ 18 ( 73 ) Assignee : DSM IP ASSETS B . V ., Heerlen (NL ) 435 / 32 ( * ) Notice : Subject to any disclaimer, the term of this patent is extended or adjusted under 35 FOREIGN PATENT DOCUMENTS U . S .C . 154 (b ) by 0 days . EP 0005891 A112 / 1979 EP 0285792 Al 10 / 1988 ( 21) Appl. No .: EP 0611001 AL 8 / 1994 14 /787 , 859 EP 1639122 A1 3 /2006 WO 2005005655 AL 1 / 2005 ( 22 ) PCT Filed : Apr. 30 , 2014 wo 2013057182 AL 4 /2013 ( 86 ) PCT No . : PCT/ EP2014 / 058778 OTHER PUBLICATIONS $ 371 (c ) ( 1 ) , ( 2 ) Date : Oct. 29 , 2015 International Search Report from corresponding PCT/ EP2014 / 058778 , mailed Jul . 23 , 2014 . Gilbertson et al. , “ Modified Microbiological Method for the Screen ( 87 ) PCT Pub . No . : WO2014 / 177597 ing of Antibiotics in Milk ” , 1995 , J. Dairy Sci , vol. 78 , PCT Pub . Date : Nov . 6 , 2014 XP27050235, pp . 1032 - 1038 . (65 ) Prior Publication Data * cited by examiner US 2016 / 0076071 A1 Mar . 17 , 2016 Primary Examiner — Kade Ariani ( 30 ) Foreign Application Priority Data (74 ) Attorney , Agent, or Firm - McBee Moore Woodward & Vanik IP , LLC ; Susan McBee ; Chester May 2 , 2013 (EP ) .
    [Show full text]
  • In Vivo Antibacterial Activity of Vertilmicin, a New Aminoglycoside
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Oct. 2009, p. 4525–4528 Vol. 53, No. 10 0066-4804/09/$08.00ϩ0 doi:10.1128/AAC.00223-09 Copyright © 2009, American Society for Microbiology. All Rights Reserved. In Vivo Antibacterial Activity of Vertilmicin, a New Aminoglycoside Antibioticᰔ Xue-Fu You,†* Cong-Ran Li,† Xin-Yi Yang, Min Yuan, Wei-Xin Zhang, Ren-Hui Lou, Yue-Ming Wang, Guo-Qing Li, Hui-Zhen Chen, Dan-Qing Song, Cheng-Hang Sun, Shan Cen, Li-Yan Yu, Li-Xun Zhao, and Jian-Dong Jiang* Laboratory of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China Received 18 February 2009/Returned for modification 4 May 2009/Accepted 15 July 2009 Vertilmicin is a novel aminoglycoside antibiotic with potent activity against gram-negative and -positive bacteria in vitro. In this study, we further evaluated the efficacy of vertilmicin in vivo in systemic and local infection animal models. We demonstrated that vertilmicin had relatively high and broad-spectrum activities against mouse systemic infections caused by Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis. The 50% effective doses of subcutaneously administered vertilmicin were 0.63 to 0.82 mg/kg, 0.18 to 0.29 mg/kg, 0.25 to 0.99 mg/kg, and 4.35 to 7.11 mg/kg against E. coli, K. pneumoniae, S. aureus, and E. faecalis infections, respectively. The therapeutic efficacy of vertilmicin was generally similar to that of Downloaded from netimicin, better than that of gentamicin in all the isolates tested, and better than that of verdamicin against E.
    [Show full text]
  • Virtual Screen for Repurposing Approved and Experimental Drugs for Candidate Inhibitors of EBOLA Virus Infection [Version 2; Peer Review: 2 Approved]
    F1000Research 2015, 4:34 Last updated: 28 SEP 2021 RESEARCH ARTICLE Virtual screen for repurposing approved and experimental drugs for candidate inhibitors of EBOLA virus infection [version 2; peer review: 2 approved] Veljko Veljkovic1, Philippe M. Loiseau 2, Bruno Figadere 2, Sanja Glisic1, Nevena Veljkovic1, Vladimir R. Perovic1, David P. Cavanaugh 3, Donald R. Branch4 1Center for Multidisciplinary Research, University of Belgrade, Institute of Nuclear Sciences VINCA, P.O. Box 522, 11001 Belgrade, Serbia 2Antiparasitic Chemotherapy, UMR 8076 CNRS BioCIS, Faculty of Pharmacy Université Paris-Sud, Rue Jean-Baptiste Clément, F 92290- Chatenay-Malabry, France 3Bench Electronics, Bradford Dr., Huntsville, AL, 35801, USA 4Canadian Blood Services, Center for Innovation, 67 College Street, Toronto, Ontario, M5G 2M1, Canada v2 First published: 02 Feb 2015, 4:34 Open Peer Review https://doi.org/10.12688/f1000research.6110.1 Latest published: 16 Feb 2015, 4:34 https://doi.org/10.12688/f1000research.6110.2 Reviewer Status Invited Reviewers Abstract The ongoing Ebola virus epidemic has presented numerous 1 2 challenges with respect to control and treatment because there are no approved drugs or vaccines for the Ebola virus disease (EVD). Herein is version 2 proposed simple theoretical criterion for fast virtual screening of (revision) report molecular libraries for candidate inhibitors of Ebola virus infection. We 16 Feb 2015 performed a repurposing screen of 6438 drugs from DrugBank using this criterion and selected 267 approved and 382 experimental drugs version 1 as candidates for treatment of EVD including 15 anti-malarial drugs 02 Feb 2015 report report and 32 antibiotics. An open source Web server allowing screening of molecular libraries for candidate drugs for treatment of EVD was also established.
    [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]
  • 1 Revealing SARS-Cov-2 Functional Druggability Through Multi-Target
    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 11 May 2020 doi:10.20944/preprints202005.0199.v1 Revealing SARS-CoV-2 Functional Druggability Through Multi-Target Cadd Screening of Repurposable Drugs Yash Gupta1,2, Dawid Maciorowski1,3, Raman Mathur1, Catherine M Pearce1, David J. IIc1,3, Hamza Husein1,3, Ajay Bharti4, Daniel P. Becker3, Brijesh Rathi2,5, Steven B Bradfute6, Ravi Durvasula1,2, Prakasha Kempaiah1,2* 1 Loyola University Chicago Stritch School of Medicine, Chicago, IL, 60153, USA; 2 Department of Medicine, Loyola University Medical Center, Chicago, IL, 60153, USA; 3 Loyola University Chicago, Chicago, IL, USA; 4 Division of Infectious Diseases, Department of Medicine, University of California, San Diego, CA, 92093, USA, 5 Laboratory for Translational Chemistry and Drug Discovery, Hansraj College, University of Delhi, India; 6 Center for Global Health, Division of Infectious Diseases, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico, USA. Number of Tables: 10; Number of Figures: 16 ABSTRACT: The emergence of SARS/MERS drug resistant COVID-19 with high transmission and mortality has recently been declared a deadly pandemic causing economic chaos and significant health problems. Like all coronaviruses, SARS-CoV-2 is a large virus that has many druggable components within its proteome. In this study, we focused on repurposing approved and investigational drugs by identifying potential drugs that are predicted to effectively inhibit critical enzymes within SARS-CoV-2. We shortlisted seven target proteins with enzymatic activities known to be essential at different stages of the virus life cycle. For virtual screening, the energy minimization of a crystal structure or modeled protein was carried out using Protein Preparation Wizard (Schrödinger LLC, 2020-1).
    [Show full text]