DOCSLIB.ORG

Antibiotics Currently in Clinical Development

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Antibiotics Currently in Clinical Development A data table from Dec 2015 Antibiotics Currently in Clinical Development As of September 2015, an estimated 39 new antibiotics1 with the potential to treat serious bacterial infections are in clinical development for the U.S. market and two have been approved within the last year. The success rate for clinical drug development is low; at best, only 1 in 5 candidates 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 an external expert. It will be updated periodically, as products advance or are known to drop out of development. Because this list is updated periodically, footnote numbers may not be sequential. Please contact [email protected] with additions or updates. Expected activity Expected activity Development against resistant against a CDC Drug name Company Drug class Potential indication(s)?5 phase2 Gram-negative ESKAPE urgent threat pathogens?3 pathogen?4 Approved for: complicated urinary tract Cubist Pharmaceuticals, infections, complicated intra-abdominal Novel Ceftolozane+Tazobactam Approved Dec. 19, Inc. (wholly owned infections, acute pyelonephritis (kidney cephalosporin+beta- Yes No (Zerbaxa) 2014 subsidiary of Merck & infection); other potential indications: lactamase inhibitor Co.) hospital-acquired bacterial pneumonia/ ventilator-associated bacterial pneumonia Approved for: complicated urinary tract infections, complicated intra-abdominal infections, acute pyelonephritis (kidney Ceftazidime+Avibactam Approved Feb. 25, Allergan plc (formerly Cephalosporin + novel Yes Yes infection); other potential indications: (Avycaz) 201513 Actavis)/AstraZeneca plc beta-lactamase inhibitor hospital-acquired bacterial pneumonia/ ventilator-associated bacterial pneumonia, bacteremia WCK 4873 Phase 1 Wockhardt Ltd. No No Bacterial infections17 MGB-BP-3 Phase 110 MGB Biopharma Ltd. No Yes C. difficile infections Meiji Seika Pharma Co., Ltd./Fedora OP0595 (RG6080) Phase 110 Beta-lactamase inhibitor Possibly Possibly Bacterial infections Pharmaceuticals, Inc. (Roche licensee) Aztreonam+Avibactam7 AstraZeneca/Allergan Monobactam + novel Phase 110 Yes Yes Bacterial infections (ATM-AVI) (formerly Actavis) beta-lactamase inhibitor Basilea Pharmaceutica Multidrug-resistant Gram-negative bacterial BAL30072 Phase 1 Monosulfactam Yes Yes Ltd. infections6 Methionyl-tRNA CRS3123 Phase 1 Crestone, Inc. synthetase (MetRS) No Yes C. difficile infections inhibitor Expected activity Expected activity Development against resistant against a CDC Drug name Company Drug class Potential indication(s)?5 phase2 Gram-negative ESKAPE urgent threat pathogens?3 pathogen?4 LegoChem Biosciences, LCB01-0371 Phase 110 Oxazolidinone No No Bacterial infections Inc. Acute bacterial skin and skin structure Glycopeptide- Theravance Biopharma, infections,6 hospital-acquired pneumonia/ TD-1607 Phase 1 cephalosporin No No Inc. ventilator-associated pneumonia,6 heterodimer bacteremia6 Fluoroquinolone (WCK WCK 2349 Phase 1 Wockhardt Ltd. No No Bacterial infections17 771 pro-drug) WCK 771 Phase 1 Wockhardt Ltd. Fluoroquinolone No No Bacterial infections17 MicuRx Pharmaceuticals, Acute bacterial skin and skin structure MRX-I Phase 216 Oxazolidinone No No Inc. infections Fabl inhibitor (Debio Acute bacterial skin and skin structure Debio 1450 Phase 2 Debiopharm Group No No 1452 pro-drug) infections (staphylococci-specific) Spiropyrimidinetrione ETX0914 Phase 2 Entasis Therapeutics, Inc. No Yes Uncomplicated gonorrhea DNA gyrase inhibitor S-649266 Phase 2 Shionogi, Inc. Cephalosporin Yes Yes Complicated urinary tract infections Macrocycle (protein Ventilator-associated bacterial pneumonia POL7080 Phase 210 Polyphor Ltd. epitope mimetic) LptD Yes (Pseudomonas) No (caused by Pseudomonas aeruginosa), lower inhibitor respiratory tract infection, bronchiectasis Acute bacterial skin and skin structure Debio 1452 Phase 2 Debiopharm Group Fabl inhibitor No No infections (staphylococci-specific) Community-acquired bacterial pneumonia, Allergan plc (formerly Avarofloxacin Phase 2 Fluoroquinolone No No acute bacterial skin and skin structure Actavis) infections Acute bacterial skin and skin structure Brilacidin Phase 2 Cellceutix Corp. Defensin-mimetic No No infections AstraZeneca plc/Allergan Cephalosporin + novel Ceftaroline+Avibactam Phase 2 Yes Yes Bacterial infections6 plc (formerly Actavis) beta-lactamase inhibitor Acute bacterial skin and skin structure CG400549 Phase 2 CrystalGenomics, Inc. Fabl inhibitor No No infections, osteomyelitis6 Complicated urinary tract infections, acute pyelonephritis (kidney infection), MerLion Pharmaceuticals Finafloxacin11 Phase 212 Fluoroquinolone Yes 14 Possibly15 complicated intra-abdominal infections, Pte Ltd. acute bacterial skin and skin structure infections Respiratory tract infections, acute Gepotidacin Novel bacterial Phase 2 GlaxoSmithKline plc No Yes bacterial skin and skin structure infections, (GSK2140944) topoisomerase inhibitor uncomplicated urogenital gonorrhea Expected activity Expected activity Development against resistant against a CDC Drug name Company Drug class Potential indication(s)?5 phase2 Gram-negative ESKAPE urgent threat pathogens?3 pathogen?4 Community-acquired bacterial pneumonia, TaiGen Biotechnology Nemonoxacin8 Phase 2 Quinolone No No diabetic foot infection, acute bacterial skin Co., Ltd. and skin structure infections Acute bacterial skin and skin structure Melinta Therapeutics, Radezolid Phase 2 Oxazolidinone No No infections, community-acquired bacterial Inc. pneumonia Ramoplanin Phase 2 Nanotherapeutics, Inc. Glycolipodepsipeptide No Yes C. difficile relapse prevention6 Dong Wha Zabofloxacin Phase 2 Fluoroquinolone No No Community-acquired bacterial pneumonia Pharmaceutical Co., Ltd Summit Therapeutics, SMT 19969 Phase 2 No Yes C. difficile-associated diarrhea Inc. Community-acquired bacterial pneumonia, Paratek Pharmaceuticals, acute bacterial skin and skin structure Omadacycline Phase 3 Tetracycline Yes Possibly15 Inc. infections, complicated urinary tract infections Acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, hospital-acquired bacterial Lefamulin (BC-3781) Phase 3 Nabriva Therapeutics AG Pleuromutilin No No pneumonia/ventilator-associated bacterial pneumonia, osteomyelitis,6 prosthetic joint infections6 Complicated urinary tract infections, acute Imipenem/ pyelonephritis, complicated intra-abdominal Carbapenem + novel cilastatin+relebactam Phase 316 Merck & Co., Inc. Yes Yes infections, hospital-acquired bacterial beta-lactamase inhibitor (MK-7655) pneumonia/ventilator-associated bacterial pneumonia Acute bacterial skin and skin structure Dihydrofolate reductase Iclaprim Phase 318 Motif Bio plc No No infections; hospital-acquired bacterial (DHFR) inhibitor pneumonia Actelion Pharmaceuticals Quinolonyl- Cadazolid Phase 3 No Yes C. difficile-associated diarrhea Ltd oxazolidinone Prosthetic joint infections, acute bacterial Taksta (Fusidic acid)9 Phase 3 Cempra, Inc. Fusidane No No skin and skin structure infections Complicated urinary tract infections, complicated intra-abdominal infections, Rempex Pharmaceuticals, hospital-acquired bacterial pneumonia/ Meropenem + novel Carbavance Inc. (wholly owned ventilator-associated bacterial pneumonia, Phase 3 boronic beta-lactamase Yes Yes (RPX7009+meropenem) subsidiary of The febrile neutropenia, bacteremia, acute inhibitor Medicines Co.) pyelonephritis (some indications specifically target infections caused by carbapenem- resistant Enterobacteriaceae ) Expected activity Expected activity Development against resistant against a CDC Drug name Company Drug class Potential indication(s)?5 phase2 Gram-negative ESKAPE urgent threat pathogens?3 pathogen?4 Acute bacterial skin and skin structure infections, hospital-acquired bacterial Melinta Therapeutics, Delafloxacin Phase 3 Fluoroquinolone Possibly Possibly pneumonia,6 complicated urinary tract Inc. infections,6 complicated intra-abdominal infections6 Complicated intra-abdominal infections, Tetraphase Eravacycline Phase 3 Tetracycline Yes Yes complicated urinary tract infections, Pharmaceuticals, Inc. hospital-acquired bacterial pneumonia6 Complicated urinary tract infections, catheter-related bloodstream infections, hospital-acquired bacterial pneumonia/ ventilator-associated bacterial pneumonia, Plazomicin Phase 3 Achaogen, Inc. Aminoglycoside Yes Yes complicated intra-abdominal infections, acute pyelonephritis (kidney infection) (some indications specifically target infections caused by carbapenem-resistant Enterobacteriaceae) Community-acquired bacterial pneumonia, Macrolide Solithromycin Phase 3 Cempra, Inc. No Yes uncomplicated urogenital gonorrhea, (fluoroketolide) urethritis6 Cubist Pharmaceuticals, Inc. (wholly owned Surotomycin Phase 3 Lipopeptide No Yes C. difficile-associated diarrhea subsidiary of Merck & Co.) For definitions of drug development terms, visit: http://www.pewtrusts.org/en/research-and-analysis/analysis/2014/03/12/from-lab-bench-to-bedside-a-backgrounder-on-drug-development. Note: The following drugs have been removed from the pipeline. They will be included in future updates if development resumes: September 2015 review: No changes. March 2015 review: No changes. December 2014 review: EDP-788 (Enanta Pharmaceuticals) and TD-1792 (Theravance Biopharma) were removed during the December 2014 review. These drugs were either no longer included in the research and development pipelines on the
Load more

Recommended publications
  • The Role of Nanobiosensors in Therapeutic Drug Monitoring
    Journal of Personalized Medicine Review Personalized Medicine for Antibiotics: The Role of Nanobiosensors in Therapeutic Drug Monitoring Vivian Garzón 1, Rosa-Helena Bustos 2 and Daniel G. Pinacho 2,* 1 PhD Biosciences Program, Universidad de La Sabana, Chía 140013, Colombia; [email protected] 2 Therapeutical Evidence Group, Clinical Pharmacology, Universidad de La Sabana, Chía 140013, Colombia; [email protected] * Correspondence: [email protected]; Tel.: +57-1-8615555 (ext. 23309) Received: 21 August 2020; Accepted: 7 September 2020; Published: 25 September 2020 Abstract: Due to the high bacterial resistance to antibiotics (AB), it has become necessary to adjust the dose aimed at personalized medicine by means of therapeutic drug monitoring (TDM). TDM is a fundamental tool for measuring the concentration of drugs that have a limited or highly toxic dose in different body fluids, such as blood, plasma, serum, and urine, among others. Using different techniques that allow for the pharmacokinetic (PK) and pharmacodynamic (PD) analysis of the drug, TDM can reduce the risks inherent in treatment. Among these techniques, nanotechnology focused on biosensors, which are relevant due to their versatility, sensitivity, specificity, and low cost. They provide results in real time, using an element for biological recognition coupled to a signal transducer. This review describes recent advances in the quantification of AB using biosensors with a focus on TDM as a fundamental aspect of personalized medicine. Keywords: biosensors; therapeutic drug monitoring (TDM), antibiotic; personalized medicine 1. Introduction The discovery of antibiotics (AB) ushered in a new era of progress in controlling bacterial infections in human health, agriculture, and livestock [1] However, the use of AB has been challenged due to the appearance of multi-resistant bacteria (MDR), which have increased significantly in recent years due to AB mismanagement and have become a global public health problem [2].
    [Show full text]
  • Overcoming Fluoroquinolone Resistance: Mechanistic Basis of Non- Quinolone Antibacterials Targeting Type Ii Topoisomerases
    OVERCOMING FLUOROQUINOLONE RESISTANCE: MECHANISTIC BASIS OF NON- QUINOLONE ANTIBACTERIALS TARGETING TYPE II TOPOISOMERASES By Elizabeth Grace Gibson Dissertation Submitted to the Faculty of the Graduate School of Vanderbilt University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in Pharmacology May 10, 2019 Nashville, Tennessee Approved: Neil Osheroff, Ph.D. Joey Barnett, Ph.D. Wendell S. Akers, Pharm.D., Ph.D. Sean Davies, Ph.D. Benjamin Spiller, Ph.D. Timothy R. Sterling, M.D. DEDICATION To all my family and church family who have supported and encouraged me over all my years in school. To Him who I put all my trust. Commit your way to the Lord, trust also in Him and He shall bring it to pass. Psalm 37:5 ii ACKNOWLEDGEMENTS I want to first thank my Ph.D. advisor, Dr. Neil Osheroff, for allowing me to work in his laboratory. Thank you for all your support and encouragement and just being an overall great mentor. You really know how to bring us up when we need it or give us an ego check when we get a little high and mighty when things are going well. I appreciate your supportiveness to careers outside academia. I also appreciate that you always have our best interest at heart. To Dr. Joe Deweese, my first research mentor and the one who instilled the love of topoisomerase research. Without your guidance I would not be where I am today. Thank you for introducing me to Neil and his laboratory and helping with the transition from research in your lab to his.
    [Show full text]
  • Gonorrhea, Chlamydia, and Syphilis
    2019 GONORRHEA, CHLAMYDIA, AND SYPHILIS AND CHLAMYDIA, GONORRHEA, Dedication TAG would like to thank the National Coalition of STD Directors for funding and input on the report. THE PIPELINE REPORT Pipeline for Gonorrhea, Chlamydia, and Syphilis By Jeremiah Johnson Introduction The current toolbox for addressing gonorrhea, chlamydia, and syphilis is inadequate. At a time where all three epidemics are dramatically expanding in locations all around the globe, including record-breaking rates of new infections in the United States, stakeholders must make do with old tools, inadequate systems for addressing sexual health, and a sparse research pipeline of new treatment, prevention, and diagnostic options. Lack of investment in sexual health research has left the field with inadequate prevention options, and limited access to infrastructure for testing and treatment have allowed sexually transmitted infections (STIs) to flourish. The consequences of this underinvestment are large: according to the World Health Organization (WHO), in 2012 there were an estimated 357 million new infections (roughly 1 million per day) of the four curable STIs: gonorrhea, chlamydia, syphilis, and trichomoniasis.1 In the United States, the three reportable STIs that are the focus of this report—gonorrhea, chlamydia, and syphilis—are growing at record paces. In 2017, a total of 30,644 cases of primary and secondary (P&S) syphilis—the most infectious stages of the disease—were reported in the United States. Since reaching a historic low in 2000 and 2001, the rate of P&S syphilis has increased almost every year, increasing 10.5% during 2016–2017. Also in 2017, 555,608 cases of gonorrhea were reported to the U.S.
    [Show full text]
  • Activity of the Investigational Fluoroquinolone Finafloxacin and Seven Other PD Dr
    Contact information: CORRESPONDING AUTHOR Activity of the Investigational Fluoroquinolone Finafloxacin and Seven Other PD Dr. Reiner Schaumann 49 th ICAAC Institute for Medical Microbiology and Epidemiology of Infectious Diseases San Francisco 2009 Antimicrobial Agents Against 83 Obligately Anaerobic Bacteria. University of Leipzig Liebigstr. 24 1 1 2 1 2 1 D-04103 Leipzig R. SCHAUMANN , G. H. GENZEL , W. STUBBINGS , C. S. STINGU , H. LABISCHINSKI , A. C. RODLOFF Germany E - 1973 Phone +49 341 97 15 200 1Inst. f. Med. Microbiology and Epidemiology of Infectious Diseases, Univ. of Leipzig, Leipzig, Germany; 2MerLion Pharmaceuticals GmbH, Berlin, Germany. Fax +49 341 97 15 209 E-Mail: [email protected] AbstractAbstract MethodsMethods ResultsResults andand DiscussionDiscussion Background: Finafloxacin (FIN) is a novel Bacterial Strains The Figures 2 and 3 show the scatter fluoroquinolone belonging to a 8-cyano subclass 83 obligately anaerobes including reference strains were taken from the histograms of MIC values obtained for FIN culture collection from the Institute for Medical Microbiology and and exhibits enhanced activity at slightly acidic and the seven other antimicrobial agents pH. FIN exhibited superior activity to comparator Epidemiology of Infectious Diseases, University of Leipzig, Germany. The fluoroquinolones in a wide range of rodent strains were collected from clinical specimens at the Institute and from against 83 obligately anaerobic bacteria infection models. With the present study the national and international studies and obtained in part from other included in this study. activity of FIN against 83 recently isolated strains laboratories. The following strains were used: Bacteroides fragils group of obligately anaerobic bacteria including (n=62): B.
    [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]
  • Antibacterial Efficacy of Eravacycline in Vivo Against Gram-Positive And
    crossmark Antibacterial Efficacy of Eravacycline In Vivo against Gram-Positive and Gram-Negative Organisms Marguerite L. Monogue,a Abrar K. Thabit,a,b Yukihiro Hamada,a,c David P. Nicolaua,d Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USAa; Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabiab; Aichi Medical University Hospital School of Medicine, Aichi, Japanc; Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut, USAd Members of the tetracycline class are frequently classified as bacteriostatic. However, recent findings have demonstrated an im- > proved antibacterial killing profile, often achieving 3 log10 bacterial count reduction, when such antibiotics have been given for periods longer than 24 h. We aimed to study this effect with eravacycline, a novel fluorocycline, given in an immunocompetent murine thigh infection model over 72 h against two methicillin-resistant Staphylococcus aureus (MRSA) isolates (eravacycline to 0.25 ␮g/ml). A humanized Downloaded from 0.125 ؍ and 0.25 ␮g/ml) and three Enterobacteriaceae isolates (eravacycline MICs 0.03 ؍ MICs eravacycline regimen, 2.5 mg/kg of body weight given intravenously (i.v.) every 12 h (q12h), demonstrated progressively en- hanced activity over the 72-h study period. A cumulative dose response in which bacterial density was reduced by more than 3 log10 CFU at 72 h was noted over the study period in the two Gram-positive isolates, and eravacycline performed similarly to comparator antibiotics (tigecycline, linezolid, and vancomycin). A cumulative dose response with eravacycline and comparators (tigecycline and meropenem) over the study period was also observed in the Gram-negative isolates, although more variability in bacterial killing was observed for all antibacterial agents.
    [Show full text]
  • Against Helicobacter Pylori in Vitro and in Vivo Merlion Pharmaceuticals Pte Ltd, Washington DC 2008 05-01 the Capricorn, 1 2 1 1 3 3 1 Science Park 2, A
    Contact information: 48th ICAAC / 46th IDSA, WILL STUBBINGS Antimicrobial Activity of Finafloxacin (FIN) against Helicobacter pylori In Vitro and In Vivo MerLion Pharmaceuticals Pte Ltd, Washington DC 2008 05-01 The Capricorn, 1 2 1 1 3 3 1 Science Park 2, A. BUISSONNIÈRE , H-O. WERLING B. BERGEY , P. LEHOURS , W. STUBBINGS , H. LABISCHINSKI , F. MEGRAUD . Singapore 117528 F1-2038 Phone +65 6829 5600 1INSERM U853, Bordeaux, France, 2Bayer HealthCare AG, Elberfeld, Germany, 3MerLion Pharmaceuticals Pte Ltd, Singapore. [email protected] RevisedRevised abstractabstract MethodsMethods ResultsResults andand DiscussionDiscussion Introduction: FIN is a novel fluoroquinolone (FQ) belonging to a new 8- Minimum inhibitory concentration (MIC) determination Murine model of H. felis infection cyano subclass. FIN exhibits optimal efficacy at slightly acidic pH (5.0 - 6.0), Finafloxacin Levofloxacin Clearance % under which other FQs lose activity. FIN is intended for therapeutic use MICs were determined for FIN and LVX against H. pylori strains (n= 55) that were MIC MIC MIC MIC W 8801, X 7328, 17-8299, H. felis was passaged in mice to achieve a persistent infection that pH 50 90 50 90 X 2752, X 9181, Y 1304 against bacterial infections associated with an acidic environment such as H. obtained from patients gastroscoped in the Southwest of France. MICs were 100 [mg/L] [mg/L] [mg/L] [mg/L] 34-6601 exhibited a similar response to therapy as H. pylori in humans. Triple pylori eradication. The antibacterial activity of FIN, was determined against performed by agar dilution at 3 different pHs: 7.3, 6.3 and 5.3. An inoculum FIN FQ RES and susceptible strains at acidic pH, and against H.
    [Show full text]
  • 200 and 800 Mg) in Healthy Volunteers Receiving a Single Oral Dose
    Pharmacology Chemotherapy 2011;57:97–107 Received: June 9, 2010 DOI: 10.1159/000321028 Accepted after revision: August 30, 2010 Published online: February 28, 2011 Urinary Pharmacokinetics and Bactericidal Activity of Finafloxacin (200 and 800 mg) in Healthy Volunteers Receiving a Single Oral Dose a b d Florian M.E. Wagenlehner Christine M. Wagenlehner Birgit Blenk d e e c Holger Blenk Sabine Schubert Axel Dalhoff Kurt G. Naber a Department of Urology, Pediatric Urology and Andrology, Justus Liebig University Giessen, and b c Department of Anesthesia, Evangelisches Krankenhaus, Giessen , Technical University of Munich, Straubing , d e Department of Microbiology, Nürnberg , and University Hospital Schleswig-Holstein, Campus Kiel, Kiel , Germany Key Words Introduction ؒ Finafloxacin ؒ Urine pharmacokinetics ؒ Pharmacodynamics Urinary bactericidal titers Urinary tract infection (UTI) is one of the most com- mon reasons for medical consultation. Uncomplicated UTI are predominantly caused by Escherichia coli, but Abstract also by Proteus mirabilis and occasionally Klebsiella spp., Background: Finafloxacin is a novel 8-cyano-fluoroquino- other Enterobacteriaceae and Staphylococcus saprophyti- lone under investigation for treatment of urinary tract infec- cus ( ! 5% each) [1–3] . Infections with P. mirabilis are sig- tion. Methods: Urinary concentrations and urinary bacteri- nificantly more common in patients over 50 years, where- cidal titers (UBT) of finafloxacin 200- and 800-mg single dos- as infections with S. saprophyticus are more common in es in 6 healthy volunteers were measured up to 48 h. UBT younger patients. Nosocomial UTI, almost always com- were determined for a reference strain and 9 selected clin- plicated, are caused by a wide range of pathogens, most ical uropathogens at the pH of native, acidified (pH 5.5) frequently E.
    [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]
  • The Study Listed May Include Approved and Non-Approved Uses, Formulations Or Treatment Regimens
    The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product. Before prescribing any product mentioned in this Register, healthcare professionals should consult prescribing information for the product approved in their country. GSK Medicine: Gepotidacin Study Number: 207625 Title: Meta-analysis to estimate the microbiological treatment effect of nitrofurantoin for determination of the non-inferiority margin in a phase 3 clinical trial of uncomplicated urinary tract infection (uUTI). Rationale: Active-comparator, non-inferiority study designs are generally used in uUTI trials, given the ethical implications of placebo treatment. In order to design, execute, and analyze a non-inferiority trial, an estimate of the treatment effect (M1) of the planned active comparator (nitrofurantoin), must be obtained from historical randomized or open label studies. Once an estimate of M1 (nitrofurantoin treatment effect) is obtained, a non-inferiority margin (M2) or the largest clinically acceptable difference of the test drug compared to the active comparator must be determined. Determination of M1 and M2 is critical to the design, analysis and interpretation of a non-inferiority trial. The rationale for this study was to estimate the treatment effect of an active comparator (nitrofurantoin) in order to determine the non-inferiority margin for a Phase III study, which will demonstrate the efficacy of a new
    [Show full text]
  • In Vitro Activity of Eravacycline and Comparator Antimicrobials Against
    In Vitro Activity of Eravacycline and comparator antimicrobials *Presenting Author: against 143 recent strains of Bacteroides species Diane M. Citron 1209 [email protected] Diane M. Citron, Kerin L. Tyrrell, and Ellie J. C. Goldstein R. M. Alden Research Laboratory, Culver City, CA 90230 Introduction Results Discussion Eravacycline (ERV) is a novel, fully-synthetic fluorocycline antibiotic in Resistance to tetracycline has become common among Bacteroides species and Table 1. In vitro activity (µg/ml) of eravacycline and comparators development for the treatment of serious infections, including those caused by the MIC90 for all of the strains was >32 µg/ml. Eravacycline was four- to eight- multidrug-resistant (MDR) pathogens. ERV recently completed phase 3 clinical against Bacteroides species. All results for the quality control fold more active than tigecycline against these strains with MIC at 1–4 µg/ml. strains were within acceptable CLSI ranges (4). 90 development for the treatment of complicated intra-abdominal infections (cIAI) Eravacycline was active against several strains that showed resistance to and is in phase 3 clinical development for complicated urinary tract infections piperacillin-tazobactam and meropenem. (cUTI), including pyelonephritis. Organism (no.) / Agent Range MIC MIC 50 90 Resistance to clindamycin was also common and all of these strains were ERV has potent activity against a broad range of Gram-positive, Gram- B. caccae (10) Eravacycline 0.25–4 0.5 2 susceptible to eravacycline. negative and anaerobic pathogens. Like other tetracyclines, ERV inhibits protein Tigecycline 0.25–16 4 16 Metronidazole resistance was not encountered in this group of isolates, although, synthesis by binding to the 30S ribosomal subunit.
    [Show full text]
  • Lactamase-Producing Carbapenem-Resistant Enterobacteriaceae (CRE) to Eravacycline
    The Journal of Antibiotics (2016) 69, 600–604 & 2016 Japan Antibiotics Research Association All rights reserved 0021-8820/16 www.nature.com/ja ORIGINAL ARTICLE In vitro susceptibility of β-lactamase-producing carbapenem-resistant Enterobacteriaceae (CRE) to eravacycline Yunliang Zhang, Xiaoyan Lin and Karen Bush Eravacycline is a novel, fully synthetic fluorocycline antibiotic of the tetracycline class being developed for the treatment of complicated urinary tract infections and complicated intra-abdominal infections. Eravacycline has activity against many key Gram-negative pathogens, including Enterobacteriaceae resistant to carbapenems, cephalosporins, fluoroquinolones and β-lactam/β-lactamase inhibitor combinations, including strains that are multidrug-resistant. Carbapenem-resistant Enterobacteriaceae (CRE) isolates from 2010 to 2013 (n = 110) were characterized for carbapenemase genes by PCR and sequencing. MICs for eravacycline, tetracycline, tigecycline, amikacin, imipenem, ceftazidime, cefotaxime and levofloxacin were determined in broth microdilution assays. All isolates produced at least one carbapenemase, most frequently KPC-3. Nine isolates produced both a KPC serine carbapenemase and a metallo-β-lactamase, NDM-1 (n = 1) or VIM-1 (n = 8). The 110 isolates were highly resistant to all the β-lactams tested and to levofloxacin, and had MIC50/MIC90 values in the intermediate − 1 − 1 range for tetracycline and amikacin. MIC50/MIC90 values for eravacycline were 1/2 μgml compared with 2/2 μgml for tigecycline. Eravacycline MICs were often twofold lower than for tigecycline, with 64% of the eravacycline MICs o2 μgml− 1 as compared with o4% of tigecycline MICs. Overall, eravacycline demonstrated the lowest cumulative MICs against this panel of recent CRE and may have the potential to treat infections caused by CRE.
    [Show full text]