DOCSLIB.ORG

Antibiotics Currently in Clinical Development Note: This Data Visualization Was Updated in May 2017 with New Data

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Antibiotics Currently in Clinical Development Note: This Data Visualization Was Updated in May 2017 with New Data A data table from May 2017 Antibiotics Currently in Clinical Development Note: This data visualization was updated in May 2017 with new data. As of March 2017, approximately 41 new antibiotics1 with the potential to treat serious bacterial infections are in clinical development for the U.S. market. 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 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 against resistant against a CDC Drug name Company Drug class Target Potential indication(s)?5 Gram-negative urgent threat ESKAPE pathogens?3 pathogen?4 New Drug Application (NDA) submitted2 Acute bacterial skin and skin structure infections, Baxdela Melinta Thera- Bacterial type II Fluoroquinolone Possibly Possibly community-acquired bacterial pneumonia, complicated (delafloxacin) peutics Inc. topoisomerase urinary tract infections6 Complicated urinary tract infections, complicated Rempex Phar- intra-abdominal infections, hospital-acquired bacterial maceuticals Inc. β-lactam (carbapenem) Meropenem + pneumonia/ventilator-associated bacterial pneumonia, (wholly owned + β-lactamase inhibitor PBP; β-lactamase Yes Yes Vaborbactam febrile neutropenia, bacteremia, acute pyelone-phritis subsidiary of The (cyclic boronate)16,18 (some indications specifically target infections caused by Medicines Co.) carbapenem-resistant Enterobacteriaceae) Phase 12 Methionyl-tRNA CRS3123 Crestone Inc. Diaryldiamine16 No Yes C. difficile infections synthetase17 β-lactam (sulbactam) Entasis Bacterial infections (caused by ETX2514SUL10 + β-lactamase inhibitor PBP; β-lactamase Yes No Therapeutics Inc. Acinetobacter baumannii)6 (diazabicyclooctane) GlaxoSmithKline GSK-334283010 PLC (Shionogi β-lactam (cephalosporin) PBP Possibly Possibly Bacterial infections licensee) Continued on the next page Expected activity Expected activity against resistant against a CDC Drug name Company Drug class Target Potential indication(s)?5 Gram-negative urgent threat ESKAPE pathogens?3 pathogen?4 Phase 12 (continued) KBP BioSciences 30S subunit of KBP-7072 Pharmaceutical Tetracycline Possibly No Community-acquired bacterial pneumonia6 bacterial ribosome Technical Co. Ltd. LegoChem 50S subunit of LCB01-037110 Oxazolidinone No No Bacterial infections Biosciences Inc. bacterial ribosome 50S subunit of Oxazolidinone-quinolone bacterial ribosome; MCB3837 Morphochem AG No Yes C. difficileinfections 6 hybrid bacterial type II topoisomerase MGB Biopharma MGB-BP-310 Distamycin16 DNA minor groove17 No Yes C. difficile-associated diarrhea Ltd. Meiji Seika Pharma Nacubactam Co. Ltd./Fedora β-lactamase inhibitor (OP0595/ Pharmaceuticals β-lactamase, PBP2 Possibly Possibly Bacterial infections (diazabicyclooctane) RG6080)10 Inc. (Roche licensee) SPR7416,10,19 Spero Therapeutics Polymyxin Cell membrane17 Possibly Possibly Bacterial infections Acute bacterial skin and skin structure infections,6 Theravance Glycopeptide-β-lactam PG chain TD-1607 No No hospital-acquired pneumonia/ventilator-associated Biopharma Inc. (cephalosporin) hybrid elongation; PBP bacterial pneumonia,6 bacteremia6 Tetraphase 30S subunit of TP-271 Pharmaceuticals Tetracycline Possibly Possibly Community-acquired bacterial pneumonia bacterial ribosome Inc. Tetraphase 30S subunit of TP-60766 Pharmaceuticals Tetracycline Possibly Possibly Bacterial infections bacterial ribosome Inc. Fluoroquinolone (WCK Bacterial type II WCK 2349 Wockhardt Ltd. No No Hospital-acquired bacterial pneumonia6 771 pro-drug) topoisomerase Bacterial type II WCK 771 Wockhardt Ltd. Fluoroquinolone No No Hospital-acquired bacterial pneumonia6 topoisomerase Continued on the next page Expected activity Expected activity against resistant against a CDC Drug name Company Drug class Target Potential indication(s)?5 Gram-negative urgent threat ESKAPE pathogens?3 pathogen?4 Phase 12 (continued) Cefepime + β-lactam (cephalosporin) Complicated urinary tract infections,6 Zidebactam Wockhardt Ltd. + β-lactamase inhibitor PBP; β-lactamase Yes Possibly hospital-acquired bacterial pneumonia/ventilator- (WCK 5222) (diazabicyclooctane) associated bacterial pneumonia6 Phase 22 Aztreonam + Pfizer Inc./Allergan β-lactam (monobactam) Avibactam7,10 PLC (formerly + β-lactamase inhibitor PBP; β-lactamase Yes Yes Complicated intra-abdominal infections (ATM-AVI) Actavis) (diazabicyclooctane) Brilacidin Cellceutix Corp. Defensin mimetic16 Cell membrane No No Acute bacterial skin and skin structure infections CrystalGenomics Acute bacterial skin and skin structure infections, CG400549 Benzyl pyridinone16 FabI17 No No Inc. osteomyelitis6 Afabicin Debiopharm Benzofuran Acute bacterial skin and skin structure infections and FabI17 No No (Debio 1450) International SA naphthyridine16 osteomyelitis (Staphylococcus-specific) Complicated urinary tract infections, acute MerLion Bacterial type II pyelonephritis (kidney infection), complicated intra- Finafloxacin11,12 Pharmaceuticals Fluoroquinolone Yes 13 Possibly topoisomerase abdominal infections, acute bacterial skin and skin Pte Ltd. structure infections Bacterial type II Complicated urinary tract infections,6 uncomplicated Gepotidacin GlaxoSmithKline topoisomerase urinary tract infections, acute bacterial skin and skin Triazaacenaphthylene16 No Yes (GSK2140944)15 PLC (novel A subunit structure infections, uncomplicated urogenital gonorrhea, site)17 and community-acquired bacterial pneumonia6 MicuRx 50S subunit of MRX-I14 Pharmaceuticals Oxazolidinone No No Acute bacterial skin and skin structure infections bacterial ribosome Inc. Nafithromycin 50S subunit of Wockhardt Ltd. Macrolide No No Community-acquired bacterial pneumonia (WCK 4873) bacterial ribosome TaiGen Community-acquired bacterial pneumonia, diabetic Bacterial type II Nemonoxacin8 Biotechnology Co. Quinolone No No foot infection, acute bacterial skin and skin structure topoisomerase Ltd. infections Ventilator-associated bacterial pneumonia (caused by Murepavadin Antimicrobial peptide Polyphor Ltd. LptD17 Yes (Pseudomonas) No Pseudomonas aeruginosa), lower respiratory tract infection, (POL7080)10 mimetic16 bronchiectasis Continued on the next page Expected activity Expected activity against resistant against a CDC Drug name Company Drug class Target Potential indication(s)?5 Gram-negative urgent threat ESKAPE pathogens?3 pathogen?4 Nanotherapeutics Ramoplanin Lipodepsipeptide16 Lipid I,II No Yes Prevention of recurrent C. difficileinfection 6 Inc. Ridinilazole Summit Bis-benzimidazole16 Unknown No Yes C. difficile infection (SMT 19969) Therapeutics Inc. Bacterial type II Zoliflodacin Entasis Spiropyrimidenetrione16 topoisomerase No Yes Uncomplicated gonorrhea (ETX0914) Therapeutics Inc. (GyrB)17 Phase 32 50S subunit of Actelion Oxazolidinone-quinolone bacterial ribosome; Cadazolid Pharmaceuticals No Yes C. difficile infection hybrid bacterial type II Ltd. topoisomerase Cefiderocol (S- Siderophore-β-lactam Complicated urinary tract infections, carbapenem- Shionogi & Co. Ltd. PBP Yes Yes 649266)15 (cephalosporin) resistant Gram-negative bacterial infections Tetraphase 30S subunit of Complicated intra-abdominal infections, complicated Eravacycline Pharmaceuticals Tetracycline Yes Yes bacterial ribosome urinary tract infections Inc. Dihydrofolate Acute bacterial skin and skin structure infections; Iclaprim Motif Bio PLC 2,4-diaminopyrimidine No No reductase hospital-acquired bacterial pneumonia Imipenem/ Complicated urinary tract infections, acute β-lactam (carbapenem) cilastatin + pyelonephritis, complicated intra-abdominal infections, Merck & Co. Inc. + β-lactamase inhibitor PBP; β-lactamase Yes Yes relebactam (MK- hospital-acquired bacterial pneumonia/ventilator- (diazabicyclooctane) 7655) associated bacterial pneumonia Acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, hospital- Lefamulin (BC- Nabriva 50S subunit of Pleuromutilin16 No No acquired bacterial pneumonia/ventilator-associated 3781) Therapeutics AG bacterial ribosome bacterial pneumonia,6 osteomyelitis,6 prosthetic joint infections6 Paratek Community-acquired bacterial pneumonia, acute 30S subunit of Omadacycline Pharmaceuticals Tetracycline Yes Possibly bacterial skin and skin structure infections, complicated bacterial ribosome Inc. urinary tract infections Continued on the next page Expected activity Expected activity against resistant against a CDC Drug name Company Drug class Target Potential indication(s)?5 Gram-negative urgent threat ESKAPE pathogens?3 pathogen?4 Phase 32 (continued) Complicated urinary tract infections including acute pyelonephritis, catheter-related bloodstream infections, hospital-acquired bacterial pneumonia/ventilator- 30S subunit of Plazomicin Achaogen Inc. Aminoglycoside Yes Yes associated bacterial pneumonia, complicated intra- bacterial ribosome abdominal infections in patients with limited treatment options (some indications specifically target infections caused by carbapenem-resistant Enterobacteriaceae) Solithera 50S subunit of Community-acquired bacterial pneumonia, Cempra Inc. Macrolide No Yes (Solithromycin) bacterial
Load more

Recommended publications
  • Activity of Cefepime-Zidebactam Against Multidrug-Resistant (MDR) Gram-Negative Pathogens
    antibiotics Article Activity of Cefepime-Zidebactam against Multidrug-Resistant (MDR) Gram-Negative Pathogens Kenneth S. Thomson 1,* , Sameh AbdelGhani 1,2, James W. Snyder 1 and Gina K. Thomson 1,3 1 Department of Pathology and Laboratory Medicine, School of Medicine, University of Louisville, Louisville, KY 40202, USA; [email protected] (S.A.); [email protected] (J.W.S.); [email protected] (G.K.T.) 2 Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt 3 Microbiology Department, University of Louisville Hospital, Louisville, KY 40202, USA * Correspondence: [email protected] Received: 18 February 2019; Accepted: 19 March 2019; Published: 23 March 2019 Abstract: This study compared the activity of cefepime + zidebactam (FEP-ZID) and selected currently available antibacterial agents against a panel of multidrug-resistant (MDR) clinical isolates chosen to provide an extreme challenge for antibacterial activity. FEP–ZID had a very broad and potent in vitro spectrum of activity, and was highly active against many MDR isolates of Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii. Notably, it inhibited isolates producing carbapenemases of Ambler classes A, B, and D, and P. aeruginosa isolates with multiple resistance mechanisms including combinations of upregulated efflux, diminished or non-functional OprD porins, and AmpC overproduction. Its clinical role will be determined initially by the breakpoints assigned to it, comparison studies with other investigational β-lactamase inhibitor combinations, and ultimately by the developing body of therapeutic outcome data. Keywords: carbapenemase-producing organism; carbapenemase; zidebactam; therapy 1. Introduction Gram-negative multidrug-resistant (MDR) pathogens, particularly carbapenemase-producing organisms (CPOs), cause infections of high mortality that are typically treated with antibiotic combinations that include toxic drugs such as polymyxins and aminoglycosides [1].
    [Show full text]
  • General Items
    Essential Medicines List (EML) 2019 Application for the inclusion of imipenem/cilastatin, meropenem and amoxicillin/clavulanic acid in the WHO Model List of Essential Medicines, as reserve second-line drugs for the treatment of multidrug-resistant tuberculosis (complementary lists of anti-tuberculosis drugs for use in adults and children) General items 1. Summary statement of the proposal for inclusion, change or deletion This application concerns the updating of the forthcoming WHO Model List of Essential Medicines (EML) and WHO Model List of Essential Medicines for Children (EMLc) to include the following medicines: 1) Imipenem/cilastatin (Imp-Cln) to the main list but NOT the children’s list (it is already mentioned on both lists as an option in section 6.2.1 Beta Lactam medicines) 2) Meropenem (Mpm) to both the main and the children’s lists (it is already on the list as treatment for meningitis in section 6.2.1 Beta Lactam medicines) 3) Clavulanic acid to both the main and the children’s lists (it is already listed as amoxicillin/clavulanic acid (Amx-Clv), the only commercially available preparation of clavulanic acid, in section 6.2.1 Beta Lactam medicines) This application makes reference to amendments recommended in particular to section 6.2.4 Antituberculosis medicines in the latest editions of both the main EML (20th list) and the EMLc (6th list) released in 2017 (1),(2). On the basis of the most recent Guideline Development Group advising WHO on the revision of its guidelines for the treatment of multidrug- or rifampicin-resistant (MDR/RR-TB)(3), the applicant considers that the three agents concerned be viewed as essential medicines for these forms of TB in countries.
    [Show full text]
  • New Β-Lactamase Inhibitor Combinations: Options for Treatment; Challenges for Testing
    MEDICAL/SCIENTIFIC AffAIRS BULLETIN New β-lactamase Inhibitor Combinations: Options for Treatment; Challenges for Testing Background The β-lactam class of antimicrobial agents has played a crucial role in the treatment of infectious diseases since the discovery of penicillin, but β–lactamases (enzymes produced by the bacteria that can hydrolyze the β-lactam core of the antibiotic) have provided an ever expanding threat to their successful use. Over a thousand β-lactamases have been described. They can be divided into classes based on their molecular structure (Classes A, B, C and D) or their function (e.g., penicillinase, oxacillinase, extended-spectrum activity, or carbapenemase activity).1 While the first approach to addressing the problem ofβ -lactamases was to develop β-lactamase stable β-lactam antibiotics, such as extended-spectrum cephalosporins, another strategy that has emerged is to combine existing β-lactam antibiotics with β-lactamase inhibitors. Key β-lactam/β-lactamase inhibitor combinations that have been used widely for over a decade include amoxicillin/clavulanic acid, ampicillin/sulbactam, and pipercillin/tazobactam. The continued use of β-lactams has been threatened by the emergence and spread of extended-spectrum β-lactamases (ESBLs) and more recently by carbapenemases. The global spread of carbapenemase-producing organisms (CPOs) including Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii, limits the use of all β-lactam agents, including extended-spectrum cephalosporins (e.g., cefotaxime, ceftriaxone, and ceftazidime) and the carbapenems (doripenem, ertapenem, imipenem, and meropenem). This has led to international concern and calls to action, including encouraging the development of new antimicrobial agents, enhancing infection prevention, and strengthening surveillance systems.
    [Show full text]
  • Neomycin and Polymyxin B Sulfates and Gramicidin
    NEOMYCIN AND POLYMYXIN B SULFATES AND GRAMICIDIN- neomycin sulfate, polymyxin b sulfate and gramicidin solution/ drops A-S Medication Solutions ---------- Neomycin and Polymyxin B Sulfates and Gramicidin Ophthalmic Solution, USP (Sterile) Rx only DESCRIPTION: Neomycin and Polymyxin B Sulfates and Gramicidin Ophthalmic Solution, USP is a sterile antimicrobial solution for ophthalmic use. Each mL contains: ACTIVES: Neomycin Sulfate, (equivalent to 1.75 mg neomycin base), Polymyxin B Sulfate equal to 10,000 Polymyxin B units, Gramicidin, 0.025 mg; INACTIVES: Sodium Chloride, Alcohol (0.5%), Poloxamer 188, Propylene Glycol, Purified Water. Hydrochloric Acid and/ or Ammonium Hydroxide may be added to adjust pH (4.7-6.0). PRESERVATIVE ADDED: Thimerosal 0.001%. Neomycin Sulfate is the sulfate salt of neomycin B and C, which are produced by the growth of Streptomyces fradiae Waksman (Fam. Streptomycetaceae). It has a potency equivalent of not less than 600 micrograms of neomycin base per milligram, calculated on an anhydrous basis. The structural formulae are: Polymyxin B Sulfate is the sulfate salt of polymyxin B1 and B2 which are produced by the growth of Bacillus polymyxa (Prazmowski) Migula (Fam. Bacillaceae). It has a potency of not less than 6,000 polymyxin B units per milligram, calculated on an anhydrous basis. The structural formulae are: Gramicidin (also called gramicidin D) is a mixture of three pairs of antibacterial substances (Gramicidin A, B and C) produced by the growth of Bacillus brevis Dubos (Fam. Bacillaceae). It has a potency of not less than 900 mcg of standard gramicidin per mg. The structural formulae are: CLINICAL PHARMACOLOGY: A wide range of antibacterial action is provided by the overlapping spectra of neomycin, polymyxin B sulfate, and gramicidin.
    [Show full text]
  • Penicillin Allergy Guidance Document
    Penicillin Allergy Guidance Document Key Points Background Careful evaluation of antibiotic allergy and prior tolerance history is essential to providing optimal treatment The true incidence of penicillin hypersensitivity amongst patients in the United States is less than 1% Alterations in antibiotic prescribing due to reported penicillin allergy has been shown to result in higher costs, increased risk of antibiotic resistance, and worse patient outcomes Cross-reactivity between truly penicillin allergic patients and later generation cephalosporins and/or carbapenems is rare Evaluation of Penicillin Allergy Obtain a detailed history of allergic reaction Classify the type and severity of the reaction paying particular attention to any IgE-mediated reactions (e.g., anaphylaxis, hives, angioedema, etc.) (Table 1) Evaluate prior tolerance of beta-lactam antibiotics utilizing patient interview or the electronic medical record Recommendations for Challenging Penicillin Allergic Patients See Figure 1 Follow-Up Document tolerance or intolerance in the patient’s allergy history Consider referring to allergy clinic for skin testing Created July 2017 by Macey Wolfe, PharmD; John Schoen, PharmD, BCPS; Scott Bergman, PharmD, BCPS; Sara May, MD; and Trevor Van Schooneveld, MD, FACP Disclaimer: This resource is intended for non-commercial educational and quality improvement purposes. Outside entities may utilize for these purposes, but must acknowledge the source. The guidance is intended to assist practitioners in managing a clinical situation but is not mandatory. The interprofessional group of authors have made considerable efforts to ensure the information upon which they are based is accurate and up to date. Any treatments have some inherent risk. Recommendations are meant to improve quality of patient care yet should not replace clinical judgment.
    [Show full text]
  • Carbapenem-Resistant Acinetobacter Threat Level Urgent
    CARBAPENEM-RESISTANT ACINETOBACTER THREAT LEVEL URGENT 8,500 700 $281M Estimated cases Estimated Estimated attributable in hospitalized deaths in 2017 healthcare costs in 2017 patients in 2017 Acinetobacter bacteria can survive a long time on surfaces. Nearly all carbapenem-resistant Acinetobacter infections happen in patients who recently received care in a healthcare facility. WHAT YOU NEED TO KNOW CASES OVER TIME ■ Carbapenem-resistant Acinetobacter cause pneumonia Continued infection control and appropriate antibiotic use and wound, bloodstream, and urinary tract infections. are important to maintain decreases in carbapenem-resistant These infections tend to occur in patients in intensive Acinetobacter infections. care units. ■ Carbapenem-resistant Acinetobacter can carry mobile genetic elements that are easily shared between bacteria. Some can make a carbapenemase enzyme, which makes carbapenem antibiotics ineffective and rapidly spreads resistance that destroys these important drugs. ■ Some Acinetobacter are resistant to nearly all antibiotics and few new drugs are in development. CARBAPENEM-RESISTANT ACINETOBACTER A THREAT IN HEALTHCARE TREATMENT OVER TIME Acinetobacter is a challenging threat to hospitalized Treatment options for infections caused by carbapenem- patients because it frequently contaminates healthcare resistant Acinetobacter baumannii are extremely limited. facility surfaces and shared medical equipment. If not There are few new drugs in development. addressed through infection control measures, including rigorous
    [Show full text]
  • Farrukh Javaid Malik
    I Farrukh Javaid Malik THESIS PRESENTED TO OBTAIN THE GRADE OF DOCTOR OF THE UNIVERSITY OF BORDEAUX Doctoral School, SP2: Society, Politic, Public Health Specialization Pharmacoepidemiology and Pharmacovigilance By Farrukh Javaid Malik “Analysis of the medicines panorama in Pakistan – The case of antimicrobials: market offer width and consumption.” Under the direction of Prof. Dr. Albert FIGUERAS Defense Date: 28th November 2019 Members of Jury M. Francesco SALVO, Maître de conférences des universités – praticien hospitalier, President Université de Bordeaux M. Albert FIGUERAS, Professeur des universités – praticien hospitalier, Director Université Autonome de Barcelone Mme Antonia AGUSTI, Professeure, Vall dʹHebron University Hospital Referee Mme Montserrat BOSCH, Praticienne hospitalière, Vall dʹHebron University Hospital Referee II Abstract A country’s medicines market is an indicator of its healthcare system, the epidemiological profile, and the prevalent practices therein. It is not only the first logical step to study the characteristics of medicines authorized for marketing, but also a requisite to set up a pharmacovigilance system, thus promoting rational drug utilization. The three medicines market studies presented in the present document were conducted in Pakistan with the aim of describing the characteristics of the pharmaceutical products available in the country as well as their consumption at a national level, with a special focus on antimicrobials. The most important cause of antimicrobial resistance is the inappropriate consumption of antimicrobials. The results of the researches conducted in Pakistan showed some market deficiencies which could be addressed as part of the national antimicrobial stewardship programmes. III Résumé Le marché du médicament d’un pays est un indicateur de son système de santé, de son profil épidémiologique et des pratiques [de prescription] qui y règnent.
    [Show full text]
  • Management of Penicillin and Beta-Lactam Allergy
    Management of Penicillin and Beta-Lactam Allergy (NB Provincial Health Authorities Anti-Infective Stewardship Committee, September 2017) Key Points • Beta-lactams are generally safe; allergic and adverse drug reactions are over diagnosed and over reported • Nonpruritic, nonurticarial rashes occur in up to 10% of patients receiving penicillins. These rashes are usually not allergic and are not a contraindication to the use of a different beta-lactam • The frequently cited risk of 8 to 10% cross-reactivity between penicillins and cephalosporins is an overestimate based on studies from the 1970’s that are now considered flawed • Expect new intolerances (i.e. any allergy or adverse reaction reported in a drug allergy field) to be reported after 0.5 to 4% of all antimicrobial courses depending on the gender and specific antimicrobial. Expect a higher incidence of new intolerances in patients with three or more prior medication intolerances1 • For type-1 immediate hypersensitivity reactions (IgE-mediated), cross-reactivity among penicillins (table 1) is expected due to similar core structure and/or major/minor antigenic determinants, use not recommended without desensitization • For type-1 immediate hypersensitivity reactions, cross-reactivity between penicillins (table 1) and cephalosporins is due to similarities in the side chains; risk of cross-reactivity will only be significant between penicillins and cephalosporins with similar side chains • Only type-1 immediate hypersensitivity to a penicillin manifesting as anaphylaxis, bronchospasm,
    [Show full text]
  • Rational Design and Synthesis of Modified Teixobactin Analogues: Ng, Vivian; Kuehne, Sarah A; Chan, Weng
    University of Birmingham Rational design and synthesis of modified teixobactin analogues: Ng, Vivian; Kuehne, Sarah A; Chan, Weng DOI: 10.1002/chem.201801423 License: Other (please specify with Rights Statement) Document Version Peer reviewed version Citation for published version (Harvard): Ng, V, Kuehne, SA & Chan, W 2018, 'Rational design and synthesis of modified teixobactin analogues: in vitro antibacterial activity against Staphylococcus aureus, Propionibacterium acnes and Pseudomonas aeruginosa', Chemistry: A European Journal. https://doi.org/10.1002/chem.201801423 Link to publication on Research at Birmingham portal Publisher Rights Statement: This is the peer reviewed version of the following article: Ng, V. , Kuehne, S. and Chan, W. (2018), Rational design and synthesis of modified teixobactin analogues: in vitro antibacterial activity against Staphylococcus aureus, Propionibacterium acnes and Pseudomonas aeruginosa. Chem. Eur. J.. Accepted Author Manuscript. doi:10.1002/chem.201801423, which has been published in final form at 10.1002/chem.201801423. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self- Archiving. General rights Unless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law. •Users may freely distribute the URL that is used to identify this publication. •Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research.
    [Show full text]
  • Polymyxin B April 2019 Background Polymyxin B Injection Is Available
    Polymyxin B April 2019 Background . Polymyxin B injection is available for inpatient use. This product is being used by the irrigation mode of administration. The proposal is to implement the intravenous route of administration with restrictions for use. Several changes were made to the FDA drug approval process in the 1960s which is after the time (1951) when polymyxin B was originally approved by the FDA.1,2 The approval process for polymyxin B was different than medications that are approved today. Thus, there is a lack of robust clinical trials on polymyxin B’s efficacy, safety and pharmacokinetics. Efficacy Polymyxin B was FDA approved for acute infections caused by susceptible strains of Pseudomonas aeruginosa and for serious infections caused by the following organisms (if susceptible) when other less toxic drugs are ineffective or contraindicated: H. influenzae (meningeal, IT route), Escherichia coli (UTI), Aerobacter (Klebsiella) aerogenes (bacteremia), Klebsiella pneumoniae (bacteremia).3 It should be noted that this drug did not go through the modern drug development process and thus, pharmacokinetic evidence since its approval has indicated that it is not appropriate for UTIs. Guidelines indicate that polymyxin B is the preferred polymyxin therapy for systemic use in invasive infections other than UTIs.5 Safety Polymyxin B has several black box warnings (BBW): administration by the IM and IT routes should only be done in hospitalized patients, nephrotoxicity and neurotoxicity can occur, safe use in pregnancy has not been established,
    [Show full text]
  • Synthesis and Structure−Activity Relationships of Teixobactin
    Ann. N.Y. Acad. Sci. ISSN 0077-8923 ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Special Issue: Antimicrobial Therapeutics Reviews REVIEW Synthesis and structure−activity relationships of teixobactin John A. Karas,1 Fan Chen,1 Elena K. Schneider-Futschik,1,2 Zhisen Kang,1 Maytham Hussein,1 James Swarbrick,1 Daniel Hoyer,1,3,4 Andrew M. Giltrap,5 Richard J. Payne,5 Jian Li,6 and Tony Velkov1 1Department of Pharmacology & Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, the University of Melbourne, Parkville, Victoria, Australia. 2Lung Health Research Centre, Department of Pharmacology & Therapeutics, the University of Melbourne, Parkville, Victoria, Australia. 3The Florey Institute of Neuroscience and Mental Health, the University of Melbourne, Parkville, Victoria, Australia. 4Department of Molecular Medicine, the Scripps Research Institute, La Jolla, California. 5School of Chemistry, the University of Sydney, Sydney, New South Wales, Australia. 6Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia Address for correspondence: Tony Velkov and John A. Karas, Department of Pharmacology & Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, the University of Melbourne, Parkville, VIC 3010, Australia. [email protected] OR [email protected] The discovery of antibiotics has led to the effective treatment of bacterial infections that were otherwise fatal and has had a transformative effect on modern medicine. Teixobactin is an unusual depsipeptide natural product that was recently discovered from a previously unculturable soil bacterium and found to possess potent antibacterial activity against several Gram positive pathogens, including methicillin-resistant Staphylococcus aureus and vancomycin- resistant Enterococci.
    [Show full text]
  • Investigation of the N-Terminus Amino Function of Arg10-Teixobactin
    molecules Communication Investigation of the N-Terminus Amino Function of Arg10-Teixobactin Shimaa A. H. Abdel Monaim 1, Sikabwe Noki 1, Estelle J. Ramchuran 1, Ayman El-Faham 2,3 ID , Fernando Albericio 1,2,4,5,6,* ID and Beatriz G. de la Torre 1,7,* 1 Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban 4001, South Africa; [email protected] (S.A.H.A.M.); [email protected] (S.N.); [email protected] (E.J.R.) 2 Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia; [email protected] 3 Chemistry Department, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 12321, Egypt 4 School of Chemistry and Physics, University of KwaZulu-Natal, Durban 4001, South Africa 5 Department of Organic Chemistry, University of Barcelona, Barcelona 08028, Spain 6 CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Barcelona 08028, Spain 7 KRISP, College of Health Sciences, University of KwaZulu-Natal, Durban 4001, South Africa * Correspondence: [email protected] (F.A.); [email protected] (B.G.d.l.T.); Tel.: +27-614-047-528 (F.A.); +27-614-009-144 (B.G.d.l.T.) Received: 28 August 2017; Accepted: 25 September 2017; Published: 28 September 2017 Abstract: Teixobactin is a recently described antimicrobial peptide that shows high activity against gram-positive bacteria as well as mycobacterium tuberculosis. Due to both its structure as a head-to-side chain cyclodepsipeptide and its activity, it has attracted the attention of several research groups.
    [Show full text]