DOCSLIB.ORG

Antibiotics Currently in Global Clinical Development Note: This Data Visualization Was Updated in September 2018 with New Data

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

A data table from Sept 2018 Antibiotics Currently in Global Clinical Development Note: This data visualization was updated in September 2018 with new data. As of June 2018, approximately 42 new antibiotics with the potential to treat serious bacterial infections are in clinical development. The success rate for clinical drug development is low; historical data show that, generally, only 1 in 5 infectious disease products that enter human testing (phase 1 clinical trials) will be approved for patients.* Below is a snapshot of the current antibiotic pipeline, based on publicly available information and informed by external experts. Please note that this resource focuses exclusively on small molecule products that act systemically (drugs that work throughout the body), contain at least one component not previously approved, and have the potential to treat serious or life-threatening infections.1 In September 2017, the antibiotics pipeline was expanded to include products in development globally. Because this resource is updated periodically, footnote numbers may not be sequential. Please contact [email protected] with additions or updates. Expected Expected activity activity against against CDC Development Drug name Company Drug class Target resistant Gram- urgent or WHO Potential indication(s)?5 phase2 negative ESKAPE critical threat pathogens?3 pathogen?4 Approved for: Complicated urinary tract Melinta infections including pyelonephritis; other Vabomere β-lactam (carbapenem) Approved Aug. 30, Therapeutics Inc. potential indications: complicated (meropenem + + β-lactamase inhibitor PBP, β-lactamase Yes Yes (CRE) 2017 (U.S. FDA) (formerly The intra-abdominal infections, hospital- vaborbactam) (cyclic boronate)11,13 Medicines Co.) acquired bacterial pneumonia/ventilator- associated bacterial pneumonia Approved for: Complicated urinary tract infections including acute pyelonephritis; Zemdri Approved June 26, 30S subunit of other potential indications: hospital- Achaogen Inc. Aminoglycoside Yes Yes (CRE) (plazomicin) 2018 (U.S. FDA) bacterial ribosome acquired bacterial pneumonia/ventilator- associated bacterial pneumonia, complicated intra-abdominal infections New drug application submitted for Acute bacterial skin and Dihydrofolate Iclaprim acute bacterial Motif Bio PLC 2,4-diaminopyrimidine No No skin structure infections and hospital- reductase skin and skin acquired bacterial pneumonia structure infections (U.S. FDA) Continued on the next page Expected Expected activity activity against against CDC Development Drug name Company Drug class Target resistant Gram- urgent or WHO Potential indication(s)?5 phase2 negative ESKAPE critical threat pathogens?3 pathogen?4 New drug application submitted for Kyorin Lascufloxacin Bacterial type II Community-acquired community- Pharmaceutical Fluoroquinolone No No (KRP-AM1977)9 topoisomerase bacterial pneumonia acquired bacterial Co. Ltd. pneumonia (Japan PMDA) New drug application submitted for Community-acquired bacterial community- Paratek pneumonia, acute bacterial skin and skin acquired bacterial 30S subunit of Omadacycline Pharmaceuticals Tetracycline Yes Possibly (CRAB) structure infections, complicated urinary pneumonia and bacterial ribosome Inc. tract infections, and uncomplicated acute bacterial skin urinary tract infections and skin structure infections (U.S. FDA) New drug application submitted for Tetraphase Xerava 30S subunit of Yes (CRE), possibly complicated Pharmaceuticals Tetracycline Yes Complicated intra-abdominal infections (eravacycline) bacterial ribosome (CRAB) intra-abdominal Inc. infections (U.S. FDA) Possibly (CRE, CRPA, AIC4999 Phase 16 AiCuris β-lactam PBP Possibly Bacterial infections CRAB) β-lactam VenatoRx Cefepime + (cephalosporin) + Yes (CRE), possibly Phase 1 Pharmaceuticals PBP, β-lactamase Yes Bacterial infections VNRX-5133 β-lactamase inhibitor (CRPA and CRAB) Inc. (cyclic boronate) β-lactam Complicated urinary tract infections6 Cefepime + (cephalosporin) + Yes (CRE), possibly and hospital-acquired bacterial zidebactam Phase 1 Wockhardt Ltd. PBP, β-lactamase Yes β-lactamase inhibitor (CRPA) pneumonia/ventilator-associated (WCK 5222) (diazabicyclooctane) bacterial pneumonia6 CrystalGenomics Acute bacterial skin and CG400549 Phase 16 Benzyl pyridinone11 FabI12 No No Inc. skin structure infections Methionyl-tRNA CRS3123 Phase 1 Crestone Inc. Diaryldiamine11 No Yes (C. difficile) C. difficile infections synthetase12 Continued on the next page Expected Expected activity activity against against CDC Development Drug name Company Drug class Target resistant Gram- urgent or WHO Potential indication(s)?5 phase2 negative ESKAPE critical threat pathogens?3 pathogen?4 Delpazolid15 LegoChem 50S subunit of Phase 1 Oxazolidinone No No Bacterial infections (LCB01-0371) Biosciences Inc. bacterial ribosome β-lactam Entasis (cephalosporin) + ETX0282CPDP Phase 1 PBP, β-lactamase Yes Yes (CRE) Bacterial infections Therapeutics Inc. β-lactamase inhibitor (diazabicyclooctane) KBP BioSciences 30S subunit of Community-acquired KBP-7072 Phase 1 Pharmaceutical Tetracycline Possibly Possibly (CRAB) bacterial ribosome bacterial pneumonia6 Technical Co. Ltd. 50S subunit Deinove SA of bacterial Oxazolidinone- MCB3837 Phase 16 (formerly ribosome, No Yes (C. difficile) C. difficile infections6 quinolone hybrid Morphochem AG) bacterial type II topoisomerase MGB Biopharma DNA minor groove MGB-BP-3 Phase 1 Distamycin11 No Yes (C. difficile) C. difficile infections Ltd. binder12 Meiji Seika Meropenem + Pharma Co. β-lactam (carbapenem) nacubactam Ltd./Fedora PBP, β-lactamase, Yes (CRE), possibly Phase 1 + β-lactamase inhibitor Yes Bacterial infections (OP0595/ Pharmaceuticals PBP2 (CRPA) (diazabicyclooctane) RG6080) Inc. (Roche licensee) Spero Possibly (CRE, CRPA, SPR74114 Phase 1 Polymyxin Cell membrane12 Possibly Bacterial infections Therapeutics CRAB) Community-acquired bacterial Spero SPR9947 Phase 16 β-lactam (carbapenem) PBP Yes No pneumonia6 and complicated Therapeutics urinary tract infections6 Tetraphase 30S subunit of Community-acquired TP-271 Phase 1 Pharmaceuticals Tetracycline No Possibly (CRAB) bacterial ribosome bacterial pneumonia Inc. Tetraphase 30S subunit of TP-6076 Phase 16 Pharmaceuticals Tetracycline Yes Yes (CRE and CRAB) Bacterial infections bacterial ribosome Inc. Afabicin (Debio Debiopharm Benzofuran Acute bacterial skin and skin structure Phase 2 FabI12 No No 1450) International SA naphthyridine11 infections (Staphylococcus-specific) Continued on the next page Expected Expected activity activity against against CDC Development Drug name Company Drug class Target resistant Gram- urgent or WHO Potential indication(s)?5 phase2 negative ESKAPE critical threat pathogens?3 pathogen?4 Innovation Acute bacterial skin and Brilacidin Phase 2 Pharmaceuticals Defensin mimetic11 Cell membrane No No skin structure infections Inc. Complicated urinary tract infection β-lactam (carbapenem) Imipenem/ including acute pyelonephritis, and Entasis + β-lactam (sulbactam) Yes (CRE and CRAB), cilastatin + Phase 2 PBP, β-lactamase Yes hospital-acquired bacterial Therapeutics Inc. + β-lactamase inhibitor possibly (CRPA) ETX2514SUL pneumonia/ventilator-associated (diazabicyclooctane) bacterial pneumonia Acute bacterial skin and skin structure MerLion Bacterial type II infections, complicated intra-abdominal Finafloxacin10 Phase 2 Pharmaceuticals Fluoroquinolone Yes No topoisomerase infections, and complicated urinary tract Pte Ltd. infections including pyelonephritis Complicated urinary tract infections,6 Bacterial type II uncomplicated urinary tract infections,6 Gepotidacin GlaxoSmithKline topoisomerase acute bacterial skin and skin structure Phase 2 Triazaacenaphthylene11 No Yes (N. gonorrhoeae) (GSK2140944) PLC (novel A subunit infections, uncomplicated urogenital site)12 gonorrhea,6 and community-acquired bacterial pneumonia6 β-lactam Complicated urinary tract infections and LYS228 Phase 2 Novartis AG PBP Yes Yes (CRE) (monobactam) complicated intra-abdominal infections Nafithromycin 50S subunit of Community-acquired Phase 2 Wockhardt Ltd. Macrolide No No (WCK 4873) bacterial ribosome bacterial pneumonia Community-acquired bacterial TaiGen Bacterial type II pneumonia, diabetic foot infection, Nemonoxacin7 Phase 2 Biotechnology Co. Quinolone No No topoisomerase and acute bacterial skin and skin Ltd. structure infections Otsuka Bacterial type II OPS-2071 Phase 2 Pharmaceutical Quinolone No Yes (C. difficile) C. difficile infections topoisomerase Co. Ltd. Ridinilazole Summit Phase 2 Bis-benzimidazole11 Unknown No Yes (C. difficile) C. difficile infections (SMT 19969) Therapeutics PLC WCK 771/WCK Bacterial type II Phase 26 Wockhardt Ltd. Fluoroquinolone No No Hospital-acquired bacterial pneumonia6 234916 topoisomerase Bacterial type II Zoliflodacin Entasis Phase 2 Spiropyrimidinetrione11 topoisomerase No Yes (N. gonorrhoeae) Uncomplicated gonorrhea (ETX0914) Therapeutics Inc. (GyrB)12 Continued on the next page Expected Expected activity activity against against CDC Development Drug name Company Drug class Target resistant Gram- urgent or WHO Potential indication(s)?5 phase2 negative ESKAPE critical threat pathogens?3 pathogen?4 Complicated urinary tract infections β-lactam including pyelonephritis, complicated Cefepime + (cephalosporin) + Phase 3 Allecra PBP, β-lactamase Yes Possibly (CRE) intra-abdominal infections, and hospital- AAI1019 β-lactamase inhibitor acquired bacterial pneumonia/ventilator- (β-lactam) associated bacterial pneumonia Complicated urinary tract infections
Recommended publications
  • The Role of Nanobiosensors in Therapeutic Drug Monitoring

    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].
  • WO 2015/179249 Al 26 November 2015 (26.11.2015) P O P C T

    WO 2015/179249 Al 26 November 2015 (26.11.2015) P O 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 WO 2015/179249 Al 26 November 2015 (26.11.2015) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C12N 15/11 (2006.01) A61K 38/08 (2006.01) kind of national protection available): AE, AG, AL, AM, C12N 15/00 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (21) Number: International Application DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US2015/031213 HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (22) International Filing Date: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, 15 May 2015 (15.05.2015) MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (25) Filing Language: English SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (26) Publication Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 62/000,43 1 19 May 2014 (19.05.2014) US kind of regional protection available): ARIPO (BW, GH, 62/129,746 6 March 2015 (06.03.2015) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, (72) Inventors; and TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (71) Applicants : GELLER, Bruce, L.
  • Oxazolidinones for TB

    Oxazolidinones for TB

    Oxazolidinones for TB: Current Status and Future Prospects 12th International Workshop on Clinical Pharmacology of Tuberculosis Drugs London, UK 10 September 2019 Lawrence Geiter, PhD Disclosures • Currently contract consultant with LegoChem Biosciences, Inc., Daejeon, Korea (LCB01-0371/delpazolid) • Previously employed with Otsuka Pharmaceutical Development and Commercialization, Inc. (delamanid, OPC-167832, LAM assay) What are Oxazolidinones • A family of antimicrobials mostly targeting an early step in protein synthesis • Cycloserine technically oxazolidinone but 2-oxazolidinone different MOA and chemical properties • New generation oxazolidinones bind to both 50S subunit and 30S subunit • Linezolid (Zyvox) and Tedizolid (Sivestro) approved for drug resistant skin infections and community acquired pneumonia Cycloserine • Activity against TB demonstrated in non- clinical and clinical studies • Mitochondrial toxicity >21 days limits use in TB treatment Linezolid Developing Oxazolidinones for TB Compound Generic Brand Sponsor Development Status TB Code- Activity/Trials PNU-100766 Linezolid Zyvox Pfizer Multiple regimen Yes/Yes TR-201 Tedizolid Sivextro Merck Pre-clinical efficacy Yes/No PNU-100480 Sutezolid Pfizer Multiple regimen studies Sequella Yes/Yes (PanACEA) TB Alliance LCB01-0371 Delpazolid LegoChem Bio EBA trial recruitment completed Yes/Yes TBI-223 - Global Alliance SAD trial launched Yes/Yes AZD5847 Posizolid AstraZenica Completed EBA Yes/No RX-1741 Radezolid Melinta IND for vaginal infections ?/No RBX-7644 Ranbezolid Rabbaxy None found ?/No MRX-4/MRX-1 Contezolid MicuRx Skin infections Yes/No U-100592 Eperezolid ? No clinical trials ?/No PK of Oxazolidinones in Development for TB Steady State PK Parameters Parameter Linezolid 600 Delpazolid 800 mg QD2 mg QD3 Cmax (mg/L) 17.8 8.9 Cmin (mg/L) 2.43 0.1 Tmax (h) 0.87 0.5 T1/2 (h) 3.54 1.7 AUC0-24 (µg*h/mL) 84.5 20.1 1 MIC90 (µg/mL) 0.25 0.5 References 1.
  • Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications

    Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications

    International Journal of Molecular Sciences Review Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications Daniel Fernández-Villa 1, Maria Rosa Aguilar 1,2 and Luis Rojo 1,2,* 1 Instituto de Ciencia y Tecnología de Polímeros, Consejo Superior de Investigaciones Científicas, CSIC, 28006 Madrid, Spain; [email protected] (D.F.-V.); [email protected] (M.R.A.) 2 Consorcio Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, 28029 Madrid, Spain * Correspondence: [email protected]; Tel.: +34-915-622-900 Received: 18 September 2019; Accepted: 7 October 2019; Published: 9 October 2019 Abstract: Bacterial, protozoan and other microbial infections share an accelerated metabolic rate. In order to ensure a proper functioning of cell replication and proteins and nucleic acids synthesis processes, folate metabolism rate is also increased in these cases. For this reason, folic acid antagonists have been used since their discovery to treat different kinds of microbial infections, taking advantage of this metabolic difference when compared with human cells. However, resistances to these compounds have emerged since then and only combined therapies are currently used in clinic. In addition, some of these compounds have been found to have an immunomodulatory behavior that allows clinicians using them as anti-inflammatory or immunosuppressive drugs. Therefore, the aim of this review is to provide an updated state-of-the-art on the use of antifolates as antibacterial and immunomodulating agents in the clinical setting, as well as to present their action mechanisms and currently investigated biomedical applications. Keywords: folic acid antagonists; antifolates; antibiotics; antibacterials; immunomodulation; sulfonamides; antimalarial 1.
  • Investigational Drug Therapies Currently in Early-Stage Clinical Development for the Treatment of Clostridioides (Clostridium) Difficile Infection Mai-Chi N

    Investigational Drug Therapies Currently in Early-Stage Clinical Development for the Treatment of Clostridioides (Clostridium) Difficile Infection Mai-Chi N

    EXPERT OPINION ON INVESTIGATIONAL DRUGS https://doi.org/10.1080/13543784.2019.1581763 REVIEW Investigational drug therapies currently in early-stage clinical development for the treatment of clostridioides (clostridium) difficile infection Mai-Chi N. Trana,b, Ravina Kullarc and Ellie J. C. Goldsteind,e aDepartment of Pharmacy, Providence St. John’s Health Center, Santa Monica, CA, USA; bDepartment of Pharmacy, Clinica Juan Pablo Medical Group, Los Angeles, CA, USA; cDoctor Evidence, LLC, Santa Monica, CA, USA; dR M Alden Research Laboratory, Santa Monica, CA, USA; eDavid Geffen School of Medicine, Los Angeles, CA, USA ABSTRACT ARTICLE HISTORY Introduction: Clostridioides (Clostridium) difficile Infection (CDI) is an urgent global threat causing Received 16 August 2018 ~500,000 infections annually in the United States of America (USA) and is associated with a 36% 30- Accepted 8 February 2019 day attributable mortality rate. Despite the availability of three therapeutic agents, CDI recurrence KEYWORDS – – occurs in 20 40% of patients, with a 30 40% second recurrence rate in these patients. Consequently, ACX-362F; DS-2969b; there is a need for novel agents for treating CDI. LFF571; ribaxamase; Areas covered: We searched MEDLINE, PubMed, Embase, Web of Science, Cochrane Central Register of ridinilazole; RBX 2660; Controlled Trials, and ClinicalTrials.gov for agents in early stages of clinical development. CRS3123; MCB3681/ These drugs include ACX-362E, DS-2969b, LFF 571, RBX2660, ribaxamase, ridinilazole that have MCB3837 advanced to at least phase 2 and several other drugs in phase 1 development. Expert opinion: The challenge for these new agents is three-fold: (1) to have a novel approach such as a different target/mechanism of action; (2) be ‘significantly’ better than existing agents in regard to ‘sustained clinical response’; or (3) be priced at a reasonable cost when it comes to market or perhaps all three.
  • Infectious Diseases

    Infectious Diseases

    2013 MEDICINES IN DEVELOPMENT REPORT Infectious Diseases A Report on Diseases Caused by Bacteria, Viruses, Fungi and Parasites PRESENTED BY AMERICA’S BIOPHARMACEUTICAL RESEARCH COMPANIES Biopharmaceutical Research Evolves Against Infectious Diseases with Nearly 400 Medicines and Vaccines in Testing Throughout history, infectious diseases hepatitis C that inhibits the enzyme have taken a devastating toll on the lives essential for viral replication. and well-being of people around the • An anti-malarial drug that has shown Medicines in Development world. Caused when pathogens such activity against Plasmodium falci- For Infectious Diseases as bacteria or viruses enter a body and parum malaria which is resistant to multiply, infectious diseases were the current treatments. Application leading cause of death in the United Submitted States until the 1920s. Today, vaccines • A potential new antibiotic to treat methicillin-resistant Staphylococcus Phase III and infectious disease treatments have proven to be effective treatments in aureus (MRSA). Phase II many cases, but infectious diseases still • A novel treatment that works by Phase I pose a very serious threat to patients. blocking the ability of the smallpox Recently, some infectious pathogens, virus to spread to other cells, thus 226 such as pseudomonas bacteria, have preventing it from causing disease. become resistant to available treatments. Infectious diseases may never be fully Diseases once considered conquered, eradicated. However, new knowledge, such as tuberculosis, have reemerged new technologies, and the continuing as a growing health threat. commitment of America’s biopharma- America’s biopharmaceutical research ceutical research companies can help companies are developing 394 medicines meet the continuing—and ever-changing and vaccines to combat the many threats —threat from infectious diseases.
  • Activity of Cefepime-Zidebactam Against Multidrug-Resistant (MDR) Gram-Negative Pathogens

    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].
  • 9-20-08 Referral

    9-20-08 Referral

    Comparative studies with antibiotics: Why should we change the rules? Paul M. Tulkens, MD, PhD Cellular and Molecular Pharmacology & Centre for Clinical Pharmacy Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium 10-10-2012 Late Phase Leaders Forum, Vienna, Austria 1 What its all about ? • We are in real need of novel antibiotics… but … most clinical studies with new compounds aim at equivalence or non-inferiority, failing to meet clinicians’ expectations and regulatory requirements for novelty. In parallel, safety issues are becoming an increasingly worrying hurdle for manufacturers Pricing make antibiotic unattractive • What are the possible solutions ? 10-10-2012 Late Phase Leaders Forum, Vienna, Austria 2 The antibiotic crisis * * A pictorial view using 4 paintings of Van Gogh (who stayed briefly in Belgium when moving from Holland to France) and with selected Belgian and International data… 10-10-2012 Late Phase Leaders Forum, Vienna, Austria 3 Are antibiotics following a path to madness ? discovery in soil bacteria and fungi 1928 - … 10-10-2012 Late Phase Leaders Forum, Vienna, Austria 4 Are antibiotics following a path to madness ? and then we all saw the blooming tree of semi- synthetic and totally synthetic antibiotics 1950 – 1980 … 10-10-2012 Late Phase Leaders Forum, Vienna, Austria 5 Are antibiotics following a path to madness ? and the US General Surgeon told us that the fight was over 1970 … 10-10-2012 Late Phase Leaders Forum, Vienna, Austria 6 Are antibiotics following a path to madness ? But… 2012 … 10-10-2012 Late Phase Leaders Forum, Vienna, Austria 7 Extent of resistance of P.
  • B-Lactams: Chemical Structure, Mode of Action and Mechanisms of Resistance

    B-Lactams: Chemical Structure, Mode of Action and Mechanisms of Resistance

    b-Lactams: chemical structure, mode of action and mechanisms of resistance Ru´ben Fernandes, Paula Amador and Cristina Prudeˆncio This synopsis summarizes the key chemical and bacteriological characteristics of b-lactams, penicillins, cephalosporins, carbanpenems, monobactams and others. Particular notice is given to first-generation to fifth-generation cephalosporins. This review also summarizes the main resistance mechanism to antibiotics, focusing particular attention to those conferring resistance to broad-spectrum cephalosporins by means of production of emerging cephalosporinases (extended-spectrum b-lactamases and AmpC b-lactamases), target alteration (penicillin-binding proteins from methicillin-resistant Staphylococcus aureus) and membrane transporters that pump b-lactams out of the bacterial cell. Keywords: b-lactams, chemical structure, mechanisms of resistance, mode of action Historical perspective Alexander Fleming first noticed the antibacterial nature of penicillin in 1928. When working with Antimicrobials must be understood as any kind of agent another bacteriological problem, Fleming observed with inhibitory or killing properties to a microorganism. a contaminated culture of Staphylococcus aureus with Antibiotic is a more restrictive term, which implies the the mold Penicillium notatum. Fleming remarkably saw natural source of the antimicrobial agent. Similarly, under- the potential of this unfortunate event. He dis- lying the term chemotherapeutic is the artificial origin of continued the work that he was dealing with and was an antimicrobial agent by chemical synthesis [1]. Initially, able to describe the compound around the mold antibiotics were considered as small molecular weight and isolates it. He named it penicillin and published organic molecules or metabolites used in response of his findings along with some applications of penicillin some microorganisms against others that inhabit the same [4].
  • Effects of Probenecid and Cimetidine on the Pharmacokinetics of Nemonoxacin Open Access to Scientific and Medical Research Doi

    Effects of Probenecid and Cimetidine on the Pharmacokinetics of Nemonoxacin Open Access to Scientific and Medical Research Doi

    Journal name: Drug Design, Development and Therapy Article Designation: Original Research Year: 2016 Volume: 10 Drug Design, Development and Therapy Dovepress Running head verso: Zhang et al Running head recto: Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin open access to scientific and medical research doi: http://dx.doi.org/10.2147/DDDT.S95934 Open Access Full Text Article ORIGINAL RESEARCH Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in healthy Chinese volunteers Yi-fan Zhang1 Purpose: To investigate the effects of probenecid and cimetidine on the pharmacokinetics of Xiao-jian Dai1 nemonoxacin in humans. Yong Yang1 Methods: Two independent, open-label, randomized, crossover studies were conducted in Xiao-yan Chen1 24 (12 per study) healthy Chinese volunteers. In Study 1, each volunteer received a single oral Ting Wang2 dose of 500 mg of nemonoxacin alone or with 1.5 g of probenecid divided into three doses within Yun-biao Tang3 25 hours. In Study 2, each volunteer received a single oral dose of 500 mg of nemonoxacin alone or with multiple doses of cimetidine (400 mg thrice daily for 7 days). The plasma and urine Cheng-yuan Tsai4 nemonoxacin concentrations were determined using validated liquid chromatography–tandem Li-wen Chang4 mass spectrometry methods. Yu-ting Chang4 Results: Coadministration of nemonoxacin with probenecid reduced the renal clearance (CL ) 1 r Da-fang Zhong of nemonoxacin by 22.6%, and increased the area under the plasma concentration–time curve 1State Key Laboratory of Drug from time 0 to infinity (AUC0–∞) by 26.2%. Coadministration of nemonoxacin with cimetidine Research, Shanghai Institute of reduced the CL of nemonoxacin by 13.3% and increased AUC by 9.4%.
  • Neomycin and Polymyxin B Sulfates and Gramicidin

    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.
  • Penicillin Allergy Guidance Document

    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.