Advances in Antimicrobial Resistance Monitoring Using Sensors and Biosensors: a Review
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A Review on the Current Classification and Regulatory Provisions for Medicines in Drug & Cosmetic Act, in the Light of Present Day Context
Section Pharmaindustry Commentary A Review on the Current Classification and Regulatory Provisions for Medicines in Drug & Cosmetic Act, in the light of Present Day Context Prashant Tandon1, Varun Gupta2, Ashish Ranjan3, Purav Gandhi4, Anand Kotiyal5, 3 Aastha Kapoor 3 1Founder ;2VP & Head Medical Affair; Manager Medical Affair; 5Drug Data Analyst Medical Affair, 1mg Technologies Private Limited, 4th Floor, Motorola Building, MG Road, Sector 14, Gurugram, Haryana, 122001. 4Founder, Remedy Social, C/602, Tulip Citadel, Shreyas Tekra, Ambawadi, Ahmedabad 380015, Gujarat. ABSTRACT______________________________________________________________ Background: Current classification of medicines in Conclusions: We have recommended a revised drug India under Drug and Cosmetic Act into Schedule G, classification system that is more comprehensive in coverage and H, H1, X is outdated, evolved through patchwork over eliminates the overlaps between classes. Moreover, considering the years and needs to be thoroughly updated. The the implementation challenges for such a drug classification primary aim of the scheduling system is to ensure system in the diverse and fragmented ecosystem in India, we appropriate access to medicines while balancing recommend a technology backed platform to help monitor the public health and safety. India is experiencing a rapid implementation. transition with the rising burden of chronic non- communicable diseases where regular access of Key words: Drug Classification System, Drug and Cosmetic Act affordable medicines is critical for chronic disease India, Digitization of Prescriptions, Drug Schedules in India, management to prevent complications. Methods: We Schedule H, Monitoring Drug Schedule System analyzed drugs commonly selling across India, Received: 01.09.17 | Accepted:16.09.17 through multiple information sources including 1mg drug database, PharmaTrac (AIOCD-AWACS), Corresponding Author inventory data from distributors and retailers, Dr. -
A Computational Drug Repositioning Case Study Prashant S. Kharkar1*, Ponnadurai Ramasami2, Yee S
Electronic Supplementary Material (ESI) for RSC Advances. This journal is © The Royal Society of Chemistry 2016 Discovery of Anti-Ebola Drugs: A Computational Drug Repositioning Case Study Prashant S. Kharkar1*, Ponnadurai Ramasami2, Yee Siew Choong3, Lydia Rhyman2 and Sona Warrier1 1SPP School of Pharmacy and Technology Management, SVKM’s NMIMS, V. L. Mehta Road, Vile Parle (West), Mumbai-400 056. INDIA. 2 Computational Chemistry Group, Department of Chemistry, Faculty of Science, University of Mauritius, Réduit 80837, Mauritius 3Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Malaysia Contents Sr. No. Description Page No. 1 Table 1S 1 2 Figure 1S 28 3 Figure 2S 29 4 Figure 3S 30 5 Figure 4S 31 6 Figure 5S 32 Table 1S. Top hits (#100) identified from EON screening using query 1 Estimated Sr. EON_ Shape Free Energy Drug Structure ET_pb ET_coul ET_combo Rank No. Tanimoto of Binding (kcal/mol) OH O Br N O 1 1 S -9.88 HO O O O S O O 2 Sitaxentan S 0.633 0.914 0.926 0.294 1 -14.37 HN O Cl O N O HO 3 Alitretinoina 0.66 0.91 0.906 0.246 2 -3.91 NH 2 S N N O O HN 4 Ceftriaxone S 0.606 0.937 0.823 0.217 3 -12.33 N O S N O HO O N N O H O a 5 Acitretin O 0.637 0.936 0.809 0.172 4 -3.71 OH HO NH 2 HO N N 6 Cidofovir P O 0.473 0.633 0.783 0.31 5 -4.21 HO O O N N N N 7 Telmisartan 0.601 0.908 0.775 0.174 6 -6.46 OH O 8 Nateglinidea HN 0.54 0.874 0.745 0.205 7 -3.78 OH O O H N 2 S OH N O N S O 9 Ceftizoxime N 0.557 0.88 0.735 0.178 8 -11.35 H O N O OH O 10 Treprostinil OH 0.432 0.846 0.732 0.301 9 -3.41 O HO O O S -
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: 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. -
Nigerian Veterinary Journal 39(3)
Nigerian Veterinary Journal 39(3). 2018 Asambe et al. NIGERIAN VETERINARY JOURNAL ISSN 0331-3026 Nig. Vet. J., September 2018 Vol 39 (3): 199 -208. https://dx.doi.org/10.4314/nvj.v39i3.3 ORIGINAL ARTICLE In Vitro Comparative Activity of Ciprofloxacin and Enrofloxacin against Clinical Isolates from Chickens in Benue State, Nigeria Asambe, A.1*; Babashani, M2. and Salisu, U. S.1 ¹.Federal University Dutsinma, Katsina State. 2.Ahmadu Bello University Zaria. *Corresponding author: Email: [email protected]; Tel No:+2348063103254 SUMMARY This study compares the in vitro activities of enrofloxacin and its main metabolite ciprofloxacin against clinical Escherichia coli and non-lactose fermenting enterobacteria isolates from chickens. Ten (10) Escherichia coli and 8 non lactose fermenting enterobacteriaceae species isolated from a pool of clinical cases at the Microbiology Laboratory of the Veterinary Teaching Hospital, University of Agriculture Makurdi were used in this study. Ten-fold serial dilution of 10 varying concentrations (0.1-50μg/mL) of enrofloxacin and ciprofloxacin were tested against the isolates in vitro by Bauer’s disc-diffusion method to determine and compare their antimicrobial activities against the isolates. The 18 isolates tested were susceptible to both enrofloxacin and ciprofloxacin, and their mean values in the susceptibility of Escherichia coli and non-lactose fermenters were significantly different (p < 0.01). The study concluded that the clinical isolates are susceptible to both enrofloxacin and ciprofloxacin though ciprofloxacin exhibit higher activity. Comparatively, ciprofloxacin was found to be more potent than enrofloxacin and the difference statistically significant. Ciprofloxacin was recommended as a better choice in the treatment of bacterial infections of chicken in this area compared to enrofloxacin. -
)&F1y3x PHARMACEUTICAL APPENDIX to THE
)&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE -
Fluoroquinolones for Treating Tuberculosis (Presumed Drug- Sensitive) (Review)
Fluoroquinolones for treating tuberculosis (presumed drug- sensitive) (Review) Ziganshina LE, Titarenko AF, Davies GR This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2013, Issue 6 http://www.thecochranelibrary.com Fluoroquinolones for treating tuberculosis (presumed drug-sensitive) (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . ..... 3 BACKGROUND .................................... 5 OBJECTIVES ..................................... 6 METHODS ...................................... 6 RESULTS....................................... 9 Figure1. ..................................... 10 Figure2. ..................................... 12 ADDITIONALSUMMARYOFFINDINGS . 15 DISCUSSION ..................................... 20 Figure3. ..................................... 20 Figure4. ..................................... 21 AUTHORS’CONCLUSIONS . 23 ACKNOWLEDGEMENTS . 23 REFERENCES ..................................... 24 CHARACTERISTICSOFSTUDIES . 30 DATAANDANALYSES. 60 Analysis 1.1. Comparison 1 Fluoroquinolones plus standard regimen (HRZE) versus standard regimen alone (HRZE), Outcome1Deathfromanycause. 61 Analysis 1.2. Comparison 1 Fluoroquinolones plus standard regimen (HRZE) versus standard regimen alone (HRZE), Outcome2TB-relateddeath. -
Susceptibility of Archaea to Antimicrobial Agents: Applications to Clinical Microbiology
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector REVIEW 10.1111/j.1469-0691.2012.03913.x Susceptibility of archaea to antimicrobial agents: applications to clinical microbiology S. Khelaifia and M. Drancourt Unite´ de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UMR CNRS 6236 IRD 3R198, Me´diterrane´e Infection, Faculte´ de Me´decine, Aix-marseille-Universite´, Marseille, France Abstract We herein review the state of knowledge regarding the in vitro and in vivo susceptibility of archaea to antimicrobial agents, including some new molecules. Indeed, some archaea colonizing the human microbiota have been implicated in diseases such as periodontopathy. Archaea are characterized by their broad-spectrum resistance to antimicrobial agents. In particular, their cell wall lacks peptidoglycan, making them resistant to antimicrobial agents interfering with peptidoglycan biosynthesis. Archaea are, however, susceptible to the pro- tein synthesis inhibitor fusidic acid and imidazole derivatives. Also, squalamine, an antimicrobial agent acting on the cell wall, proved effective against human methanogenic archaea. In vitro susceptibility data could be used to design protocols for the decontamination of complex microbiota and the selective isolation of archaea in anaerobic culture. Keywords: Antimicrobial agent, archaea, methanogenic archaea, microbiota, susceptibility testing Article published online: 23 May 2012 Clin Microbiol Infect 2012; 18: 841–848 Corresponding author: M. Drancourt, Unite´ des Rickettsies, Fa- culte´ de Me´decine, 27, Boulevard Jean Moulin-Cedex 5, France E-mail: [email protected] Methanogenic archaea (herein referred to as methano- Introduction gens) are the sole organisms producing methane from H2 +CO2 [6]. -
AMEG Categorisation of Antibiotics
12 December 2019 EMA/CVMP/CHMP/682198/2017 Committee for Medicinal Products for Veterinary use (CVMP) Committee for Medicinal Products for Human Use (CHMP) Categorisation of antibiotics in the European Union Answer to the request from the European Commission for updating the scientific advice on the impact on public health and animal health of the use of antibiotics in animals Agreed by the Antimicrobial Advice ad hoc Expert Group (AMEG) 29 October 2018 Adopted by the CVMP for release for consultation 24 January 2019 Adopted by the CHMP for release for consultation 31 January 2019 Start of public consultation 5 February 2019 End of consultation (deadline for comments) 30 April 2019 Agreed by the Antimicrobial Advice ad hoc Expert Group (AMEG) 19 November 2019 Adopted by the CVMP 5 December 2019 Adopted by the CHMP 12 December 2019 Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union © European Medicines Agency, 2020. Reproduction is authorised provided the source is acknowledged. Categorisation of antibiotics in the European Union Table of Contents 1. Summary assessment and recommendations .......................................... 3 2. Introduction ............................................................................................ 7 2.1. Background ........................................................................................................ -
Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Cr
Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Crizotinib (PF-02341066) 1 4 55 Docetaxel 1 5 98 Anastrozole 1 6 25 Cladribine 1 7 23 Methotrexate 1 8 -187 Letrozole 1 9 65 Entecavir Hydrate 1 10 48 Roxadustat (FG-4592) 1 11 19 Imatinib Mesylate (STI571) 1 12 0 Sunitinib Malate 1 13 34 Vismodegib (GDC-0449) 1 14 64 Paclitaxel 1 15 89 Aprepitant 1 16 94 Decitabine 1 17 -79 Bendamustine HCl 1 18 19 Temozolomide 1 19 -111 Nepafenac 1 20 24 Nintedanib (BIBF 1120) 1 21 -43 Lapatinib (GW-572016) Ditosylate 1 22 88 Temsirolimus (CCI-779, NSC 683864) 1 23 96 Belinostat (PXD101) 1 24 46 Capecitabine 1 25 19 Bicalutamide 1 26 83 Dutasteride 1 27 68 Epirubicin HCl 1 28 -59 Tamoxifen 1 29 30 Rufinamide 1 30 96 Afatinib (BIBW2992) 1 31 -54 Lenalidomide (CC-5013) 1 32 19 Vorinostat (SAHA, MK0683) 1 33 38 Rucaparib (AG-014699,PF-01367338) phosphate1 34 14 Lenvatinib (E7080) 1 35 80 Fulvestrant 1 36 76 Melatonin 1 37 15 Etoposide 1 38 -69 Vincristine sulfate 1 39 61 Posaconazole 1 40 97 Bortezomib (PS-341) 1 41 71 Panobinostat (LBH589) 1 42 41 Entinostat (MS-275) 1 43 26 Cabozantinib (XL184, BMS-907351) 1 44 79 Valproic acid sodium salt (Sodium valproate) 1 45 7 Raltitrexed 1 46 39 Bisoprolol fumarate 1 47 -23 Raloxifene HCl 1 48 97 Agomelatine 1 49 35 Prasugrel 1 50 -24 Bosutinib (SKI-606) 1 51 85 Nilotinib (AMN-107) 1 52 99 Enzastaurin (LY317615) 1 53 -12 Everolimus (RAD001) 1 54 94 Regorafenib (BAY 73-4506) 1 55 24 Thalidomide 1 56 40 Tivozanib (AV-951) 1 57 86 Fludarabine -
Transdermal Drug Delivery Device Including An
(19) TZZ_ZZ¥¥_T (11) EP 1 807 033 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61F 13/02 (2006.01) A61L 15/16 (2006.01) 20.07.2016 Bulletin 2016/29 (86) International application number: (21) Application number: 05815555.7 PCT/US2005/035806 (22) Date of filing: 07.10.2005 (87) International publication number: WO 2006/044206 (27.04.2006 Gazette 2006/17) (54) TRANSDERMAL DRUG DELIVERY DEVICE INCLUDING AN OCCLUSIVE BACKING VORRICHTUNG ZUR TRANSDERMALEN VERABREICHUNG VON ARZNEIMITTELN EINSCHLIESSLICH EINER VERSTOPFUNGSSICHERUNG DISPOSITIF D’ADMINISTRATION TRANSDERMIQUE DE MEDICAMENTS AVEC COUCHE SUPPORT OCCLUSIVE (84) Designated Contracting States: • MANTELLE, Juan AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Miami, FL 33186 (US) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI • NGUYEN, Viet SK TR Miami, FL 33176 (US) (30) Priority: 08.10.2004 US 616861 P (74) Representative: Awapatent AB P.O. Box 5117 (43) Date of publication of application: 200 71 Malmö (SE) 18.07.2007 Bulletin 2007/29 (56) References cited: (73) Proprietor: NOVEN PHARMACEUTICALS, INC. WO-A-02/36103 WO-A-97/23205 Miami, FL 33186 (US) WO-A-2005/046600 WO-A-2006/028863 US-A- 4 994 278 US-A- 4 994 278 (72) Inventors: US-A- 5 246 705 US-A- 5 474 783 • KANIOS, David US-A- 5 474 783 US-A1- 2001 051 180 Miami, FL 33196 (US) US-A1- 2002 128 345 US-A1- 2006 034 905 Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. -
Acquired Antibiotic Resistance Genes: an Overview
REVIEW ARTICLE published: 28 September 2011 doi: 10.3389/fmicb.2011.00203 Acquired antibiotic resistance genes: an overview Angela H. A. M. van Hoek 1, Dik Mevius2,3, Beatriz Guerra4, Peter Mullany 5, Adam Paul Roberts5 and Henk J. M. Aarts1* 1 Laboratory for Zoonoses and Environmental Microbiology, Centre for Infectious Disease Control, National Institute of Public Health and the Environment, Utrecht, Netherlands 2 Central Veterinary Institute of Wageningen UR, Lelystad, Netherlands 3 Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, Netherlands 4 National Salmonella Reference Laboratory, Federal Institute for Risk Assessment, Berlin, Germany 5 Department of Microbial Diseases, University College London Eastman Dental Institute, University College London, London, UK Edited by: In this review an overview is given on antibiotic resistance (AR) mechanisms with special Timothy Rutland Walsh, Cardiff attentions to the AR genes described so far preceded by a short introduction on the dis- University, UK covery and mode of action of the different classes of antibiotics. As this review is only Reviewed by: M. Pilar Francino, Center for Public dealing with acquired resistance, attention is also paid to mobile genetic elements such as Health Research, Spain plasmids, transposons, and integrons, which are associated with AR genes, and involved Jun Liu, Mount Sinai School of in the dispersal of antimicrobial determinants between different bacteria. Medicine, USA Keywords: antimicrobial resistance mechanisms, acquired, antibiotics, mobile genetic elements *Correspondence: Henk J. M. Aarts, National Institute of Public Health and the Environment, Antonie van Leeuwenhoekla 9, 3721 MA Bilthoven, Utrecht, Netherlands. e-mail: [email protected] INTRODUCTION emergence of resistance actually began before the first antibiotic, The discovery and production of (synthetic) antibiotics in the first penicillin, was characterized.