Issues in Toxicology Alan B G Lansdown Silver in Healthcare Its Antimicrobial Efficacy and Safety in Use IS t sil v Ae nr ti in m H i ce roa blt ih ac l a Er fe fi c a c y a n d S a f e t y i n U s e L a n s d o w n Silver in Healthcare Its Antimicrobial Efficacy and Safety in Use Issues in Toxicology Series Editor: ProfessorDianaAnderson,UniversityofBradford,UK DrMichaelDWaters,IntegratedLaboratorySystems,Inc,NCarolina,USA DrTimothyCMarrs,EdentoxAssociates,Kent,UK Titles in the Series: 1: Hair in Toxicology: An Important Bio-Monitor 2: Male-mediated Developmental Toxicity 3:CytochromeP450:RoleintheMetabolismandToxicityofDrugsandother Xenobiotics 4: Bile Acids: Toxicology and Bioactivity 5: The Comet Assay in Toxicology 6: Silver in Healthcare: Its Antimicrobial Efficacy and Safety in Use How to obtain future titles on publication: Astandingorderplanisavailableforthisseries.Astandingorderwillbringdeliveryof eachnewvolumeimmediatelyonpublication. 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Lansdown CharingCrossHospitalandImperialCollege,FacultyofMedicine,London,UK IssuesinToxicologyNo.6 ISBN: 978-1-84973-006-8 ISSN: 1757-7179 AcataloguerecordforthisbookisavailablefromtheBritishLibrary rAlanB.G.Lansdown2010 Allrightsreserved Apartfromfairdealingforthepurposesofresearchfornon-commercialpurposesorfor privatestudy,criticismorreview,aspermittedundertheCopyright,DesignsandPatents Act1988andtheCopyrightandRelatedRightsRegulations2003,thispublicationmaynot bereproduced,storedortransmitted,inanyformorbyanymeans,withouttheprior permissioninwritingofTheRoyalSocietyofChemistryorthecopyrightowner,orinthe caseofreproductioninaccordancewiththetermsoflicencesissuedbytheCopyright LicensingAgencyintheUK,orinaccordancewiththetermsofthelicencesissuedbythe appropriateReproductionRightsOrganizationoutsidetheUK. Enquiriesconcerning reproductionoutsidethetermsstatedhereshouldbesenttoTheRoyalSocietyof Chemistryattheaddressprintedonthispage. TheRSCisnotresponsibleforindividualopinionsexpressedinthiswork. PublishedbyTheRoyalSocietyofChemistry, ThomasGrahamHouse,SciencePark,MiltonRoad, CambridgeCB40WF,UK RegisteredCharityNumber207890 Forfurtherinformationseeourwebsiteatwww.rsc.org Foreword Silver—is it a wolf in sheep’s clothing? Or is it another case of the Emperor’s new clothes? Many people have their own views on this old, but recently rediscovered agent,thoughtheirviewsmaybecolouredbyanumberoffactors.Forthefirst time, as far as I am aware, Alan Lansdown has provided us with a focused, academically sound and balanced view of this important and increasingly valuable metal. As a clinician I want to know before I treat my patients: is a product both safeandeffective?However,myabilitytomakeaninformedjudgementcan,if I am not careful, be influenced by laboratory research results which may have limitedtranslationtotheclinicalsettingandthe‘‘smokeandmirrors’’oftenseen when commercial concerns become involved in developing new products with an ability to cure all ills. I am sure the number of papers and citations about silver have increased enormously over the past decade, but how balanced are these papers? The analogies I drew at the beginning are very true in this situation and we all risk being ‘‘duped’’ into sitting one side of the fence or other. This book provides a comprehensive review of silver in a way that I believe will allow clinicians, academics, product developers and decision- makers who control the availability of silver-containing products to make an informed decision. The chapters provide a logical analysis of the current situation and under- standing of this element’s use in healthcare. Understanding the chemistry of silver,itsuptake,metabolismandtoxicologyanditsuseinmedicaldevicesare all scene setters for the main body of this work, which focuses on silver as an antimicrobial agent in wounds. Infection causes great concerns in clinical practice. The simple question of—is this wound infected?—can not be answered simply in all cases. As a consequence,theappropriateselectionofantimicrobialagentsandmeasuresof theirefficacyarefraughtwithdifficulty.Foravarietyofreasonstherehasbeen anexplosionofinterestinsilverasanantimicrobialagentinwoundhealingin recent years. Discussions and debates on its value are still ongoing and the limited amount of high quality evidence published in the peer reviewed litera- ture all make for a confusing picture at the present time. The interest and v vi Foreword apparentsuccessofmanynewwoundtreatmentscontainingsilvershouldmean that new data and consensus will eventually emerge. Silver is an old element. The resurgence of interest in its use clinically has sparkedconsiderablediscussion.Alan’sbookshouldbeseenassomethingthat helps provide an informed balanced view of this element’s use in clinical practice.Thepotentialforfurtherinnovationsandusesareconsiderablebut,in keepingwiththecommentsmadeatthebeginningofthispiece,weshouldnot ‘‘wanttothrowthebabyoutwiththebathwater’’.Thisworkhelpsusallresolve questionsandconcernswemayhaveand,assuch,Iwouldrecommendallwho are involved in this area to read it. Professor Keith Harding Head of Department of Dermatology and Wound Healing Academic Director of Innovation & Engagement School of Medicine, Cardiff University, Upper Ground Floor, Room 18, Heath Park, Cardiff, UK Preface This book owes much to my initial training and guidance in experimental pathology and toxicology by Professor Paul Grasso and his team in the British Industrial Biological Research Association. At different times, I can look back on the fruitful discussions that I have held with Paul and other col- leagues in industry and academia. I acknowledge the support that I have received from companies within the pharmaceutical and healthcare industries; this has enabled me enrich my knowledge, to pursue research, and to travel and lecture in Britain and overseas. It is noteworthy that my first research with silver was as a collaborative project with Dr Pisamai Laupattarakasem and Dr Auranut Vuttivirojana of the Faculty of Medicine, Khon Kaen University (Thailand), who visited my laboratory in Britain with support from the British Council. Their interest and enthusiasm is greatly appreciated. This publication is the fruit of many years of experimental study on the action and interaction of metals in biological systems fostered by discussion and collaboration with clinical and academic colleagues at Charing Cross Hospital and the former Charing Cross and Westminster Medical School. IappreciatetheclosecollaborationandfriendshipofBarrySampson whohas taught me much about the analysis of metals in body tissues and fluids, and fostered my interest in zinc and metal-carrier proteins as essential modulators in all living systems. Angela Williams in the Department of Vascular Surgery has been a good friend and teacher in the clinical evaluation of silver-con- taining wound therapies. Her nursing experience and devotion to patient care has been highly beneficial in aiding my understanding patterns of clinical woundhealing.Inwoundcare, asmuchdependsuponthebedsidemanner,as upon treatment of the wound with appropriate silver therapy. I should like to acknowledge with sincere thanks the constant support and tolerancethatmywifeVeronicahasgivenmeovermanyyears.Herinvaluable adviceandhelpfulcriticismhasencouragedmetopresentmyideasonasubject thatispresentlytopicalandofwide-reachingimplicationinhumanhealthand welfare. IssuesinToxicologyNo.6 SilverinHealthcare:ItsAntimicrobialEfficacyandSafetyinUse ByAlanB.G.Lansdown rAlanB.G.Lansdown2010 PublishedbytheRoyalSocietyofChemistry,www.rsc.org vii viii Preface Wehavesoughttolocateownersofall reproducedmaterial notinourown possession. In a few cases we have been completely unsuccessful, but trust we have not inadvertently infringed any copyrights. Should we have done so inadvertently we shall of course take appropriate action for any subsequent editions. Contents Acknowledgements xii Chapter 1 Silver in Health and Disease 1 References 6 Chapter 2 Silver and its Compounds, Chemistry and Biological Interactions 9 2.1 Silver: the Essentials 9 2.2 Silver in the Environment and Ecosystem 14 2.3 Analysis of Silver in Biological Materials 15 2.4 Nanotechnology 22 2.5 SilverCompoundsinAntibioticTherapyandMedical Devices 24 References 33 Chapter 3 Uptake and Metabolism of Silver in the Human Body 43 3.1 Introduction 43 3.2 Oral Exposure 46 3.3 Dermal Contact and Percutaneous Absorption 49 3.4 Inhalation and Absorption of Silver through the Respiratory Tract 53 3.5 MiscellaneousRoutesofSilverExposureandSystemic Absorption 56 3.6 Silver in Textiles 58 3.7 Metabolism of Silver in the Human Body 59 References 61 IssuesinToxicologyNo.6 SilverinHealthcare:ItsAntimicrobialEfficacyandSafetyinUse ByAlanB.G.Lansdown rAlanB.G.Lansdown2010 PublishedbytheRoyalSocietyofChemistry,www.rsc.org ix