12 Pharmacology of Azole Antifungal Agents

484 Pages·2010·4.56 MB·English

Antifungal
Therapy

Antifungal
Therapy
Edited by
Mahmoud A. Ghannoum
University Hospitals Case Medical Center
Case Western Reserve University
Cleveland, Ohio, USA
John R. Perfect
Duke University Medical Center
Durham, North Carolina, USA
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ISBN-13:978-0-8493-8787-6(hardcover:alk.paper)
ISBN-10:0-8493-8787-6(hardcover:alk.paper) 1. Antifungalagents. 2.
Mycoses–Treatment. I.Ghannoum,MahmoudA.(MahmoudAfif) II.Perfect,JohnR.,
1949–
[DNLM:1. Mycoses–drugtherapy. 2. AntifungalAgents–therapeuticuse. WC
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Preface
Thisbookisdesignedtoprovideacomprehensivebutinsightfulexaminationofantifungalther-
apyinthechangingclinicmilleniumofmodernmedicine.Itisclearthatasmedicineadvances
totreat and cure severe underlying diseases,the collateral consequences of this management
canbeimmunosuppressionandopportunisticfungalinfections.Furthermore,thereareaseries
ofprimaryfungalinfectionssuchasdermatophytosisandendemicmycoseswhichcontinueto
plaguenormalhosts.Furthermore,thepandemicofHIVwhichhasimpactedtheentireworld
laidinitsimmunosuppressivepaththeriseofinvasivemycoses.Itisclearthatmostclinicians
whocarefortheseriouslysickwillbefacedattimeswiththeappearanceofafungalinfection
andaneedtomanageitsdisease.Therearemanyaspectsofinvasivemycosesincludinggenetic
susceptibility,riskfactorpredictions,diagnosis,epidemiologyandoutcomeofunderlyingdis-
easeswhichrequireapresentandfutureknowledgebaseformedicalpractice.Inthisbook,we
haveattemptedtofocusthepresentationonthemanagementaspectoffungaldisease.Withthe
risingnumberoffungalinfectionsworldwideandthedevelopmentandclinicaluseofavariety
ofantifungalagents,itisquiteclearthatthestatement:“AmphotericinBisthegoldstandard
fortheinvasivemycoses”isnolongertrue.Wehavesaferandeffectivealternativedrugstouse.
Itisourmissioninthisbooktoprovideclinicianswithafoundationandinsightsintocurrent
antifungalmanagement.
There are four sections in this book. First, we approach some general antifungal agent
issuesfromthehistoryofantifungal,fungalepidemiology,antifungalagentpreclinicaldevel-
opmenttodrugresistance.Second,weexamineindepththeantifungalclassesofdrugs,Third,
thereisanattempttoprovideclinicalmanagementissuesandstrategiesaroundspecificfungal
infectionsinwhichtheclinicianmayfacefrequentlyorrarelydependingonthepatientpopula-
tionintheirpractice.Inthesesectionsthereareinsightsprovidedintodosing,choiceofdrugs,
concerns about complications and outcome which are both evidence—based but mixed with
personal opinions and experiences. Fungal infections are treated “one patient at a time” and
thereisno“cookbookrecipe”thatfitsallpatientsallthetime.Infact,theunderlyingdisease
simplygetsinthewaytoooftenorourevidence-basedmaterialiseitherweakornon-existent.
Finally, we conclude with management of several risk groups or unique patient populations
or infection sites and their fungal infections. It is not an exhaustive list but provides illustra-
tiveexposuretothesepatientsbutalsolaysthegroundwork/foundationfortheprinciplesof
managingotherriskgroupswhichoccurtodayormayoccurtomorrow.
Fungaldiseaseshaverisentoprominenceoverthelast50years.Theyhaveparalleledthe
technologicaladvancesinthecareofseriousmedicaldiseases.Fungi,aseukaryoticorganisms,
playaninterestingroleinthehumancondition.Theyhavebeenharnessedtohelpmakeour
breadandbeverages.Infact,weeatsomeofthemandduringthetrafficoflife,weareconstantly
exposed to millions of them. During health they are rarely a problem for us and after death
they degrade us. Many of our critical exposures for health and fungi come between these
stations of life. It is in this arena as a “human petri dish” that fungal disease raises its ugly
consequences. It is the hope of these authors that this book reveals the tools, strategies, and
insightstomanagetheseirritating,costlyandlife-threateninginfections.Attimes,itmayseem
thepatientisdefenselessagainstthesemauradersbutinfact,presentantifungaltherapyisvery
good and applied early and correctly can make a difference in patient outcome. This success
storyistoldinthefollowingpages.
MahmoudA.Ghannoum
JohnR.Perfect

Contents
Preface .... v
Contributors .... ix
I. GeneralIntroductiontotheManagementIssues
1. HistoryofAntifungals 1
AliAbdulLattifandKimSwindell
2. EpidemiologyofFungalInfections:What,Where,andWhen 11
SylviaF.CostaandBarbaraD.Alexander
3. ExperimentalAnimalModelsofInvasiveFungalInfections 49
YoshifumiImamuraandMahmoudA.Ghannoum
4. AntifungalDrugResistance:SignificanceandMechanisms 63
PranabK.MukherjeeandMingyueWang
5. AntifungalProphylaxis:AnOunceofPreventionisWorthaPoundofCure 87
AimeeK.Zaas
6. PreemptiveAntifungalTherapy:DoDiagnosticsHelp? 97
KimberlyE.Hanson
7. TheImmuneResponsetoFungalChallenge 125
JefferyJ.Auletta
8. Immunomodulators:WhatistheEvidenceforUseinMycoses? 139
J.AndrewAlspaugh
9. FungalBiofilmsandCatheter-AssociatedInfections 149
JyotsnaChandraandMahmoudA.Ghannoum
II. AntifungalDrugClasses
10. PolyenesforPreventionandTreatmentofInvasiveFungalInfections 163
RichardH.Drew
11. Flucytosine 184
RichardH.Drew
12. PharmacologyofAzoleAntifungalAgents 199
ElizabethS.DoddsAshley
13. EchinocandinsforPreventionandTreatmentofInvasiveFungalInfections 219
MelissaD.JohnsonandJohnMohr
viii Contents
14. NovelAdministrationsofAntifungals 243
RichardH.Drew
III. ManagementofSpecificMycoses
15. Dermatophytosis 258
SusanA.KeilerandMahmoudA.Ghannoum
16. InvasiveCandidiasis 278
RanaTraboulsiandMahmoudA.Ghannoum
17. InvasiveAspergillosis 293
RanaTraboulsi
18. ManagementofCryptococcosis 308
JohnR.Perfect
19. ManagementofEndemicMycoses 320
JohnR.Perfect
20. HumanHyalohyphomycoses:AReviewofHumanInfectionsDuetoAcremoniumspp.,
Paecilomycesspp.,Penicilliumspp.,andScopulariopsisspp. 327
MahmoudA.Ghannoum
21. ManagementofPhaeohyphomycosis 343
JohnR.Perfect
22. Pneumocystis 351
KimSwindell
23. ManagementofZygomycosis 361
JohnR.Perfect
IV. TheParadigmofRiskGroup/InfectionSiteAssessments
24. AntifungalManagementinRiskGroups:TransplantRecipients 367
SylviaF.CostaandBarbaraD.Alexander
25. ProphylaxisandTreatmentofInvasiveFungalInfectionsinNeutropenicCancerand
HematopoieticStemCellTransplantPatients 386
SelminA.AtaerginandHillardM.Lazarus
26. Infants:YeastsAreBeastsinEarlyLife 404
P.BrianSmithand DanielK.Benjamin,Jr.
27. NewerAntifungalAgentsinPediatrics 414
ChristinaHennandWilliamJ.Steinbach
28. FungalInfectionsinBurnPatients 427
JoseA.Vazquez
29. AllergicBronchopulmonaryAspergillosis 436
RanaTraboulsi
30. FungalInfectionsoftheGenitourinaryTract 445
RanaTraboulsiandSouhaKanj
Index .... 459
Contributors
BarbaraD.Alexander DepartmentofMedicine/InfectiousDiseases,DukeUniversity
MedicalCenter,Durham,NorthCarolina,U.S.A.
J.AndrewAlspaugh DepartmentofMedicine/InfectiousDiseases,DukeUniversity
MedicalCenter,Durham,NorthCarolina,U.S.A.
SelminA.Ataergin DepartmentofMedicalOncologyandBoneMarrowTransplantation
Unit,Gulhane(GATA)FacultyofMedicine,Ankara,Turkey
JefferyJ.Auletta PediatricHematology/OncologyandInfectiousDiseases,RainbowBabies
andChildren’sHospital;DepartmentofPediatrics,CaseComprehensiveCancerCenter,
NationalCenterforRegenerativeMedicine,CaseWesternReserveUniversity,Cleveland,
Ohio,U.S.A.
DanielK.Benjamin,Jr. DepartmentofPediatrics,DukeUniversityMedicalCenter,
Durham,NorthCarolina,U.S.A.
JyotsnaChandra CenterforMedicalMycology,UniversityHospitalsCaseMedicalCenter,
CaseWesternReserveUniversity,Cleveland,Ohio,U.S.A.
SylviaF.Costa DepartmentofMedicine/InfectiousDiseases,DukeUniversityMedical
Center,Durham,NorthCarolina,U.S.A.
ElizabethS.DoddsAshley DepartmentofPharmacy,UniversityofRochesterMedical
Center,Rochester,NewYork,U.S.A.
RichardH.Drew CampbellUniversityCollegeofPharmacyandHealthSciences,Buies
Creek,andDukeUniversitySchoolofMedicine,Durham,NorthCarolina,U.S.A.
MahmoudA.Ghannoum CenterforMedicalMycology,UniversityHospitalsCaseMedical
Center,CaseWesternReserveUniversity,Cleveland,Ohio,U.S.A.
KimberlyE.Hanson DivisionofInfectiousDiseasesandInternationalHealth,Department
ofMedicine;MolecularMicrobiology,DepartmentofPathology,DukeUniversityMedical
Center,Durham,NorthCarolina,U.S.A.
ChristinaHenn DepartmentofPediatrics,DukeUniversityMedicalCenter,Durham,North
Carolina,U.S.A.
YoshifumiImamura DepartmentofMolecularMicrobiologyandImmunology,Nagasaki
UniversityGraduateSchoolofBiomedicalSciences,Nagasaki,Japan
MelissaD.Johnson CampbellUniversityCollegeofPharmacy,BuiesCreek,andDivisionof
InfectiousDiseasesandInternationalHealth,DukeUniversityMedicalCenter,Durham,North
Carolina,U.S.A.