Medical Microbiology

ThePrinciplesofAntibioticTherapy 187

ThePrinciplesofAntibioticTherapy...............................

&Specificantibacterialtherapyreferstotreatmentofinfectionswithanti-

infectiveagentsdirectedagainsttheinfectingpathogen.Themostimportant

groupofanti-infectiveagentsaretheantibiotics,whichareproductsoffungi

andbacteria(Streptomycetes).Anti-infectiveagentsarecategorizedashaving

abroad,narrow,ormediumspectrumofaction.Theefficacy,oreffectiveness,

ofasubstancereferstoitsbactericidalorbacteriostaticeffect.Anti-infective

agentshavemanydifferentmechanismsofaction.Undertheinfluenceof

sulfonamides and trimethoprim, bacteria do not synthesize sufficient

amountsoftetrahydrofolicacid.Allbetalactamantibioticsirreversiblyblock

thebiosynthesisofmurein.RifamycininhibitstheDNA-dependentRNApoly-

merase(transcription).Aminoglycosides,tetracyclines,andmacrolidesblock

translation.All4-quinolonesdamagecellularDNAtopologybyinhibiting

bacterialtopoisomerases.Duetotheirgeneticvariability,bacteriamaydevel-

opresistancetospecificanti-infectiveagents.Themostimportantresistance

mechanismsare:inactivatingenzymes,resistanttargetmolecules,reduced

influx,increasedefflux.Resistantstrains(problematicbacteria)occurfre-

quentlyamonghospitalflora,mainlyEnterobacteriaceae,pseudomonads,

staphylococci,andenterococci.Laboratoryresistancetestingisrequired

forspecificantibiotictherapy.Dilutionsseriestestsarequantitativeresis-

tance tests used todeterminethe minimuminhibitoryconcentration

(MIC).Thedisktestisasemiquantitativetestusedtoclassifythetestbacteria

asresistantorsusceptible.Incombinationtherapiesitmustberemembered

thattheinteractionsoftwoormoreantibioticscangiverisetoanantagonistic

effect.Surgicalchemoprophylaxismustbeadministeredasashort-termanti-

microbialtreatmentonly. &

Definitions.................................................

Specificantibacterialtherapydesignatestreatmentofinfectionswithanti-

infectiveagentsdirectedagainsttheinfectingpathogen(syn.antibacterial

chemotherapeutics,antibiotics).Onefeatureofthesepharmaceuticalsis

“selectivetoxicity,”thatis,theyactuponbacteriaatverylowconcentration

levelswithoutcausingdamagetothemacroorganism.Themostimportant

groupofanti-infectiveagentsistheantibiotics.Thesenaturalsubstances

areproducedbyfungiorbacteria(usuallyStreptomycetes).Theterm“anti-

biotic”isoftenusedinmedicalcontextstorefertoallantibacterialpharma-

ceuticals,notjusttoantibioticsinthisnarrowersense.Fig.3. 28 illustrates

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Kayser, Medical Microbiology © 2005 Thieme