Medical Microbiology

ThePrinciplesofAntibioticTherapy 199

DetailsoftheMechanismsofActionofAnti-InfectiveAgents

Sulfonamidesandtrimethoprim Tetrahydrofolicacid(THFA)actsasacoenzyme

toregulatetheC1metabolismfortransferof

thehydroxymethylandformylgroups.Too

littleTHFAresultsinthecessationofgrowth.

The combination of sulfamethoxazole and

trimethoprim(cotrimoxazole)resultsinapo-

tentiatedefficacy.

Betalactamantibiotics ThemechanismsdescribedinTable3. 5 referto

penicillin andpneumococci. They probably

holdinsimilar formforotherbetalactams

andotherbacteriaaswell.Allbacteriawith

cellwallscontainingmureinpossessautolysins.

Theseenzymescreategapsinthemureinsac-

culuswhilethebacteriumisgrowing,these

gapsarethenfilledinwithnewmureinmateri-

al.Bacteriathegrowthofwhichisinhibited,but

whicharenotlysed,showbetalactamtoler-

ance(bacteriostatic,butnotbactericidalef-

fects).

Proteinsynthesisinhibitors Thebiosynthesisofbacterialproteinsdiffersin

detailfromthatobservedineukaryotes,per-

mittingaselectiveinhibitionbyantibiotics.

Theprincipleofselectivetoxicitystillapplies.

4-Quinolones DNAgyrase,whichonlyoccursinbacteria,

catalyzesthecounterclockwisesupercoilingof

thedoublehelix,whichis,initself,woundto

theright,aboutitshelicalaxis(seeFig.3. 17 ,

p. 1 67).Onlyin supercoiledformcan the

DNAfiteconomicallyintothecell.DNAreplica-

tiondependsonthissupercoiled topology.

4-Quinolonesalsoinhibitbacterialtopoisome-

raseIVofGram-positivebacteria.

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Kayser, Medical Microbiology © 2005 Thieme