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Drug DrugClass MechanismofAction Indications AdverseEffects Resistance
B-LactamAntibiotics
CellWallSynthesisInhibitorsBacteriocidal
4-MemberNitrogenContainingB-LactamRingInhibitCellWallSynthesis
---------------------------------------Bacteriocidal:
MoreEffectivewhentheCellsareActivelyDividing/GrowingandSynthesizingCellWall
PenicillinB-Lactam
CellWallSynthesisInhibitorsBacteriocidal
5-MemberSulfurContainingThiazolidineRingFusedtoaB-LactamRing
------------------------------------------------------------------BacterialCellWall:
Cross-LinkedPolymerofPolysaccharidesandPentapeptides
PenicillinsInterferewithCellWallSynthesis(Peptidoglycan)byBindingPenicillinBindingProtein(PBP)
ThisInhibitsCross-LinkingofPeptideChains(TranspeptidationInhibition)
-----------------------------------------------------------------------ResultsinFormationofCellWallDeficienctBacteria,
WhichareEasilyLysed(CellDrawsWateruntilitBursts)
MoreEffectivewhenCellsareActivelyDividing/Growing(Bacteriocidal)
ActivityDependsontheConcentrationaboutMICfortheEntireDosing
Interval
HypersensitivityReactions:Anaphylaxis(Cross-AllergicReactions)
UrticarialRashes(Common)Angioedema:SwellingofLips,Tongue,PeriorbitalAreas
Anaphylaxis:DoNotUseANYB-LactamAfterReactionHappensDesensitizationCanBeAccomplishedwithGradually
IncreasingDosesofPenicillin(EspeciallyinEnterococcalEndocarditisorNeurosyphilis)
MajorAntigenicDeterminant:DegradationProductsofPenicillins:
PenicilloicAcidProductsofAlkalineHydrolysisBoundtoHostProtein
------------------------------------------------------------Nephrotoxicity:Methicillin
Neurotoxicity:HighDoses=SeizuresandConvulsionsPlateletDysfunction:Carbenicillin,Ticarcillin
Neutropenia:NafcillinGIDistress:Nausea,Vomiting,Diarrhea(Ampicillin!)
PseudomembranousColitis+VaginalCandida:AmpicillinJarish-HerxheimerReaction:PenicillinInjectedinaSyphiliticPatientProducesFever,Malaise,JointPain,
ExasterbationofLesions,Hypotension--DoNOTInterrupttheTherapy.
CellWallisUniquetoBacteriasoPenicillinsareRelativelyNon-Toxicto
Humans--------------------------------------------------
Resistance:NaturalResistance:
OccursinOrganismsthatLackaPeptidoglycanCellWall(Mycoplasma )orHaveCellsWallsImpermeabletoDrugs
AcquiredResistance:OccursbyPlasmidTransfer(SignificantClinicalProblem)
----------------------------------------------------MechanismsofResistance:
EnzymaticHydrolysisofB-LactamRingbyB-LactamaseEnzyme(MostCommon)
------------------StructuralChangeofPBPs(MRSA)
-----------------ChangeinPorinStructure(Pseudomonas)
---------------Gram-OrganismsMayHaveEffluxPumps,
whichEfficientlyTransportSomeB-LactamAntibioticsfromthePeriplasm
AcrosstheOuterMembrane
PenicillinGPenicillinV
StandardNatrualPenicillinsB-Lactam
CellWallSynthesisInhibitorsBacteriocidal
NarrowSpectrumSusceptibletoHydrolysisbyB-Lactamases
------------------------------HighlyWaterSolubleStableinDryState
SolutionsareFreshlyPreparedFormulatedtoDelayAbsorption
ResultlsinProlongedBloodandTissueConcentration-------------------------------------------------------
PenicillinG:(BenzylPenicillin)Acid-Labile
Half-Life:30MinutesParenteralRepository(Depot)FormforIMInjection
DestroyedbyGastricAcid(GiveIV!)DistributedWidely(DoesNOTCrossBBB)
DuringInflammation,(Meningitis)EntryisFacilitatedExcreted,UnchangedinUrine
--------------ProbenecidInhibitsTubularSecretionofPenicillin
ThisRaisesBloodPenicillinLevels----------------------------------------------------------------
PenicillinV:AcidResistance
Oral
Spectrum:GreatestActivityAgainst:Gram+andGram-Cocci
Non-B-LactamaseProducingAnaerobeNOTACTIVEAganistGram-RodsGoodActivity:TreponemaPallidum
----------------------------------------HighIncidenceofResistantStrains
------------------------------------PenicillinG:
DoC:Syphilis
ProphylacticDrug:RheumaticHeartDisease
(RheumaticFever)GonorrheaSyphilis
------------------------------------PenicillinV:
IndicatedinMinorInfectionsBecauseItIs:
PoorlyBioavailableDosing4x/Day
NarrowSpectrum(AmoxicillinUsedInstead)
HighTheraputicIndexPruriticRashAnaphylaxis
SafetoUseinPregnancy
MethicillinNaficillinOxacillinClocacillinDicloxacillin
Anti-StaphylococcalPenicillins(PenicillinaseResistant)
B-LactamCellWallSynthesisInhibitors
Bacteriocidal
VeryNarrowSpectrumResistanttoStaphylococcalB-Lactamases-------------------------------------------------------
Nafcillin:LipidSolubleCrossesBBB
ExcretedinBileCANBEGIVENinRenalImpairment
Spectrum:Staphylococci(NotMRSA)
StreptococciNOTACTIVEAgainst:
Enterococci,AnaerobicBacteria,Gram-Cocci/Rods
----------------------------------------StaphylococcalInfections:Anti-StaphPenicillins
DrugofChoice:NafcillinOxacilin
-----------------------------IftheStaphis"MethicillinResistant",
treatwithVancomycin---------------
IftheStaphis"VancomycinResistant",treatwithLinezolid,Quinupristin,
Dalfopristin
Methicillin:NephrotoxicityNoLongerUsed
-------------------------------------------IsoxazolylPenicillins:
Cloxacillin,Oxacillin,DicloxacillinFoodInterfereswithAbsorption
Administer1HourBefore/AfterMeals----------------------------------------------
Nafcillin:Neuropenia
MechanismsofResistance:AlteredPBPs
AmpicillinAmoxicillin
AminopenicillinsB-Lactam
CellWallSynthesisInhibitorsBacteriocidal
ExtendedSpectrumB-LactamaseSensitive
-------------------------------------------------------CanbeCombinedwithB-LactamaseInhibitors:
ClavulanicAcid,Sulbactam,Tazobactam--------------------------------------------
Ampicillin:Amoxicillin:
BetterOralBioavailability
Spectrum:GramPositiveCocci
(NOTSTAPH)GreaterActivityAgonist
Gram-BacteriathanPenicillin---------------------------------------------------
Ampicillin:DoC:ListeriaMonocytogenes
(Meningitis)------------------
SalmonellaGastroenteritisTyphoidCarrierState
Shigellosis----------------------------------------------
Amoxicillin:URTIs
(Pharyngitis,Sinusitis,OtitisMedia,Bronchitis)
-------------------UTIs:
Enterobacteriaceae,E.Coli-------------------
BorreliaBurgdorgeri(LymeDisease)H.Pylori
Ampicillin:FoodInterfereswithAbsorption
Causes:Diarrhea
PeudomembranousColitis---------------------------------
Amoxicillin:CompletelyAbsorbed
FoodDoesNOTInterferewithAbsorptionNoDiarrhea
NoPseudomembranousColitis
MechanismsofResistance:InactivationbyB-Lactamase(Penicillinase)
HighestResistance:E.ColiandH.Influenzae
-------------ProtectAgainstResistance:
GiveClavulanicAcidorSulbactam
CarbenicillinTicarcillinPiperacillinAzlocillinMezlocillin
Anti-PseudomonalPenicillinsB-Lactam
CellWallSynthesisInhibitorsBacteriocidal
ExtendedSpectrumB-LactamaseSensitive
-------------------------------------------------------
Carboxypenicillins:Carbenicillin,Ticarcillin:
NosocomialPseudomonasInfections:BurnPatients
CysticFibrosisPatients----------------
Ureidopenicillins:Piperacillin,Azlocillin,Mezlocillin
PseudomonasEnterobacterKlebsiella
HighDoseCarbenicillin,Ticarcillin:InterfereswithPlateletFunction:Bleeding
ClavulanicAcidSulbactamTazobactam(Augmentin)
B-LactamaseInhibitors
Lactamases:EnzymesProducedbyGram+/-OrganismsthatInactivate
B-LactamAntibioticsbyOpeningB-LactamRing---------------------------------------------------------------------------B-LactamaseInhibitorsResembleB-LactamMolecules,but,byThemselves,DoNOTHaveSignificantAnti-
BacterialActivity.
AvailableOnlyinFixedCombinationswithSpecificPenicillins:
Preparations:Amoxicillin+ClavulanicAcid(Oral)
Ticarcillin+ClavulanicAcid(Parenteral)Ampicillin+Sulbactam(Parenteral)
Piperacillin+Tazobactam(Parenteral)
Drug DrugClass MechanismofAction Indications AdverseEffects Resistance
CephalosporinsBacteriocidal
MoreStabletoManyBacterialB-LactamasesBroaderSpectrumofActivity
Allhave7-AminocephalosporanicAcidMechanismofAction:SameasPenicillin
1-4GenerationsGram-BacterialActivity:Increasesfrom1-->4
NotActiveAgainstLAME:ListeriaMonocytogenes
Atypital(Chalmydia,Mycoplasma)MRSA
Entercocci----------------------------
PoorOralAbsorption(GiveIV/IM)GoodBodyDistribution
Cefoperazone,Cefamondole,Cefotetan,Cefmetazole:Bleeding(Hypoprothrombinemia)
MTT,MethylthiotetrazoleSideChainGiveVitaminK--------------------------------------------------------
Diarrhea--------------------------------------------------------
Cephaloridine:Nephrotoxicity(Withdrawn)
GrowingResistanebyStrainsofE.ColiandKlebsiella
MechanismofResistance:SameasPenicillin
-------------------------------------------HypersensitivityReactions:
AnaphylaxisFever
SkinRashesCompleteCross-AllerginicityBetweenIndividualCephalosporinsandPartialCross-AllerginicitywithPenicillins-----------------------------------------------
IfpatienthashistoryofAnaphylaciswithPenicillins,doNOTgiveCephalosporinsGram+Organisms:GiveMacrolidesGram-Organisms:GiveAztreonam
Cefazolin---------------CephalexinCefadroxil
First-GenerationCephalosporins
DoesNotCrossBBB(CannotUseinMeningitis)WaterSoluble
(EliminatedbyKidneyGFandTubularSecretion)ProbenecidIncreasesSerumLevelSubstanstially
HighActivityAgainstGram+Cocci(NOTMRSA)
WeakGram-Activity(Pseudomonas)Effective:(PEcK)ProteusMirabilis
E.ColiKlebsiella
--------------------------------------Cefazolin:(Parenteral)
SurgicalProphylaxisAgainstGram+Bacteria
OrthopedicSurgery(PenetratesBone)------------------
Cephalexin:(Oral):URTIs(Pharyngitis)
Penicillin/Sulfonamide-ResistantUTIs------------------
Cefadroxil:(Oral)
CefuroximeCefamondoleCefoxitinCefotetan
Cefmetazole---------------Cefaclor
CefuroximeAxetil
Second-GenerationCephalosporins
Cefuroxime,Cefamondole,Cefaclor:ActiveAgainstH.InfluenzaeNOTActiveAgainstB.Fragilis
-------------------------------------------------------------------Cefoxitin,Cefotetan,Cefmetazole:
ActiveAgainstB.FragilisNOTActiveAgainstH.Influenzae
HighGram-Activity(B.Fragilis)Effective:(HENPEcK)HemophilusInfluenzaeEnterobacteraAerogenes
N.Meningitis+PEcK
-------------Upper/LowerRITsAnaerobicInfections
Community-AcquiredPneumonias-----------------------------------------
CefuroximeCefamondoleCefoxitinCefotetan
Cefmetazole:(Parenteral)----------------Cefaclor
CefuroximeAcetil:(Oral)
CefuroximeCANCrossBBB,butislesseffectivethanCeftriaxoneorCefotaxime,andisnotused.
CefotaximeCeftriaxoneCeftazidimeCefoperazone
---------CefiximeCefdinirCefibuten
CefpodoximeProxetil
Third-GenerationCephalosporins
ExpandedGramNegativeCoverageResistancetoMostLactamases
-----------------------------------------------------------CANENTERBBB
Excretion:BiliaryTract(SafeinRenalInsufficiency)
HighlyActiveAgainstGram+ANDGram-Cocci
ENHANCEDActivityAgainstGram-Bacilli
(HENPEcK)Pseudomonas,Serratia,Citrobacter,
Providencia--------------------------
EmpiricManagementofSepsisofUnknownCauseCeftazidime:
UsedinNeutropenicPatientsPseudomonas(Cefoperazone)----------------------------------------Ceftriaxone/Cefotaxime:
DoFforMeningitis:Pneumococci,Meningococci,H.Influenzae,Gram-Rods
NOTLISTERIAMONOCYTOGENES---------------------
Cefixime:UTIs
------------------------------------------TyphoidFever
1stGenerationsAreBetteratGram+Cocci,butthesehaveawiderspectrum.
CefepimeCefpirome
Fourth-GenerationCephalosporins
MoreResistancetoMost-BetaLactamases
CombinesGram+Activityof1stGenwithWiderGram-Activityof3rdGen
(DOESNOTINCLUDEMRSA)------------Cefepime:
PseudomonasEnterobacteriacaeae
S.AureusS.PneumoHemophilusNeiserria------------
CeftarolineFosamil:Pro-DrugofCeftarolineCommunityAcquiredBacterialPneumonia
AcuteBacterialSkinInfections
Drug DrugClass MechanismofAction Indications AdverseEffects Resistance
DoripenemErtapenemImipenemMeropenem
Carbapenems
MechanismofAction:SameasPenicillinandCephalosporin
B-LactamaseResistantException:
CarbapenemasesMetallo-B-Lactamases-----------------------------
IV/IMInjectionsErtapenem:
GiveWith1%Lidocaine(PreventsIrritation)
Spectrum:MostPotent
WidestSpectrumLactamsActiveAgainstPenicillinase-Producing
Gram+Cocci,Gram-Rods(Pseudomonas)AnaerobesErtapenem:
CannotBeUsedforPseudomonas------------------------------------------
UsedinHospitalforEmpiricUseofSevere,Life-ThreateningInfections
---------------------------DrugofChoice:Enterobacter
DrugFever:PartialCross-AllergenicitywithPenicillin
Imipenum Carbapenems
LimitingFeature:HydrolysisbyDehydropeptidasebyBrushBorderTubular
CellsofKidneyPrevention:
GiveCilastatin:InhibitsRenalDehydropeptidase
IfCilastatinIsn'tGiven,MetabolitesFormedbyDehydropeptidasearePotentiallyNephrotoxic
---------------------------------------------CausesSeizures
Drug DrugClass MechanismofAction Indications AdverseEffects Resistance
Aztreonam Monobactams
MechanismofAction:SameasPenicilin,Cephalosporins,Carbapenems
B-LactamaseResistant---------------------------------------------------
IV/IMInjections(OnlyIVforGram-Rods)
UsedforAerobicGram-RodsNOACTIVITYAgainst:Gram+orAnaerobes
-------------------------------------------------SafeinPatientswithPENICILLIN
ALLERGIES-------------------------------
UsedinHospitalAcquiredInfectionsandinPseudomonalInfectionswith
PenicillinAllergies
Drug DrugClass MechanismofAction Indications AdverseEffects Resistance
VancomycinTeicoplanin
GlycopeptideAntibioticsBacteriocidal
InhibitionoftheSynthesisofPeptidoglycanofBacterialCellWall
BindstoB-Ala-D-AlaTerminisofNascentPeptidoglycanPentapeptideSideChainandInhibitsTransglycosylation
PreventsElongationandCross-Linking**DoesNOTDependonBindingwithPBPstoProduce
Effect**------------------------WaterSoluble
PoorOralAbsorption(UsedforC.Diff)MostlyGivenIV
DoesNOTCrossBBB
MRSAGram+BacteriaOnly
Enterococci-----------------------------------------------
Vancomycin+Gentamycin:EnterococcalEndocarditis
ifPenicillinAllergies---------------------------------
Vancomycin+CefotaximeorCeftriaxone,orRifampin:
Penicillin-ResistantMeningitis
ExcretedbyGlomularFiltrationMustDecreaseDoseinRenalDysfunctionorToxicityMay
Occur-----------------
RedMan/RedNeckSyndrome:TypeIHSV
FlushingPruritusErythemaofHead/UpperBody
Hypotension(HISTAMINERELEASE)
Prevention:ProlongInfusionPeriodorAnti-HistaminePre-Treatment
-----------------------------------------Ototoxicity:
PermanentLossofHearing/Balance------------------------------------------------------------
Nephrotoxicity
Rare:VancomycinResistantStaphylococcusAureusandVancomycinResistantEnterococcalStrainsareRAREbut
Emerging(EspeciallyinSurgical/BurnUnits)---------------------------------------------
Mechanism:InvolvesaDecreasedAffinityforthe
BindingSiteDuetotheReplacememtoftheTerminalD-AlabyD-Lactate
--------------------------IfResistanceOccurs:
GiveLinezolid,Quinupristin,Dalfopristin
Fosfomycin GlycopeptideAntibioticsBacteriocidal
InhibitionofBacterialWallSynthesis
ActiveAgainstGram+andGram-Oral/ParenteralPrepsSAFEINPREGNANCY
UsedforUTIs
Bacitracin GlycopeptideAntibioticsBacteriocidal
TripleAntibioticComponentforSuppressionofMixedBacterialFlorainSurfaceLesionsoftheSkin,inWounds,
oronMucusMembranesTopicalApplication Nephrotoxicity
Daptomycin GlycopeptideAntibioticsBacteriocidal
SimilartoVancomycinBindstoCellMembraneViaCalcium-DependentInsertionofitsLipidTail,ResultinginDepolarizationoftheCellMembranewithPotassium
EffluxandRapidCellDeath
Skin/SoftTissueInfectionsBacteremiaEndocarditis
MyopathyAllergicPneumonitis
Keep Imipenum Lastin with Cilastin
When Others Fail, We Get the Job Done Broad Spectrum + Pseudomonas