Antibiotic Chart Final(1)

8/8/2019 Antibiotic Chart Final(1)

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Drug Class General Action Mode of Action

Fosfomycin

D-Cycloserine

Vancomycin

Bacitracin

B-Lactam

Tetracyclines

Block cell wallsynthesis

Structural analog ofphosphoenolpyruvate(PEP)


Structural analog ofD-Alanine


Steric hindrance,Inhibitstranspeptidation of D-alanine


Membrane structureprecursorregenerationblockade


BlocksTranspeptidation/Cro

ss-linking; substarteanalog of D-ala-D-ala-COOH region ofpentapeptide

Linezolid(oxazolidinones)

Inhibit proteinsynthesis

Inhibits formation of70S initiationcomplex

Aminoglycosides-StreptomycinKanamycinTobramycinGentamycinNeomycin AmikacinParamomycin

Inhibit proteinsynthesis,inhibitors ofrecognition

- Bind 30S ribosomalsubunit

Spectinomycin (anaminocyclitol)

Inhibit proteinsynthesis(recognition)


Inhibit proteinsynthesis(recognition)



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- Inhibit DNA gyrase

Fluccytosine

QuinolonesNalidixic acidNorfloxacinCiprofloxacinOfloxacin LevofloxacinLomefloxacinSparfloxacin

Inhibit DNAsynthesis(replication)

Metronidazole(Flagyl)

Inhibit DNAsynthesis

Disrupts DNAstucture, inhibits DNAreplication, causesDNA breaks andsecondary mutations

PolymyxinColistin

Cell membranedamage

- Membraneperforation

Amphotericine B(polyeneantibiotics)

Cell walldisruption

- Membraneperforation, targetsergosterol!

Azoles:fluconazole,itraconazole,ketoconazole,

ravuconazole,posaconazole,voriconazole

Inhibit synthesisof ergosterol

Block the 14-alpha-demethylase

Terbinafine(allylamines)

Inhibit synthesisof ergosterol

Glucan SynthesisInhibitors/Echinocandins CaspofunginMicofungin

Anidukafungin

Block fungal cellwall synthesis

FungalAntimetabolite

Inhibits fungal proteinsynthesis


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Mechanism Selectivity Cidal/Static

Broad

Broad Bacteriostatic

Narrow



Spectru

- Block reaction:UDP-GluNAc + PEP --> --> UDP-MurNAc

- Inactivate pyruvyl transferase by binding covalently toactive site

- Cell wall structuresunique to bacteria

Bacteriocidal

- Block synthesis of UDP-MurNAc-Pentapeptide by:- Inactivate Alanine Racemase: L-Ala --> D-Ala- D-Alanine Ligase: D-ala+D-ala+ATP-->D-ala-D-ala- Competitive inhibition of both enzymes


- Inhibit Transglycosylase Rxn: inhibits translocation ofpeptidoglycan from cytoplasmic face to outer face ofmembrane)- Binds tightly to D-alal-D-ala residue of pentapeptide- Prevents precursor unit from binding to the synthase- Occurs on outerface of c to lasmic membrane


Bacteriocidal

- Inhibit GCL-P regeneration from GCL-PP:- Binds to the lipid pyrophosphate with Mg2+ or Zn2+, preventdephosphorylation


Bacteriocidal

- Prevents pentapeptide from cross-linking- Inhibit/covalently bind to transpeptidase

- Only effective in Actively Growing bacterias

- Host does nothave peptidoglycan

membrane structure

Narrow(old) and

Broad(new)

Bacteriocidal

Prevents formation of the 70S ternary complex binding tothe 23S peptidyltransferase center of the 50S ribosomalsubunit

70S ribosomalsubunit unique tobacteria

Bacteriocidal(streptococci) ANDBacteriostatic(staphylococci andenterococci)

- Cause misreading of mRNA (insertion of incorrect aminoacid)- Cyclic Polysomal Blockade (70S complex forms and falls

apart)- Faulty protein synthesis (translational misreading results

in mutant outer membrane that cause membrane to beleaky. More drug can be taken up by cell)- Premature mRNA release

- 30S ribosomesubunit unique tobacteria; activelytransported intobacteria, noteukaryotic cells

Broad,effectiveagainstPseudomonas

Bacteriocidal

- Formation of unstable 70S, does not inhibit:- Polyribosome- Misreading

- 30S ribosomesubunit unique tobacteria

- Bind to 30S ribosomal subunit and inhibit binding of aa-tRNA to the A site

- Selectivelyuptaken by bacteriabut not host


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Narrow

Narrow

Fungocidal

Block the 14-alpha-demethylase Fungocidal

Inhibit Squalene epoxidase Fungocidal

Inhibit 1,3-beta-glucan synthase Fungocidal

Fungocidal

- Prevent DNA unwinding, blocking DNA replication,transcription, repair

specifically inhibitsbacterial DNAgyrases

NalidixicAcid:NarrowAll others:Broad

Bacteriocidal

This is administered as a prodrug, It is inactive until theprodrug is metabolized in vivo into an active form. The nitrogroup of metronidazole is reduced by bacterialoxidoreductases to become active.

Enzymes required toconvert drug toactive form arepresent in somebacteria and nothost cells.

Bacteriocidal

- Hydrophobic tail inserts into cell membrane, hydrophilichead binds to the polar region of phosphatidylethanolamine(PE) and LPS and disrupts cytoplasmic membrane- High affinity for bacterial membrane PE, LPS

- Association --> leaky membrane, active againstGROWING and NON-GROWING cells

- LPS and PEspecific to bacterialcell wall

Bacteriocidal

- Amphoteric structure, the drug inserts into membraneshydrophobic portion associates with sterols, forminghydrophilic "channel".- High affinity forfungal cell wallergosterol- Association --> leaky membrane

- Ergosterol specificto fungal cell wall




Repaces uracil with 5-flurouracil in fungal RNA. Inhibitsthymidylate synthetase via 5-fluorodeoxy-uridinemonophosphate, interfering with fungal DNA synthesis


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Resistance Usage/Limitation Side Effect Representative Rx

High frequency - Many

- Tuberculosis- UTI- Infrequent usage due to itsneurologic effect

-Neurotoxic

- Staphlococci- Enterococci

Note: this is noteffective for GNbacteria because itis is too large of amolecule to getthrou h

- Topical tx of GP- Staphlococci

Block by B-lactamase that

cleaves B-lactamring.

- GP- New generation also

effective against GN entericand P. aeruginosa

- Penicillin- Cephalosporin

- Cephamycin- Carbapenems- Monobactam

Not approved for thetreatment of catheter-related bloodstream,catheter-site, or GNinfections

Altered 30Sribosome/target,decreaseduptake into cell,enzymaticmodifications oftheaminoglycoside

- GP/GN- Aerobe only- Antagonized by low pH,

Mg2+, PO42-, andanaerobiasis

Ototoxic,nephrotoxic

Ineffective againstintracellularbacteria. Inducebiofilm formation

- Gonorrhea (B-lactamase-producing gonococci orpatients allergic to penicillin)

- Decreaseduptake (OmpFporin)- Active efflux- Elongation

factor-likeproteins protect30S

- Selected GP/GN- Chlamydia- Mycoplasma- Richettsiae


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- Plasmid-transferredresistance(acetyltransferase that catalyzesthe acetylaton os-OH groups.Prevents 50S

binding

- Methylation of23S ribosomeprevents bindingto 50S

- GP- very effective!- Staphylococcal- Anaerobic GN- Bacterioides

Methylation of23S ribosomewhich preventsbinding of drug,hydrolysis of

Mycoplasma, Legionella,Chlamydia, Campylobactor,and GP in patients allergicto Penicillin

Staphylococci, streptococci,and vancomycin-resistantEnterococcus faeciuminfections.

- GP/GN- Chlamydia- Protozoa

- Acute UTI- Pneumocystis cariniiwithtrimethoprim

Only inhibit NEWsynthesis oftetrohydrofolic acid.

- Acute/chronic UTI- GP/GN- Pneumocystis cariniiwithsulfonamides

Precludes theutilization of pre-existing pools ofdihydrofolate.

- TB (sulfonamides are noteffective against M.tubercolosis)

- GP (staph and

streptococci)- Neisseria- Mycobacteria- M. avium (rifabutin)(rifabutin)


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Nephrotoxic

- Antifungal

- Antifungal

- Mutation ofDNA gyrase- Decreased

uptake

- Nalidixic Acid: UTI of GN(E.coli, Proteus, Flebsiella,Enterobactor, bur notPseudomonas). The restARE effective againstPseudomonas.

Mutations in theoxidoreductasesthat affectconversion to thepro-drug

Treatment of anaerobicinfections, H. pyloriinfections and Protozoalinfections due toEntamoeba histolytica andGiardia lamblia

- in GN bacteria,structuralmodification oflipid A moiety of

LPS, render OMimpermeable todrugs

- Pseudomonas infections

- Mammalian celllack ergosterol

- Antifungal (treatment ofsystemic mycoses andtopically in ointments)

Nausea,vomiting,diarrhea,nephrotoxic, andanemia

changes in drugtarget andincreased effluxfrom cell.

- Antifungal (Voriconazoleis effective againstAspergillus)

Side effectsnot as badasAmphoterici

n B

drug degradation,increased target,possible efflux

increase beta-glucan synthaseexpression

- Antifungal, effectiveagainst Azole resistantstrains

changes in genesinvolved inDNA/RNAsynthesis

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Antibiotic Chart Final(1)