Antimicrobials and antimicrobial action

Lina Cavaco
Rene Hendriksen
Susanne Karlsmose Pedersen
Outline
• Overview targets for antimicrobial action
• Modes of antimicrobial action
• Modes of action vs antimicrobial spectrum

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Targets of antimicrobial action
Cell wall synthesis DNA replication
RNA-polymerase
b-lactams: Fluoroquinolones
Rifampicin
Penicillins Metronidazole
Cephalosporins
Monobactams
Carbapenems Protein syntese
Vancomycin DNA Inhibitors (50s)
RNA Macrolides
DHF A- THF A Chloramphenicol
Clindamycin
50 50 50
30 30 30

Anti-metabolites Protein syntese

Sulfonamides PABA Inhibitors (30s)
Cell membrane
Trimethroprim Tetracyclines
Polymyxin/Colistin
Aminoglycosides
Amphotericin E- learning
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Fusidic acid Module1
Modes of antimicrobial action
• Inhibition of cell wall synthesis
– Beta lactams, bacitracin, vancomycin

• Inhibition of DNA synthesis

– Quinolones, Rifampicin

• Inhibition of protein synthesis

– Aminoglycosides, phenicols, tetracycline,
macrolides, lincosamides, streptogramins

• Inhibition of folic acid synthesis

– Sulphonamides, trimethroprim
Note - A limited number of targets
• Disruption of osmotic integrity
– Polymyxin/Colistin E- learning
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Cell wall synthesis

Gram positive cell wall Gram negative cell wall

Porin

Outer envelope
Periplasmic space

Peptidoglycan

Bacterial membrane

Penicillin-binding proteins

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Inhibition of RNA and protein synthesis

Transscription Replication

RNA polymerase

Nucleotides Ribosome
A G

T C
RNA polymerase
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Inhibition of DNA synthesis
quinolones

topoisomerases

DNA cannot
replicate- Resulting
in cell death

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Inhibition of folic acid synthesis
Dihydropteroate diphosphate +
paraminobenzoic acid (PABA)
Dihydropteroate synthetase sulphonamides

Dihydropteroic acid

Dihydrofolic acid
Dihydrofolate reductase trimethroprim
Tetrahydrofolic acid

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 Antibiotic spectrum – beta-lactam type
Antibiotic /
Staphylococcus Streptococcus H. influenzae E. coli Pseud. aerug Bact. fragilis
organisms

Penicillin

Ampicillin

Cefuroxime

Ceftazidime

Pip/ Tazo

Imipenem

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Spectrum of beta-lactams
• Penicillins
– Penicillin G/V narrow spectrum (Gram-positive)
– Methicillin, oxacillin (antistaph penicillins)
– Aminopenicillins (more active against Gram-negative)
– Carboxypenicillins (active against Pseudomonas and other
problematic Gram-negative such as Proteus, etc.)

• Cephalosporins
– 1st generation (injectable, mainly Gram-positive)
– 2nd generation (more active against Gram-negative)
– 3rd generation (broader spectrum incl Pseudomonas)
– 4th generation (both Gram-positive and negative, less susceptible
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to beta-lactamases, can cross blood-brain barrier) Module1
 Spectrum of beta-lactams

• Carbapenems
– Imipenem, meropenem, ertapenem (highly resistant to beta-
lactamases injectable)

• Monobactams
– Aztreonam (only Gram-negative, IV admin, resistant to most to
beta-lactamases except ESBL)

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Antibiotic spectrum –
target ribosomes or DNA synthesis

Antibiotic /
Staphylococcus Streptococcus H.influenzae E. coli Pseud. aerug Bact. fragilis
organisms

Macrolides

Tetracycline

Fluoroquinolone
(ciprofloxacin)

Gentamicin

Metronidazol

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Spectrum of activity

Mycobacteria Gram negative Gram positive Chlamydias Rickettsias

bacteria bacteria

Penicillins
Tobramycin

Sulphonamides
Cephalosporins
Streptomycin

Tetracyclines

Isoniazid Polymyxins

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 On behalf of the EURL-AR team:
Thank you very much!

www.antimicrobialresistance.dk

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