Antibiotic mechanisms of action Flashcards
Penicillins
Examples, mechanism
End in -cillin
- Intact beta-lactam ring is essential for activity
- **Time-dependent bacteriacidal action **
- Affect cell wall synthesis by binding to active serine site on penicillin binding protein -> irreversible de-activation of transpeptidase enzyme responsible for forming peptidoglycan cross-links.
Cephalosporins
Examples, mechanism
Ceflaclor (first gen), cefuroxime (2nd gen), cefotaxime, ceftriaxone (3rd gen), cefepime, cefpirome (4th gen), ceftaroline, ceftobripole (5th gen)
Beta-lactam ring is fused with a dihydrothiazine ring to produce the cephem nucleus
Bacteriacidal
Affect cell wall synthesis by disrupting peptidoglycan cell wall integrity
Carbapenems
Examples, mechanism
Imipenem, meropenem, ertapenem
- Beta-lactam.
- Due to subtle modification of beta-lactam ring some groups are changed and ring is fused - significant resistant to most beta-lactamases.
- Bactericidal - disrupt cell wall synthesis
Glycopeptides
Examples, structure, mechanism
Vancomycin, teicoplanin, semi-synthetic analogues (2nd gen): dalbavancin, telavancin
- Glycosylated non-ribosomal heptapeptides that do not contain a beta-lactam ring
- Time-dependent bactericidal action.
- Inhibit cell wall synthesis by binding to subunits of the peptidoglycan: preventing addition of new molecules and cell wall synthesis. Similar mechanism to beta-lactams but no competition between peniciilins and glycopeptides for the active binding site.
Aminoglycosides
Examples, structure, mechanism
Gentamicin, amikacin, neomycin, streptomycin, tobramycin
- **Concentration-dependent bactericidal **
- Inhibit protein synthesis by binding irreversibly to bacterial 30S ribosomal subunit.
Chloramphenicol
Family, mechanism
An amphenicol
- Bacteriostatic
- Inhibits protein synthesis.
- Binds to residues of the 50S ribosomal subinit by preventing peptide bond formation and subsequent protein synthesis.
Tetracyclines
Examples, structure, mechanism
Doxycycline, tetracycline, lymecycline, tigecycline, demeclocycline
- Lienar fused tetracyclic nucleus with differing side chains
- Bacteriostatic
- Inhibit protein synthesis
Macrolides
Examples, structure, mechanism
Erythryomycin, clarithromycin, azithromycin
- Lactone ring at centre
- Bacteriostatic (may be bacteriocidal depending on concentration and bacterial species)
- Inhibit protein synthesis
Clindamycin
Family, mechanism
A licosamide.
- Inhibits protein synthesis
- May be bacteriostatic or bactericidal
Linezolid
Family, mechanism
A oxazololidinone, also tedizolid
- Inhibits protein synthesis
- Bacteriostatic vs enterococci and staphylococci
- Bactericidal vs streptococci
Metronidazole
Family, mechanism
Nitroimidazole (also tinidazole)
- Concentration-dependent bactericidal action
- Inhibits normal nucleic acid replication
Co-trimoxazole
Sulfamethoxazole (sulphonamide) + trimethoprim
- Sulfamethoxazole alone is bacteriostatic
- Co-trimoxazole is bacteriocidal and inhibits normal nucleic acid replication
Fluoroquinolones
Examples, mechanism
Ciprofloxacin, moxifloxacin
- Concentration dependent bactericidal action
- Inhibit normal nucleic acid replication
Rifampicin
Family, mechanism
A rifamycin (also rifabutin, rifamixin)
- Bacteriacidal
- Inhibit normal nucleic acid replication
Time-dependent bactericidal action
Mechanism, dosing, post antibiotic effects, examples (3)
- Slow bactericidal drugs, need drug concentration to be >MIC for at least 50% of the dosing interval. Magnitude of concentration above MIC has little relevance (more killing does not occur at higher concentrations)
- Minimum bactericidal concentration similar to minimum inhibitory concentration
- Often given in multiple daily doses, Amenable to continuous infusions following loading dose: aim to keep trough serum levels of free drug >MIC. Larger doses work by increasing duration of time drug concentration is above MIC
- Minimal post-antibiotic effects.
Penicillins, vancomycin, teicoplanin
Concentration-dependent bactericidal action
Mechanism, dosing, post antibiotic effects, examples
- Efficacy depends on maximum concentration achieved and time spent above MIC. Higher the concentration -> more bacteria killed
- Minimum bactericidal concentration similar to minimum inhibitory concentration
- Amount of drug rather than frequency of dosing determines efficacy. Maximising serum concentrations of drugs by increasing dose will maximise the rate and extent of bactericidal activity (if adverse effects are not also concentration-dependent)
- Significant and prolonged post-antibiotic effects
Aminoglycosides
Fluoroquinolones
Daptomycin
Colistin
Metronidazole
Bacteriostatic
- Efficacy determined by time spent above MIC
- Minimum bactericidal concentration»_space;> minimum inhibitory concentration
- Prolonged post-antibiotic effects
Chloramphenicol
Tetracyclines e.g. doxycycline
Macrolides e.g erythromycin (can be bacteriacidal at high concentrations)
Linezolid (vs enterococci and staphylococci)
Sulfonamides e.g. sulfamethoxazole (if used alone)
