L20: Antibiotics Flashcards
Bacteriostatic
Inhibit growth (don’t kill bacteria) – used when host defense can be counted on
Bactericidal
Kill bacteria – used for invasive bacteria (ex. bacteremia, meningitis, endocarditis) or for immunocompromised patients
Antibiotic synergism
Combination of two antibiotics with enhanced bactericidal activity when used together
Antibiotic antagonism
Combination of antibiotics in which one interferes with the activity of the other
Broad-spectrum antibiotic
Effective against a large variety of bacteria; used in emergency situation when lab results are not available but might have consequences due to interrupting normal microbiota
Narrow-spectrum antibiotic
Effective against only a small subset of bacteria; used when specific disease-causing agent is known, avoids disruption of the normal microbiota
Principles of rational and effective antibiotic use
- -Only for bacterial infections
- -Important to collect representative sample before therapy
- -Empiric therapy followed by targeted therapy
- -Adjustments if needed
How can we help stop antibiotic resistance?
- -Prescribe the right antibiotics
- -Make sure patients take the whole course
- -Use combinatorial therapy
- -Antibiotic prophylaxis – prevents rather than treats disease (for any immunocompromised or surgical patients and exposure to certain bacteria)
General mechanisms of antimicrobial resistance
–Breakdown of antibiotic by hydrolysis
–Chemical modification of an antibiotic
–Alteration of the target
by mutations/gene acquisition
–Altered permeability, decreased influx or increased efflux
–Lack of target
Minimum inhibitory concentration (MIC)
Lowest concentration of antibiotic that inhibits growth
Minimum bactericidal concentration (MBC)
Lowest concentration of antibiotic that kills 99.9%
Kirby-Bauer test (disc-diffusion assay)
A antimicrobial agent is placed on a plate and bacteria is tested to see how it goes (grows on top of disc = resistant); measures MIC
E-test
Measures MIC with strips to see what concentration is needed
Broth-based method
Can see where MIC/MBC are based on concentration of cultures
Mechanisms of action
- -Cell wall synthesis inhibitors (peptidoglycan)
- -DNA replication inhibitors
- -RNA synthesis inhibitors
- -Protein synthesis inhibitors (30S and 50S)
- -Antimetabolites
Cell wall active antibiotics
Disrupt peptidoglycan synthesis – ONLY effective against actively DIVIDING bacteria
Membrane active antibiotics
Disrupt or interfere with membrane integrity/synthesis – effective against resting AND actively dividing bacteria
Examples of cell wall synthesis inhibitors
- -β-lactams
- -Vancomycin (glycopeptides)
- -Bacitracin (polypeptides)
β-lactams
Inhibit cell wall synthesis (ex. penicillins, cephalosporins, etc.)
Mechanism of penicillin (and β-lactams in general)
Functions by blocking serine site in penicillin-binding protein (PBP) so that cross-linking cannot occur
Resistance mechanisms of β-lactams
- -Altered/mutated transpeptidases (ex. PBP) that decrease affinity for antibiotic
- -Altered outer membrane permeability (ex. mutation in porins)
- -Presence of efflux pumps
- -Chemical modification of antibiotic (ex. β-lactamase)
Vancomycin
Inhibits cell wall synthesis
Mechanism of vancomycin
- -Recognizes and binds two D-ala residues on end of peptide chains
- -Binds to peptide chains and prevents them from interacting properly with transpeptidase
Resistance mechanisms of vancomycin
Last D-ala residue is replaced by D-lactate so vancomycin cannot bind (cross-links successfully formed)
Bacitracin
Inhibits cell wall synthesis by interfering with dephosphorylation in cycling of lipid carrier that transfers peptidoglycan subunits to the growing cell wall
Protein synthesis inhibitors – target and examples
- -Target bacterial ribosome (70S)
- -Includes tetracyclines, aminoglycosides, and macrolides
Tetracyclines
Bacteriostatic that bind to 30S subunit and bind to it; broad spectrum
Aminoglycosides
Bactericidal (generally) that bind to 30S subunit, oxygen-dependent and only effective against aerobic organisms
Macrolides
Bacteriostatic that bind to 50S subunit; used as alternative to penicillin for those with allergies
Examples of tetracyclines
Tetracycline, doxycycline
Examples of aminoglycosides
Gentamicin, kanamycin
Examples of macrolides
Erythromycin, azithromycin (Z-pack)
Nucleic acid synthesis inhibitors examples
- -Quinolones
- -Rifampin, rifabutin
- -Metronidazole
Quinolones
Bactericidal that inhibit DNA replication, recombination, and repair by affecting gyrase (topoisomerase)
Rifampin and rifabutin
Bactericidal that bind to DNA-dependent RNA polymerase and inhibit initiation of RNA synthesis
Metronidazole
Bactericidal that is reduced by bacteria to make toxic compounds that damage DNA
Examples of antimetabolites
Sulfonamides and trimethoprim
Antimetabolites
Target folate metabolism (since bacteria need to make it –> make DNA/RNA)
