Antibiotics - Mechanism and Spectrum Flashcards
What is the central principle of antibiotic use ?
• Anti-bacterials target processes that humans to not possess (e.g., bacterial cell wall) OR processes that humans possess but the bacterial versions are sufficiently different (in that case, the toxicity of anti-bacterials is greater to bacteria than it is to human, i.e. selective toxicity)
What processes/structures in bacteria do the main antibiotics target ?
- Bacterial Cell Wall Inhibitors
- Bacterial Folate Antagonists
- Inhibitors of Bacterial Ribosomal Action
- Topoisomerase II Inhibitors
Explain the general mechanism used by bacterial cell wall inhibitors.
Inhibit cell wall synthesis which creates an inbalance in the cell wall architecture which triggers bacterial autolysis that kill the cell.
Identify the main classes of bacterial cell wall inhibitors, giving examples for each class and identify the main target of each.
1) b-Lactams (penicillins, cephalosporins, carbapenems)- peptidoglycan cross-linking (by targeting penicillin binding protein)
2) Glycopeptides (Vancomycin)- synthesis of peptidoglycan (especially transglycolation and transpeptidation)
3) Cyclic peptides: Bacitracin- prevents carriage of building-blocks of peptidoglycan bacterial cell wall outside of the inner membrane
Identify the main kinds of penicillin. State whether each of these is narrow or broad spectrum.
- Penicillins G and V (natural penicillins)- Narrow
- B-Lactamase-resistant Penicillins (synthetic)- Narrow
- Broad-spectrum penicillins- Broad
- Extended-spectrum penicillins- Extended
What classes of pathogens does penicillin G and V target ? Name specific pathogens in these classes and the illnesses they might cause.
(a) Gram positive and gram negative Cocci.
– Staphyloccus (infections of wounds, boils)
– Streptococcus haemolytic types (septic infections)
– Enterococcus (endocarditis)
– Pneumococcus (pneumonia)
(b) Gram positive rods. Clostridium (tetanus, gangrene)
(c) Spirochaetes
Treponema (syphillis)
Actinomyces (abscesses)
Identify examples of beta-lactamase resistant penicillins.
Methicillin, Oxacillin, Nafcillin
Identify examples of broad-spectrum antibiotics. Name specific pathogens they target and the illnesses they might cause.
Ampicillin and Amoxicillin
B-lactamase-free strains of H. Influenzae, N. Gonorrhoeae, E. Coli, Salmonella, Morasella catarrhalis (sinusitis)
Identify examples of extended-spectrum antibiotics. What classes of pathogens do extended spectrum antibiotics target ? Name specific pathogens in these classes.
Carbenicillin, Ticaracillin, Azlocillin
Broad-spectrum bacteria plus Pseudomonas Aeruginosa.
Describe the following features of carbapenems:
- Spectrum:
- Mechanism of action:
- Target pathogens:
- Other special features:
CARBAPENEMS
-Spectrum: Broad antibacterial spectrum, much broader than other penicillins and cephalosporins
-Mechanism of action: Bind β-lactamase and acylating the enzyme, rendering it inactive (therefore prevent peptidoglycan cross-linking)
-Target pathogens: Active against both Gram positive and Gram negative bacteria
and anaerobes, poorly active against MRSA, not active against bacteria lacking a cell wall
-Other special features: Generally resistant to the typical beta-lactamases
Explain the possible mechanisms of bacterial resistance to beta-lactam antibiotics.
- Destruction by b-lactamase e.g., S. aureus
- Failure to reach target enzyme- changes to outer membrane porins and polysaccharide components of gram-negative organisms Pseudomonas spp.,
- Failure to bind to the transpeptidase S. pneumoniae
What antibiotics can we use in case of bacterial resistance to beta-lactam antibiotics ?
• Co-administration of b-lactamase inhibitors with a b-lactam antibiotic OR use of b-lactamase-resistant antibiotics.
Identify specific beta-lactamase inhibitors and which beta lactamase each inhibitor targets.
B-lactam compounds CLAVULANIC ACID and SALBACTAM act as strong inhibitors of class A but not B or C or D beta-lactamases.
What are the indications for cephalosporins ?
- Similar indications as penicillins and are often alternatives to penicillins (same group, beta lactams)
- Specifically, septicaemia, pneumonia, meningitis, biliary tract infections, urinary tract infections, sinusitis..
Identify examples of cephalosporins.
Cefalexin, cefuroxime, cefotaxime, cefadroxil.
What is a possible issue arising as a result of cephalosporin overuse ?
Overuse of cephalosporins may facilitate emergence of C. difficile.
What group of antibiotics does vancomycin belong to ? What is the specific mechanism of this group of antibiotics ?
Glycopeptides
Glycopeptides prevent synthesis of peptidoglycan, especially by binding to the peptide chain of the peptidoglycan and interfering with the elongation of the peptidoglycan backbone. They specifically target C-terminal D-Ala-D-Ala.
What explains the minimal development of antibiotic resistance in glycopeptides ?
Very specific interaction with C-terminal D-Ala-D-Ala explains the minimal development of resistance to this antibiotic.
What are the indications for vancomycin ?
MRSA and resistant streptococci and enterococci
What group of antibiotics does bacitracin belong to ? What is the specific mechanism of this group of antibiotics ?
Cyclic peptides
Prevent carriage of building-blocks of peptidoglycan bacterial cell wall outside of the inner membrane by interfering with the dephosphorylation of the lipid carrier which moves the early cell wall components through the membrane.
