02 Study guide: cell wall & membrane COPY Flashcards
What are the 4 major classes of beta lactam antibiotics, and how can one recognize names of drugs in each class?
Penicillins: (-cillin)
Cephalosporins: (-cef-)
Carbapenems: (-penem)
Monobactams (aztreonam)
What are the 4 major classes of penicillins?
- Natural Penicillins:
- Penicillin G
- Penicillin V
- Anti-staphylococcal:
- Nafcillin and Oxacillin
- Dicloxacillin
- Amino/ Broad spectrum:
- Ampicillin
- Amoxicillin
- Extended Spectrum:
- Piperacillin + tazobactam
Name 4 examples of beta lactamase inhibitor drugs.
- Clavulinic Acid
- Sulbactam
- Tazobactam
- Avibactam
What feature is shared in the names of all glycopeptide antibiotics?
-van-
Name the classes (and the 2 additional “other” drugs) that target bacterial cell membranes.
- Other cell wall antibiotics: fosfomycin, bacitracin
- Lipopeptides: dapotomycin
- Polymyxins (-myxin)
Name 2 drugs that primarily target bacterial cell membranes.
Daptomycin: disrupts cytoplasmic membrane
Polymyxins: disrupt the outer membrane + cytoplasmic membrane
What are the two major components of peptidoglycan?
Polysaccharides: 2 alternating sugars - N-acetylglucosamine (G) and N-acetylmuramic acid (M)
Peptides: five amino acid chain, linked N-acetylmuramic acid sugar
What are the 3 major steps in PG synthesis – what happens in each step?
Monomer synthesis & transport: in cytoplasm, building blocks are made from amino acids & sugar by enzyme (Mur enzyme), then transported to the cell surface by lipid carriers.
Glycan polymerization: at cell surface, N and M sugars are connected into strands via transglycosylation by penicillin binding proteins (PBPs)
Polymer cross-linking: strands are linked by transpeptidation, when penicillin binding proteins (PBPs) remove the peptide’s terminal D-alanine to cross-link it to another peptide
What are the roles of PBP (both roles), Mur enzymes, and flippase II enzymes?
PBP often have both transpeptidase domain and glycosyltransferase domain
Mur A enzyme: building blocks made from amino acids and sugar
_Flippase II enzyme_s: transport building blocks to cell surface
Which steps in the PG synthesis pathway are targeted by: β lactams, glycopeptides, fosfomycin and bacitracin - and to what target does each one bind?
Photo attached below
What are 2 drugs that target the cell membrane, and how does each work?
Daptomycin: disrupts cytoplasmic membrane
Polymyxins: disrupt the outer membrane + cytoplasmic membrane
What are the 4 primary mechanisms by which bacteria become resistant to β lactam drugs?
- Inactivation of antibiotic by bacterial beta-lactamase: these enzyme catalyzed opening of the antibiotic’s beta-lactam ring
- Reduced uptake of antibiotic: specific to gram-negative bacteria (impervious outer membrane)
- Antibiotic efflux: gram negative bacteria may produce drug efflux pumps which toss some beta-lactam antibiotics back out
- Alteration of the antibiotic’s target: bacteria produce slightly different PBPs that antibiotics can’t bind to: development of a new PBP (PBP2a) by S. aureus is how the “superbug” MRSA arose
Which of the 4 mechanisms of how bacterial resistance develops against cell wall / membrane-targeted agents is the most common?
Inactivation of antibiotic by bacterial beta-lactamase
What is the function of bacterial beta lactamase enzymes?
they protect beta-lactam antibiotics from ring-destruction (counter-defense)
What type of bacteria are more likely to develop antibiotic resistance by altering drug uptake / efflux – gram positive or negative (and why)?
Gram negative. They have an impermeable outer membrane.
Example: development of a new PBP (PBP2a) by S. aureus is how the “superbug” MRSA arose
Give 3 examples of how bacteria can develop antibiotic resistance by altering antibiotic binding targets.
- these enzymes catalyze opening of the antibiotic’s beta-lactam ring
- most but not all bacteria produce beta-lactamase enzyme to defend themselves from antibiotics
- bacteria make hundreds of different beta-lactamase enzymes, each degrades a particular range of beta-lactam antibiotics
What is the mechanism by which MRSA developed resistance to penicillins?
Alteration of the antibiotic’s target: bacteria produce slightly different PBPs that antibiotics can’t bind to
- all available beta lactam antibiotics (except two new cephalosporins) fail to bind to MRSA’s new PBP (PBP2a)
- MRSA is currently treatable with vancomycin, daptomycin and ceftaroline
Which class of beta lactam antibiotics has the broadest spectrum of activity?
Carbapenems (-penem): Imipenem, Meropenem
Which 1 class of beta lactams antibiotics has activity against gram negative bacteria only?
Monobactams: Aztreonam (gram negative only)
Among the 4 categories of penicillins, which 2 have a narrow spectrum of activity, and which 1 has the broadest spectrum of activity?
-
Narrow spectrum:
- Natural Penicillins: Penicillin G (IV), Penicillin V (PO)
- Anti-Staphylococcal: Naficillin and Oxacillin (IV), Dicloxcillin (PO)
-
Broadest spectrum:
- Extended Spectrum: Piperacillin + tazobactam (IV/IM)
All penicillins have activity against which type of bacteria – gram positive or gram negative?
Gram Positive!
Name 6 antibiotic classes / subclasses / drugs that can be used to treat MDR strains of bacteria
- Cephalosporins (5th generation, IV): Ceftaroline, ceftolozane + tazobactam
- Carbapenems: Imipenem (combine with beta-lactam inhibitor to provide activity against MDR bacteria)
- Glycopeptide: Vancomycin (more use recently due to rise in MDR bacteria)
- Other cell wall agents: Fosfomycin
- Cell membrane agents: Polymyxins
Which of the β lactams is least likely to have cross-reactivity in patients with penicillin allergy?
Monobactams: Aztreonam (NO CROSS REACTIVITY)
Which β lactam drug class is associated with the highest risk of C difficile colitis?
Cephalosporins (3rd generation): cefituten (PO), cefotaxime, ceftriaxone (-one, -ten, -ime)
