BACT-3113 Antibacterials and Antimetabolites

what is prophylaxis

use of a drug to prevent infection or disease in an at risk individual

what is an antibiotic

substances produced by some microorganisms that inhibit or destroy others

what is an antibacterial spectrum

the range of activity of an antimicrobial against bacteria (broad-spectrum vs narrow-spectrum)

what is bacteriostatic activity

level of antimicrobial activity that inhibits the growth of an organism

what is the minimum inhibitory concentration (MIC)

the lowest concentration of an antimicrobial that inhibits the growth of an organism

what is bactericidal activity

level of antimicrobial activity that kills the test organism

what is the minimum bactericidal concentration (MBC)

the lowest concentration that kills 99.9% of the population of bacteria

what are antibiotic combinations

combinations of antibiotics that may be used to broaden the antibacterial spectrum, prevent the emergence of resistant organisms, or achieve a synergistic killing effect

what is antibiotic synergism

combinations of two antibiotics that have enhanced bactericidal activity when tested together compared with the activity of each antibiotic

what is antibiotic antagonism

combinations of antibiotics in which the activity of one antibiotic interferes with the activity of the other

what is β-Lactamase

and enzyme that hydrolyzes the β-lactam ring in the β-lactam class of antibiotics thus inactivating the antibiotic

what are the 8 desireable characteristics of antimicrobials

1. selectively toxic to the pathogen but not the host

2. soluble in water

3. remains active in tissues and body fluids

4. can get to infection

5. not broken down or excreted quickly

6. not lead to antimicrobial resistance

7. not cause allergies or predispose to other infections

8. reasonably priced

what can antibacterials inhibit

cell wall synthesis, dna replication, rna synthesis, protein synthesis, antimetabolites

what do β-lactam antibiotics do

block the synthesis of peptidoglycan via penicillin bonding proteins (PBPs)

what percentage of antibiotics are β-lactam antibiotics

over half

what are examples of β-lactam antibiotics

penicillins, cephalosporins, cephamycins, carbopenems, monobactams

what must β-lactam antibiotics be able to do to be effective against G- bacteria

penetrate the outer membrane

what three things can cause resistance to β-lactam antibiotics

mutations in porins (which are present in G- cell wall), mutations in PBPs, Beta-lactamases

what do β-lactamases do

break down the Beta-lactam ring structure

what are the characteristics of vanomycin

glycopeptide, narrow-spectrum, inhibits peptide cross-linking, can cause renal toxicity, last line of defense drug

what are the non β-lactam cell wall inhibitors

vancomycin, bacitractin, cycloserine, isoniazid, ethionamidem, ethambutol

what are the characteristics of Bacitracin

polypeptide, narrow-spectrum, affects carrier subunits (responsible for moving peptidoglycan precursors to the cell wall), binds metal ions and does DNA damage, used topically

what are the characteristics of cycloserine

interferes with early step in peptidoglycan synthesis, has rare but serious neurological side effects

what are the characteristics of Isoniazid, Ethionamise, and Ethambutol

interfere with mycolic acid synthesis

why are antibacterials that disrupt cell membrane function difficult to specify

because all cells have a cell membrane (must target specific phospholipids)

what are the characteristics of polymyxins

for G- bacteria, interact with phospholipids in outer membrane and phospholipid membrane, can cause significant neurotoxicity

what are the characteristics of daptomycin

binds cytoplasmic membrane, disrupts ion gradients, can't penetrate G- cell wall

what are the characteristics of clofazimine

acts as the final electron acceptor, breaks down phospholipids, stimulates production of toxic oxygen species

which antibacterial disrupt cytoplasmic membrane function

polymyxins, daptomycin, clofazimine

how do antibacterials that block protein synthesis work

exploit the difference between prokaryotic and eukaryotic ribosomes

what is a downside of antibacterials that block protein synthesis

can also damage mitochondrial ribosomes

what type of bacteria do antibacterials that target protein synthesis target

aerobic G- rods and certain G+ bacteria

what are 5 types of antibacterials that target protein synthesis

aminoglycosides, chloramphenicol, oxazolidinones, streptogramins

how do aminoglycosides work

permanently bind to proteins (bactericidal), causes misreading and premature release of ribosomal complex

how does chloramphenicol work

binds to peptidyl transferase (enzyme that joins amino acids together) and blocks formation of peptide bonds (similar mechanism to clindamycin)

how do oxazolidinones work

blocks tRNA binding to 50S ribosomal subunit (bacteristatic)

how do streptogramins work

group A promotes group B binding, group B is antimicrobal

what antibacterial drugs act on DNA synthesis

fluoroquinolones (cipro), metronidazole, and clofazimine

how do fluotoquinolones work

bind to bacterial enzymes that control supercoiling, promote separation of chromosomes at the end of replication

what is a major concern of cipro (fluoroquinolones)

overuse

how does metronidazole work

specific enzymes from anaerobic microbes reduce nitro group to activate the drug, once active the drug causes DNA damage

what drugs block RNA synthesis

rifampin and rifubutin

how do rifampin and rifubutin work

bind DNA-dependent RNA polymerase, inhibit the initiation of transcription

what are the concerns for rifampin and rifubutin

liver toxicity, drug interactions (induce expression of enzymes that break down other drugs)

what do antimetabolites do

target specific enzymes in specific pathways, promote synergistic effect, competitive inhibitors (bind active site)

how does the adaptive response that causes resistance work

microorganisms begin to tolerate a greater amount of a drug; intrinsic or acquired

what are the mechanisms for antibiotic resistance

break down or modify the drug (Beta-lactamases), limit or inhibit entry of the drug into the cell, export drug out of the cell (drug pumps), alter target binding site, use alternative pathways