4 - Antibiotics 2 Flashcards
What is the action of vancomycin?
Vanc is a glycopeptide that inhitbits PG synthesis by physically binding to D-ala-D-ala on the PG precursor and preventing penicillin binding proteins from recognizing them as their substrate.
What are glycopeptides and what is their mechanism of action? What type of bacteria are they effective on?
Glycosylated, non-cyclic non-ribosomally synthesized peptide antibiotics (bactericidal).
Bind to Dala-Dala at the end of the peptide side chain in PG precursors, blocking penicillin binding proteins from recognizing them as their substrate. (This inhibits PG synthesis. )
Effective on gram + , NOT effective on gram - due to OM.
What mechanism do vancomycin-resistant bacteria use for resistance? What bacteria are associated with this?
Modification: acquire gene encoding machinery to produce altered PG structure that lacks D-ala-D-ala and contain D-ala-D-lac instead so Vancomycin is unable to bind to these precursors.
These genes can easily be transferred. And vanc resistance is associated with enterococci in hospital settings.
What is cycloserine and what is its mechanism of action? What is it often used to treat?
Inhibits PG by competitively inhibiting D-alanine in 2 sequential reactions involving alanine racemase and D-alanyl-D-alanine synthetase.
Higher affinity for enzyme than D-alanine.
Structurally similar to D-alanine and used in 2nd line treatment for TB
What is bacitracin? What is its mechanism of action? How is it used?
Peptide antibiotic that binds to pyrophosphate on the lipid carrier for PG precursors (bactoprenol-PP) and blocks its recycling.
Without a lipid carrieor, PG synthesis cannot continue.
Used topically b/c it’s toxic systemically.
What antibiotics work by targeting the cell envelope? What types of bacteria does each work on?
Daptomycin: gram +
Polymyxins such as polymixin B and colistin: gram -
What is the mechanism of action of daptomycin?
It’s a bactericidal, narrow spectrum lipopeptide that works on gram-positives.
Binds and disrupts cytoplasmic membrane, possibly via loss of membrane potential. Confers activity against antibiotic-resistant bacteria.
What is the mechanism of action of polymixins such as polymixin B and colistin?
It’s a bactericidal, narrow spectrum lipopeptide that works on gram-negatives.
Binds to LPS in OM of gram - bacteria, leading to disruption of the OM and cytoplasmic membrane. Confers activity against antibiotic resistant gram -s.
Describe protein synthesis (translation) in bacteria?
Protein synthesis occurs in 2 phases, initiation and elongation.
30S forms an initiation complex with mRNA message and initiator tRNA.
50S subunit joins in the functional 70S that forms peptide bonds to make proteins.
What are the names of some tetracyclines?
Tetracycline, doxycycline, and minocycline.
What is the mechanism of action of tetracyclines such as tetracycline, doxycycline, and minocycline?
BacterioSTATIC, broad spectrum (now limited due to resistance).
Bind to 30S subunit and interferes with binding of animoacyl tRNA to complex.
What are two mechanisms of resistance to tetracycline?
Tetracycline efflux pump: most common and provide resistance to all tetracycline-fam ABx
Mutations on ribosome: modifies the antibiotic target
What is the function of Tigecycline? What sets this apart from the tetracyclines?
MAde from modified minocycline.
BacterioSTATIC
Same action as tetracycline: binds 30S and interferes with aminoacyl tRNA binding to ribosomes.
Does NOT exhibis cross-resistance with tetracyclines.
What are the names of the aminoglycosides? Are they bactericidal or bacteriostatic?
Gentamicin, amikacin, tobramycin
They are the only bactericidal ribosomal inhibitors.
What is the mechanism of action of aminoglycosides such as gentamicin, amikacin, and tobramycin?
Bind irreversibly to 30S subunit to stop initiation of protein synthesis, causing premature release of mRNA from ribosome and causes misreading by translating ribosomes.
What is the mechanism of resistance to aminoglycosides such as gentamicin, amikacin, and tobramycin?
Enzymatic modification of the antibiotic: transferases catalyze addition of adenyl, acetyl, or phosphoryl group to prevent aminoglycoside binding to the ribosome.
What are the names of the macrolides? What type of antibiotic are they and what type of bacteria do they work on?
Erythromycine, azithromycin, and clarithromycin.
Bacteriostate and primarily work on gram-positive bacteria. (don’t cross OM of gram negatives)
What is the mechanism of action of macrolides such as Erythromycine, azithromycin, and clarithromycin?
Bind 502 ribosome subunit to block elongation of proteins.
What are the two mechanisms of resistance of macrolides such as Erythromycine, azithromycin, and clarithromycin?
- Methylation of ribosomal RNA: erythromycin can’t bind methylated ribosome.
- Efflux pump: can expel macrolides from cells and enable protein synthesis to continue
What is the mechanism of action of Clindamycin? What is it used to treat?
Bacteriostatic; binds 50s subunit to block elongation.
Doesn’t work on gram negative; often used for treatment of community acquired MRSA, less so for hospital acquired MRSA.
Often used to treat infections by toxin-producing S. aureas but can cause C. diff colitis.
What is the mechanism of resistance to clindamycin? What types of bacteria are resistant to this?
Methylation of rRNA so clindamycin can’t bind to the methylated ribosome.
Exhibits cross-resistance with macrolides - ie bacteria resistant to macrolides due to the presence of an erm gene are also resistant to clindamycin
What is the mechanism of action of chloramphenicol? what are some side effects?
Bacteriostatic; broad-spectrum.
Toxicity due to lack of specificity limits use to very specific infections such as typhoid fever and rocky mt spotted fever.
Binds 50S ribosome to inhibit peptidyl transferase activity (elongation)
What is the mechanism of resistance to chloramphenicol? How do bacteria become resistant?
Bacterial enzyme (chloramphenicol acetyltransferase; CAT) catalyzes addition of acetyl group to the drug, preventing ribosome binding by the drug.
Typically plasmid-borne.
What is the mechanism of action of linezolid? What bacteria is it not affective on?
Binds unique site on 50S subunit (23S rRNA) preventing formation of 70S initiation complex.
Bacteriostatic, orally bioavailable. Narrow spectrum, not affective against more gram - or anaerobes.