Describe the structure and function of the bacterial cell wall
Describe the multiple sites of inhibition by antibacterial agents
- Cell wall synthesis (ICWS)
- Membrane integrity
- Protein synthesis
- Nucleic acid synthesis
- Nucleic acid integrity
Explain the mechanisms of resistance to ICWS
- No cell wall, no activation of murein hydrolases, metabollically inactive
- Inaccessible PBPs - Gram neg or MRSA (structural change of PBP)
- B-lactamase production (major mechanism of resistance, plasmid-mediated)
Explain the role of the ß-lactam ring in the pharmacokinetics and pharmacodynamics of ICWS
The beta-lactam ring allows the antibiotic to mimic D-ala-D-ala structure of the peptidoglycan cell wall. This mimicry allows for covalent binding of PBPs which ultimately disrupts transpeptidation necessary for constructing the peptidoglycan cell wall
Describe the role of transpeptidases/penicillin binding proteins (PBP) and murein hydrolases (autolysins)
PBP allows for the transpeptidation reaction necessary for construction the peptidoglycan cell wall
Describe the chemotherapeutic spectrum of penicillins
Primarily gram +
Describe the unique properties and indications for use of other ß-lactams
Name the anti-pseudomonal penicillins
Ticarcillin, piperacillin, mezlocillin
Name the extended spectrum penicillins
Ampicillin, amoxacillin, ticarcillin, piperacillin, mezlocillin
(increased gram - activity)
What are the 2 main types of penicilin?
Pen G and Pen V
Name the anti-staphylococcal penicillins
Nafcillin, isoxazolyl penicillins (ox-,clox-)
What are the two adverse effects of penicillin?
What is true about cephalosporins in comparison to penicillins?
Poor oral absorption
More renal toxicity
What are the general trends b/t the cephalosporin generations?
Which cephalosporins belong to each of the four generations?
What are the adverse effects of cephalosporin?
Renal toxicity - enhanced by aminoglycosides
Cefotetan -- disulfrim effect -> bleeding and platelet disorders
What are the monobactams and carbapenems? Give some characteristics.
How does vancomycin differ from penicillin in its MOA?
Vancomycin inhibits transglycosylation by binding directly to the D-ala-D-ala of cell walls being synthesized
Penicillin - inhibits PBPs blocking transpeptidation
What is the MOA of fosfomycin?
Inhibits cytoplasmic step in cell well precursor synthesis
Know this chart
What is the target of bacterial protein synthesis?
Targeting of 70S ribosome of bacteria (either the 30S or 50S subunit)
What is the target of tetracycline?
Reversible binding of 30S ribosome
What are the adverse effects of tetracyclines?
GI irritation, superinfections, impaired liver function, photosensitization, and calcium chelation
What is the major mechanism of resistance to tetracyclines?
Another mechanism: altered ribosomal proteins or RNA are secondary mechanisms
What is unique about tigecycline?
Not effected by the efflux pump (effective in bugs that have developed resistance to tetracyclines through efflux pumps)
Name the macrolide antibiotics
Erythromycin, clarithromycin, azithromycin
What is the target of the protein synthesis inhibitors?
What are some pharmacokinetic characteristics of macrolides?
What are the clinical uses and adverse effects of macrolide abx?
What are the mechanisms of resistance to macrolide abx?
Altered (methylated) rRNA
Esterase which hydrolyzes erythromycins (enterovacteriaceae)