Compare the differences between ribosomal subunits in bacteria vs eukaryotes.
Bacteria: 70s ribosome; 30s and 50s subunits
Eukaryotes: 80s ribosome; 40s and 60s subunits
Define time dependent antibiotic and list examples.
Time dependent: Serum concentrations remain above MIC during dosing interval (t>MIC)
Greater concentrations do not result in greater effectiveness
Minimal to no post-antibiotic effect (PAE)
Examples: β-Lactams, clindamycin, macrolides
Define concentration dependent antibiotic and list examples.
High concentrations at the binding site eradicates microorganism (peak/MIC ratio).
Greater concentrations do result in more bacterial killing.
Associated concentration-dependent PAE; bactericidal action continues for a period of time after antibiotic level falls below MIC.
Examples: aminoglycosides, fluoroquinolones, tetracyclines
Which antibiotic classes are bacteriCIDAL?
Topicals: Mupirocin, silver sulfadiazine, nitroimidazoles
Which antibiotic classes are bacterioSTATIC?
Define post antibiotic effect (PAE). Do time or concentration dependent antibiotics have a greater PAE?
PAE= Bactericidal action continues for a period of time after antibiotic level falls below MIC Concentration dependent drugs have increased PAE
Give examples of antibiotic synergism.
Drug combination generates an effect greater than the sum of the effects of each component alone
- Aminoglycosides and β-lactams
- Aminoglycosides increase access to the cell wall
- Polymyxin B and miconazole
- Polymyxin B increases penetration of hydrophobic drugs and allows access to IC space
- Trimethoprim and sulfonamides
- Inhibit sequential steps in folic acid pathway
What is antibiotic antagonism? Give examples.
Two drugs given together have an opposite effect of one another
- Penicillin and tetracycline: tetracyclines are bacteriostatic and penicillins require cell growth to be effective
- Erythromycin and chloramphenicol: Compete for binding site
Define mutant prevention concentration
Antibiotic’s ability to minimize or limit the development of resistant organisms
MIC of least susceptible single-step mutation
What is the significance if bacterial growth occurs when antibiotic concentration is greater than MPC?
Bacteria has developed two or more resistance-causing spontaneous chromosomal point mutations
What is the area between the MIC and MPC called?
Mutant selection window
Give examples of antibiotics that are cell wall synthesis inhibitors.
What is the b-lactam ring composed of?
Cyclic amide- contains 3 carbon and 1 nitrogen atom
Name 3 b-lactamase inhibitors
Clavulanate Sulbactam Tazobactam
What are the classes of penicillins and give examples of each
a. Natural penicillins: penicillin G, penicillin V
b. β-lactamase-resistant penicillins: methicillin, naficillin, oxacillin
c. Aminopenicillins: ampicillin, amoxicillin, talampicillin, bacampicillin, pivampicillin, talampicillin
d. Carboxypenicillins: carindacillin, carfecillin, carbenicillin, ticarcillin
e. Ureidopenicillins: azlocillin, mezlocillin, piperacillin
What are the generations of cephalosporins and give examples of each.
a. 1st generation: cephalothin, cephaloridine, cephapirin, cefazolin, cephalexin, cephradine, cefadroxil b. 2nd generation: cefamandole, cefoxitin, cefotiam, cefachlor, cefuroxime, ceforanide c. 3rd generation: cefpodoxime, ceftiofur, ceftriaxone, cefsulodin, cefotaxime, cefoperazone d. 4th generation: cefixime, cefclidine, cefluprenam, cefoselis, cefozopran e. 5th generation (not in vet med): ceftobiprole, ceftaroline
What is the MOA of b-lactam antibiotics?
Interfere w synthesis of cell wall
-PBPs catalyze transpeptidase reaction that removes terminal alanine to form crosslink with neighboring peptide
-B-lactam antibiotics attach to penicillin binding protein (PBP) and inhibit this step
-Cell wall synthesis is blocked , cell dies
What are the resistance mechanisms of b-lactam antibiotics?
1) Inactivation of Abx by b-lactamase- **most common**, plasmid encoded
2) Modification of PBPs- resistant organisms produce PBPs with low affinity for binding, chromosomal (i.e MecA)
3) Impaired penetration of drug to target PBP- occurs in Gram- only
4) Presence of efflux pump
How are b-lactam antibiotics excreted?
Renal. Plasma levels can be increased in renal insuff patients
What are the AE of penicillins?
Hypersensitivity to penicilloyl group- immediated and delayed HS;
anaphylaxis, drug eruption, EM, TEN/SJS, vasculitis, PF
Dogs, cats: hives, fever, joint pain
What are the AE of cephalosporins?
Similar to penicillins (HS) but not as common. GI upset, renal toxicity can occur
What enzyme breaks down imipenem into nephrotoxic metabolites?
What drug inhibits dehydropeptidase-1 and is usually incorporated with imipenem?
What is the specific MOA of bacitracin?
Forms complex with bactroprenol pyrophosphate which interferes with dephosphorylation Peptidoglycan cross links fail to form and osmotic pressure lysis bacteria
What is specific MOA of vancomycin?
Modification of D-Ala-D-Ala binding site of PG cell wall;
D-Ala terminal is replaced with D-lactate which blocks synthesis
Also interferes with RNA synthesis
What are the AE of vancomycin?
Humans- fever, chills, phlebitis with injection, erythroderma (Red Man Syndrome- caused by non specific mast cell degranulation)
Describe bacterial protein synthesis.
a. Initiation: ribosome assembled on mRNA b. Elongation: AA brought to ribosome by tRNA, joins immature polypeptide chain and entire assembly moves one position along mRNA c. Termination: reach a stop codon and entire assembly separates
Which antibiotics inhibit at the 30s ribosomal unit?
Which antibiotics inhibit at the 50s ribosomal unit?
Macrolides Lincosamides Chloramphenicol
What is the MOA of tetracyclines?
a. Reversibly bind to 30s ribosome subunit b. Inhibits binding of tRNA to mRNA during translation c. Amino acids can’t attach to peptide strand