Antimicrobial Agents & Resistance Flashcards
Semi-Synthetic Derivatives
Examples:
Penicillins:
-Penicillin G (Natural)
-Methicillin (Semi-Synthetic)
Cephalosporins:
-Cephalothin (Semi-Synthetic)
Monobactams:
-Aztreonam (Semi-Synthetic)
Modified to be More Effective, Longer Lasting, Easier to Administer, and Less Toxic to patients.
More than half of all Natural and Semi-Synthetic drugs are Derived from different species of **Streptomyces
**Synthetic Drugs: Tend to have Higher Toxicity!
Spectrum
Narrow-Spectrum:
- Effective against limited group of microbes
- Lower Toxicity
Broad-Spectrum:
- Effective against many types of microbes
- Higher Toxicity
Bactericidal:
–Causes Cell Death and Lysis
Bacteriostatic:
–Inhibits Bacterial Growth
(Table Examples)
Prokaryotes:
1) Penicillin:
- Narrow-spectrum
- Gram Positive
- Some Gram Negative
2) Erythromycin, Tetracycline:
- Broad-spectrum
- Gram Positive
- Gram Negative
- Chlamydias, Rickettsias
3) Sulfonamides:
- Broad-spectrum
- Gram Positive
- Some Gram Negative
- Chlamydias, Rickettsias
- Some Protozoa
4) Streptomycin:
- Gram Negative
- Mycobacteria
5) Polymyxin:
- Narrow-spectrum
- Some Gram Negative
6) Isoniazid:
- Mycobacteria
- Some Gram Negative
Eukaryotes:
1) Azoles:
- Broad-spectrum
- Protozoa
- Fungi
- Some Helminths
2) Niclosamide:
- Narrow-spectrum
- Some Helminths
3) Praziquantel:
- Narrow-spectrum
- Most Helminths
Viruses:
Arildone, Ribavirin, Acyclovir:
-Narrow-spectrum
-Some viruses
Antibiotic Targets Image
Cell Wall Synthesis:
- Penicillins
- Cephalosporins
- Vancomycin
- Bacitracin
- Cephamycins
- D-cycloserine
Cell Wall Integrity:
-Beta-lactamases
DNA Replication:
1) DNA Synthesis:
- Metronidazole
2) DNA Gyrase:
- Quinolones
RNA Polymerase:
(DNA Transcription)
-Rifampicin
Translation @ Ribosomes: Protein Synthesis (50S Inhibitors) -Erythromycin -Chloramphenicol -Cindamycin -Lincomycin
(30S Inhibitors)
- Tetracyclines
- Streptomycin
- Spectinomycin
- Kanamycin
Metabolic Pathways:
- Suflonamides
- Trimethoprim
Cytoplasmic Membrane:
(Phospholipid Membranes)
-Polymyxins
Mechanism of Action:
Cell Wall Inhibitors
1) Beta-Lactam Drugs:
- -Inhibit Penicillin-Binding Proteins (PBPs)
- -Thus, Interfere with the Formation of the Peptide Side Chains between adjacent strands of Peptidoglycan.
Penicillin-binding proteins are important for the Cross-Linking of NAG-NAM.
2) Vancomycin:
- -Binds to the Amino Acid Side Chains of NAM molecules
- -Thus, interferes with Peptidoglycan Synthesis.
3) Bacitracin:
- -Interferes with the Transport of Peptidoglycan Precursors across the cytoplasmic membrane.
Penicillins
Cell Wall Synthesis Inhibitors: Beta-Lactams
(Narrow Spectrum)
Bactericidal!! (Cause Cell Lysis)
Active Against:
- Gram Positive
- Gram Negative Cocci
- Some Spirochetes
Little Activity Against:
-Most Gram Negative Bacilli
Become Inactivated by Penicillinase
Penicillinase-Resistant Penicillins:
- -Methicillin
- -Nafcillin
- -Oxacillin
Cephalosporins
Cell Wall Synthesis Inhibitors: Beta-Lactams
Resistant to Hydrolysis by Penicillinases and Beta-Lactamases of certain Gram Negative Bacilli
Generations:
1st: Inhibit Gram Positive
2nd: Expanded Activity Against
–Enterobacteriaceae species
–Anaerobes
3rd: Increased Potency Against Gram Negative.
Lower Toxicity (preferred for Meningitis)
4th: Enhanced Ability to Penetrate Outer Membrane
Vancomycin and Teicoplanin
Cell Wall Synthesis Inhibitors:
Glycopeptide Antimicrobials
Inhibit Assembly of the Linear Peptidoglycan molecule
Bind to the Terminal Amino Acids of the Peptide Side Chains
Bactericidal Against Gram Positive
Used for Multi-Resistant microbes, such as MRSA.
Mechanism of Action:
Cellular Membrane Disruption
Gram Negatives have 2 lipid membranes (Outer membrane and Inner Plasma Membrane) and have a Much Thinner Peptidoglycan layer (which is why stains pink on gram stain).
Polymyxin B binds to Outer Membane and Inner Membrane, punching holes into it, causing cell lysis!
Bactericidal.
Mechanism of Action:
DNA Replication and Transcription Inhibitors
**Broad Spectrum Antibiotics
Rifampin:
–Inhibits RNA Synthesis
Fluoroquinolones:
–Bind to DNA Gyrase and Prevent DNA unwinding
Clofazimine:
–Binds to Guanine
Mechanism of Action:
Translation Inhibitors
Bacteriostatic because Inhibit Growth
Streptomycin:
- -Changes shape of 30S portion
- -causing code on mRNA to be incorrectly read
Tetracyclines:
–Interfere with attachment of tRNA to mRNA-Ribosome complex
Erythromycin:
- -Binds to 50S portion
- -preventing translocation-movement of Ribosome along mRNA
Chloramphenicol:
- -Binds to 50S portion
- -Inhibiting formation of peptide bond
Mechanisms of Action:
Metabolic Inhibitors
Prokaryotes can synthesize their own Folic Acid; eukaryotes must obtain it from their diet.
Sulfonamide Inhibits Folic Acid Synthesis by binding to its binding site on its enzyme because Sulfonamide is a structural analog of Folic Acid.
(PABA, para-aminobenzoic acid is prevented from binding; it is the precursor of folic acid)
Kirby-Bauer Disk Diffusion Test
Test for Drug Efficacy
Put bacteria on the plate and grow it.
Then put diff drugs on the plate to see what works. The larger the vacant rim around the drug, the greater its efficacy.
Minimal Inhibitory Concentration (MIC) Test
Test for Drug Efficacy
Used to determine the Lowest Dose of drug that is able to kill or inhibit growth of a microbe.
Each test tube has a diff concentration of the drug in it. Compare the amount of microbe able to grow in each tube.
Another variation: to test diff drugs at once:
Stripes of drug; increasing concentration of drug from outer rim of plate towards the center.
Breakpoint
Determines Susceptibility
*Based on obtainable serum concentrations of the drug in clinical trials.
Lower the MIC is below Breakpoint, the more effective the drug is; strain is susceptible.
Drug Resistant Organisms
MRSA:
Methicillin / Oxacillin-Resistant Staphylococcus aureus
VRE:
Vancomycin-Resistant Enterococci
ESBLs:
Extended-Spectrum Beta-Lactamases
(Resistant to Cephalosporins and Monobactams)
PRSP:
Penicillin-Resistant Streptococcus pneumoniae
