Amikacin

1. Mechanism of Action

2. Resistance

Aminoglycoside

1. Mechanism of Action

2. What bacteria do they affect/not affect?

3. Resistance

4. Family Members

1. Ribsome/Translation inhibitors. Aminoglycosides interact with the 16S rRNA in the 30S subunit of the ribosome, preventing the binding of f-Met (formyl-methionine), which is the 1st amino acid of most bacterial proteins.

2. Affects gram negative and gram positives but they need to respire. Requires strong PMF to get transported. Intestinal tract flora not affected

3. Resistance: inactivated by N-acetylation, O-phosphorylation, O-adenylation

4. Amikacin, Tobamycin, Gentamicin, Netimicin, Neomycin, Streptomycin

Carbapenems

1. Mechanism of Action

1. Interferes with cell wall synthesis - cell wall steps

Cephalosporins

1. Mechanism of Action

2. Resistance

1. Interferes with cell wall synthesis - cell wall steps, transpeptidase reaction. Highly selective.

2. Antibiotic Target Site: Cell wall. Mechanism of Plasmid Resistance: Enzymatic hydrolysis. Plasmid Product: Beta lactamase

Chloramphenicol

1. Mechanism of Action

2. Resistance

1. Ribsome/Translation inhibitors. Interact with the 50s subunit and block the formation of the peptide bond. Inhibit chain elongation.

2. Can be inactivated by acetylation

Ciprofloxacin (Quinolone)

1. Mechanism of Action

Clindamycin

1. Mechanism of Action

2. Resistance

1. Inhibit chain elongation, binds to 50s.

2. Resistance - Target site: Ribosome 50S. Mechanism of Resistance: Modification of 23S RNA Plasmid Product: Methylase

D-cycloserine

1. Mechanism of Action

1. Interferes with cell wall synthesis - cytoplasmic steps. Blocks ala racemase.

Erythromycin (Macroslides)

1. Mechanism of Action

2. Resistance

3. Family Members

1. Ribsome/Translation inhibitors. Interact with the 23S rRNA in the 50s subunit and cause the release of the growing peptide chain. 

2. Target site: Ribosome 50S. Mechanism of Resistance: Modification of 23S RNA Plasmid Product: Methylase. Methyltransferases do this.

3. Aithromycin, clarithromycin, ditrithromycin, troleandomycin

Floroquinolones

(Sparfloxacin, ofloxacin, enoxacin, lomefloxacin, trovafloxacin, levofloxacin)

Resistance - Antibiotic target site: ribosome

Mechanism of plasmid resistance: interference with transport into the cell

Plasmid product: enzyme for O-nucleotidylation, O-Phosphorylation or N-acetylation of antibiotic

Lincosamides

Ex: lincomycin, clindamycin, chloramphenicol

Spectrum: Ribsome/Translation inhibitors. Interact with the 50s subunit and block the formation of the peptide bond.

Resistance: methylation of subunits in the ribosome

Metronidazole

1. Mechanism of Action

1. Inhibits DNA synthesis. It causes breaks in DNA

Penicillin

1. Mechanism of Action

2. Resistance

3. Solution to Resistance

1.Works by inhibiting PBP during cell wall synthesis - transpeptidase reaction. Bacteriocidal. Highly sellective. Lipophilic - can pass through gram - bacterial membrane. Procaine and bezathine, penicillin G are highly insoluble, they slowly diffuse into the blood and become Na Penicillin. This allow us to reach therapeutic level.

2. Antibiotic Target Site: Cell wall. Mechanism of Plasmid Resistance: Enzymatic hydrolysis. Plasmid Product: Beta Lactamase - inactivates penicillin by cleaving the beta lactam ring. Works in gram+ and - bacteria.

3. Inhibitors of beta lactamase can be administered with penicillin. Ex: Clavulanate-amoxicillin = augmentin, clauvenate-ticarcillin = timentin, sulbactam-ampicillin = unasyn, tazobactam-piperacillin = zocin

Problem: Extended spectrum beta lactamases: can cleave most drugs including methicillin

Polymycin

1. Mechanism of Action

2. Uses

1. Interferes with cell membrane. It's a polypeptide antibiotic that forms pores - bind to phosphatidyl ethanolamine rich areas of the membrane. It is highly toxic, especially in the kidney.

2. Mostly on skin

Rifampin

1. Mechanism of Action

2. Resistance

1. Inhibits DNA synthesis. Binds RNA polymerase to prevent transcription

2. Changes in RNA polymererase prevent interaction of antibiotic with RNA

Resistance - Antibiotic target site: ribosome

Mechanism of plasmid resistance: block transport into cell

Plasmid product: O nucleotidylation - adenylation or O-phosphorylation of antibiotic

Spectrum: Ribsome/Translation inhibitors. Bind 50s subunit and block translocation of the peptide chain to the E(P) site.

Resistance: methylation of the ribosomal subunit

Streptomycin

1. Mechanism of Action

2. Resistance

1. Bind and block 30s subunit blocking protein synsthesis. Bactericidal.

2.  Antibiotic target site: ribosome. Mechanism of plasmid resistance: block transport into cell. Plasmid product: O nucleotidylation - adenylation or O-phosphorylation of antibiotic.

Sulfonamides

1. Mechanism of Action

2. Resistance

3. Family Members

1. Inhibits DNA synthesis by inhibiting dihydropteorate synthetase. It ia a PABA analog that inhibits folic acid synthesis. (PABA binds to this enzyme). It is bacteriostatic.

2. Via metabolic bypass, the creation of new enzymes or mutation of existing enzymes (like the one above) that prevent antibiotic from working 

3. Trimethorprim: inhibits dihydrofolate reductase. Can be combined with Sulfonamide - ex: bactrim, it is now bactericidal. 

Tetracycline

1. Mechanism of Action

2. Resistance

2. Family Members

1. Ribsome/Translation inhibitors. Interact with the 16srRNA portion of the 30s ribosomal subunit and block the transfer of tRNA into the acceptor site. Bacteriostatic.

2. Mechanism of plasmid resistance: pumps antibiotic out. Plasmid product: inducible membrane proteins

3. Oxytetracycline, Deocycycline, Demeclocycline

Trimethoprim

1. Mechanism of Action

2. Resistance

1. Inhibits DNA synthesis. Inhibits dihydrofolate reductase, therefore inhibitting folic acid synthesis. Bacteriostatic. Bactericidal when combined with sulfonamides.

2. Via metabolic bypass, that is the creation of new enzyme or mutation on existing enzymes (like the one above), prevent antibiotic from working

Vancomycin (glycopeptide)

1. Mechanism of Action

2. Resistance

1. Interferes with bacterial cell wall formation - wall steps, bind to D-Ala-D-Ala

2. Vancomycin resistant enterococci (VRE) - Modifies D-Ala to either D-Ser or D-Lac so that vancomycin is cannot bind here.

Bacitracin

1. Mechanism of Action

1. Block early steps in cell wall synthesis

Neomycin

1. Mechanism of Action

1. Binds to 30s subunit preventing protein synthesis