Note to the student: The student is advised to review - Streptogramin: quinupristin, dalfopristin

basic biochemistry and parts of the bacterial cell D. Chloramphenicol

before proceeding to the lesson. You may also use - Binds to 50S ribosomal subunit and inhibits the
your drug handbook as supplementary material. Refer addition of new amino acids to the growing peptide
to your course syllabus for the lesson’s objectives. chain

Principles of Antimicrobial Action and Resistance E. Oxazolidinones

General Principle: - Linezolid
Active drug  Anatomic approximation  Surface - Newest class of antimicrobial agent
binding  Intracellular uptake  Target binding  - Not affected by resistance mechanisms
Bacterial lysis/ Growth inhibition - Binds to 50S ribosomal subunit

Targets of Antimicrobial Action IV. Inhibitors of DNA synthesis (Bactericidal)

1. Cell wall peptidoglycan synthesis A. Fluoroquinolones
2. Cell membrane - Derivatives of nalidixic acid
3. Protein synthesis - Bind o and interfere with DNA gyrase enzyme
4. DNA/ RNA synthesis involved in the regulation of bacterial DNA
5. Enzymatic activity supercoiling, a process that is essential for DNA
replication and transcription
I. Cell wall synthesis inhibitors (Bactericidal) - Ciprofloxacin, ofloxacin
A. Beta-lactam agents
- Classes: B. Metronidazole
Penicillins - Direct interaction between activated drug and DNA
Cephalosporins results in breakage of DNA strands
Monobactams - Activation of metronidazole requires reduction under
Carbapenems conditions of low redox potential
- Penicillin binding proteins (PBP’s): enzymes, such as - Most potent against anaerobic and gram negative
transpeptidases and transglycosylases, which produce bacteria
and maintain the peptidoglycan layer
- Beta lactams bind to PBP’s inhibiting cell wall C. Rifampin
synthesis - Binds to the enzyme DNA-dependent RNA
polymerase and inhibits synthesis of RNA
B. Glycopeptides - Does not penetrate outer membrane of gram
- Most commonly used: Vancomycin negative bacteria well.
- Binds to precursors of cell wall synthesis instead of
PBP’s. The binding interferes with the PBP’s ability to V. Folic acid pathway inhibitors
incorporate the precursors to the growing cell wall Folic Acid Pathway:
- Cannot penetrate the outer layer of gram negative P-Aminobenzoic Acid (PABA)
bacteria due to its large size l Dihydropterate synthase
Dihydrofolic acid
C. Bacitracin l Dihydrfolate reductase
- Toxic to human cells; topical use only Tetrahydrofolic acid
- Inhibits recycling of certain metabolites required for l
maintaining peptidoglycan synthesis Purines
l + Other precursors
II. Cell membrane function inhibitors DNA
A. Polymyxin B and Colistin A. Sulfonamides
- More active against gram negative bacteria - Target and bind to dihydropteroate synthase and
- Disrupts cell membrane resulting to leakage of disrupt the folic acid pathway
macromolecules and ions essential for the bacteria’s - No effect on Pseudomonas auruginosa
survival
B. Trimethoprim
III. Protein synthesis inhibitors - Binds to dihydrofolate reductase and disrupts the
A. Aminoglycosides (Bactericidal) folic acid pathway
- Binds to 30 S ribosomal subunit  disruption of initial - Often combined with sulfonamides (trimethoprim-
formation of the protein synthesis complex, accurate SXT)
reading of the mRNA code, ribosomal-mRNA complex
- Gentamycin, amikacin, netilmicin, streptomycin, and VI. Nitrofurantoin
kanamycin - Used to treat urinary tract infections
- NO EFFECT ON ANAEROBES - Has several targets involved in bacterial protein and
enzyme synthesis and also damages DNA
B. Tetracyclines
- Binds to 30S ribosomal subunit so that incoming References:
tRNA-amino acid complexes cannot bind to ribosome 1. Bailey & Scott's Diagnostic Microbiology 11th Ed.
thus halting peptide chain elongation 2. Burton’s Microbiology for the Health Sciences 8th
Ed.
C. Macrolide-Lincosamide-Streptogramin (MLS)
- Binds to 50S ribosomal subunit and disrupts peptide
chain elongation
- Generally NOT EFFECTIVE against GRAM Negative
bacteria
- Macrolides: erythromycin, azithromycin,
clarithromycin
- Lincosamide: clindamycin