Lesson 11 Flashcards
Lowest
concentration of a drug that inhibits bacterial growth
Minimum Inhibitory Concentration (MIC)
Ratio of the toxic dose to the
therapeutic dose (Higher TI = Higher Effectivity
Therapeutic Index
Lowest concentration of a drug that kills bacterial growth
Minimum Lethal Concentration (MLC)
DNA Elements that encode transposition and excision functions
Transposons
Enzymes that mediate
peptidoglycan cross-linking
Penicillin-binding proteins
Genetic elements capable of integrating genes
Integrons
Chemical substances produced by a microorganism with the capacity to inhibit other microorganisms (bacteriostatic) or destroy/kill the organisms (bactericidal)
Antimicrobials
Agents that kill bacterial cells
Bacteriocidal
Agents that inhibit bacterial growth
Bacteriostatic
Naturally found in bacteria
(chromosomal)
Intrinsic Resistance
Acquired from exogenous DNA
(Plasmid or through conjugation
Extrinsic Resistance
-He knew Arsenic can kill syphillis organism but is toxic to humans
-Systematically tried combinations of Arsenic with organics
Paul Ehrlich
He coined the term “Selective Toxicity”
Paul Ehrlich
He created Prontosil:
Effective against infections in animals despite a lack of activity in the test tube
Gerhardt Domagk
Introduced into field hospitals during WWII and saved countless lives from surgical wound infections
Sulfa Drugs
He discovered Penicillin
Sir Alexander Fleming
o Work only on gram-positives (cannot penetrate
the outer cell membrane)
o Exception: Doripenem, carbapenem
Used to treat gram-positive and gramnegative bacillus
(including Pseudomonas aeruginosa)
Narrow Spectrum
Work on a broad variety of bacteria (can penetrate the outer membrane)
Broad Spectrum
Produced by bacteria or fungi
Natural Drugs
Chemically modified natural drugs with added extra chemical groups
Semisynthetic Drugs
Chemically produced drugs
Synthetic Drugs
Basic Structure of Penicillin
Aminopenicillanic Acid
o Closely related to Penicillin
o Have a beta lactam ring as part of the basic structure
Cephalosporins
Binds to and inhibits the
transpeptidases (Known as Penicillinbinding proteins, PBPs)
B-Lactam Ring
o Examples: Vancomycin, Teicoplanin
o Blocks the Transpeptidation step
o Narrow spectrum antibiotic
o Useful for staphylococci, streptococci, and
enterococci
o Vancomycin
Does not bind to PBP but to the DAlanyl-D-Alanine termini of
Peptidoglycan precursors.
Interference with elongation and
cross-linking of the Peptidoglycan
weakens the cell wall and the
organisms lyse.
Glycopeptides
Competitively inhibits
Dihydropteroate synthetase
Needs constant levels of drug to
inhibit enzyme (High therapeutic
index)
Sulfonamides
Competitively inhibits Dihydrofolate
reductase
Needs constant levels of drug to
inhibit enzyme
Thrimetoprim
o Most effective against Gram-Negative organisms
o Drug binding is irreversible
o Uptake: Dependent on Oxidative
Phosphorylation
Drug is not active in anaerobes or
facultative anaerobes (I.e.,
Streptococcus pneumoniae)
Aminoglycosides
o Broad spectrum, Bacteriostatic
o Binding of drug to Ribosome is reversible
Tetracycline
o Broad spectrum, Bacteriostatic
o Has good penetration into the CSF
Use restricted due to side effect
(Aplastic Anemia) following or during
treatment
Chlorampenicol
Synthetic derivative of Rifamycin B,
targets DNA transcription
Interferes with production of mRNA
✓ Prevents Protein synthesis
via blocking of RNA
Polymerase
Principle therapeutic use:
Combination with other antibacterial
classes to treat Mycobacterium
tuberculosis
Rifampin
Interferes with Bacterial Gyrase
(Supercoiling of the DNA)
Examples: Nalidixic Acid,
Norfloxacin, Ciprofloxacin
Quinolones
Irreversibly binds to 30S subunit
✓ Prevents docking of
Aminoacyl-tRNA
Also contributes to misreading the
genetic code
Aminoglycosides
Binds to 30S subunit
✓ Interferes with the stability
of peptidyl tRNA by
inhibiting elongation factor
Spectinomycin
Natural consequence of drug exposure and results from the use and inappropriate use of
antimicrobial agents
Antimicrobial Drug Resistance
•
Present only on certain isolates that are different from
the parental strain.
•
Result of chromosomal mutations (transformation and
recombination), acquisition of extrachromosomal DNA
or by horizontal transfer of preexisting resistance genes.
Acquired Resistance
