Lecture 6: Antibacterial Agents Flashcards
What is the germ theory of disease
The idea that microorganisms cause disease
Who discovered the first treatment for syphilis and what was it
Paul Ehrlich discovered Arsphenamine (Salvarsan)
Discovery of Arsphenamine (Salvarsan) also led to the foundation of the concept of ____
Chemotherapy
What was the first widely available antimicrobial
Prontosil
What antibiotic was discovered that started the “golden era” of antibiotics and by who
Alexander Fleming discovered penicillin
What is an antibiotic
Chemical substance that has the capacity to inhibit the growth of or kill bacterial cells
What does antimicrobial mean
Refers to agents that act against all types of microorganisms
What does it mean to be narrow spectrum
Effective against limited number of bacteria
What does it mean to be broad spectrum
Effective against a wider array of bacteria
What are the pros and cons of narrow spectrum agents
pros: treats only specific organisms, less resistance developed
Con: only effective if ID of bacterium is known/correct
What are some pros and cons of broad spectrum agents
Pro: less need to make ID
Con: increased development of resistance, disruption of normal microbiome
What does bactericidal mean
Kills bacteria
What does bacteriostatic mean
Inhibits growth of bacteria
Why don;t you want to give bacteriostatic agents to immunocompromised
Relying on immune system to make antibiotics and fight infection
What is selective toxicity
Target and kill bacterial cells and not host cells
What makes an antibiotic effective
- Selective toxicity
- Soluble in body fluids
- Toxicity is not easily altered
- Nonallergenic
- Stability
- Bacterial resistance is not easily acquired
- Reasonable cost
What are the 5 classes of antibiotics
- Inhibition of cell wall synthesis
- Disruption of membrane function
- Inhibition of protein synthesis
- Inhibition of nucleic acid synthesis
- Action as antimetabolites
How is peptidoglycan synthesized
- NAG and NAM subunits synthesized in cytoplasm
- NAG-NAM transported across cell membrane into periplasm
- AA side chains cross linked by transpeptidase
What are the 3 classes of cell wall synthesis inhibitors
- Beta-lactams
- Vancomycin
- Bacitracin
Are cell wall synthesis inhibitors bactericidal or bacteriostatic
Bactericidal
What is the most effective and most extensively used class of antibiotics
Cell wall synthesis inhibitors
What is the Beta-lactam ring
Active site of antibiotic
What are some notable examples of B-lactam antibiotics
Penicillin and cephalosporins
What bacteria does Beta-lactam target
Gram positive and negative
What is the mode of action of Beta-lactams
Binds and blocks activity of transpeptidase, preventing cross linking of peptidoglycan layers- resulting in loss of regulation of osmotic pressure- burst and die
Which generation of cephalosporins has highest activity against gram positives
First generation
What generation of cephalosporins have increasing coverage for gram negatives
Generations 2-5
What type of antibiotic is vancomycin
Glycopeptide antibiotic
What is vancomycin effective in tx? Narrow or broad spectrum
Narrow spectrum- mainly tx MRSA
What is the mode of action for vancomycin
Binds to end the of pentapeptide chains (D-Ala-D-Ala) on NAM blocking transglycosylation and transpeptidation steps of peptidoglycan synthesis
How is bacitracin administered and why
Topical use only due to toxicity
What is bacitracin effective against, narrow or broad spectrum
Narrow spectrum: use for gram positive organisms, especially those causing skin infections
What is the mode of action of bacitracin
Prevents dephosphorylation of bactoprenol (lipid carrier) preventing assembly and transport of NAG-NAM
What class of antibiotic is polymixin
Disruption of cell membrane
What is polymixin effective against, broad or narrow spectrum
Moderate spectrum against gram negative bacteria
How is polymixin administered
Topical or ophthalmic due to toxicity
What is the mode of action of polymixin
Acts as cationic detergent disrupting the membrane structure
What ribosomes subunits are used in protein synthesis for bacteria
30S and 50S
What do aminoglycosides target, narrow or broad spectrum
Broad spectrum- most common use is for tx of severe infections cause by aerobic gram negative bacilli
What is the mechanism of action against aminoglycosides
Irreversibly bind to the 30S subunit and block the initiation complex, causing misreading of premature release of mRNA from the ribosome. Halts protein synthesis
Are aminoglycosides bactericidal or bacteriostatic
Bactericidal
What toxicities do aminoglycosides cause
Ototoxic and nephrotoxic in dogs and cats
What are tetracyclines effective against, narrow or broad
Broad spectrum against many gram positives and negatives, many atypical pathogens
What is the mode of action of tetracyclines
Binds to the 30S subunit to prevent attachment of the aminoacyl-tRNA to the RNA ribosome complex- prevents adding amino acids to peptide chain, halting protein synthesis
Is tetracycline bactericidal or bacteriostatic
Bacteriostatic
What antibiotic is toxic to human mitochondria causing aplastic anemia and bone marrow suppression? And which animals can it not be used in
Chloramphenicol- can’t be used in food animals
What is the mode of action of amphenicols
Binds to the 50S subunit, inhibiting peptidyl transferase- prevents elongation of peptide chain, halting protein synthesis
Are amphenicols bactericidal or bacteriostatic
Bacteriostatic
What do macrolides tx, narrow or broad spectrum
Narrow spectrum against some gram negatives and mycoplasma
What is the mode of action of macrolides
Binds to 50S subunit, blocking the formation of the initiation complex and translocation- prevents elongation, disrupt protein synthesis
Are macrolides bactericidal or bacteriostatic
Bacteriostatic
What do lincosamides tx,broad or narrow spectrum
Moderate spectrum- gram positive bacteria, anaerobes, some mycoplasms
What is the mode of action for lincosamides
Binds the 50S subunit blocking the formation of initiation complex and translocation
Is lincosamides bacteriostatic or bactericidal
Both
What species is lincosamides toxic in
Rabbits, guinea pigs and hamsters
What species are lincosamides contraindicated in
Horses, neonatal animals, oral administration in ruminants
What does streptogramins tx, broad or narrow spectrum
Narrow spectrum for gram positive cocci resistant to other antibiotics
What is the mode of action of streptogramins
Bind to different sites on the 50S ribosomal subunit, inhibition of protein synthesis at different steps
What do quinolones/ fluoroquinoloes tx, broad or narrow spectrum
Broad spectrum used for enteric infections and intracellular pathogens
What is the mode of action of quinilones/ fluoroquinolones
Bind to and inhibit DNA gyrase (topoisomerase II) and toposiomerase IV, preventing bacterial DNA from unwinding and duplicating
Are quinolones/ fluoroquinolones bactericidal or bacteriostatic
Bactericidal
What do rifamycins tx, broad or narrow spectrum
Moderate spectrum used for mycobacterial infections, some gram positive cocci, select gram negative, rhodoccous equin infections
What is the mode of action for rifamycins
Inhibits DNA dependent RNA polymerase, prevents transcription of mRNA
Are rifamycins bactericidal or bacteriostatic
Bactericidal
What does metronidazole tx, broad or narrow specteum
Narrow spectrum mostly anaerobes and protozoans
What is the mode of action of metronidazole
Covalently binds DNA, causing DNA. Breaks
Is metronidazole bactericidal or bacteriostatic
Bactericidal
What do sulfonamides and diaminopyrimidines tx, broad or narrow spectrum
Broad spectrum against a wide array of gram positive and negative
What is the mode of action of sulfonamides and diaminopyrimidines
Interferes with folic acid synthesis needed for DNA synthesis
Sulfonamides inhibit diphydropteroate synthetase
Trimethoprum- inhibits enzyme dihydrofolate reductase
What are some pros of antibiotic use
Reduce pain and suffering, weight gain, livestock live longer, prevent zoonotic diseases, prevent containment of potentially large scale epidemics
What is the biggest con of antibiotic use
Multi drug resistant pathogens
