47: Antibiotics I Flashcards
pairs chains grapelike clusters rods spiral shaped
diplococci streptococci staphylococci bacilli spirochetes
all bacteria have a cell wall that consists of _____
peptidoglycan
a macromolecule composed of peptides and sugars that provide a rigid support structure that is found only in bacteria
thick wall v. thin wall
gram + = thick
gram - = thin
makes up the outer membrane structure of gram - bacteria cell wall
lipoplysaccharide LPS
effect of LPS on antibiotics (g-)
retards or prevents penetration of bulk, high molecular weight antibiotics, such as erythromycin
effect of lipid bilayer of cytoplamic membrane on antibiotics (g-)
penetration of water-soluble drugs is severely hindered
effect of hydrophillic pores on antibiotics (g-)
allow penetration of water-soluble mkolecules up to 650 Da such as sulfonamides
effect of nutrient receptor prtns on outer membrane on antibiotics (g-)
agents structurally related to nutrients (sideromycins) utilize these natural receptors
effect of teichoic and teichuronic acid on antibiotics (g+)
strong anionic character of these polymers may affect rate of penetration
effect of lipid bilayer of cytoplasmic membrane on antibiotics (g+)
rate of penetration depends on lipophilicity (water soluble drugs are hindered)
effect of nutrient transport prtns of cytoplasmic membrane on antibiotics (g+)
facilitate rapid penetration of agents similar in structure
treatment of a disease with the use chemicals to kill or impair the growth of microorgansims or cancerous cells
chemotherapy
EC50 v. Emax
inhibitory concentration at which 50% of the organisms are killed or stop growing
maximum effect
aimed at killing or impairing growth of the specific target organism without harming the host
selective toxicity
bactericidal v. basteriostatic
agent that will kill the bacteria
agent that will inhibit growth of bacteria but will not will bacteria
lowest concentration of a n antimicrobial agent that will inhibit the visible growth of bacteria in liquid culture
MIC minimum inhibitory concentration
concentration of antibiotic from the original MIC plate that shows NO growth after subculture
MBC minimum bactericidal concentration
treatment in the absence of infection in order to prevent disease
prophylactic therapy
treatment of high-risk patients that have become infected but are asymptomatic
pre-emptive therapy
treatment of a symptomatic patient without further testing or confirmation of the organism
empirical therapy
treatment once the pathogenic organism has been identified and appropriate drug identified
definitive therapy
generally a low dose therapy used as a secondary prophylaxis. Problem that caused initial infection is likely still present
suppressive therapy
resistance develops due to (6) …
- reduced drug entry in to the organism
- increased drug export from the organism
- expression of enzymes by the organism that destroy the drug
- changes in expression enzymes that activate the drug
- impaired drug binding to the original target
- development of new or different pathways that are not inhibited by the drug
bacteria will development resistance through (2)
- acquisition of new genetic material
- mutation in the existing genome
“ESKAPE” bacteria
enterococcus faecium staphylococcus aureus Klebsiella pneumoniae Acinetobacter baumanni Pseudomonas aeruginosa Enterobacter species
resistance of daptomycin
increased positive charge due to the addition of L-lysine to phosphatidylglycerol of the membrane –> reduced drug entry in to the organism
resistance of tetracycline
efflux pump is expressed on the cytoplasmic membrane and actively pumps drug out of the cell –> increased drug export from the organism
resistance of metronidazole
chemical reduction of metronidazole “activates” the drug. Mutation in reducing enzymes will result in impaired drug activation –> changes in expression enzymes that activate the pro-drug
resistance of aminoglycosides
phosphorylation, adenylation, and acetylation of streptomycin can alter target (bacterial ribosome) binding –> expression of enzymes by the organism that destroy the drug
resistance of amoxicillin
expression of the enzyme b-lactamase which can hydrolyze the lactam ring of amoxicillin (as well as other penicillins and cephalosporins) and render the compound ineffective –> expression of enzymes by the organism that destroy the drug
resistance of trimethoprim & sulfonamides
expression of the drug-insensitive enzymes dihydropteroate synthase and dihydrofolate reductase –> impaired drug binding to the original target
resistance of vancomycin
substitution on the peptidoglycan stem so that agent can no longer bind to target –> development of new or different pathways that are not inhibited by drug
