intro antibiotics Flashcards
(21 cards)
Describe cell wall
- all bacteria have a cell wall that consists of PEPTIDOGLYCAN
–> Peptidoglycan = a macromolecule comprosed of peptides and sugars that provide a rigid support structure that is found ONLY IN BACTERIA
- Gram + = thick wall of peptidoglycan
- Gram - = Thin wall of peptidoglycan
Lipoplysaccharide (LPS)
- Lipopolysaccharide makes up the OUTHER MEMBRANE STRUCTURE of GRAM (-) bacteria cell wall and consists of phospholipid and polysaccharides
Cytoplasmic membranes in bacteria
- Similar in structure to eukaryotic cell membrane EXCEPT FOR STEROLS
Describe lipopolysaccharide effects on antibioitcs
- retards or prevents penetration of BULKY, HIGH MOLECULAR WEIGHT antibiotics such as ERYTHROMYCIN
Lipid bilayer of cytoplasmic membrane effects on antibiotics
- Penetration of water-soluble drugs is SEVERELY HINDERED
hydrophillic pores effects on antibiotics
- allow penetration of water-soluble molecules up to 650 daltons, such as SULFONAMIDES
Nutrient receptor proteins on outer membrane effects on antibiotics
- agents strucurally related to nutrients (sideromycins) utilize these natural receptors
Teichoic and teichuronic acid effects on antibiotics
found in gram positive bacteria
- Strong anionic character of these polymers may affect RATE OF PENETRATION
What are common strategies for killing or inhibiting microorganism growth..
1) disrupt coding/genetic machienery (target folate syntheis need to make DNA, disruping mRNA synthesis)
2) blocking protein synthesis
3) disrupting cell wall or membrane synthesis
Bactericidal vs bacteriostatic
Bactericidal = an agent that will kill the bacteria
- once the organism is exposed to the drug, it is no longer viable
Bacteriostatic = an agent that will inhibit growht of the bacteria but will not kill the bacteria
–> therapeutic success is depdent upon the host defense mechanisms to clear the infection
–> if drug is removed, the bacteria will once again begin to grow
describe MIC
minimum inhibitory concentration (MIC)
- the lowest conc of an antimicrobial agent that will inhibit the visible growth of bacteria in liquid culture
describe MBC
Minimum bactericidal conc (MBC)
- conc of antibiotic from the original MIC plate that shows NO GROWTH after subculture
Define resistance
- chemotherapeutic agent is no longer or less effective towards an organisms
- develops due to:
–> reduce drug entry in the organism
–> increased drug export from the organisms
–> expression of enzymes by the organism that destroy the drug
–> changes in expression enzymes that activate the drug (pro-drug)
–> imapired drug binding to the original target
–> development of new or different pathways that are not inhibited by the drug
- DEVELOP RESISTANCE THROUGH ACQUISITION OF NEW GENETIC MATERIAL OR MUTATION IN THE EXISTING GENOME
ESKAPE
- Enterococcus faecium
- staphyloccus aureus
- Klebsiella pneumoniae
- Acinetobacter baumanni
- Pseudomonas aeruginosa
- Enterobacter species
Daptomycin
- used in the TX of complicated skin infections, bacteremia and endocarditis
- Specific gene mutation results in a change in membrane charge –> overall increase in net positive charge which will repel the antibiotics with cationic properties (REDUCED DRUG ENTRY IN THE ORGANISMS)
Tetracycline
- Use as a Broad spectrum antibiotic in the tx of acne, bronchitis, gonorrhea and syphilis
- Resistance occurs through expression of an EFFLUX PUMP –> INCREASED DRUG EXPORT FROM THE ORGANISM
Metronidazole
- Use in the TX of abdominal infections, vaginitis, CLOSTRIDIUM DIFFICILE Colitis, and brain abscess
- Resistance occurs due to a mutation in rdxA gene (oxygen-insensitve nitroreductase) which alters or decreases the activation of the drug
–> CHANGE IN EXPRESSION OF ENZYME THAT ACTIVATES THE PRO-DRUG
Aminoglycosides (streptomycin)
- USED in combo with other agents to tx unusal and severe conditions such as endocarditis, tularemia, plaque and tuberculosis
- REsistance occurs via aminoglycoside-modifying enzymes chemically modify the antibiotic and alter binding of the drug to its target
–> EXPRESSION OF ENZYMES BY THE ORGANISMS THAT DESTROY THE DRUG
Amoxicillin
- USED as borad spectrum antibiotic used for variety of infections
- RESISTANCE OCCURS BY expression of enzyme Beta-Lactamase which can hydrolyze the lactam ring of amoxicilin and render the compound ineffective
–> EXPRESSION OF ENZYMES BY ORGANISMS THAT DESTORY THE DRUG
Trimethoprim and sulfonamides
- Used in combo to treat urinary tract infections
- resistance occurs via drug-insensitive enzymes dihydropteroate synthase and dihydrofolate reductase
–> IMPAIRED DRUG BINDING TO THE ORIGINAL TARGET
VANCOMYCIN
- USED in the tx of bloodstream infections, endocarditis and meningitis
- REsistance occurs by subsitition of the peptidoglycan stem so that agent can no longer bind to the target
–> development of new or different pathways that are no inhibited by the drug
