Antibiotics Flashcards
empiric therapy
application of knowledge of the organisms most likely to cause infection in a given clinical setting and its most likely susceptibility to an antibiotic
factors to be considered when determining optimal choice of antimicrobial agent
history of adverse reactions, age, pregnancy, renal and hepatic function, site of the infection
pharmacokinetics
encompasses all the ways that the body manipulates the drug, including absorption, distribution, metabolism, and excretion
pharmacodynamics
describes the biochemical and physiologic effects of the drug and its mechanism of action on the bacteria
bacteriostatic
antimicrobial agents that inhibit the growth and/or reproduction of the infecting agent but fail to actually kill the agent
bacteriocidal
antimicrobial agent that is capable of causing irreversible damage or death to the organism
Antibiotics mechanisms of actions (List 5)
- Interference with cell wall synthesis, 2. Interference with protein synthesis, 3. Interference with cytoplasmic membrane function, 4. Interference with nucleic acid synthesis, 5. Interference with metabolic pathway
penicillin
bacteriocidal, mechanism of action: antibiotic binds at the active site of the transpeptidase enzyme that cross-links the peptidoglycan strands (inhibits cell wall synthesis)
cephalosporins
bacteriocidal, mechanism of action: antibiotic binds at the active site of the transpeptidase enzyme that cross-links the peptidoglycan strands (inhibits cell wall synthesis)
glycopeptides
bacteriocidal, act by binding to the D-alanyl-D-alanine residues thus preventing the cross linking of peptitoglycan sheets (inhibits cell wall synthesis)
macrolids
bacteriostatic, binds to the 23S rRNA molecule (in the 50S subunit) of the bacterial ribosome blocking the exit of the growing peptide chain. (inhibits protein synthesis)
tetracyclines
bacteriostatic, blocks attachment of transfer RNA amino acid to the ribosome 30S subunit. (inhibits protein synthesis)
fluoroquinolones
bacteriocidal, inhibits DNA gyrases or topoisomerases required for supercoiling of DNA (inhibits nucleic acid synthesis)
aminoglycosides
bacteriocidal, binds to 30S ribosome and changes its shape so it causes a misreading of the mRNA information (inhibits protein synthesis)
sulfonamides/trimethoprim
bacteriostatic, competes with p-aminobenzoic acid (PABA) preventing synthesis of folic acid
beta-lactam antibiotics
bacteriocidal, mechanism of action: antibiotic binds at the active site of the transpeptidase enzyme that cross-links the peptidoglycan strands (inhibits cell wall synthesis)
4 main classes of beta lactam antibiotics
Penicillin, Cephalosporins, Monobactams, Carbapenems
Antibiotics that inhibit protein synthesis
Aminoglycosides (bacteriocidal), Linezolid (bacteriostatic), Macrolids (bacteriostatic), Clindamycin (bacteriostatic), Chloramphenicol, Tetracyclines (bacteriostatic)
Intrinsic Resistance
innate ability of bacterial species to resist activity of antimicrobial agent through structure or functional characteristics
chromosomally mediated and is predictable
Mutational Resistance
due to chromosomal mutation. can be spontaneous or random
secondary resistance occurring after therapy with the antimicrobial in question has begun
Acquired Resistance
microorganism obtains ability to resist activity of antimicrobial agent to which it was previously susceptible
transferable drug resistance is plasmid mediated through conjugation, transduction, transformation
horizontal gene transfer
process of swapping genetic material between neighboring bacteria
transformation
uptake of short fragments of naked DNA
transduction
transfer of DNA from one bacterium into another via bacteriophages
conjugation
transfer of DNA via sexual pilus and requires cell to cell contact
major mechanisms by which bacteria may be resistant to antibiotics (8 of them)
enzymatic inactivation, decreased permeability, efflux, alteration of target site, protection of target site, overproduction of target, bypass of inhibited process, binding of antibiotic
classifications of beta lactamases
classified according to amino acid structure from A to D.
action of beta lactamase
resists beta lactam antibiotics by splitting amide bond of the beta lactam ring (which is part of the molecular structure of beta lactam antibiotics).
action of beta lactamase inhibitors
inhibitor prevents hydrolysis of antidote, restores activity.
mechanism of resistance responsible for VRE (Vancomycin-Resistant Enterococci)
sequesters vancomycin so antibiotic can’t do anything
mechanism of resistance responsible for MRSA
MecA gene that produces PBP2a gene product
PBP2a has structural changes that result in energetically unfavorable interactions between
role of transposons in antimicrobial resistance
can translocate as a unit from one area of the bacterial chromosome to another or between the chromosome and plasmid or bacteriophage DNA
role of integrons in antimicrobial resistance
mobile DNA elements with the ability to capture genes by site specific recombination
Enzymatic Inactivation
Example: beta lactamases are enzymes that inactivate beta lactam antibiotics by splitting the amide bond of the beta lactam ring
Decreased Permeability of Bacterial Membranes
Example: Mutations resulting in the loss of specific porins (allows passage of hydrophilic antibiotics through outer membrane)
Antibiotic Efflux
mechanism responsible for the moving of toxic substances and antibiotics out of the cell
Altered Target Sites
Prevents binding by alteration of ribosomal target sites, alteration of cell wall precursor target sites, or alteration of target enzymes
Protection of Target Sites
protects enzymes or ribosomes from binding to antibiotics
Overproduction of Target
overproduction of enzyme overwhelms inhibition by antibiotic
Bypass of Antibiotic Inhibition
stop synthesizing certain growth factors and instead rely on acquiring them externally thereby rendering antibiotic inhibition of those enzymes that synthesize those growth factors useless
Binding of Antibiotic
excess binding sites absorb antibiotics preventing it from reaching its target
