Antibacterials Flashcards
gram + has a 1 wall of peptidoglycan
gram - has a 2 wall of peptidoglycan
- thick
2. thin
Lipopolyaccharide makes up the outer membrane structure of gram 1 bacteria cell wall and consists of 2 and 3
- negative
- phospholipid
- polysaccharides
what bacteria is teichoic and teichuronic acid found in?
how does it effect the use of antibiotics
gram +
strong anionic character - affect rate of penetration (antibiotics with positive charge would be more attracted to the acid)
how do nutrient transport protiens of cytoplasmic membrane effect antibiotics?
Facilitate rapid penetration of agents similar in structure
how does LPS on gram - bacteria effect antibiotcs
prevents penetration of bulking, high MW antibiotics (e.g. erythromycin)
What on gram - bacteria allows penetration of water soluble molecules up to 650 daltons (e.g sulfonamides)
hydrophilic pores
What are extended spectrum antibiotcs effect against?
gram + primarily, but also gram -
tx of high-risk pts that have become infected but are asymptomatic
pre-emptive therapy
tx of symptomatic pt without further testing or confirmation of organism
empirical therapy
how will bacteria develop resistance
through acquisition of new genetic material
mutation in the existing genome that is selected for under clinical/antibiotic pressure
name the drug resistant bacteria
ESKAPE
Enterococcus faecium
Staph. aureus
Klebsiella pneumoniae
Acinetobacter baumanni
Psuedomonas aeruginosa
Enterobacter specieies
therapeutic use of daptomycin
tx of complicated skin infections, bacteremia, endocarditis
how does bacteria develop resistance to daptomycin
Reduced drug entry
gene mutation (mprF) - membrane changes to more positive charge and antibiotics are repelled with cationic properties
how has bacteria developed resistance to tetracycline
Expression of efflux pump
common organisms: N. gonorrhoeae, E. coli, S. pneumoniae, P. aeruginosa
how have bacteria developed resistance to metronidazole
Changs in expression enzymes that activate the pro-drug
Metronidazole needs to be reduced to generate ROS. Mutation in rdxA gene alters/decreases activated of drug
how do bacteria develop resistance against aminoglycosides such as streptomycin?
Expression of enzymes by the organism that destroy the drug
- Aminoglycoside-modifying enzymes chemically modify the antibiotic and alter binding of the drug to its target
How do bacteria develop resistance against amoxicillin
Expression of enzymes by the organism that destroys the drug
- Expression of the enzyme beta-lacatamase which can hydrolyze the lactam ring of amoxicillin and make compound ineffective
how do bacteria develop resistance against trimethoprim and sulfonamides?
Impaired drug binding to the original target:
- expression of the drug-insensitive enzymes dihydropteroate synthase and dihydrofolate reductase
how do bacteria develop resistance to vancomycin
Development of new or different pathways that are not inhibited by the drug
Substitution on the peptidoglycan stem so that the agent can no longer bind to the target
Mechanism of resistance for what drug class?
- expression of beta lactamase
- alteration in PBP binding to drug
- Alteration in porin function
Penicillins
Cephalosporins
Mechanism of resistance for what drug class?
Expression of enzymes that alter chemical structure of the drug
Aminoglycosides
Mechanism of resistance for what drug class?
- Transport of drug out of cell (drug efflux)
- Alterations of drug binding to the 50S ribosomal unit
Macrolides
Mechanism of resistance for what drug class?
Transport of drug of of cell (drug efflux)
Tetracyclines
Mechanism of resistance for what drug class?
- Less sensitive drug target
- Increased synthesis of PABA
- Scavenge or use other sources of folic acid
Sulfonamides
