Antimicrobial Agents Flashcards
Antibiotics
selectively toxic for bacteria
Bactericidal
killing
Bacteriostatic
growth inhibition
Combination therapy
- prevent emergence of resistant strains
- temporary treatment until diagnosis is made
Antibiotic synergism
better in combination
-penicillins and amino-glycosides
Antibiotic antagonism
deadly together
-penicillins and bacteriostatic antibiotics
Antibiotic activity
- Inhibition of cell wall synthesis
- Inhibition of protein synthesis
- inhibition of nucleic acid synthesis RNA DNA
B-lactam antibodies
B-lactams bind to the PBPs which inhibit the peptidoglycan cross linking (degrade cell wall)
ex.penicillins, cephalosporins, cephamycins, carbapenems
Glycopeptides
also disrupt peptidoglycan synthesis ex. vancomycin gram positive only
Polypeptides
ex. bacitracin, used topically for skin infections, interferes with dephosporylation and recycling by lipid carrier used to move peptidoglycan precursors to cell wall
Polymyxins
external treatment for localized infections eye, ear, skin
- can cause kidney damage
- insert to bacterial membrane, increase cell permeability
- gram negative
Lactam antibiotics
inactive against gram negative, no penetration of outer membrane
B-lactam resistance mechanisms
- produce penicillinase, destroys antibiotic
- modified penicillin binding proteins, dont bind to the antibiotic
- modified porins, no internalization of antibiotic
Clavulinic acid
binds strongly to B-lactamases and inhibit their activity
Treatment for mycobacterial infections
- Isoniazid and ethionamide, block mycolic acid synthesis
- ethambutol, blocks arabinogalactan synthesis
- cycloserine, blocks 2 enzymes that catalyze cell wall synthesis
Protein synthesis inhibitors
Mostly bacteriostatic
-selectivity due to differences in proka and euka
Aminoglycosides
-amikacin, gentamicin, tobramycin, bind to the 30s ribosomal subunit induces misreading of mRNA, premature release of ribosome
Tetracyclines
tetracycline, doxyxycline, minocycline
-bind to 30s ribosomal subunits block aminoacyl-tRNA binding to 30s-mRNA complex
resistance is common
Oxazolidinones
linezolid
- binds to 50s ribosomal subunits distorts tRNA binding site
- interferes wth the formation of 70s initiation complex
- used for multi-drug resistant enterococci
Also bind to 50s ribosomal subunit
- chloramphenicol
- macrolides
- clidamycin
Inhibition of nucleic acid synthesis (Qunolones)
inhibit bacterial DNA topoisomerases required for DNA replication, recombination and repair
- gram-ve type II
- gram+ve type IV
Inhibition of nucleic acid synthesis (Rifampin and rifabutin)
bind to DNA dependent RNA polymerase and inhibit initiation od mRNA synthesis
Antimicrobial drug resistance I
- can arise by mutation or gene transfer
- provides selective advantage
- can result from single or multiple steps
Antimicrobial drug resistance II
- altered permeability, influx gram -, efflux tetracycline
- altered target site, penicillin binding proteins (penicillins), RNA polymerase (rifampin), 30S ribosome (streptomycin)
- replacement of a sensitive pathway, acquisition of a resistant enzyme
