LECTURE - Antimicrobials Flashcards
bactericidal
compound that kills the organism
> important for immunocompromised
bacteriostatic
compound inhibits growth of organism ; useful when immune system is intact
lines between bactericidal and bacteriostatic properties blur when…
organisms grow more slowly = biofilm
Pharmacokinetics
describes the action of body on the administered drug that includes absorption, distribution, metabolism, and excretion to define systemic exposure
pharmacodynamics
describes the biochemical and physiologic response of the drug and its mechanism of action
selective toxicity
kill bug not patient
side effects of antimicrobials can occur when
- selectivity is not optimal or
- antimicrobial has unexpected interactions w host (penicillin combining w serum proteins = allergic rxns)
disinfectant
compound used to kill or inhibit organisms on surfaces r inanimate objects
> too toxic for body use (ex: phenolics)
> not selective
compound used to kill or inhibit organisms on skin but not internally
antiseptic > sodium hypochlorite (bleach) > povidone iodine solutions (Betadyne) > 70% ethanol > 3.0% hydrogen peroxide > benzalkonium chloride >hexachlorophene
innate resistance to disinfectants and antiseptics
hyrophilic polysaccharide chains in LPS of gram negs can keep quaternary ammonium compounds (QACs) like cetramide and benzalkonium chloride at a distance from outer membrane
acquired resistance to disinfectants and antiseptics
plasmid-encoded efflux pumps for QACs in S. aureus
general characteristics of antibiotics
- originate from microbes (actinomycetes; fungi)
- have selective toxicity
- possess a spectrum of action (broad vs narrow)
inhibitors of cell wall synthesis
- peptidoglycan pathway was first to be capitalized on with penicillin > Fosomycin > Bacitracin > Tunicamycin > Glycopeptides (vancomycin) > beta-lactam antibiotics
most important inhibitors of cell wall synthesis
beta-lactam
- penicillins
- cephalosporins
- carbapenems
- monobactams
bacitracin
- interferes w recycling bactoprenol
- systemic toxicity limits its use to topical ointment
tunicamycin
- powerful action against gram pos
- has strong antiviral activity to envelope viruses growing in cultured cells as it arrests N-glycosylation of proteins destined for viral envelope = loss of infectivity of viruses released from host cells
- no therapeutic use however as it is too toxic to animals = inhibits N-glycosylation of essential glycoproteins
inhibitors of cell membrane function
polymyxins and colistins
- bind to lipid A
- act like detergents to disrupt membrane integrity
- systemic toxicity has limited their main use to topical ointments however … will bind to lipids in our kidneys (nephrotoxicity) so dont ingest
polysporin = polymyxins
assembled ribosomes in prokaryotes vs eukaryotes
pro = 70S eukaryo = 80S
inhibitors of protein synthesis in bacteria
inhibitors of 30S
- aminoglycosides (gentamicin, kanamycin)
- tetracyclines (tetracycline, doxycyline)
inhibitors of 50S
- macrolides
- lincomides
- streptogramins
- oxazolidinones
aminoglycosides
- gentamicin, kanamycin
- prevents complex of 50S and 30S
- bactericidal
- renal failure (reversible)
- side effect of ototoxicity (hearing loss)
- have no effect on anaerobes
tetracyclines
- distorts the A site in ribosome, inhibiting tRNA binding to colon
- one of the least toxic antibiotics
- over-used, so resistance is common
- used to treat intracellular bacteria
macrolides
- inhibitors of the 50S ribosomal subunit
- inhibit translocation near 23S rRNA
- can be bacteriostaticc or bactericidal
- works intracellularly
- little toxicity
- ketolides have similar mechanism of action
lincosamides
- clindamycin
- inhibitors of 50S
- same mechanism as macrolides
- used for anaerobic infections and streptococcal infections
- kills normal anaerobic flora, too, and can lead to overgrowth of nasty organisms
- implicated in C. diff
streptogramins
- also inhibit translocation in prokaryotic ribosome
- individually they are bacteriostatic, but together = bactericidal
- used to treat MRSA and vancomycin-resistant enterococci
- past use in animals as led to selection of resistant organisms
oxazolidinones
- Zyvox
- newer class of antibiotic that acts at the initiation step of protein synthesis
- can interfere with binding of other 50S-active antibiotics
inhibitrs of DNa replication
- quinolones (nalidixic acid)
- fluoroquinolones (ciprofloxacin, norfloxacin and others)
- metronidazole
inhibitors of RNA replication
rifampin
quinolones and fluoroquinolones
- bind to two enzymes, DNA gyrase and topoisomerase IV interrupting DNA supercoiling after replication and leading to breaks in DNA
- bactericidal, but no effect on anaerobes (not a lot of effect in GI)
- works intracellularly within phagocytes
- resistance arises easily; their see in chickens hasn’t helped situation!
metronidazole
works on anaerobes and parasites (both use pathways that use a small protein called flavodoxin; reduces nitro group)
rifampin
- inhibits RNA polymerase
- effective as prophylactic treatment of gram neg meningitis
- used to treat TB; especially isoniazid-resistant strains
inhibitors of folic acid pathway
sulfonamides and trimethoprim
tri = used in combo with sulfonamide, sulfamethoxazole as ‘cotrimoxazole’ aka Bactrim
to treat UTIs
- concentrated right where u need them in urine for urinary tract infections
5 main microbial targets and mechanisms of action
- cell wall (peptidoglycan synthesis)
- cell membrane integrity
- protein synthesis
- NA synthesis
- competitors of metabolic pathways (eg, folic acid pathway)
glycopeptides
- vancomycin, teichoplanin
- bind to D-Ala-D-Ala portion of the UDP-muramyl pentapeptide after it is transferred out of the cytoplasm of the bacterial cell
- inhibits both final steps of peptidoglycan synthesis, glycosyltransferase (GT) and transpeptidation (TP)
- critical use in MRSA (beneficial narrow spectrum)
** too big to go through OM; so for gram pos **
Fosfomycin
- inhibits conversion of UDP-NAG to UDP-NAM early in synthesis of peptidoglycan
- used for treatment of uncomplicated UTI with E. coli and Enterococcus faecalis
this catalyzes the polymerization step of cell wall biosynthesis and are highly conserved across all bacteria
peptidoglycan glycosyltransferase (GTs)
