LECTURE - Antimicrobials

Question 1

bactericidal

Answer 1

compound that kills the organism

> important for immunocompromised

Question 2

bacteriostatic

Answer 2

compound inhibits growth of organism ; useful when immune system is intact

Question 3

lines between bactericidal and bacteriostatic properties blur when…

Answer 3

organisms grow more slowly = biofilm

Question 4

Pharmacokinetics

Answer 4

describes the action of body on the administered drug that includes absorption, distribution, metabolism, and excretion to define systemic exposure

Question 5

pharmacodynamics

Answer 5

describes the biochemical and physiologic response of the drug and its mechanism of action

Question 6

selective toxicity

Answer 6

kill bug not patient

Question 7

side effects of antimicrobials can occur when

Answer 7

• selectivity is not optimal or

- antimicrobial has unexpected interactions w host (penicillin combining w serum proteins = allergic rxns)

Question 8

disinfectant

Answer 8

compound used to kill or inhibit organisms on surfaces r inanimate objects
> too toxic for body use (ex: phenolics)
> not selective

Question 9

compound used to kill or inhibit organisms on skin but not internally

Answer 9

antiseptic
 > sodium hypochlorite (bleach)
 > povidone iodine solutions (Betadyne)
 > 70% ethanol
 > 3.0% hydrogen peroxide
 > benzalkonium chloride
 >hexachlorophene

Question 10

innate resistance to disinfectants and antiseptics

Answer 10

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

Question 11

acquired resistance to disinfectants and antiseptics

Answer 11

plasmid-encoded efflux pumps for QACs in S. aureus

Question 12

general characteristics of antibiotics

Answer 12

• originate from microbes (actinomycetes; fungi)
• have selective toxicity
• possess a spectrum of action (broad vs narrow)

Question 13

inhibitors of cell wall synthesis

Answer 13

- peptidoglycan pathway was first to be capitalized on with penicillin
 > Fosomycin 
 > Bacitracin
 > Tunicamycin
 > Glycopeptides (vancomycin)
 > beta-lactam antibiotics

Question 14

most important inhibitors of cell wall synthesis

Answer 14

beta-lactam

• penicillins
• cephalosporins
• carbapenems
• monobactams

Question 15

bacitracin

Answer 15

• interferes w recycling bactoprenol

- systemic toxicity limits its use to topical ointment

Question 16

tunicamycin

Answer 16

• 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

Question 17

inhibitors of cell membrane function

Answer 17

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

Question 18

assembled ribosomes in prokaryotes vs eukaryotes

Answer 18

pro = 70S
eukaryo = 80S

Question 19

inhibitors of protein synthesis in bacteria

Answer 19

inhibitors of 30S

• aminoglycosides (gentamicin, kanamycin)
• tetracyclines (tetracycline, doxycyline)

inhibitors of 50S

• macrolides
• lincomides
• streptogramins
• oxazolidinones

Question 20

aminoglycosides

Answer 20

• gentamicin, kanamycin
• prevents complex of 50S and 30S
• bactericidal
• renal failure (reversible)
• side effect of ototoxicity (hearing loss)
• have no effect on anaerobes

Question 21

tetracyclines

Answer 21

• 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

Question 22

macrolides

Answer 22

• 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

Question 23

lincosamides

Answer 23

• 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

Question 24

streptogramins

Answer 24

• 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

Question 25

oxazolidinones

Answer 25

- Zyvox - newer class of antibiotic that acts at the initiation step of protein synthesis - can interfere with binding of other 50S-active antibiotics

Question 26

inhibitrs of DNa replication

Answer 26

- quinolones (nalidixic acid) - fluoroquinolones (ciprofloxacin, norfloxacin and others) - metronidazole

Question 27

inhibitors of RNA replication

Answer 27

rifampin

Question 28

quinolones and fluoroquinolones

Answer 28

- 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!

Question 29

metronidazole

Answer 29

works on anaerobes and parasites (both use pathways that use a small protein called flavodoxin; reduces nitro group)

Question 30

rifampin

Answer 30

- inhibits RNA polymerase - effective as prophylactic treatment of gram neg meningitis - used to treat TB; especially isoniazid-resistant strains

Question 31

inhibitors of folic acid pathway

Answer 31

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

Question 32

5 main microbial targets and mechanisms of action

Answer 32

- cell wall (peptidoglycan synthesis) - cell membrane integrity - protein synthesis - NA synthesis - competitors of metabolic pathways (eg, folic acid pathway)

Question 33

glycopeptides

Answer 33

- 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 **

Question 34

Fosfomycin

Answer 34

- 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

Question 35

this catalyzes the polymerization step of cell wall biosynthesis and are highly conserved across all bacteria

Answer 35

peptidoglycan glycosyltransferase (GTs)