Antibiotics (1-3) Flashcards
What 4 things must happen for an antibiotic to work?
Bind to target site(s) in the bacteria
Occupy the right number of binding site in a bacteria
Remain at the binding site for enough of the metabolic process that the bacteria is inhibited
Antibiotic must get to the right site of action
There are 2 ways that antibiotics can impact the cell wall on bacteria
Inhibition of cell wall synthesis (β-lactams, vanco)
Alteration of cell membrane function (daptomycin)
These antibiotic work outside the nucleus
There are 3 ways that antibiotic can impact the function of bacteria to exert their effect (work inside the cell)
Inhibition of protein synthesis
Inhibition of nucleic acid synthesis
Alteration of cell metabolism
What groups of antibiotic inhibit protein synthesis?
Macorlides
Tertracyclines
Aminioglycosides
Linezolids
Clindamycin
What groups of antibiotic inhibit nucleic acid synthesis?
Fluroquinolones
What groups of antibiotic alter cell metabolism?
Sulphonamides
Trimethoprim
What is the breakpoint in context of minimum inhibitory concentration (MIC)?
For each organism-antibiotic pair there is a cut-off MIC that defines susceptibility - this is the breakpoint
Are antibiotic equally effective in IC pts as immunocompetent pts?
No; antibiotic work with the immune system to produce their effect
This makes it important to take into account the pts immune system when selecting antibiotic and its dosing
What is the difference between bacteriostatic and bactericidal antibiotic?
Antibiotic that are bacteriostatic will inhibit rather than kill
Antibiotic that are bactericidal will kill
However, bacteriostatic antibiotic can become bactericidal at concentrations that exceed their MIC
What are the 4 mechanisms of resistance bacteria can use to avoid being killed by antibiotic?
Enzymatic destruction
Modified cell wall porins (antibiotic cant get in)
Efflux pumps (antibiotic gets pumped out)
Altered binding sites (antibiotic cant attach where it needs to)
How do β-lactams work?
Bind to penicillin binding proteins (PBPs) and interfere with formation of the peptidoglycan barrier —> cell wall dysfunction and cell death
- β-lactams bind to many different PBPs
What are the most common mechanisms of bacterial resistance to β-lactams?
Enzymatic destruction via β-lactamases
Alteration of PBP sites
What is the most common adverse drug reaction associated with β-lactams (esp penicillin and cephalosporins)?
Hypersensitivity reactions, type 2 more than type 1 and others
Of the oral penicillins which one absorbed well orally?
Amoxicillin
Which cephalosporins have poor oral absorption?
Cefuroxime
Cefixime
Which β-lactams must be taken on an empty stomach?
Pen V
Cloxacillin
Cloxacillin is effective against strep spp. (mostly) but not against one type of staph aureus. Which one is it and why?
MRSA
This type of staph aureus has developed resistances to β-lactams as it had developed or acquired the ability to make β-lactamase
What staph spp. are susceptible to cloxacillin?
MSSA are susceptible; the only one not susceptible is MRSA
How can susceptibility to β-lactams be restored in bacteria?
Using β-lactamase inhibitors (ex. Clavulanate and tazobactam)
Using this these drugs with β-lactams —> better gram (-) susceptibility and is very effective vs bacteria that make only β-lactamase
This IV antibiotic has a longer side chain allowing it to bind to different PBPs —> better gram (-) susceptibility. It is the most comprehensive penicillin to date
Pipercillin/tazobactam
Between the long side chain and the presence of tazobactam (β-lactamase inhibitor) it gives very strong coverage for gram (-) bacteria inc those that make β-lactamase
What 2 areas did cephosporins improve on from penicillins?
Better stability against β-lactamses by some gram (+) and gram (-)
Improved on activity agasint gram (-) organisms
What aspect of coverage improves as you move along the generations of cephalosporins?
Ability to cover gram (-) organisms but you may lose some S. aureus susceptibility
1st gen celphalosporins have good coverage against these 3 gram (-) bacteria
Proteus spp.
E. Coli
Klebsiella spp.
2nd gen celphalosporins have better coverage than 1st gen for these 4 gram (-) bacteria
H. Influenzae
Proteus spp.
E. Coli
Klebsiella spp.
This was the first cephalosporin that was effective against p. aeruginosa. It also has poor activity against gram (+) bacteria.
Ceftazidime
What coverage problem did carbapenems solve that penicillins and cephalosporins couldn’t cover?
Works against serious anaerobes like b. fragilis
What final problem were macrolides able to solve that weren’t covered with β-lactams, cephalosporins, and carbapenems?
They also work against cell wall deficient organisms
Which macrolide is the worst for causing stomach upset?
Erythromycin
Tetracyclines are similar in MoA and spectrum to which class of antibiotic?
Macrolides
What is a something to consider when taking tetracycline by mouth?
Should not be taking with foods rich in multivalent cations (Al, Ca, Fe, Mg, Zn)
Up to 20% of drug can bind these molecules when taken with foods rich in these molecules
Avoid taking with milk
Dose adjustments are needed for this tetracycline based on renal function
Doxycycline
How do quinolones work?
- Block bacterial DNA synth by inhibiting bacterial topoisomerase II and topoisomerase IV
- Topoisomerase IV important to gram (+), topoisomerase II more important to gram (-)
What is a notable adverse effect of fluoroquinolones?
Can affect sugars (+ or -) esp in diabetics
Aminoglycosides exhibit a significant post-abx effect of 6hrs. What is the importance of this?
They are dosed once a day as serum level below the MIC is still capable of killing the organism with these antibiotic
These are very important ADRs to look for when giving TMP-SMX
Common presentation of sulfa exposure — morbilliform or maculopapular rash
Rare for cross reactivity with other sulphonamides
Monitor for SJS, TENs, and DRESS (all rare)
↑ in serum Cr (competes with tubular secretion of Cr)
↑ K (blocks tubular secretion of K)
↓ Na
Possible teratogenicity and increased risk of kernicterus in newborn
Quinolones work by inhibiting nucleic acid synthesis. Which topoisomerase is important to gram (+) bacteria?
Topoisomerase IV
Quinolones work by inhibiting nucleic acid synthesis. Which topoisomerase is important to gram (-) bacteria?
Topoisomerase II
