Antimicrobials: actions against the cell wall

why are there generations or categories of drugs

lab takes initial abx and makes changes to be able to be used for other things

what may the changes be made for

increase activity against another class of organisms (gram + vs -), improve accessibility, counteract resistance

MOA against the cell wall

inhibit synthesis or weaken cell wall to allow fluid into cell, cell then swells and bursts

why does action against the cell wall work

bc humans don't have cell walls, only bacteria does

gram + bacteria have

only the cell wall layer

gram - bacteria have

3 layers- outer membrane, cell wall, cytoplasmic membrane

why may some abx be effective on gram + but not -

it is harder to get through gram - bacteria cell wall bc more layers

penicillin

naturally occurring in mold, broad activity against many organisms, low toxicity (only allergy!)

penicillin MOA

disrupts synthesis of peptidoglycan which is needed for healthy cell wall, increases speed of cellular processes, leading to autolysis activation

why do we not have to worry about issues with penicillin

only works on cell wall which humans do not have

4 categories of penicillin

narrow spectrum penicillinase sensitive, narrow spectrum penicillinase resistant, broad spectrum aminopenicillins, extended spectrum anti pseudomonal

difference between category 1 penicillins

PCN G- IV, IM, unstable in gastric acid

PCN V- oral!! stable in acid bc has potassium

what two drugs in category 2 are interchangeable

methicillin, oxacillin

main category 4 penicillin

piperacillin + tazobactam (Zosyn)

how is penicillin metabolized

liver, eliminated by kidneys

how is piperacillin-tazobactam excreted and what does this mean with kidney failure

kidneys- dose is adjusted but don't need peak/trough

adverse effect of piperacillin-tazobactam

disrupt platelet function

cephalosporin

found in sewer water, bind to penicillin-binding protein, disrupt cell wall synthesis, activate autolysis

adverse effects of cephalosporins

low toxicity- avoid in penicillin anaphylactic reaction, often see maculopapular rash

how can we recognize cephalosporins

ceph-, cef-

huge 3rd generation cephalosporin to know

ceftriaxone (Rocephin)

what is ceftriaxone used in

1st line bacterial meningitis, gonorrhea

5th generation cephalosporins

newer, less resistance, more expensive

how are cephalosporins usually given

IV bc poor oral absorption

cephalosporin elimination

kidneys- don't need peak and trough to adjust dose

carbapenems

broad coverage, last resort d/t huge resistance (carbapenem resistant organisms)

how can we recognize carbapenems

-penem

imipenem

combined with cilastin to decrease kidney destruction

huge teaching for imipenem

can induce seizures, give other drugs that can induce seizure far apart

meropenem

broad coverage, no destruction by kidneys, less seizure activity

vancomycin

glycopeptide abx with NO b-lactam ring

what is vancomycin often used for

gram + infections, MRSA!!!

vancomycin elimination

by kidneys- need peak and trough levels

how is vancomycin given and why

oral, IV- but no oral absorption (given orally for GI)

toxic side effects of vancomycin

ototoxicity (can be reversed), immune-mediated thrombocytopenia, vanc infusion-related reaction

vancomycin infusion-related reaction (VIRR)

rapid infusion s/s- flushing, rash, pruritus, blister, tachycardia, hypotension

what should we do if someone is experiencing VIRR

SLOW INFUSION!!!! 2+ hrs

daptomycin

newer abx that dispruts cell membrane, used in gram + and MRSA (if resistant to vanc)

big teaching for daptomycin

cannot be given if lung infection bc surfactant inhibits it

aztreonam

b-lactam ring not fused so resistant to b-lactamase, works on gram -

how is aztreonam given

IV

how is aztreonam eliminated

kidneys- do not need peak/trough

adverse effects of aztreonam

thrombophlebitis, cross-allergy to pcn or cephalosporins

what can we do to prevent thrombophlebitis with aztreonam

give through central line

if a pt has a pcn or cephalosporin allergy, would we give aztreonam

we can- just monitor pt and be aware of possible allergy