Antibiotics Flashcards
General cell wall composition of bacteria
What enzyme catalyzes the formation?
Importance?
Peptidoglycan: Repeating disacharides with 4 a.a. that covalently link to other disacharides through their a.a.
Enzyme = transpeptidase/PCN bindiing protein
Important bc PCN inhibits transpeptidase -> cell wall cannot be regenerated/formed -> cell death/can’t make new cells
PCN
MOA
Must do what to be effective?
Resistance mechanisms?
MOA: competitively inhibit cytosolic transpeptidase
Effective
1) penetrate cell layers (in G - must go through porin)
2) keep beta lactam ring intact
3) Bind transpeptidase
Resistance
1) Porin’s (GNB)
2) beta lactamase/penicillinase
- Staph secretes it, GNB keep it in cytoplasm
3) Alter transpeptidase molecular structure
4) efflux pump
PCN G vs PCN V
PCN G is primarily IV/IM
PCN V is acid resistant, can be taken PO
Aminopenicillins
General Use
More effective in gram negatives, have amino group… still sensitive to beta-lactamase’s
Ampicillin (IV, oral is meh)
Amoxicillin (good oral)
Amox: Listeria! Triple therapy H. Pylori!
Penicillinase-Resistant PCN’s
General use
IV/ORAL?
Good at Gram +, not Gram -, too bulky
Use staph A serious infections that aren’t resistant (cellulitis, endocarditis, sepsis)
IV: Methicillin (d/c), nafcillin, oxacillin. “Met Nasty Ox”
Oral: cloxacillin, dicloxacillin
CLOX!!!
Antipseudomonal PCN’s
Car, Tic, Pipe
Carbenicillin, ticarcillin, piperacillin
Tx; Pseudomonas and anaerobic coverage
** These are sensitive to penicillinase so don’t really work against Staph ect. unless combined with an inhibitor
Beta-lactamase inhibitors
As the name implies
Clavulanitc acid, sulbactam, tazobactam
Cephalosporins
MOA
General Generational considerations
Who has innate resistance?
Also contain beta-lactam ring, but add a chemical group that makes them much more resistant to penicillinases
Generations:
1st Strong G positive action, poor G negative, Alt. to PCN
**Have ph in name (must first get PHD), don’t let cefazolin FAZE you (also 1st gen and only IV first gen)
2nd Medium on G+- and streptococci
** impossible to remember, good at anaerobic coverage and unknown com-acq-pneumonia
3rd Poor G positive action, strong gram negative
* * All have t for tri in the name (note that cefotetan is second gen, not third.)
* *use in-hospital for Comm-acq-pneumoina, meningitis, pyelo
ONLY ONE OF EACH BELOW
4th Strong Gram positive and negative coverage! Cefepime
5th Works against MRSA (Ceftaroline)
**Enterococci are resistant to cephalosporin, as is MRSA, except Ceftatoline
Allergies: 10% ppl with allergy to PCN will be allergic to cephalosporins. IgE mediated
Enterococci resistances
Innate to PCN G and cephalosporins, used to use ampicillin but they are becoming resistant. They are also becoming resistant to vancomycin, which we used after resistance to ampicillin began.
Vancomycin MOA Use Side effect and prevention Resistance profile Allergies
Complexes with D-alanine D-alanine to prevent transpeptidation
Use in all Gram Positives, not absorbed orally (good for C. Diff), synergistic with aminoglycosides
Side effects: Red man syndrome: release of histamine -> red rash of torso/pruritis, can prevent with slow infusion or antihistamine premedication
Resistance Profile: Most notable is resistance by Enterococcus and Staphylococcus. Resistance occurs by altering D-alanine-D-alanine to D-alanine-D-lactate
MRSA resistance
What’s the only beta-lactam that will work?
S. Aureus resistance to ALL PCN’s, including the cephalosporins EXCEPT 5th gen ceftaroline
What’s special about Cefazolin?
Only first gen cephalosporin that is fiven IV, also the only one without a PH in the name.
What is special about ceftaroline?
Ceftaroline is the only 5th generation cephalosporin with action against MRSA.
What is special about Cefepime?
Only 4th generation cephalosporin. Good at gram positives and gram negatives. Useful against pseudomonas.
Ceftazidime (3rd gen) is also effective against pseudomonas
What generation of cephalosporin is ceftriaxone?
Activity against what?
3rd gen
best at gram negatives, nt bad against streptococci, poor Gram positive
Ceftriaxone and cefotaxime uniqueness
Both have excellent CSF penetration -> tx meningitis (usually due to gram negatives).
Ceftriaxone is used in adults
Cefotaxime in children (bc ceftriaxone interferes with bilirubin metabolism)
Carbapenems MOA USE Resistance Side effects Notes
Similar action as PCN, inhibit transpeptidase. They are super small and have GREAT coverage of gram positive and negative organisms.
BROADEST spectrum we have.
Resistant to beta-lactamase and ESBL but cabapenemases are emerging. MRSA is also resistant. Works on SOME pseudomonas.
SE: 10% cross reactivity, lowers seizure threshold (don’t use for meningitis/strokes)
Notes: Imipenem needs cilastatin which inhibits an enzyme in kidney that breaks it down. The other carbapenems are resistant to breakdown.
Aztreonam
MOA
Use
SE
Has beta lactam ring, but ONLY used against gram negatives. Including pseudomonas
Not useful with anaerobic or gram positive bacteria
SE PCN allergy is not a concern
MRSA mechanism of resistance
Altered binding site of PCN on transpeptidase
anti-ribosomal antibiotics
Name the 7 important antibiotics using the mnemonic (including which ribosome subunit they inhibit)
Which 2 are IV only (the rest are orally available)
CLEan TAG
CLEan is 50s Chloramphenicol Clindamycin Linezolid Erythromycin (clarithromycin, azythromycin, telithromycin)
TAG is 30s
Tetracycline
Tigecycline
Aminoglycosides
** Aminoglycosides and Tigecycline are solely IV/IM
Chloramphenicol MOA USE Side/adverse effects Notes
Bacteriostatic. inhibit 50s subunit bacteria
USE #Wide spectrum of activity (G+, G-, anaerobes) #CNS penetration = use for meningitis #Use when severe allergies to PCN's
SE #may cause reversible anemia #May cause irreversible aplastic anemia -> death # Gray Baby Syndrome: shock, abdominal distention, cyanosis in neonates that cannot fully conjugate it
Clindamycin MOA USE Side/adverse effects Notes
Bacteriostatic. Inhibit 50s subunit
USE #NOT useful with gram negatives. Strong with gram positive and anaerobes #Use in toxic shock syndrome combined with another drug (it will limit the toxic shock protein production -> increase survivability) #Use in anaerobic infections ABOVE diaphragm (aspiration pneumonia/lung abscess/oral infection)
Adverse effect #Prototypical cause of pseudomembranous colitis, though many PCN's and other drugs do this as well... tx with metranidazole or vanco.
Linezolid MOA USE Side/adverse effects Notes
Inhibit 50s subunit +- bactericidal/static USE #Gram + bugs #Active against VRE and MRSA
Adverse #occasional bone marrow suppression #Can cause serotonin syndrome (don't use in pts on antidepressants)
NOTES:
EXPENSIVE!!!!
Macrolides/Ketolide MOA USE Side/adverse effects Notes
Bacteriostatic. Inhlblt 50s subunit, specifically translocation
(Erythromycin was first, now largely replaced by azithromycin) + Clarithromycin
Ketolide: Telithromycin
USE: Well tolerated #Gram positives, some gram negative #Atypical pneumonia: Legionella, chlamydia pneumoniae, Mycoplasma pneumonia + Chlamydia STI #Some syphillis though resistance increasing #pneumococcus is fairly resistant except to telithromycin, use as alternate to PCN
Adverse: MACRO pneumonic General: #motility issues (abdominal discomfort) #arrhythmia (prolonged QT #cholestatic hepatitis (microsomal enzyme inhibitor) #Rash #eOsinophilia
NOTES Telithromycin can cause acute respiratory failure in myasthenia gravis patients!!!!
Resistance: methylation of 23s rRNA binding site
