Cell Wall Inhibitor Lecture Sep 12 Flashcards
What are the 4 types of beta lactam ABx?
penicillins
cephalosporins
carbapenems
aztreonam
How do all beta lactam abx work?
they bind to the penicillin binding proteins, which are transpeptidases that catalyze the terminal reactions in bacterial cell wall synthesis
this blocks cell wall synthesis and causes a build-up of cell wall precursors which leads to the activation of autolytic enzymes
the cells lyse
Specifically what site do beta lactams bind?
they bind the d-alanyl-d-alanine substrate site ON the transpeptidase, so the dipeptide on the other sugar can’t enter the binding site and undergo the transpeptidase reaction
Are beta lactams bacteriostatic or bacteriocidal?
bacteriocidal
Would swelling be more likely to occur when the cell is in a hypotonic or hypertonic solution?
A hypotonic because the water will want to flow where there are more ions.
What are penicillins active againse?
gram positive organisms
What drug is given in tandem with penicillins to reduce the renal secretion of the penicillin?
probenecid
What are the side effects of penicillins?
seizures, nausea, and diarrhea
Hypersensitivity reactions are very common-mild rash to anaphylaxis
What are the antistaphylococcal penicillins?
aka Penicillinase-resistance penicillins?
Nafcillin
Dicloxacillin
(methicillin no longer used)
What are nafcillin and dicloxacillin reserved for?
Methicillin Sensitive Staphylococci aureus
What three drugs are used as penicillinase inhibitors?
clavulanate (combined with penicillin and amoxicillin)
Sulbactam Icombined with ampicillin)
Tazobactam (combined with piperacillin)
Why is penicillin ineffective against gram negative bacteria?
It is unable to penetrate across the outer membrane of gram negative bacteria.
THe LPS blocks access and the penicillin can’t pass through the porins
What class of penicillins are able to cross the membranes of gram negative bacteria?
Aminopenicillins
AMPICILLIN
AMOXICILLIN
Their R-groups are more water soluble and can therefore pass through the porin channels of the outer membrane.
THis means they can be used to treat influenza, e. coli, listeria and salmonella
THey can still result in hypersensitivity reactions
What additional side effect is associated with the aminopenicillins that is not associated with penicillin?
They’re more likely to cause c. diff because their spectrum is broader
What are the two penicillins used as antipseudomonals?
Ticarcillin
Piperacillin
What combination of the antipseudomonals are given if the bacteria produces beta lactamases?
ticarcillin/clavulanate
piperacillin/tazobactam
What are the symptoms of a penicillin allergy?
What percentage of the population has had an allergic response to a penicillin?
What percent will have a recurrence?
Symptoms include urticaria, angioedema, and anaphylasic (which can be fatal)
3-10% have had a reaction
5_10% will have a recurrence
How does penicillin cause an allergic reaction?
Penicillin and other beta lactams combine with host proteins to form hapten protein complexes that stimulate the immmune system and results in production of specific antibodies to the antigen
What drug should you use if the patient is allergic to penicillin?
Why won’t it cause cross-reactivity?
What is the spectrum?
Use the monobactum AZTREONAM
It won’t cause cross reactivity because it only has only one ring and is therefore less likely to form hapten proteins.
The spectrium is very narry, however, and only covers gram negative rods such as klebsiella, pseudomonas, and serratia
Where are cephalosporins secreted?
in the urine
Describe the 1st generation cephalosporins
CEFAZOLIN
use the same method of action as penicillins
narrow spectrum: gram + cocci
Used for surgical prophylaxis
Do NOT cross the blood brain barrier
Describe the 2nd generation cephalosporins
cefoxitin
cefuroxime
They have better gram - activity than gram +
Used immedately prior to surgery to prevent infection
Don’t cross the blood brain barrier
Can inhibit Vitamin K production to prolong bleeding and will cause a disulfiram-like reaction when coadministered with ethanol
Describe the 3rd generation cephalosporins
Ceftriaxone
Cefotaxime
Ceftazidime
These are used for streptococci and more serious Gram - infections resistant to other beta-lactams
CAN cross the blood brain barrier–used for meningitis
cetriaxone will interact with calcium containing meds to form crystals that precipitate in lungs and kidneys
STRONG association with C. diff
Describe the 4th generation beta lactams
Cefepime
This has the broadest spectrum of the cephalosphorins because it’s a 1st generation combined with a 3rd generation
It’s used against Gram +, gram - (including pseudomonas)
Often used for empiric therapy
Describe the 5th generation cephalosporin
Ceftaroline
It’s engineerd to bind to PBPs that have been mutated in MRSA infections
!!!!!!!
What makes carbapenems unique among the beta lactams?
They have a low susceptibility to beta lactamases
Describe the carbapenems
Imipenem (given with cilastatin)
meropenem
They containe beta lactam rings and bind to PBPs
Broad spectrum, but MRSA is resisant
Administered parenterally
Low susceptibility to beta lactamases
What drug is always given with imipenem?
Imipenem is administered with cilastatin to decrease inactivation of the drug by renal dehydropeptidase I and prevent formation of potentially toxic nephrotoxic metabolite.
What does vancomycin do?
WHat is its target?
WHat is it’s spectrum?
It is not a beta-lactam but it does block cell wall synthesis
It binds with high affinity to the D alanyl D alanine terminues of the cell wall precursor unit, inhibitin release form the bactoprenol carrier, thus preventing peptidoglycan synthesis. It inhibits the polymerization or the transglycosylase reaction.
It’s bactericidal
It’s spectum is narrow: gram + BUT it’s especially reserved for MRSA and C. difficile treatment
WHy is vancomycin given orally for the treatment of C. diff, but IV for the treatment of other infections?
Because oral vanco is poorly absorbed, which is good for C diff because it needs to reach the colon, but bad for, say, a skin infection
How has enterococci developed resistance to vancomycin?
It replaced the D-alanyl-D-alanine with a D-alanyl-D-latate or a D-alanyl-D-serine
This prevents the vanco from binding to its target
What are the toxicities of vancomycin?
It causes hypersensitivity reactions often
Ototoxicity and Nephrotoxicity if toxic levels are reached due to renal insufficiency
How does bacitracin work?
What is it used for? Why?
It prevents the dephosphorylation of the bactoprenol lipid carrier, thus continued elongation of the peptidoglycan cell wall cannot occur.
It is never used systemically because it is highly nephrotoxic, but it can be used occasionally in TOPICAL ophthalmic and dermatologic preparations
Describe polymyxin B
It works by binding to phosphatidylethanolamine in the membrane, creating holes leading to the release of cellular contents
Spectrum: used on multidrug resistant gram negative bacteria including pseudomonas
Side effects are nephrotoxicity
Resistance is infrequent and slow to develop
cross resistance does NOT happen with any other ABx
Describe daptomycin
Daptomycin binds to the cell membrane to gram positive bacteria leading to depolarixation of membrane and cell death
This is bactericidal
Used to treat Gram positive organisms and is effective against MRSA
How does resistance to daptomycin occur?
resistance occurs by the addition of a positively charged lysin to the cell surface, which repels the positively charged drug
This does not cause cross-resistance
WHat two antibiotics target the cell membrane?
Which is used for gram negative and which is used for gram positive?
Polymyxin B (for gram negative)
Daptomycin (gram positive)
What antibiotics can be used to treat MRSA?
Vancomycin
Daptomycin
Ceftaroline (5th Gen)
What antibiotics can be used to treat pseudomonas
Piperacillin
Ticarcillin
Cefepime (4th Gen)
Polymyxin B
