Inhibitors of Cell Wall Synthesis Flashcards
Antibiotics that inhibit cell wall synthesis require what?
Require a cell that is actively dividing. Little to no effect if not growing.
Which antibiotics are cell wall inhibitors by peptidoglycan?
Bacitracin and vancomycin
What antibiotics are cell wall inhibitors by transpeptidase
Pencillins
Cephalosporins
Penicillins. Differences in drugs are due to
Structure. Side chain affects antimicrobial spectrum, stability to stomach acid, cross hypersensitivity and susceptibility to degradative enzymes.
What do all penicillins have in common?
All have the B-lactam ring.
MOA by penicillins
B lactam antibiotics form a covalent bond with the bacterial enzyme transpeptidase. This inhibits the catalytic activity of the enzymes.
- Prevents elongation or cross linking of peptidoglycan.
- Leads to autolysis
Transpeptidase enzymes
Group of bacterial enzymes that are anchored in the cytoplasmic membrane and extend into the periplasmic space.
responsible for the assembly, maintenance, and regulation of the peptidoglycan portion of the bacterial cell wall.
“easy to kill gram negative” and “hard to kill gram negative”
Gram negative are surrounded by outer envelope that acts as a barrier.
Easy to kill have channels that allow entry.
hard to kill have restrictive porins and are resistant to many antibiotics (pseudomonas)
Example of a hard to kill gram negative bacteria
pseudomonas
Natural penicillins are obtained from
mold fermentation. Susceptive to inactivation by enzymes that bacteria produce, called Beta lactamases. Beta lactamases can destroy penicillin molecule.
beta lactamase
Enzymes that bacteria produce to destroy penicillin molecule.
Same as penicillinase.
penicillinase.
Enzymes that bacteria produce to destroy penicillin molecule.
Same as beta lactamase.
When are penicillinase-resistant penicillins used?
For the treatment of penicillinase producing staph. Avoid over use to prevent resistance.
examples of penicillinase-resistant penicillin
Nafcillin
Oxacillin
Methicillin. When should it be used?
High toxicity. causes interstitial nephritis.
Used only to identify resistant strains of S. Aureus (MRSA.) MRSA is resistant to all available B-lactam antibiotics.
MRSA is susceptible to
Vancomycin.
Extended spectrum penicillins
designed to maintain Gram + and easy gram negatives
Resistance is a major problem. Often combined with a penicillinase inhibitor.
natural resistance vs acquired resistance
Natural: organisms that lack a cell wall or have a cell wall that is impermeable to the drug.
Acquired: occurs via plasmid transfer. Can encode for resistance to multiple agents.
Beta lactamase activity
Enzyme hydrolyzes the beta lactam ring in the antibiotic. Results in loss of the bactericidal activity.
3 methods of acquired resistance
Beta lactamase activity
Decreased permeability (efflux pump)
Altered penicillin binding proteins- newer acquired resistance. Cause of MRSA resistance. Lower affinity to antibiotics. Would need to increase conc to an impossible amount.
How are antibiotics absorbed
Most are INcompletely absorbed after oral administration. Reach intestine in sufficient amounts to affect intestinal flora (GI issues).
Amoxicillin is almost completely absorbed in stomach- not as much GI issues.
Absorption of penicillinase-resistant penicillins.
Destroyed in acidic environments. Must be taken 30-60 minutes before food or 2-3 hours after. Need to decrease acidic environment of food.
Distribution of antibiotics
All cross the placenta, but are not teratogenic.
Cannot penetrate bone or CNS unless inflammation.
Cannot reach prostate
Hypersensitivities with antibiotics
5-10% of patients have reactions.
- Rash
- Angioedema
- Anaphylaxix
Adverse reactions to antibiotics
Diarrhea due to disruption of flora
Nephritis (inflamed kidney) especially with methicillin.
Neurotoxicity
Hematologic toxicities causes decreased coagulation in blood. Be aware if they are on blood thinner!!
Cation toxicity
Why you should be aware if your patient is on blood thinners and you want to rx an antibiotic
Antibiotics adverse effects include hematologic toxicities- causes decreased coagulation in blood. Will thin blood even more.
Why can cephalosporins be given by itself more often?
Because they tend to be more resistant to certain beta lactamases.
Spectrum of cephalosporins
First generation: Gram positive coverage. Little gram negative.
Second: Extended coverage. Same gram positive and improved gram negative with anaerobic coverage.
Third: Less gram positive. Gram negative.
4th: Borad spec. Gram positive like first gen and gram negative like 3rd gen with pull coverage against cefepime. No anaerobic coverage.
5th. Similar to 3rd. Also against MRSA and pneumonia. And against anaerobic. Advanced. Injection only.
Which gen to use of cephalosporins.
- Skin infections
- Intra-abdominal infections
- Pneumonia
- Serious infections for immunocompromised patients
- 1st
- 2nd
- 3rd
- 4th
What cephalosporin to treat MRSA
Ceftaroline
Which cephalosporin to treat pseudomonas
Ceftazidime
Cefepime
Ceftolozane
Are cephalosporins susceptible to staph penicillinase?
NO.
If patients are allergic to penicillin, what generation of cephalosporins should be used
3rd gen.
If patients are allergic to penicillin, which gen of cephalosporins should you avoid
1st gen
Beta lactamase inhibitors
Do not have significant antibacterial activity by themselves.
They bind to penicillinases and inactivate. This protects the antibiotic from resistance mechanisms.
Examples of Beta lactamase inhibitors
Clavulanic Acid
Sulbactam
Tazobactam
Bacitracin is only available
Topically. When given systemically, will cause nephrotoxicity.
Mechanism of action of Vancomycin
Inhibits cell wall synthesis. Binds to alternative proteins in the cells all- weakens peptidoglycan polymerization and damages underlying cell membrane.
Not effective against gram negative cell wall synthesis. Very effective against gram positive.
Restrict use to treatment with serious infections. Don’t want to develop resistance.
Administration of Vancomycin
Slow IV fusion
Oral absorption poor
Orally? Minimal metabolism and eliminated via kidneys.
Adverse effects of Vancomycin
Fever
Chills
Phlebitis at injection site (inflammation at vein)
Flushing or shock if rapid infusion.
Telavancin
Synthetic derivative of vancomycin. No evidence that it is more effective than vancomycin. Basically same thing. Inhibits cell wall synthesis.
Telavancin adverse effects
Taste disturbances Nausea Vomitting Insomnia Foamy urine Not be used during pregnancy Caution in cardiac conditions
Bacitracin MOA
Interferes with peptidoglycan synthesis great gram positive coverage Rare toxicity and allergic reactions Safe on pregnancy Only available topically. Very nephrotoxic when given systematically.
What infections do you use bacitracin on
Infectious blepharitis and overnight coverage in treatment of bacterial corneal ulcers.
Daptomycin MOA
Induces rapid depolarization of the cell membrane. Not a true cell wall antibiotic.
Daptomycin spectrum
Limited to gram positive. Used for skin infections. Inactivated by pulmonary surfactants- never use for pulmonary infection.
Daptomycin pharmacokinetics
90% bound to protein
No hepatic metabolism
Adverse effects of daptomycin
Constipation Nausea headache Myalgias - muscle aches Insomnia
Most commonly prescribed cell wall antibiotics
Augmentin (500mg bid for 5-7 days)
Reflex (500 mg bid for 5-7 days)
^good for eyelid infections.
Bacitracin ophthalmic ointment for overnight coverage.
