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Penicillin Types (PCN) B-Lactams
- Natural Penicillins
- Antistaphylococcal penicillins
- Extendend spectrum penicillins:
- 1. Aminopenicillins
- 2. Carboxypenicillins
- 3. Ureidopenicillins
Bacteria: Gram Positive
thick peptidoglycan cell wall
Bacteria: Gram Negative: hard for antibiotics to penetrate
- Outer membrane: extra lipopolysaccharide membrane surrounding the cell wall and includes porins channels which allow entry into cell
- Inner membrane: thin peptidoglycan layer which makes up the cell wall
Bacteria Cell Wall
is composed of cross linked polysaccarides.
cause a change of PBP or an alteration
- cause the penicillin binding proteins to block/prevent or STOP crosslinking or formation of a rigid bacterica cell wall from occuring. No crosslinking of bacteria cell wall=bateria death. Crosslinking=viable bacterial
- B-Lactams prevent development of a normal bacterial cell wall
Bacteria Cell Wall Crosslinking
bacteria live, bacteria strong, bacteria spread
Bacteria Cell wall NO crosslinking
weak bacteria, death of bacteria
Different Antibiotics work on
different penicillin binding proteins (PBP) and prevent cell wall synthesis
Penicillin Binding Proteins (PBP)
Are enzymes that break off a part of the polysaccaride wall to promote cross linking. There are thousands of different PBP. If crosslinking occurs then bacteria are viable and the infection spreads. PBP are different in gram+ bacteria, gram- bacteria and anaerobic bacteria
B-Lactam is only effective if
the bacteria is in the growing/active stage
bacteria need to be actively multiplying
Bacteria are very smart and have figured out over the years to
change their PBP shape and therefore lower their affinity for B-lactams or lower their affininty to PCN. Now betalactam will no longer be effective. Now it will no longer prevent that crosslinking
Bacteria talk, they will share their knowledge of resistence mechanisms.
MOA for Bacterial Resistance to B-Lactams
1. change shape of PBP. This causes B-Lactams to no longer be effective
2. Enzyme B-Lactamase breaks the B-Lactam ring. The bacteria produce this enzyme. If this ring is broken we lose our antibacterial activity. Very common
3. Gram- bacteria change the structure of their porins. So the antibiotic can no longer get through to the cell wall. this is called Decreased Antibiotic Permeabitity. Impaired B-lactam penetration. If antibiotics dont get to the cell wall they will have no effect on it.
4. Efflux Pump: bacteria has this pump. When antibiobics do get into the cell wall the bacteria just "PUMP" the antibiotic back out! This reduces the amount of intracellualar drug and there is never a strong enough concentration of antibiotic in the cell wall to have an effect.
B-Lactamase Inhibitors: prevents breaking of bond on the b-Lactam structure
combat resistance issues.
- PCN G-IV
- PCN VK-PO oral
- Benzathine PCN-IM: used to treat SYPHILLIS. SYPHILLIS is a slow grwoing bacteria slowly absorbed, long acting
- Procaine PCN-IM: not rx very often. slowly absorbed, prolonged low concentrations (weeks), contains local anesthetic
Natural PCN MOA: overall limited/focused
work on gram+. work well on strep but not the best for staph, limited to gram-
Antistaphylcoccal PCN: great choice! most potent to tx staph and strep, NOT MRSA
PCN was developed and we were using it. The staph got smart and started producing penicilinase which inactivated PCN
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