(From Lippencott’s and lecture, 22 Feb 2001, by Brian Buschman)
Return to Semester Four Goodies
Return to The
Unofficial Ross Page
There are three MOAs for penicillins:
1) They bind to PBPs which are involved in the final steps of cell wall synthesis. They bind to the PBPs and cause them not to function therefore inhibiting cell wall synthesis.
2) They inhibit the cross linkages through special PBPs that are involved in cell wall cross linking.
3) Some cells constantly break down and rebuild their cell walls. Penicillins block the synthesis so this combination makes penicillins bactericidal.
Methicillin is rarely used because of severe toxicity, specifically nephrotoxicity.
Many of the gram + bacilli like E. coli and H. influenzae are penicillinase producing so you need to administer Amp or Amox in combination with a penicillinase inhibitor like clavulanic acid or sulbactam.
Resistance is natural in some because penicillin is not able to get through the cell wall. In others it is acquired through either mutation or plasmid transfer. Mechanisms include:
1) Penicillinase production.
2) Decreased cell wall permeability.
3) Altered PBPs.
Oral absorption is good in amoxacillin which makes amoxacillin bad for GI problems like Shigella or salmonella. Penicillin G has a poor oral absorption therefore it stays in the gut and is good for GI bacteria.
Distribution is all over the body but low in the CNS. You need something else, like 3rd generation cephalosporins for meningitis.
Penicillins are excreted. Probenecid decreases the excretion of penicillins therefore increasing the T˝.
Penicillins are among the world’s safest drugs but they can still cause:
1) Hypersensitivity which may cross react with other b-lactam antibiotics.
2) Methicillin is nephrotoxic.
3) Penicillins can be neurotoxic in epileptic patients.
4) Superinfections can develop because of eradication of normal flora.
Cephalosporins are similar to penicillins but are more b-lactamase resistant.
1st generation cephalosporins have good coverage of gram + cocci and specific coverage against PEcK, Pseudomonas, E. coli and Klebsiella. They do well against the gram + strep and staph just like penicillin so long as they are not penicillin resistant. 1st generations are used in pharyngitis.
They are the DOC for Bacteroides, have a weaker gram + spectra and stronger gram – bacilli spectra. They focus on HNPEcK, H. influenzae, Neisseria, Pseudomonas, E. coli and Klebsiella.
They have good gram – bacilli coverage. They also enter the CNS so can be used for meningitis. Their focus is HNPEcKS, H. influenza, Neisseria, Pseudomonas, E. coli, Klebsiella and Serratia.
Cefepime is the one 4th generation cephalosporin that covers both 1st and 3rd generation spectra. It is specifically used against Enterobacter, Serratia and PSEUDOMONAS.
Other than the pneumonic given focus on learning the cephalosporin coverage holes. Enterococcus, MRSA, MRSE, Listeria and atypicals.
Resistance is by the same mechanisms as penicillins.
Distribution can be to any part of the body but only 3rd generations do a good job or making it into the CNS. Only cefazolin does a good job of making it into bone.
Adverse effects include, hypersensitivity and disulfiram-like effects when drinking while on cephalosporins. Don’t drink while taking these drugs.
Imipenem-cilastatin are the broadest spectrum of b-lactam antibiotics. They cover gran +, -, anaerobes and Pseudomonas, aeruginosa. It is DOC for Enterobacter.
It goes everywhere and is excreted by the kidney. Imipenem is metabolized to a nephrotoxic compound so cilastatin is put with imipenem to prevent it’s breakdown.
Aztreonam is a b-lactamase resistant drug but has a very narrow spectrum because of it’s lack of ability to bind to PBPs. It does get gram – rods making it good on enterobacteria.
Aztreonam is given IV/IM and is excreted. It is able to cause abnormal liver function. It has little hypersensitivity and little cross reaction with other b-lactams.
Clavulanic acid, sulbactam and tazobactam are the b-lactam molecules with no antibiotic effects but are useful for binding to and inhibiting b-lactamase molecules.
Vancomycin inhibits production of phospholipids and peptidoglycan at a step much earlier than b-lactam drugs do.
Vancomycin is only useful against gram + cocci and rods. It is the DOC for MRSA and MRSE. It is used by dentists prophylacticly in patients with heart valve problems.
Side effects are significant causing “Red-man”/”Red neck” syndromes due to histamine release if it’s given to rapidly. It can also cause ototoxicity and nephrotoxicity.
Bacitracin is a part of triple antibiotic ointments. It’s the part that kills gram + bugs and it’s very nephrotoxic if it were to go systemic.
Return to Semester Four Goodies
Return to The
Unofficial Ross Page