Cephalosporins, Carbapenems, and Monobactams Flashcards
The cephalosporins are divided into generations based on:
- antimicrobial activity
- resistance to beta-lactamase enzymes
Which is the only beta-lactam that does NOT exhibit cross-allergenicity?
aztreonam (a monobactam)
Describe the structure of cephalosporins and how it relates to function.
contain a beta-lactam ring attached to a 6-membered dihydrothiazine ring; this confers greater stability against some beta-lactamase enzymes
What are the 3 main mechanisms of resistance for the cephalosporins?
1) Production of beta-lactamase enzymes
2) Alteration of PBPs, leading to decreased binding affinity (MRSA, PRSP)
3) Alteration of outer membrane, leading to decreased penetration of PBPs
What is the most common mechanism of resistance to the cephalosporins?
production of beta-lactamase enzymes (hydrolyze beta-lactam ring and cause inactivation)
Which generation of cephalosporins is the most stable against beta-lactamase enzymes?
4th generation
Which generation of cephalosporins has activity against anaerobes?
2nd generation (specifically, cephamycins)
Which of the 3rd generation cephalosporins retain the best activity against gram (+) aerobes?
ceftriaxone and cefotaxime (esp. against PRSP)
Which of the 3rd generation cephalosporins have activity against pseudomonas aeruginosa?
ceftazidime and cefoperazone
Which is the only 4th generation cephalosporin currently available?
cefepime
Which organisms are cephalosporins NOT active against?
- MRSA
- Enterococcus spp.
- Listeria monocytogenes
- Stenotrophomonas maltophilia
- C. diff
- Atypical bacteria (incl. Legionella)
What are the major adverse effects associated with cephalosporins?
- hypersensitivity
- MTT side chain (leading to hypoprothrombinemia and ethanol intolerance)
Which antibiotics are considered to be the most broad spectrum agents available?
carbapenems
Which bacteria are NOT covered by carbapenems?
- MRSA
- PRSP
- VRE
- Coag. (-) Staph
- C. diff
- Atypical bacteria
- S. maltophilia
The structural changes in carbapenems result in what?
extended spectrum of activity and beta-lactamase stability
What are the 4 carbapenem antibiotics commercially available in the U.S.?
DEMI (doripenem, ertapenem, meropenem, imipenem)
What is the primary target for carpanemens (MOA)?
PBP-2
Which carbapenems are used more often for gram (+) vs. gram (-) aerobes?
- gram (+): imipenem and doripenem
- gram (-): meropenem and doripenem
What is the only monobactam currently available?
aztreonam
Which carbapenem is UNABLE to target Pseudomonas aeruginosa?
ertapenem
Which carpabenem is the best for CSF penetration?
meropenem
What is unique about elimination of imipenem?
It undergoes hydrolysis by a dihydropeptidase enzyme in the renal brush border to a nephrotoxic metabolike; thus, it is co-marketed with cilastatin, a DHP inhibitor, to reduce nephrotoxicity.
What is an important carbapenem adverse effect to know?
CNS effects, including confusion, dizziness, hallucinations, and seizures
*risk factors for seizures=pre-existing CNS disorder, high doses, renal insufficiency
Describe the spectrum of activity of monobactams.
preferentially work on gram (-) aerobes (including pseudomonas) and have little-no activity against gram (+)s or anaerobes.
