Cephs/Carbas/Monos - SOA Flashcards
List the first generation cephalosporins:
- cefazolin - IV
- cephalexin - oral
List the second generation cephalosporins:
- cefprozil - oral
- cefuroxime - IV + oral
- cefoxitin - IV
- cefotetan - IV
List the third generation cephalosporins:
- ceftriaxone - IV
- ceftazidime - IV
- cefpodoxime - oral
List the fourth generation cephalosporin:
cefepime - IV
Which cephalosporin is Anti-MRSA?
ceftaroline
It is a misc cephalosporin because it doesn’t fit into the generation patterns.
Which cephalosporin is miscellaneous?
cefiderocol
What is the mechanism of action of cephalosporins?
Cephalosporins inhibit cell wall synthesis by binding to and inhibiting PBPs.
Same for all B-lactams
What is the mechanism of action of cefiderocol?
misc
Cefiderocol functions as a siderophore and binds to extracellular free ferric iron. It then gets actively transported across the outer cell membrane of bacteria using a siderophore iron uptake mechanism.
trojan horse effect
What are the mechanisms of resistance to cephalosporins?
- production of B-lactamase enzymes
- alterations in PBPs
- altered porin proteins leading to poor membrane penetration
3rd and 4th gen cephalosporins are resistant to degradation by B-lactamases of some bacteria
Explain how the generations of cephalosporins differ from one another:
- Gram-positive activity decreases as you go down the generations
- Gram-negative activity increases as you go down the generations
- Stability against B-lactamase increases as you go down the generations
What is the general SOA of first gen cephalosporins?
cefazolin, cephalexin
- Excellent GP
- Limited GN
Which target organisms do 1st gen cephalosporins cover?
cephalexin, cefazolin
MSSA
What is the general SOA of second generation cephalosporins?
cefuroxime, cefprozil, cefoxitin
- slightly less GP than 1st gen
- expanded coverage against GN
- BDA
Which cephalosporins cover below the diaphragm anaerobes?
- Second generation:
- cefoxitin
- cefotetan
- cefmetazole
These are the only cephalosporins with activity against BDA
Which target organisms do the second generation cephalosporins cover?
cefuroxime, cefprozil, cefoxitin
- MSSA
- BDA
Acknowledge: Ceftriaxone does NOT cover pseudomonas.
I acknowledge.
What is the general SOA of the third generation cephalosporins?
ceftriaxone, ceftazidime, cefpodoxime
- less active than 2nd gen for GP
- expansive GN activity
Which cephalosporins have activity against penicillin-resistant Streptococcus pneumoniae (PRSP)?
- ceftriaxone (3rd gen)
- cefotaxime (3rd gen)
- cefepime (4th gen)
- ceftaroline
3rd gens are primary agents
Which target organisms do 3rd generation cephalosporins cover?
ceftriaxone, ceftazidime, cefpodoxime
- PRSP
- MSSA
- pseudomonas aeruginosa
Which target organisms does cefepime cover?
4th generation cephalosporin
- PRSP
- MSSA
- pseudomonas aeruginosa
Which cephalosporin covers MRSA?
ceftaroline
Which target organisms does ceftaroline cover?
- PRSP
- MSSA
- MRSA
What is the general SOA of cefiderocol?
- no relevant GP activity
- similar to 4th gen for GN
Which cephalosporins have activity against pseudomonas aeruginosa?
- ceftazidime
- cefepime
- ceftolozane-tazobactam
- ceftazidime-avibactam
What is the general SOA for ceftolozane-tazobactam and ceftazidime-avibactam?
- mainly used for GN activity
- covers pseudomonas aeruginosa
What pharmacodynamic parameter correlates with clinical efficacy of cephalosporins?
same as pcns and other B-lactams
- T>MIC
- time-dependent bactericidal activity
Which cephalosporins get into the CSF?
- parenteral cefuroxime (2nd gen)
- parenteral 3rd gen
- parenteral 4th gen
- 3rd gen = ceftriaxone, ceftazidime, cefpodoxime
- 4th gen = cefepime
Which cephalosporins are NOT eliminated by the kidneys?
- ceftriaxone –> biliary system
- cefoperazone –> liver
All other cephalosporins require dose adjustment in renal impairment
What is the half-life of ceftriaxone?
8 hours
Can cephalosporins be used in patients with history of pcn allergy?
- If history of anaphylaxis, no
- If history of delayed rxn, proceed with caution
- first gen demonstrate the highest risk
Cefazolin has a unique R1 side chain, so it does not pose the same risk.
Which adverse effects are seen with cephalosporins?
- hypersensitivity
- hypoprothrombinemia
- disulfram rxn
- C. diff
- nonconvulsive status epilepticus
Which cephalosporins have the 5-NMTT side chain that confers hypoprothrombinemia and disulfiram reaction?
exam Q
- cefamandole
- cefotetan
- cefmetazole
- cefoperazone
- moxalactam
cefotetan is pictured
Which cephalosporins can cause nonconvulsive status epilepticus?
- cefepime (4th gen)
- ceftazidime (3rd gen)
- cefiderocol
List the carbapenems:
- imipenem
- meropenem
- ertapenem
- doripenem
List the carbapenems with B-lactamase inhibitors:
- meropenem-vaborbactam
- imipenem-relebactam
What is the mechanism of action of carbapenems?
- inhibits cell wall synthesis by binding to and inhibiting PBPs
- displays time-dependent bactericidal activity
like all B-lactams
What is the general SOA of carbapenems?
- most broad spectrum abx
- many GP
- many GN
- anaerobes
- no atypicals
Which carbapenems display the best GP activity?
- imipenem
- doripenem
What kind of bacteria are carbapenems the drugs of choice for?
ESBL- and AmpC- producing bacteria
carbapenems display intrinsic resistance against B-lactamases
Which target organisms do the carbapenems cover?
imipenem, meropenem, ertapenem, doripenem
- MSSA
- BDA
- pseudomonas aeruginosa **
Ertapenem does NOT cover pseudomonas aeruginosa
Which carbapenem does NOT cover pseudomonas aeruginosa?
ertapenem
Which carbapenem gets into the CSF better than the others?
meropenem
How are the carbapenems eliminated?
renally like most other B-lactams
Why is imipenem formulated with cilastatin?
- Imipenem undergoes hydrolysis in the kidney by DHP – which turns it into microbiologically inactive yet nephrotoxic metabolites
- cilastatin is a DHP inhibitor that prevents the renal metabolism of imipenem and protects against nephrotoxicity
- 1 beta methyl prevents the other carbapenems from having this issue
Which carbapenem has the longest half-life?
- ertapenem has a half-life of 4 hours
- all other have a 1-hour half-life
Which carbapenems require dosage adjustments in renal dysfunction?
all carbapenems require dosage adjustment in patients with renal dysfunction
Can patients with pcn allergy receive carbapenems?
- if history of anaphylaxis –> no
- if history of delayed reaction –> proceed with caution
What are the adverse effects associated with carbapenems?
imipenem, meropenem, ertapenem, doripenem
- Seizures
- GI
What are the risk factors for developing seizures from carbapenem use?
- preexisting CNS disorders
- high doses (>2g imipenem/day)
- presence of renal dysfunction
What is the only available monobactam?
aztreonam
What is the MOA of aztreonam?
monobactam
- Inhibits cell wall synthesis by binding to and inhibiting PBPs
- displays time-dependent bactericidal activity
like all other B-lactams
What are the mechanisms of resistance to aztreonam?
monobactam
- B-lactamase production
- decreased penetration through outer cell membrane in GN
What is unique about the aztreonam mechanism that impacts its SOA?
Aztreonam binds preferentially to PBP-3 in aerobic GN bacilli.
has poor affinity for GP and anaerobic
What is the SOA for aztreonam?
- Only active against a wide range of GN
- pseudomonas aeruginosa
Does aztreonam penetrate the CSF?
Yes
How is aztreonam useful clinically?
Aztreonam is especially useful for the tx of GN infections in patients with history of severe pcn or B-lactam allergy.
It’s structure is different enough so it doesn’t cause cross-reactivity
How is aztreonam eliminated?
- renally
- needs dose adjusted
