Beta-Lactam Characteristics Flashcards
What are the two anti-pseudmonal penicillins?
Ticarcillin, piperacillin
What beta-lactams are NOT excreted by the kidneys?
Nafcillin, oxacillin, ceftriaxone, cefoperazone
What beta-lactam does NOT demonstrate cross-reactivity?
Aztreonam
What PKPD do beta-lactamase drugs exhibit?
Time > MIC, time-dependent bactericidal
What are the two drugs of choice for MSSA?
Nafcillin and cefazolin
What cephalosporins demonstrate activity against anaerobes?
2nd generation cephalosporins cefoxitin, cefotetan, and cefmetazole
What is the only penicillin that can cover Klebsiella?
piperacillin
What five penicillins have a significant sodium load?
pen G sodium, piperacillin, ticarcillin, nafcillin, carbenicillin
What penicillin might you use for a respiratory tract infection, listeria, or enterococcus?
Aminopenicillins – ampicillin, amoxicillin
What type of penicillin is used for PSSP and syphilis?
Natural penicillins – pen G, pen VK
What are the four primary adverse reactions seen with the penicillins?
Neurotoxicity, hematologic toxicity, allergenicity, interstitial nephritis (nafcillin esp)
What gram-negative bacteria are covered by first-generation cephalosporins?
PEK = Proteus mirabilis, E. coli, K. pneumoniae
What gram-negative bacteria are covered by second-generation cephalosporins?
HENPEK = H. influenzae (BL-), Enterobacter (some), Neisseria, Proteus mirabilis, E. Coli, K. pneumoniae. M. catarrhalis
What is the “big hole” for cephalosporins?
Enterococcus – totally inactive
What is the anti-MRSA cephalosporin?
Ceftaroline
What cephalosporins cover pseudomonas?
Ceftazidime, cefoperazone, cefepime
What cephalosporins cover PRSP?
ceftriaxone, cefotaxime
What cephalosporin is active against KPC-producing bacteria?
Ceftazidime-avibactam
Which drug class demonstrates synergy when combined with a beta-lactam drug?
aminoglycosides
What cephalosporin has a much longer half life?
Ceftriaxone – 8 hours
What cephalosporins penetrate into the CSF?
cefuroxime, cefepime, 3rd generation (ceftazidime, ceftriaxone, cefpodoxime)
What is the only cephalosporin that does not cover pseudomonas?
ertapenem
What drug class demonstrate useful synergy with carbapenems when used for gram-negative aerobes?
aminoglycosides
What carbapenem best penetrates the CNS?
meropenem
What carbapenem has a longer half life and can be dosed once daily?
Ertapenem
What is the spectrum of activity for aztreonam?
Gram-negative aerobes only.
NO gram-positive or anaerobic coverage
Name some clinical roles for the carbapenems
Empiric therapy for hospital acquired infections, polymicrobial infections, SPICE/ESBL/AmpC bacteria, pseudomonas (except ertapenem)
Name the clinical role for aztreonam
Infections due to gram-negative aerobes, especially in penicillin-allergic patients.
What is the renal mechanism for penicillin excretion?
Tubular secretion
How does the side chain lipophilicity and degree of protein binding affect penicillin characteristics?
lipophilic side chain = Increased protein binding
less degradation, less bioavailability, same half life
Why is cephapirin unstable?
the acetyl group is hydrolyzed off, leaving a hydroxyl group that can react with the essential carbonyl group, resulting in an inactive ring version
What is the key group on cefazolin and what is its purpose?
the thio-linked thiodiazole is stable to hydrolysis so it does not inactivate the cephalosporin. However, it still forms a good leaving group so it is potent parenterally
What are the oral cephalosporins?
1st gen: cephalexin
2nd gen: cefuroxime, cefaclor
3rd gen: cefixime
What sets oral cephalosporins apart?
Unreactive side chains at C-3 (next to carboxyl group)
What role does a methoximino group plan on a cephalosporin?
Conveys resistance to hydrolysis via steric hindrance. However, only syn isomer is helpful.
What does the prime ether on C-7 do for a cephalosporin?
Enhances stability against beta-lactamase (steric hindrance)
How does an amine group off of C-7 help a cephalosporin?
The positive charge draws away electron density, making it more stable to acidic hydrolysis and potentially orally active (cephalexin/ceclor)
Important aspects of cefazolin
1st generation DOC for MSSA, surgical prophylaxis parenteral tho-linked thiadiazole is stable to hydrolysis, but still good leaving group that activates B-lactam ring strong inducer of AmpC
Important aspects of cephalexin
1st generation
orally active
methyl group on C-3 not chemically reactive
ampicillin-type amino side chain stabilizes it in acid
Strong inducer of AmpC
Important aspects of cefoxitin
2nd generation
parenteral
covers anaerobes - methoxy group off BL ring
Strong inducer of AmpC
Important aspects of cefotetan
2nd generation
covers anaerobes
NMTT side chain can cause hypoprothrombinemia and disulfiram reaction
Important aspects of cefuroxime
2nd generation
parenteral or oral (carbamate group more stable to acid, poor leaving group. prodrug available)
Oxime ether makes resistant to BL hydrolysis
penetrates the BBB
Important aspects of cefotaxime
3rd generation (not for SPICE) good activity against PRSP
Important aspects of ceftriaxone
3rd generation (not for SPICE) Good activity against PRSP No pseudomonas coverage Half life 8 hours, not adjusted for renal function
Important aspects of ceftazidime
3rd generation (not for SPICE)
Covers Pseudomonas
Parenteral
Oxime ether enhances stability vs BL enzymes
charged pyridinium group is good leaving group
Important aspects of cefoperazone
3rd generation (not for SPICE) Has MTT side chain -- disulfiram plus thrombocytopenia Does not need to be adjusted for renal function Covers pseudomonas
Important aspects of cefprozil
2nd generation
Important aspects of cefpodoxime
3rd generation (not for SPICE)
Important aspects of cefepime
4th generation
parenteral with good leaving group
Syn-methoxyimino makes stable vs BL, improves gram-negative activity
Covers pseudomonas and BL-producing enterobacter
What does SHEP stand for, and which drug class does it describe the spectrum for?
Shigella, salmonella, H. influenzae (BL-), E. Coli, Proteus
aminopenicillins
What does SHEP-MEPP stand for, and which drug class does it describe the spectrum for?
Shigella/salmonella, H. influenzae, E. coli, Proteus, Morganella, Enterobacter, Providencia, Pseudomonas
Carboxypenicillin – ticarcillin
What penicillin has the gram-negative spectrum SHEP-MEPP + KS?
Penicillin–covers serratia and klebsiella in addition to stuff covered by ticarcillin.
When do penicillins have a PAE?
for gram-positive bacteria
What are the primary clinical uses for the aminopenicillins?
Listeria, enterococcus
Which carbapenem shows best CSF penetration?
Meropenem
Could aztreonam be used for meningitis?
Yes, penetrates well
