Cephalosporins

Question 1

What are the 6 different cephalosporin drugs?

Answer 1

cephalexin (vetolexin paste, cefaseptin tablet)

cefltiofur

• excenel (sodium salt)
• excenel RTU (HCl)
• exceed (crystalline free acid)
• spectramast (intramammary)

Cefovecin (convenia injectable solution)

Cefpodoximine (simplicef tablets)

Cephapirin

• cefa-lak (sodium)
• cefa-dry, metricure (benzathine)

Cefazolin - IV
- evidence with perioperative at surgery

Question 2

What is the MOA of cephalosporins?

Answer 2

b-lactam drug so same as penicillin
act by disrupting synthesis of bacterial cell wall
inhibit the PBP
interferes with cell wall peptidoglycan synthesis

Question 3

what are the advantages of cephalosporins?

Answer 3

stable against soem b-lactamase enzymes
good affinity for PBPs
good ability to penetrate cell wall (gram - included)

Question 4

What is the cause of the emergence of resistance with cephalosporins?

Answer 4

different B-lactamase enzymes

• extended spectrum B- lactamase enzymes (ESBL)
• ampC cephalosporinases
• metallo B-lactamase enzymes

modify the PBPs (mecA, others)

reduce cellular concentrations

• decrease wall permeability
• efflux pums

Question 5

What is the cephalosporin spectrum of activity?

Answer 5

Gram +
- strep
- staph aureus, pseudointermedius
- many others
Gram -
- enterobacteriaciae (e.coli, salmonella, klebsiella, histophilus, mannheimia, pasturella)
most anaerobes

Question 6

Where is cephalosporin resistance seen?

Answer 6

Gram +
- MRS (altered PBP)
- enterococcus
Gram -
- many enteric pathogens with EXBL activity
- rhodococcus equi
- pseudomonas
- mucobacteria
anaerobes
 (except cefoxitin)`

Question 7

What is the absorption PK of cephalosporins?

Answer 7

oral = generally good
- simplicef: sefpodoxime proxetil –> prodrug (can interact with GI) GIVE WITH FOOD

parenteral

• cefazolin (most rapid)
• excenel (very rapid)
• excenel RFU (slower
• exceed (very slow, long acting)

Question 8

What is the distribution of cephalosporins?

Answer 8

low Vd
- metabolism for some
ceftifur --> less active metabolite
cephapirin --> liver
- intramammary will stay there

Question 9

Where are cephalosporins eliminated?

Answer 9

renal elimination

- glomerular + tubular

Question 10

What cephalosporins are extremely protein bound and what is their half life?

Answer 10

cefpodoxime (5-6h dogs) and cefovecin (5.5-6.9d SC) (95% PB)

• causes decrease clearance in kidney
• 1 dose every 2w
• dangerous

Ceftiofur

• sodium (2-3h cattle)
• HCl (20h pigs)
• exceed - crystaline free acid (40+ cattle, 50 pigs)

excenel RTU - swine
excede 200 (injection in ear - no condemnation)

Question 11

What are cephalosporin AE?

Answer 11

mostly same as penicillin

• hypersensitivity
• GI
• nephrotoxicity
• coagulopathies/blood dyscrasias (rare)

Question 12

What regulations have been put in place with cephalosporins due to concerns about AMR?

Answer 12

FDA banned extralabel use in food animal (punishable by vet board)

• cant alter dose, route, frequency, or duration
• can use in minor species (sheep, goat)
• can use for diff indications (septicemia)
• cant use IV
• cant use for prevention

Question 13

What are risk factors that could cause vancomycin resistant enterococci?

Answer 13

prolonged hospital stays, exposure to intensive care, transplants, hemtaologic malignancies, eposure to antibiotics
- cephalosporins can predispose