6b - Cephalosporins Flashcards
Cephalosporins
- Part of beta-lactam family and still have side chains
- Spelling: old ones “ph”, new ones “f”
- Various generations
o Early=older ones are more NARROW SPECTRUM or can’t administer by certain routes of administration
What are the need to know cephalosporins in Vet med?
- Cephalexin
- Ceftiofur
- Cefovecin (Convenia injectable solution)
- Cefpodoxime (Simplicef tablets)
- Cephapirin (dry and lacting cows)
- *Cefazolin (NOT A VET PRODUCT)
Cephalexin
- Only ORAL products
- Indicated for canine superficial pyoderma caused by susceptible strains of S. pseudointermedius
Ceftiofur
- 3 salt forms
o Sodium (Excenel): cattle, horses, pigs, sheep and dogs (not labeled for IV, but can go IV), SHORT TERM
o HCl: milky, long acting, once a day, cattle and pigs
o Excede: crystalline free acid, very LONG acting, slow release, cattle, horses, pigs
Convenia for dogs
- *injectable, long acting
o Not first choice for routine infections
o Works well when poor owner compliance - Skin infections
- Urinary tract infections
Convenia for cats
- *injectable, long acting
- infections
Cefazolin
- Human sterile injectable formulation
- Once mixed: refrigerate, but still don’t last long (use within 24hrs)
- *used perioperatively and IV in clinic
o Need to give it at the RIGHT time=use it immediately before you cut
o Want effective plasma concentrations when you are actually doing the surgery (NOT long acting ones)
o Only use for as long as you need (short=1 dose is likely fine)
Antimicrobials (potassium Pen G and cefazolin) and orthopedic surgery
- Saline: slightly higher risk of infection
- Slightly lower in antimicrobial group
o Didn’t make a difference between potassium Pen G vs. cefazolin
Compounded Ceftiofur sodium biobullets
- Big deal in US and Canada (BANED BY FDA in US)
- *BULLSHIT
o Shooting animals (NOT good animal welfare): if sick enough you could probably get them
o Dosing: 500mg for a cow=shooting it 5 times (100mg)
o PK? No one knows, depends where they got shot and the power of the gun, injection site lesions and drug residues?
Cephalosporins: mechanism of action (same as penicillin)
- Act by disrupting synthesis of bacterial cell wall
- Inhibit the penicillin-binding proteins (‘beta-lactam binding proteins’)
- Interferes with cell wall peptidoglycan synthesis
What are the general advantages of cephalosporins over some penicillins?
- Stable against SOME beta-lactamase enzymes
- Good affinity for target proteins
- Good ability to penetrate bacterial cell wall: including Gram +
Emergence of resistance to cephalosporins
- Different beta-lactamase enzymes
o Extended-spectrum beta-lactamase enzymes (ESBL)
o AmpC cephalosporinases
o Metallo-beta-lactamase enzymes - EXAM:Modify by PBPs (mecA gene, others): methicillin resistant
- Reduce cellular concentrations
o Decrease bacterial cell wall permeability
o Induction of efflux pumps
What are the bacteria typically susceptible to cephalosporins?
- Gram +
o Strep
o Stap. Aureus and pseudintermedius
o Many gram + (does NOT mean it is more susceptible than penicillins) - Gram –
o Many enterbacteriaciae (Histophilius, Mannheimia, Pasteurella) - Most anaerobes
What are the bacteria typically RESISTANT to cephalosporins?
- Gram +
o Methicillin resistant
o **enterococcus: INTRINSICALLY resistant to cephalosporins - Gram –
o Many enteric pathogens with ESBL activity
o R. equi
o Pseudomonas
o Mycobacteria - Anaerobes (except cefoxitin)
Cephalosporins: PK oral absorption
- generally good
- Ex. Simplicef: Cefpodoxime proxetil=prodrug
o De-esterified in GI tract
o Cefpodoxime absorbed - give cephalexin with food: minimize adverse events and slightly better bioavailability
Cefazolin: PK parenteral absorption
- Extremely rapid
- Can go IV
Ceftiofur sodium (Excenel): PK parenteral absorption
- Very rapid
- Can go IV (but only labeled for IM/SC)
Ceftiofur HCl (Excenel RTU EZ (ready to use, and easy)): PK parenteral absorption
- Slower
Ceftiofur crystalline free acid (Excede): PK parenteral absorption
- Very slow
- Long-acting formulation
- *base of ear (cut off when go into food chain and prolonged absorption)
Cephalosporin: PK distribution
- Low volume of distribution
Which cephalosporins undergo metabolism?
- Ceftiofur
- Cephapirin
- *doesn’t change our use of it, the metabolites are pretty much as effective
Cephalosporin PK elimination
- Renal elimination
o Glomerular filtration + tubular secretion
Cephalosporin: half life
- Short (1-2 hrs)
Cefpodoxime and cefovecin PK exceptions with half life
- *extremely protein bound
- Cefpodoxime: 5-6hrs in dogs, once a day dosing
- Cefovecin (convenia): 5.5-6.9 days after SC administration
o Protein bound: Decreased clearance and not having antimicrobial activity
o Result=one dose every 2 weeks
o Above MIC for 5 days, but just some hanging around=antimicrobial resistance, NOT good for long term
Ceftiofur half life varies by formulation
- Ceftiofur sodium (excenel): 2-3h in cattle
- Ceftiofur HCl (excenel RTU): 20h in pigs
- Ceftiofur crystalline free acid (exceed): 40+ in cattle, 50h in pigs
Excede 200 injection site in cattle
- Dorsal posterior aspect of the ear
- *Just administer at base of ear: less likely to get in auricle artery
Cephalosporins AE
- Hypersensitivity
- GI upset
- Nephrotoxicity (very unlikely)
- Coagulopathies/blood dyscrasias (rare)
Cephalosporin hypersensitivity
- Not as likely penicillin? (not sure if trust that)
- Lower cross-reactivity between cephalosporins and penicillins
- *higher cross-reactivity between older cephalosporins with aminopenicillins (SIMILAR side R chains)
Cephalosporin GI upset
- Vomit: especially cephalexin
- diarrhea
- Loss of normal GI flora can lead to bacterial overgrowth (Ex. difficile)
Cephalosporin coagulopathies/blood dyscrasias
- Ceftiofur: thrombocytopenia
- Cephalexin: IMT
- *rare, should go away once drug is stopped
Cephalosporins and concerns about AMR: FDA rules
- Can NOT use in an extra-label manor
o Can’t alter dose, route, frequency or duration - Can use extra-label in MINOR species (sheep, goats, alpacas, etc.)
- Can use different indication (ex. respiratory disease)
o But cannot use for PREVENTION
What are extra-label use of cephalosporins that are prohibited? (chickens + cattle, USA)
- Ovo chicken injections
- Use of bio-bullets in cattle
- *can’t ban extra-label use in Canada
Vancomycin-resistant enterococci (VRE)
- **risk for patients that receive cephalosporins=more likely to get an enterococcus infection
- *risk for vancomycin-resistance to occur
o Very tough to get rid of enterococci
