Cephalosporin
Derivatives of 7-aminocephalosporanic acid
With 2 sites of attachment for various R1 and R2 groups
More stable to many bacterial β–lactamases, has broader spectrum of activity
Giuseppe Brotzu
Isolated Cephalosporin C compound in from the fungus Acremonium, previously known as "Cephalosporium” in 1945.
Found in the sea near a sewage outfall in Su Siccu, by Cagliari harbour in Sardinia, Italy
R group at 7-position
alters antibacterial activity
R group at 3-position
modifies pharmacokinetic profile
whether they can traverse the blood-brain barrier or not
hydrophobic or hydrophilic
biliary or urinary
Cephalexin
Cefazolin
Cefadroxil
Cephalotin
Cephradine
Cephapirin
First generation
Cefuroxime
Cefoxitin
Cefotetan
Cefamandole
Second generation
Ceftriaxone
Cefotaxime
Cefoperazone
Ceftazidime
Cefixime
Third generation
Cefepime
Fourth generation
Ceftaroline
Ceftolozane
Fifth generation
Bind to PBPs
inhibit cell wall synthesis, similar to penicillins
Structural differences
___ render them less susceptible to penicillinases produced by staphylococci
MRSA
resistant to cephalosporins
Most are parenteral
administered or occurring elsewhere in the body than the mouth and alimentary canal.
renal excretion
Major elimination
hepatic metabolism
some with side chains
Cefoperazone and ceftriaxone
excreted in the bile
1st- and 2nd-generation
Do not enter the CSF when the meninges are inflamed1st- and 2nd-generation
1st Gen: Cefazolin and cephalexin
against G+ cocci, E coli, K pneumoniae
Surgical prophylaxis
Minimal activity (Gram (-) cocci, Enterococci. MRSA, Most gram (-) rods)
Second Generation
Less activity against gram (+)
Extended coverage for gram (-)
Marked differences in activity occur among the drug
Cefotetan, Cefoxitin
Anaerobic coverage
B. fragilis
Cefamandole, cefuroxime, cefaclor
H influenzae, M catarrhalis
Ceftazidime, cefoperazone, cefotaxime
penetrates BBB except cefoperazone, cefotaxime
Increased activity against gram (-) organisms resistant to other beta-lactam drugs
Ability to penetrate the blood-brain barrier
Ceftriaxone
gonococcal urethritis - purulent discharge
Single injection for acute otitis media
As effective as 10 days of amoxicillin
Ceftriaxone (IV) and cefixime
Drug of choice for gonorrhea
Cefepime
more resistant to beta lactamases
combines gram positive activity / coverage of 1st gen with wider gram neg
Ceftaroline
active against MRSA that is resistant to Cephalosporins
rashes to anaphylactic shock
Allergy
Complete cross reactivity should be assumed
less frequently than penicillins
5-10%
Partial cross reactivity between penicillin and cephalosporin
Pain at IM injection site
Phlebitis after IV injection
Increase nephrotoxicity of aminoglycosides
Other adverse effects
Cefamandole, cefoperazone, cefotetan
Drugs containing a methylthiotetrazole group
May cause hypoprothrombinemia
Disulfiram-like reactions with ethanol
Listeria
Atypicals
Methicillin-resistant staphylococcus aureus (MRSA)- except Ceftaroline
Enterococcus
Cephalosporins are “LAME” because they are inactive against
Cephalexin
effective against pharyngitis (above umbilicus infections) which (back then) were mostly gram-positive
cell wall will be thicker for gram-positive
gram-negative are resistant with beta lactams
Cefazolin
parenteral route (IV)
longer duration of action, but similar spectrum
Cefuroxime
given parenterally
longer half life
it can cross blood brain barrier
used for community-acquired bronchitis & pneumonia
Cefuroxime axetil
twice daily
quite resistant even against to beta-lactamase-producing organism
Ceftriaxone
effective against genital, anal and pharyngeal penicillin-resistant neisseria gonorrhoeae
excreted through the bile
Ceftazidine
anti-pseudomonal coverage
Pseudomonas are hospital-acquired germ with numerous resistance
Cefotaxime
good choice for infections (bacterial encephalitis & bacterial meningitis)
Cefepime
anti-pseudomonal property
interstitial nephritis and tubular necrosis
if combined with aminoglycoside (protein synthesis inhibitor
cephalosporin don’t go along well w/ aminoglycoside
Renal
Hypoprothrombinemia and bleeding disorders
Hematologic