Cephalosporins
|
Cephalosporins
- Beta
lactam antibiotics; possess beta-lactam ring and dihydrothiazine ring
in their nucleus (6 - ACA; 6 amino-cephalosporanic acid)
- Classified as first, second and third generation agents
|
Antibacterial
Activity
- Bactericidal
- Act by inhibition of bacterial cell wall synthesis
|
A Guide
to Antibacterial Activity of Cephalosporins
|
Gm
+ve bacteria
|
Gm
-ve bacteria
|
1st
Generation
|
+++
|
+
|
2nd
Generation
|
++
|
++
|
3rd
Generation
|
+
|
+++
|
|
Cephalosporins
First
Generation
|
Second
Generation
|
Third
Generation |
Cephalexin
(o)
Cefazolin (p)
Cefadroxil (o)
|
Cefuroxime
(o/p)
Cefaclor (o)
Cefoxitin (p)
|
Cefotaxime
(p)
Ceftriaxone (p)
Ceftazidime (p)
Cefoperazone (p)
Ceftizoxime (p)
Cefixime (o) |
o = Oral, p =
Parenteral
|
First Generation
Cephalosporins
eg., cephalexin, cefadroxil, cefazolin
- Oral first
generation agents are widely used
- Chiefly useful in gram + ve infections and common gram -ve infections
eg., caused by E. coli, Klebsiella and Proteus
- May cover staphylococci, but not be stable against all beta-lactamases
- Well tolerated
- Useful in RTI, UTI and perioperatively
- Cefazolin is an agent of choice in surgical prophylaxis
|
Second
Generation Cephalosporins
eg., cefuroxime, cefaclor, cefoxitin
- Greater coverage
of gram negative bacteria than first generation drugs
- Cefuroxime / cefuroxime axetil available for parenteral and oral
use respectively
|
Third
Generation Cephalosporins
- Reputed for efficacy
- Administered parenterally (except cefixime)
- Generally expensive
- May be appropriate for hospitalised patients, severe infections
- Ceftazidime, cefoprazone are effective against Ps. aeruginosa. Cefotaxime
may also have some coverage
|
Notable Features
of Key Cephalosporins
Cephalexin
: Widely
used oral cephalosporin; covers gram +ve and gram -ve bacteria; q.d.s.
administration
Cefadroxil
: Similar activity to cephalexin but superior absorption and
higher AUC; b.d. administration orally
Cefazolin :
Parenteral 1st generation cephalosporin
Cefoxitin
: Cephalosporin with anaerobicidal activity
Cefaclor :
Oral cephalosporin
with greater efficacy against H. influenzae than cephalexin & cefadroxil
|
Notable
features of key cephalosporins (Contd…)
Cefuroxime
: For parenteral administration and available as cefuroxime
axetil for oral use
Cefotaxime
: Most widely used third generation cephalosporin administered
4 - 6 hourly
Ceftriaxone
: Similar coverage to cefotaxime, but administered once daily
Ceftazidime
: Highest activity amongst cephalosporins against Ps. aeruginosa
Cefoperazone
: Covers Ps. aeruginosa, but less thanceftazidime
|
Beta
Lactamase Stability
- Cephalosporins
possess some beta-lactamase stability- Useful against beta-lactamase
producers
|
Pharmacokinetics
- Cephalexin,
cefadroxil, cefaclor, cefixime are oral cephalosporins; others are
administered parenterally
- IV route may be preferred because IM route is painful Renal excretion
plays a major role in elimination
- Cefotaxime is partly metabolised in the liver
|
Tolerability
- Currently
available cephalosporins are generally well tolerated
- IM injections are painful, thrombophlebitis may occur with IV injection
- Allergy
- Contraindication : hypersensitivity
|
Dosage
and Administration
Cephalexin
|
250
- 500 mg
|
6
hourly
|
oral
|
Cefadroxil
|
500
- 1000 mg
|
12
hourly
|
oral
|
Cefazolin
|
0.5
- 2 g
|
8
hourly
|
IM
/ IV
|
Cefuroxime
|
0.75
- 1.5 g
|
8
hourly
|
IV
|
Cefuroxime
axetil
|
250
mg
|
12
hourly
|
oral
|
Cefoxitin
|
1
- 2 g
|
4
- 8 hourly
|
IM
/ IV
|
Cefaclor
|
250
- 500 mg
|
8
hourly
|
oral
|
Cefotaxime
|
1
- 2 g
|
4
- 6 hourly
|
IM
/ IV
|
Ceftriaxone
|
1
- 2 g
|
12
- 24 hourly
|
IM
/ IV
|
Ceftazidime
|
1
- 2 g
|
8
hourly
|
IV
|
Cefoperazone
|
1
- 2 g
|
12
hourly
|
IV
|
Ceftizoxime
|
1
- 2 g
|
6
- 8 hourly
|
IV
|
|
Place
of Cephalosporins in Therapy
- Generally
expensive; should not be used where cheaper alternatives are available
- Beta-lactamase stability; hence may be effective against organisms
resistant to penicillins
- First generation cephalosporins have good activity against gram
positive bacteria and moderate activity against gram negative bacteria
- Gram negative activity increases from first to second to third generation
- Cephalosporins are not the drugs of choice for enterococci (Strep.
faecalis) and anaerobes
- Cefotaxime, ceftriaxone, ceftazidime and ceftizoxime are useful
in gram negative bacillary meningitis other cephalosporins have poor
CNS penetration
|
|