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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 than ceftazidime

 

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