Cephalosporins

Cephalosporins

Similar to Penicillins:

- Chemically.

- Mechanism of action.

- Toxicity.

Cephalosporins are divided into Generations:

·        First generation have better activity against gram positive organisms.

·        Later compounds has improved activity against gram negative anaerobic organisms.

1-First Generation Cephalosporins:

·        Cefadroxil     (Duricef)

·        Cefazolin

·        Cephalexin   (Keflex)

·        Cephalothin (Keflin)

·        Cephradine  (Velosef)

Very active against gram positive:

     Pneumococci

     Streptococci

     Staphylococci

Not active against MRSA

(Methicillin Resistant Staphylococcus Aureus)

Proteus, E.coli and Klebsiella are sensitive.

Pharmacokinetics and dosage:

·        Oral

Cephalexin, Cephradine, Cefadroxil

Cephalexin is given orally 500 mg four times daily

Cefadroxil twice daily

Glomerular filtration and tubular secretion

Dosage reduced in renal impairment

·        Parenteral:

Cefazolin is used 500- 1000 mg 8 hourly IV.

Clinical uses:

Rarely drug of choice

- UTI

- Cellulitis

- Soft tissue infection

Not relied upon in serious systemic infection

2- Second generation cephalosporins:

·        Cefaclor            (Ceclor)

·        Cefamandole   (Mandol)

·        Cefuroxime      (Zinacef, Zinnat)

·        Cefprozil

Active against organisms affected by first generation = extended gram negative coverage

Klebsiella and H.influenzae are usually sensitive.

Second generation are less active on gram positive than first generation

None are active against Pseudomonas aeruginosa.

Pharmacokinetics and dosage:

Oral

- Cefaclor

- Cefuroxime axetil

- Cefprozil.

Except Cefuroxime axetil these drugs are not predictably active against penicillin resistant pneumococci

Used cautiously to treat pneumococcal infection

Dose adjustment is important in renal failure

Clinical uses:

     - Sinusitis

     - Otitis media

     - Lower respiratory tract infection

Cefuroxime is used in community acquired pneumonia.

Beta lactamase producing H.influenzae

Klebsiella are usually sensitive.

3- Third generation cephalosporins:

·        Cefotaxime.       (Claforan)

·        Ceftazidime.  

·        Ceftriaxone.       (Rocephin)

·        Cefixime.            (Suprax)

Expanded gram negative coverage ability of some to cross Blood Brain Barrier and some are active against Pseudomonas aeruginosa.

Pharmacokinetics and dosage:

Ceftriaxone Half Life = 7- 8 hours and can be injected once every 24 hours.

A single daily dose is useful for any infection

4 grams daily dosage can be used to treat meningitis

Cefixime (Suprax) can be given orally 200 mg 400 mg once daily

 Suprax

Ceftriaxone is excreted by the bile

And no dose adjustment is required in renal failure.

Clinical Uses:

Wide variety of serious infections

Ceftriaxone and Cefixime are drug of choice in gonorrhea.

Single dose.

Commonly misused to treat trivial infection

Can be used to treat meningitis

Penicillin resistant pneumococci

Sepsis of unknown cause

Neutropenic febrile immune-compromised patients

Used in combination with aminoglycoside

4- Fourth generation cephalosporins:

·        Cefepime   

More resistant to beta-lactamase

Good activity against

        Pseudomonas aeruginosa

        Staph aureus

        Streptococcus pneumonia

Adverse effects:

1-Allergic reactions:

      -Hypersensitivity reactions similar to penicillins

      -Anaphylaxis

      -Fever

      -Skin rashes

      -Hemolytic anemia

Cross allergy is 5-10 %

Others adverse reactions including:

  - Local irritation.

  - Pain after IM injection.

  - Thromophlebitis after IV injection.

  - Nausea and vomiting after rapid IV injection.

  - Interstitial nephritis. 

  - Super infection of resistant microorganisms can occur.