Cell Wall Synthesis Inhibitors: 2

Cephalosporins

Advantages: The greatest advantage of the cephalosporins are their relative resistance to staphylococcal penicillinase and somewhat broad antibacterial spectrum which includes P. mirabilis, E. coli, and Klebsiella (drugs of choice for Klebsiella).

MOA: Same as penicillins.

Characteristics: 1st generation do not penetrate CSF; 2nd-4th generation penetrate CSF; as you advance thru the generation you gain G(-) coverage and lose G(+) coverage.

First-generation cephalosporins: Higher nephrotoxicity than subsequent generations.

1. Cephalothin – Parenteral; agent of choice to treat staph infection (endocarditis)

2. Cefazolin – Parenteral; effective against E. coli and Klebsiella; surgical prophylaxis.

3. Cephalexin – Oral; acid-stable and well-absorbed.

4. Cefadroxil – Oral; UTIs.

Second-generation cephalosporins

1. Cefaclor – Oral; used for sinusitis and otitis media if allergic to amoxicillin.

2. Cefamandole – Parenteral; good G(+), G(-), and anaerobic coverage; adverse effect on vitamin-K dependent clotting.

3. Cefoxitin – Parenteral; good for anaerobes and mixed infections.

4. Cefuroxime – Parenteral; passes thru BBB and useful in treatment of meningitis.

Third-generation cephalosporins

1. Cefixime – Oral.

2. Cefoperazone & Moxolactam – Adverse effect on vitamin-K dependent clotting; “don’t use this one.”

3. Cefotaxime – Parenteral; good for multiple drug-resistant G(-) bacilli nosocomial infections.

Fourth-generation cephalosporins: Cefepime – Parenteral; excellent CSF penetration; active against G(+,-).

Adverse effects: Nephrotoxicity (1st generation); bleeding problems (2nd and 3rd generation) due to methylthiotetrazole; disulfiram-like reaction. Superinfection may also be a problem with broad-spectrum (3rd generation) cephs.

Hypersensitivity: Cephalosporins may demonstrate cross-allergenicity with the penicillins.

Summary: Cephalothin & cephaloridine (1st generation) are good against endocarditis but nephrotoxic. Cefamandole (2nd) and moxolactam and cefoperazone (3rd) have bleeding problems due to methylthiotetrazole side group.

Category: Pharmacology Notes