Cephalosporins

Cephalosporins can be classified into four generations depending mainly on the spectrum of antimicrobial activity. First-generation compounds have better activity against gram-positive organisms and the later compounds exhibit improved activity against gram-negative aerobic organisms.

First-generation cephalosporins

Members: Cefadroxil, cefazolin, cephalexin, and cephalothin. These drugs are very active against gram-positive cocci (pneumococci, streptococci, and staphylococci). Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis are often sensitive, but activity against Pseudomonas aeruginosa, indole-positive Proteus, Enterobacter, Serratia marcescens, Citrobacter, and Acinetobacter is poor. Anaerobic cocci (eg, Peptococcus, Peptostreptococcus) are usually sensitive, but B fragilis is not.

Cephalexin, and cefadroxil are absorbed from the gut to a variable extent. Urine concentration is usually very high, but in most tissues levels are and generally lower than in serum. Cefazolin is given IM/IV (the only first generation administered parentrally).   Excretion is via the kidney and probenecid may increase serum levels substantially.

Clinical Uses: Oral drugs may be used for the treatment of urinary tract infections, for minor staphylococcal lesions, or for minor polymicrobial infections such as cellulitis or soft tissue abscess.

Second-generation cephalosporins

Members: Cefaclor, cefamandole, and cefuroxime. The group is heterogeneous, with marked individual differences in activity, pharmacokinetics, and toxicity. All second-generation cephalosporins are less active against gram-positive bacteria than the first-generation drugs; however, they have an extended gram-negative coverage. Klebsiella and H influenzae are usually sensitive. Can be given orally or parentrally

Clinical Uses: Sinusitis, otitis, or lower respiratory tract infections, mixed anaerobic infections, and community-acquired pneumonia.

Third-generation cephalosporins

Members: cefotaxime, ceftazidime, ceftriaxone, and proxetil.

Antimicrobial activity: The major features of these drugs are the ability of some to cross the blood-brain barrier and their expanded gram-negative coverage (active against Citrobacter, Serratia marcescens, Providencia, and beta-lactamase-producing strains of Haemophilus and Neisseria). Ceftazidime is effective in pseudomonas infections.

They can be given orally or IM or IV. They penetrate body fluids and tissues well. Cefotaxime, ceftazidim, and ceftriaxone crosses blood brain barrier, hence inhibit most pathogens, including gram-negative rods.

Clinical uses: Gonorrhea (ceftriaxone and cefixime), meningitis (pneumococci, meningococci, H influenzae, and susceptible enteric gram-negative rods), penicillin-resistant strains of pneumococci (ceftriaxone, cefotaxime), and sepsis

Fourth-generation cephalosporins (e.g.cefepime)

It is similar to third-generation agents; however, it is more resistant to hydrolysis by beta- lactamases. It has good activity against P aeruginosa.

Adverse Effects: Cephalosporins are sensitizing and may elicit a variety of hypersensitivity reactions that are identical to those of penicillins. Overgrowth of resistant organisms and fungi may induce superinfection.

Monobactams contain a monocyclic beta-lactam ring(e.g. aztreonam). They are relatively resistant to beta-lactamases and active against gram-negative rods. It resembles aminoglycosides in its spectrum of activity.

Carbapenems include imipenem and meropenem and have a broad spectrum of activity (against most Gram-positive and negative bacteria). Imipenem is inactivated by a renal proteolytic enzyme and must therefore be combined with cilastatin which inhibits the enzyme.

Beta-lactamase inhibitors: (clavulanic acid, sulbactam, and tazobactam).

They have no antimicrobial activity, and usually combined with beta lactamase labile antibiotics, irreversibly inhibit beta-lactamases. Examples: Ticarcillin and clavulanate [Timentin], Ampicillin and sulbactam [Unasyn], Amoxicillin and clavulanate [Augmentin]