Cefixime

Cefixime is the first available orally administered third-generation cephalosporin, with approved indications for usage in adults and in children 6 months of age or older for treatment of otitis media, uncomplicated urinary tract infection, pharyngitis, and bronchitis. The drug has broad activity against a variety of bacterial pathogens and is resistant to beta-lactamases that inactivate many currently available oral antibiotics. A favorable pharmacokinetic profile enables administration once to twice daily, and stability at room temperature permits convenient storage.

CHEMICAL PROPERTIES

Cephalosporins are beta-lactam antibiotics derived semisynthetically from cephalosporin C, which is produced by the fungus Cephahsporium acremonium. Cephalosporins are structurally and pharmacologically related to penicillins. Generally, substitutions at position 7 of the cephem nucleus alter antibacterial activity, and modifications at position 3 change pharmacokinetic properties of the drug. Like many other third-generation cephalosporins, Cefixime contains a beta-2-aminothiazolyl acetamide side chain at the 7 position that contributes to its broad spectrum of activity and stability to beta-lactamases. A vinyl group in the 3 position of the cephem nucleus, unique among oral cephalosporins, contributes to the improved oral absorption.1,2

ANTIBACTERIAL ACTIVITY

Like other cephalosporins, Cefixime appears to inhibit mucopeptide synthesis in the cell wall of bacteria by binding to target enzymes known as penicillin-binding proteins (PBP). It has high affinity for PBP-3, the major binding site for cephems, and for the PBP- 16, which is the killing target for betalactams. Cefixime is stable to the common plasmidmediated beta-lactamases and is not hydrolyzed (degraded) by most chromosomal beta-lactams.1'5 Compared with amoxicillin and other available oral beta-lactam antibiotics Table 1), it has superior activity against Hemophilus influenzae and Moraxella catarrhalis, and similar or slightly better activity compared with eiythromycin'Sulfasoxazole and trimethoprim-sulfamethoxazole. Cefixime has equivalent to inferior activity against viridans streptococci, inferior activity against Streptococcus pneumoniae, and no activity against Staphylococcus aureus and Staphylo' coccus epidermidis. Listeria monocytogenes and Enterococcus species are resistant to Cefixime, as they are to other cephalosporins, because of the inability of these agents to bind to their PBPs.

Cefixime has excellent activity against many gramnegative bacteria including Escherichia coU, Klebsiella species, Proteus species, Citrobacter diversus, and some Providencia, Salmonella, and Shigella species. Pseudomonas and Acinetobacter species are not inhibited by Cefixime because of the inability of the drug to penetrate their outer cell membrane. Enterobacter...