Since cephalosporin C is only one-thousandth as active as benzylpenicillin, its use is
very limited. However, it is remarkably resistant to enzymatic hydrolysis and becomes
highly concentrated in the urine, which makes it useful in urinary tract infections
caused by Gram-negative organisms.
Among the semisynthetic derivatives, cephalothin (9.47) is the most widely used
since it is a broad-spectrum antibiotic resistant to lactamase. Its main drawback is that
it must be injected. Cefazolin (9.48) and cephaloridine (9.49) are metabolized to a
lesser extent; cephalexin (9.50, analogs to ampicillin) is orally active and has a much
higher acid stability than the penicillins. Cefotaxime (9.51) and moxalactam (9.52) are
highly active against meningitis.
9.4.1.3 Other β-Lactam Antibiotics
Otherβ-lactam antibiotics have revolutionized our understanding of the structure–activity
relationships in this large group of antibiotics. Thienamycin (9.53), discovered in 1976,
is a broad-spectrum antibiotic of high activity. It is lactamase resistant because of its
hydroxyethyl side chain but is not absorbed orally as it is highly polar. Unfortunately,
568 MEDICINAL CHEMISTRY