Monobactams

MONOBACTAMS

Another interesting group of compounds produced by several bacterial genera are the monocyclic β-lactams (monobactams). The natural monobactams have little antimicrobial activity. A synthetic derivative, aztreonam (Azactam), has excellent activity against gram-negative organisms, including P. aeruginosa. Aztreonam has low affinity for penicillin-binding proteins in streptococci, staphylococci, and anaerobes and therefore has no sig-nificant activity against gram-positive bacteria or anaer-obes. Specific activity against gram-negative organisms relates to the aminothiazolyl oxime moiety on the acyl side chain. Addition of two methyl groups and a car-boxylic acid group on the oxime side chain enhances ac-tivity against P. aeruginosa. Aztreonam is stable to most β-lactamases (chromosomal and plasmid).

The pharmacokinetic properties of aztreonam are similar to those of the parenteral cephalosporins (Table 45.2). Aztreonam is not bioavailable after oral adminis-tration. During its distribution phase, the drug can achieve therapeutic concentrations in cerebrospinal fluid in the presence of inflamed meninges. Conse-quently, aztreonam is an alternative antibiotic to the cephalosporins for the therapy of meningitis caused by gram-negative bacilli.

Aztreonam may be used as a substitute for an aminoglycoside in the treatment of infections caused by susceptible gram-negative organisms. Most of the ad-verse effects of aztreonam are local reactions at the site of injection. Interestingly, aztreonam rarely causes al-lergic reactions in patients with a history of type I hy-persensitivity to other β-lactam antibiotics.