Aztreonam: clinical pharmacology

Abstract

Monocyclic beta-lactam antibiotics (monobactams) are structurally unique from the traditional bicyclic beta-lactams because of their single ring configuration. Aztreonam, the first of these monobactams, has been studied extensively in order to determine its pharmacologic and pharmacokinetic profile in adults and children with bacterial infections. It has been established, for example, that with intramuscular or intravenous dosing (30 to 50 mg/kg in children and 1 to 2 g in adults), serum concentrations above the minimum inhibitory concentrations of most aerobic Gram-negative bacteria can be maintained for up to 8 hours. Against a less susceptible pathogen such as Pseudomonas aeruginosa, every-6-hour dosing allows for preservation of the bactericidal effect, although longer intervals may be practical in low birth weight infants. The drug is primarily (80%) excreted by renal mechanisms and serum clearance varies with postnatal age. Distribution into body fluids is similar to that of other beta-lactams. For example in the presence of meningeal inflammation, cerebrospinal fluid concentrations are 17 to 33% of serum values. Urinary concentrations are high and prolonged with greater than 80% appearing as the active drug. Preliminary data from cystic fibrosis patients suggest that there are very minor pharmacokinetic differences in this population. The pharmacologic profile indicates that aztreonam may provide an appropriate alternative to traditional therapy for serious Gram-negative aerobic infections in infants and children.