Safety of aztreonam and SQ 26,992 in elderly patients with renal insufficiency

Abstract

Aztreonam is hydrolyzed (2%-7%) in vivo to a noncyclic compound, SQ 26,992, which has a serum half-life of 26 hr in healthy volunteers. In a study of whether SQ 26,992 accumulates to potentially toxic levels in patients with renal insufficiency, serum concentrations were measured daily in nine elderly patients (average age, 72 years) with diminished renal function and urinary tract infections. The dosage of aztreonam (1.5, 3.0, or 6.0 g per day) was selected according to the creatinine clearance rate (5-49 ml/min) and the severity of infection. Trough levels of aztreonam for eight patients averaged 34.2 micrograms/ml before the third or fourth dose and 32.7 micrograms/ml on the fifth day of therapy (P = .77). Trough levels of SQ 26,992 at the same times averaged 3.2 and 9.1 micrograms/ml, respectively (P = .04). In the one patient who was undergoing hemodialysis, trough levels of aztreonam averaged 55 micrograms/ml for seven days, and trough levels of SQ 26,992 increased progressively from 2.6 to 38.2 micrograms/ml. For all nine patients, the ratio of the SQ 26,992 concentration on day 5 to that on day 1 was inversely related to the creatinine clearance rate (r = -.89). No adverse clinical reactions or laboratory test abnormalities were detected during therapy. Thus, aztreonam should prove to be safe in elderly patients with diminished renal function.