Aztreonam Activity in Pneumology. Part 1: Clinical activity and pulmonary bioavailability of two different administration regimens

Abstract

Twenty-three patients suffering from lower respiratory tract infections caused by Gram-negative germs were treated with aztreonam (AZT) administered according to two different regimens: 17 subjects (Group A) with 2 g i.v. every 12 h and 6 patients (Group B) with 4 g in 100 ml of saline every 24 hours. Group A included 8 cases of superinfected bronchiectasis, 8 purulent bronchitis and 1 gangrene caused by Gram-negative and anaerobic agents. Group B comprised 6 patients with severe bronchiectasis infection. Pseudomonas aeruginosa was isolated from the sputum in 10/23 cases. The treatment was performed for 10 days on the average. The local and systemic tolerability was good. Group B, with higher antibiotic sputum concentrations for at least 12 hours, attained a better response than Group A: with clinical cure in 100% vs 76% cured plus 18% improved patients; therapy lasted 9.5 days for Group B vs 10.8 days for Group A. Moreover, in 14 subjects affected by pulmonary interstitial diseases who underwent diagnostic broncho-alveolar lavage, we dosed AZT in lavage fluids about 1 hour after the injection of a 2 g dose (Group C: 8 cases) or a 4 g dose (Group D: 6 cases). In group D antibiotic concentrations were significantly higher (P less than 0.005) than group C, while all the parameters that usually define the intensity of the alveolar alterations were not significantly different. Therefore, aztreonam administration in a daily monodose seems able to assure higher and longer lasting concentrations at the site of infection.

Clinical Pharmacokinetics of Aztreonam

“…In a third study, in a total of23 patients, concentrations were determined in sputum or in bronchoalveolar lavage fluid 30 to 90 minutes after an intravenous bolus administration of 2 or 4g (Velluti et al 1991). Sputum concentrations determined during the first 3 hours postdose were low (1.98 ± 1.41 mg/L and 4.75 ± 3.61 mg/L after 2 and 4g doses, respectively) and drug concentrations in the lavage fluid were even lower (0.23 ± 0.09 mg/L and 0.60 ± 0.25 mg/L, respectively).…”