Combined aztreonam and gentamicin therapy for pseudomonal lower respiratory tract infections

A multicenter, open-label study was performed to assess the efficacy and safety of aztreonam plus gentamicin in the treatment of lower respiratory tract infections due to Pseudomonas aeruginosa. Patients with documented P aeruginosa infections were given aztreonam 2 g every 8 hours (q8h) plus gentamicin 3 to 5 mg/kg per day in three equal doses. Clindamycin, 600 mg q8h, was added to the regimen for patients with infections also involving gram-positive and/or anaerobic bacteria. Therapy was continued for at least 5 days or until obvious failure to respond to treatment. Of 64 patients with suspected P aeruginosa infections, 57 were eligible for clinical evaluation and 51 for microbiologic evaluation. At entry, impaired host defense was present in 35% of patients, and chronic obstructive pulmonary disease in 28%, in addition to other predisposing conditions such as emphysema, history of tuberculosis, and pneumothorax. The clinical response rate for the combination regimen was 48/57 (84%), which included 27 (47%) cures and 21 (37%) partial responses. The microbiologic response rate was 35/51 (69%), of which 25 (49%) outcomes were classified as eradication and 10 (20%) as eradication with relapse. Superinfection was observed in 3 (6%) patients. The combination of aztreonam and gentamicin was synergistic in the initial isolates obtained from 33 (72%) patients. A total of 16 patients died of pulmonary or other underlying disease, for a mortality rate of 28%. The monobactam-aminoglycoside combination was generally well tolerated. Two other patients were withdrawn because rashes emerged on treatment. This study demonstrates that aztreonam can be administered as one component of a synergistic monobactam-aminoglycoside therapy in the treatment of nosocomial lower respiratory tract infections involving P aeruginosa.