Objective: To evaluate the efficacy and tolerability of intravenous empiric treatment with meropenem compared with ceftazidime-tobramycin in patients with hospital-acquired lower respiratory tract infections.
Design: Prospective, nonblind, randomized trial.
Setting: Multicenter trial conducted at 22 centers.
Patients: Two hundred eleven patients were enrolled and 121 were evaluable for the analysis of both clinical and bacteriologic efficacy.
Interventions: One hundred four patients were randomized to receive intravenous meropenem (1000 mg) every 8 hrs and 107 patients were randomized to receive intravenous ceftazidime (2000 mg) plus tobramycin (1 mg/kg) every 8 hrs. Sixty-three meropenem-treated patients and 58 ceftazidime-tobramycin-treated patients were eligible for the analysis of clinical and bacteriologic efficacy. In the ceftazidime-tobramycin group, 32 (55%) evaluable patients received more than six doses of tobramycin, 24 (41%) received six doses or fewer, and two (3%) did not receive any tobramycin.
Measurements and main results: The analysis of efficacy was based on the clinical and bacteriologic responses at the end of treatment. Satisfactory clinical responses occurred in 56 (89%) of 63 of the meropenem-treated patients and in 42 (72%) of 58 of the ceftazidime-tobramycin-treated patients (p = .04). Corresponding bacteriologic response rates were 89% and 67%, respectively (p = .006). The frequency and profile of drug-related adverse events was similar across treatment groups. Seizures were reported in three meropenem-treated patients, but these seizures were considered by the investigator to be unrelated to treatment.
Conclusions: Meropenem is well tolerated and more efficacious than the combination of ceftazidime and tobramycin for the initial empiric treatment of hospital-acquired bacterial pneumonia.