Piperacillin/tazobactam plus tobramycin versus ceftazidime plus tobramycinfor the treatment of patients with nosocomial lower respiratory tract infection

An open-label, randomized, comparative, multi-centre study was conducted at 25 centres in the USA and Canada to compare the safety and efficacy of pip eracillin/tazobactam plus tobramycin with ceftazidime plus tobramycin in pa tients with lower respiratory tract infections. Piperacillin/ tazobactam (3 g/375 mg) every 4 h or ceftazidime (2 g) every 8 h were administered iv fo r a minimum of 5 days. Tobramycin (5 mg/kg/day) given in divided doses ever y 8 h was administered to all patients. Patients with Pseudomonas aeruginos a isolated from respiratory secretions at baseline were to continue tobramy cin for the duration of the study. Tobramycin could be discontinued in othe r patients after the baseline culture results were known, A total of 300 pa tients was randomized, 155 into the piperacillin/tazobactam group and 145 i nto the ceftazidime group. Of these, 136 patients (78 in the piperacillin/t azobactam group and 58 in the ceftazidime group) were considered clinically evaluable. Both groups were comparable for age, sex, duration of treatment and other demographic features, The clinical success rate in evaluable pat ients was significantly greater (P = 0.006) in the piperacillin/tazobactam treatment group (58/78; 74%) than in the ceftazidime group (29/58; 50%), Er adication of the baseline pathogen was significantly greater (P = 0.003) in the piperacillin/tazobactam group (66%) than in the ceftazidime group (38% ), The clinical and bacteriological responses of those patients with nosoco mial pneumonia were similar to the overall results. Twelve (7.7%) piperacil lin/tazobactam-treated patients and 24 (17%) ceftazidime-treated patients d ied during the study(P = 0.03), Seven of the 24 deaths in the ceftazidime t reatment group but only one of the 12 deaths in the piperacillin/ tazobacta m treatment group were directly related to failure to control infection. Th e majority of adverse events were thought by the investigator to be attribu table to the patients' underlying disease and not drug related, In this stu dy, piperacillin/tazobactam plus tobramycin was shown to be more effective and as safe as ceftazidime plus tobramycin in the treatment of patients wit h nosocomial LRTI.