Once-daily versus thrice-daily dosing of netilmicin in combination with β-lactam antibiotics as empirical therapy for febrile neutropenic patients

Abstract

In a prospective, randomized trial, netilmicin given once daily (OD) was compared in terms of efficacy and safety with the conventional 8-hourly dosing regimen (TD), both in combination with a broad spectrum β-lactam, as initial empirical therapy for febrile neutropenic patients; the total daily dosage of netilmicin in each group was 6 mg/kg body weight. Twenty-nine of the 116 (25%) evaluable patients had micro-biologically documented septicaemia, most of which were caused by Gram-positive bacteria, 41(35%) had microbiologically documented infection without bacteraemia and 46 (4.0%) had possible infection. Highest peak serum concentrations of netilinicin in the OD group were significantly higher and trough serum concentrations signifi cantly lower than in the TD group. A multivariate analysis revealed that neither the dosage regimen nor the peak serum concentration of netilmicin were determinants of a favourable outcome. The response rates of both groups to the initial treatment regimens were comparable and increased similarly following modification of the initial therapy. Response rates were particularly poor in patients with lower respiratory tract infection and in those who remained neutropenic throughout the course of treatment. The incidence of nephrotoxicity was low and did not differ significantly between groups. Once-daily dosing of netilmicin appears to be as effective and as safe as thrice-daily dosing, but is unlikely to further improve the response of febrile neutropenic patients to empirical therapy.