Pharmacodynamic Parameters and Toxicity of Netilmicin (6 Milligrams/Kilogram/Day) Given Once Daily or in Three Divided Doses to Cancer Patients with Urinary Tract Infection

The pharmacologic parameters and toxicity of netilmicin (6 mg/kg/day) given once daily (qd) or thrice daily (tid) for the treatment of urinary tract infections were studied in a randomized prospective study of 60 cancer patients. The overall efficacy was 96%. Nephrotoxicity, assessed by the measure of urinary excretion of phospholipids, was lower for the patients receiving the qd regimen than for those receiving the tid regimen. Elevation of serum creatinine (20 % over baseline) occurred in one patient receiving the qd regimen and in three receiving the tid regimen. Cochleotoxicity, assessed by pure-tone audiometry (250 to 18,000 Hz) occurred in one patient receiving the qd regimen and none receiving the tid regimen. Concentrations in sera were measured on days 1 and 5. No significant accumulation was observed in either group. Median serum bactericidal titers, expressed as reciprocal values (percentage of the sera with a titer.8), were measured against 25 test organisms in samples collected 6 h after the administration of netilmicin and were, for the qd group, 16 (82%) against members of the family Enterobacteriaceae and <2 (8%) against Pseudomonas aeruginosa, and for the tid group, 4 (57%) against members of the Enterobacteriaceae and <2 (0%) against P. aeruginosa. The rate of killing in serum was rapid (2 to 3 log in 2 h against P. aeruginosa; 3 to 5 log in 2 h against members of the Enterobacteriaceae) and correlated with the sampling time and hence the concentration in serum of netilmicin