Abstract
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 greater than or equal to 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 less than 2 (8%) against Pseudomonas aeruginosa, and for the tid group, 4 (57%) against members of the Enterobacteriaceae and less than 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. The duration of the postantibiotic effect in serum depended also on the strain and the sampling time of the serum.
Highlights
The pharmacologic parameters and toxicity of netilmicin (6 mg/kg/day) given once daily or thrice daily for the treatment of urinary tract infections were studied in a randomized prospective study of 60 cancer patients
A favorable outcome in patients with gram-negative bacillary bacteremia or pneumonia treated with aminoglycosides is related directly to the initial peak concentration in serum [20, 21] and to achieving a ratio of initial peak serum concentration to the MIC for the offending pathogen of greater than 6:1 [19]
The purpose of the present investigation was to further evaluate the tolerance of netilmicin given qd versus tid in cancer patients suffering from urinary tract infections who were treated with netilmicin alone
Summary
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. Gram-negative infections are a major cause of morbidity in cancer patients, especially when they are neutropenic Treatment of these infections consists of the administration of a broad-spectrum P-lactam antibiotic often in combination with an aminoglycoside. A favorable outcome in patients with gram-negative bacillary bacteremia or pneumonia treated with aminoglycosides is related directly to the initial peak concentration in serum [20, 21] and to achieving a ratio of initial peak serum concentration to the MIC for the offending pathogen of greater than 6:1 [19]. Blood samples were obtained from these patients to derive several pharmacodynamic parameters which may be predictive of efficacy in treating gram-negative bacillary bacteremia and bronchopneumonia, including the serum bactericidal titers, the rate of killing in serum [7], and the duration of the PAE in serum [30]
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