Pharmacokinetic aspects of streptomycin treatment of neonatal septicemia.

Patients with suspected neonatal septicemia were treated with ampicillin, cloxacillin, and streptomycin. The plasma concentrations of streptomycin were followed. First, the levels were determined during a full dose interval (12 h) in 11 infants. The results were used for development of a routine system for monitoring the plasma levels in all streptomycin treated newborns. This system, the "3-point check", involved blood sampling at 1, 3, and 5 h after administration during every second dose interval. The results of this routine procedure were evaluated both in a retrospective and prospective study. The "3-point check" gave a sufficient description of the total exposure to streptomycin under routine clinical conditions and continuous information to the physician in charge of the patient about the drug level. In 9 cases of 50, the report from the laboratory resulted in dose change for correction of a too low or too high plasma concentration. The dosage used, 7.5 mg streptomycin intramuscularly every 12th hour, appeared to be satisfactory in most patients. Peak values rarely exceeded 30 microgram/ml and were usually lower than 25 microgram/ml. Almost half of the children had plasma levels below 5 microgram/ml at the end of the dose interval (after 12 h). Although the correlation between pharmacokinetics and clinical outcome is difficult to establish in neonatal sepsis, we suggest that our guiding principle to avoid plasma levels above 25 microliter/ml is reasonable. In 35 out of 78 patients an otological examination of the newborns was performed within 13 months after streptomycin treatment and no signs of hearing defects were noted.