Sisomicin, at 4.5 mg/kg per day, was prescribed for the therapy of serious bacterial infections of hospitalized infants, children, and adolescents. Eleven children received full treatment courses, with 10 clinical and 9 bacteriological cures. Three patients with underlying disease (two cystic fibrosis and one aplastic anemia) accounted for the failures. Mean half-life was 98.3 min (range, 26.1 to 159.3), and peak serum concentrations 10 min after intravenous infusion were similar (5 to 6 ,g/ml) on days 1, 3, and 5 of therapy. Mean urinary concentrations were 54.3 isg/ml; 31 to 47% of the drug was excreted within the 8-h dosage interval.The drug was tolerated well by all patients; however, one patient, receiving the longest duration of therapy (26 days), developed reversible nephrotoxicity.The emergence of gentamicin-resistant bacteria in hospitalized patients has emphasized the importance of evaluating alternative antibiotics. Sisomicin is a new aminoglycoside antibiotic derived from the fermentation broth of Micromonospora inyoenis that has many properties in common with gentamicin as well as the advantage of activity against selected gentamicinresistant bacteria (4,6,9,14). The purpose of this study was to examine some of the pharmacokinetic, clinical, and toxicological properties of sisomicin in the therapy of serious infections of children. MATERIALS AND METHODSSisomicin was administered to 12 patients hospitalized at the Montreal Children's Hospital. These patients were selected by the attending physician as candidates for aminoglycoside therapy using standard clinical and laboratory criteria. Once a patient was selected to receive aminoglycosides, sisomicin was offered in lieu of gentamicin after carefully explaining the nature of the study and the differences between the two drugs to the parents and only after obtaining informed consent. Appropriate bacterial cultures and base-line laboratory studies were obtained in each case. When positive cultures were obtained before therapy, appropriate cultures were repeated during and after therapy as well. Sisomicin was administered in a dosage of4.5 mg/kg per day intravenously (divided every 8 h) over 0.5 h, and the duration of treatment was determined by standard clinical and bacteriological criteria.All patients were carefully examined for tolerance to the drug and for hematological, hepatic, and renal toxicities by the following tests: hemoglobin, hematocrit, white blood count and differential, platelets, serum glutamic oxaloacetic transa inase, bilirubin, alkaline phosphatase; urea nitrogen, creatinine, and urinalysis. These tests were carried out before, during, and after therapy.Audiological evaluations were performed within 72 h of initiation of therapy, and again after completion of the course of sisomicin. School-age children were studied by standard pure-tone and standard speech audiometry and impedance testing, pre-school children and infants by behavioral observation, play, and conditioned orienting response audiometry, and impedance measurements when...