chloramphenicol-succinate and Bacterial-Infections

Chloramphenicol serum concentration is often monitored to assure efficacy and prevent toxicity. We studied the relationship between steady-state chloramphenicol serum concentration and hematologic adverse effects in 45 pediatric patients. The mean peak serum concentration of chloramphenicol in patients with and without toxicity were not different (p less than 0.01): 22.7 micrograms/ml in neutropenic patients versus 23.1 micrograms/ml in those without neutropenia; 18.2 micrograms/ml in leukopenic patients versus 23.3 micrograms/ml in those without leukopenia; 22.2 micrograms/ml in patients with eosinophilia versus 23.9 micrograms/ml in those without eosinophilia; 23.7 micrograms/ml in patients with anemia versus 22.1 micrograms/ml in those without anemia. None of the patients developed thrombocytopenia. These data clearly demonstrate that chloramphenicol toxicity may not be predictable by serum concentration in pediatric patients receiving therapeutic doses of chloramphenicol succinate. Thus, frequent monitoring of chloramphenicol serum concentration does not appear warranted unless a patient appears unresponsive to a therapeutic dose or has received an excessive dose.

Topics: Bacterial Infections; Blood Cell Count; Central Nervous System Diseases; Child; Child, Preschool; Chloramphenicol; Dose-Response Relationship, Drug; Humans; Infant; Infant, Newborn

17 cases of purulent meningitis in 15 children, aged 1 day to 5 years (median 8 months) were treated with continuous i.v. infusion of chloramphenicol succinate. Free chloramphenicol in serum and cerebrospinal fluid (C.F.) was assayed by high performance liquid chromatography (HPLC). CF chloramphenicol levels averaged 45 +/- 14% of the serum level. Out of 16 patients only five received the usually recommended dosage. In three others because of initially or progressively high serum levels the dose had to be diminished. In eight others because of subtherapeutic levels the dose had to be raised. The highest dose (390 mg/kg body weight/d) was required in a 2 month old boy. He was shown to have a clearance rate for free chloramphenicol considerably higher than has been reported so far. Maturation of the metabolism could be observed in a small-for-date newborn who acquired a grey baby syndrome during the treatment of his first meningitis. Several weeks later he required exactly the recommended dose to reach therapeutic chloramphenicol levels. As a consequence of these observations we strongly recommend meticulous drug monitoring of chloramphenicol in order to meet the large biological variations seen particularly in neonates and young infants in their capacity to reach and maintain therapeutic serum levels.

Topics: Bacterial Infections; Child, Preschool; Chloramphenicol; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Female; Humans; Infant; Infant, Newborn; Kinetics; Male; Meningitis; Metabolic Clearance Rate

Topics: Bacterial Infections; Chloramphenicol; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infusions, Parenteral; Meningitis

Topics: Bacterial Infections; Child; Child, Preschool; Chloramphenicol; History, 20th Century; Humans; Infant; Infant, Newborn; Pediatrics; United States; United States Food and Drug Administration

Chloramphenicol succinate and chloramphenicol kinetics were examined on two occasions at steady state, separated by 2 to 17 days, in 10 pediatric patients on the same intravenous dose of chloramphenicol succinate. The steady-state peak serum concentration of chloramphenicol succinate fell from an average of 77.1 micrograms/ml during the first study to 42.2 micrograms/ml during the second. The steady-state peak serum concentration of chloramphenicol also decreased from an average of 27.8 micrograms/ml to 24.9 micrograms/ml. There was a marked decrease in the steady-state trough serum concentration of chloramphenicol, which averaged 8.4 micrograms/ml during the first and 5.3 micrograms/ml at the time of the second study. Mean area under the serum concentration-time curve (AUC) of chloramphenicol succinate decreased from 59.7 micrograms . hr/ml to 24.0 micrograms . hr/ml. The AUC of chloramphenicol averaged 105.7 micrograms . hr/ml at the time of the first and decreased to 79.5 micrograms . hr/ml during the second study. Mean percent decrease in the AUC of chloramphenicol was about 28% and occurred most substantially in patients with high AUCs during the first study. Mean elimination chloramphenicol half-life was 3.0 hr during the first study and fell to 2.3 hr at the time of the second study. Our data indicate that chloramphenicol serum concentration should be monitored frequently, especially in patients not responsive to a set dose.

Topics: Adolescent; Bacterial Infections; Brain Diseases; Child; Child, Preschool; Chloramphenicol; Female; Humans; Infant; Kinetics; Male