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Lack of predictability of chloramphenicol toxicity in paediatric patients
1College of Pharmacy, Ohio State University, Columbus.
Insights
Chloramphenicol treatment for central nervous system infections in children was effective, with reversible adverse effects like anemia and neutropenia. A high cumulative dose may increase the risk of toxicity in pediatric patients.
Area of Science:
- Pediatric Pharmacology
- Infectious Diseases
- Hematology
Background:
- Central nervous system (CNS) infections in children require effective antimicrobial therapy.
- Chloramphenicol sodium succinate is an intravenous antibiotic used for severe infections.
- Monitoring for adverse effects is crucial during pediatric antibiotic treatment.
Purpose of the Study:
- To evaluate the efficacy and safety of chloramphenicol sodium succinate in pediatric patients with CNS infections.
- To identify potential risk factors for adverse effects associated with chloramphenicol therapy.
- To assess the correlation between serum drug concentrations and hematological parameters.
Main Methods:
- A cohort of 45 pediatric patients (newborn to 12 years) received intravenous chloramphenicol sodium succinate.
- Serum chloramphenicol concentrations were measured using high-performance liquid chromatography (HPLC).
- Hematological parameters including hemoglobin, white blood cell, neutrophil, eosinophil, and platelet counts were monitored.
Main Results:
- Chloramphenicol therapy was effective in all patients, with reversible adverse effects observed.
- Common adverse effects included anemia, leukopenia, neutropenia, and eosinophilia, occurring between 3 and 34 days of therapy.
- No significant correlation was found between demographic factors, dose, duration, or serum concentrations and adverse effects; however, a higher cumulative dose was noted in patients with adverse effects.
Conclusions:
- Chloramphenicol sodium succinate is an effective treatment for pediatric CNS infections.
- Adverse effects are generally reversible, but a high cumulative dose might predispose some children to toxicity.
- Predicting chloramphenicol toxicity in pediatric patients remains challenging, highlighting the need for careful monitoring.
Abstract:
We studied 45 patients (new-born to 12 year olds) who received 50-100 mg/kg/day chloramphenicol sodium succinate i.v. over 2-49 days for the treatment of central nervous system infections. Multiple blood samples were obtained to measure serum concentrations of chloramphenicol and its succinate ester by high pressure liquid chromatography (HPLC). Haematological parameters (haemoglobin, white cell, neutrophil, eosinophil and platelet counts) were also determined. Chloramphenicol therapy was effective in all patients. Anaemia was present in 10, leukopenia in four, neutropenia in four, and eosinophilia in 16 patients. These adverse effects occurred between 3 and 34 days after the initiation of therapy. Chloramphenicol therapy had to be discontinued only in three patients, who had absolute neutrophil counts less than 800/mm3. All adverse effects were reversible. Demographic factors, daily dose, duration of therapy, steady-state peak and trough serum concentrations, area under the serum concentration-time curve normalized for dose, and the elimination half-life were not correlated with the occurrence of adverse effects of chloramphenicol. The mean cumulative dose of chloramphenicol succinate was the only factor always higher but not statistically different in patients with adverse effects compared to those without. The mean cumulative dose of chloramphenicol succinate ranged from 1.2 to 1.8 g/kg in patients with adverse effects and 0.9-1.1 g/kg in those without. These data suggest that the adverse effects of chloramphenicol may not be predictable in paediatric patients. However, a high cumulative dose may possibly be an important factor in predisposing some patients to certain chloramphenicol toxicity.