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Chloramphenicol in paediatrics: current prescribing practice and the need to monitor
A Mulhall1, D J Berry, J de Louvois
1Department of Microbiology, Queen Charlotte's Maternity Hospital, London, U.K.
Insights
Chloramphenicol dosing in children is often incorrect, leading to toxic or subtherapeutic levels, especially in neonates and infants. Adjusting dosages based on serum concentration assays is crucial for safe and effective treatment.
Area of Science:
- Pediatric Pharmacology
- Infectious Diseases
- Clinical Pharmacy
Background:
- Chloramphenicol is a broad-spectrum antibiotic used for serious infections.
- Optimal dosing is critical, particularly in neonates and infants, due to immature metabolic pathways.
- Previous studies suggest variability in chloramphenicol dosing and therapeutic drug monitoring.
Purpose of the Study:
- To evaluate chloramphenicol dosing regimens and serum concentrations in neonates, infants, and children.
- To assess the incidence of subtherapeutic, therapeutic, and toxic serum levels.
- To identify factors influencing chloramphenicol levels and associated adverse events.
Main Methods:
- Prospective study involving 255 pediatric patients receiving chloramphenicol.
- Assay of serum and cerebrospinal fluid (CSF) for chloramphenicol concentrations.
- Analysis of patient treatment regimens, including dosage, frequency, and concomitant medications.
- Correlation of serum levels with clinical outcomes and adverse events.
Main Results:
- Less than 50% of neonates and 25% of infants received recommended chloramphenicol doses.
- Only 34% of infants and 50% of older children had therapeutic serum concentrations (15-25 mg/l).
- 31% of neonates and infants had potentially toxic serum concentrations; 5.5% experienced toxic effects, with 4 deaths.
- Higher serum levels were observed when co-administered with penicillin.
- Subtherapeutic peak levels were more common in neonates receiving chloramphenicol every 6 hours compared to every 12 hours.
- Impaired renal function was associated with elevated serum levels and toxicity.
- Dosage regimens were altered in 22% of patients following assay.
Conclusions:
- Inadequate chloramphenicol dosing is prevalent in neonates and infants, leading to suboptimal therapeutic outcomes and toxicity.
- Therapeutic drug monitoring of chloramphenicol serum concentrations is essential for optimizing treatment and preventing adverse events in pediatric patients.
- Dosing adjustments are frequently required, particularly in neonates, infants, and patients with renal impairment.
Abstract:
Two hundred and fifty-five neonates, infants and children, from 45 hospitals, who were receiving chloramphenicol therapy for serious infections were the subject of this study. Samples of serum and cerebrospinal fluid (CSF) were assayed for chloramphenicol and the patients' treatment regimens analysed. Less than 50% of neonates and 25% of infants received the "recommended" dose of chloramphenicol. In older children the recommended dose was used. Only 34% babies under 1 year of age and 50% older children had serum concentrations within the therapeutic range (15-25 mg/l). Thirty-one percent of neonates and infants had potentially toxic serum concentrations. Forty-three percent of neonates receiving chloramphenicol every 6 h had subtherapeutic peak serum levels compared to 20% of those receiving the antibiotic every 12 h. Concomitant administration of phenobarbitone or phenytoin had no effect on mean serum chloramphenicol levels. Serum concentrations of chloramphenicol were significantly higher in patients also receiving penicillin. CSF levels in 77 samples (39 patients) ranged from 1-60 mg/l. CSF from 44% patients contained less than 4 mg/l. Twelve neonates and infants (5.5%) suffered toxic side effects, four died. A further eight babies received an accidental 2- to 10-fold overdose and in three others an overdose was assumed following assay. No overdoses or toxic effects were reported in children over 1 year of age. Eight patients with impaired renal function had elevated serum levels and three showed toxic effects. In 22% patients dosage regimens were altered following assay.(ABSTRACT TRUNCATED AT 250 WORDS)