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Thiamphenicol in treatment of Haemophilus influenzae meningitis
Insights
Thiamphenicol showed limited efficacy in treating pyogenic meningitis, with relapses and complications observed in some patients. This antibiotic demonstrated dose-related bone marrow toxicity, suggesting it cannot replace chloramphenicol for meningitis treatment.
Area of Science:
- Pediatric Infectious Diseases
- Pharmacology
- Bacteriology
Background:
- Pyogenic meningitis remains a significant threat to infants and children.
- Evaluating alternative antibiotics for bacterial meningitis is crucial for improving patient outcomes.
Purpose of the Study:
- To assess the efficacy and safety of thiamphenicol as a single-agent treatment for pyogenic meningitis in pediatric patients.
- To compare the outcomes of thiamphenicol treatment with ampicillin in a matched cohort.
Main Methods:
- A cohort of 17 pediatric patients with pyogenic meningitis received intravenous thiamphenicol (100 mg/kg/day).
- Treatment outcomes, including cure rates, relapses, and complications like subdural effusions, were recorded.
- Serum and cerebrospinal fluid (CSF) thiamphenicol concentrations were measured.
- Minimum inhibitory concentrations (MICs) of H. influenzae were determined.
- A historical control group treated with ampicillin was used for comparison.
Main Results:
- In the *Haemophilus influenzae* group, 10 out of 14 patients were cured, with 4 experiencing relapses and 3 developing subdural effusions.
- The ampicillin-treated group showed a higher cure rate (all cured) with fewer complications.
- Thiamphenicol achieved therapeutic serum levels (10-12 mcg/ml) and CSF levels (1-1.9 mcg/ml).
- A dose-related, reversible bone marrow toxicity was observed with thiamphenicol treatment.
Conclusions:
- Thiamphenicol is not a suitable replacement for chloramphenicol in treating pyogenic meningitis as a single antibiotic.
- The observed toxicity and relapse rates indicate limitations in thiamphenicol's efficacy for this indication.
- Further investigation into specific indications for thiamphenicol in meningitis may be warranted.
Abstract:
17 infants and children with pyogenic meningitis (14 Haemophilus influenzae, 2 Diplococcus pneumoniae, 1 Neisseria meningitidis) were treated with thiamphenicol, 100 mg/kg body weight/day in 4 doses i.v., as single drug. In the H. influenzae group 10 patients were cured, 4 had relapses of meningitis, 3 with documented subdural effusions. This group is compared with 14 children matched for age, initial leucocyte and CSF cell count treated with ampicillin: all of these were cured, 1 had a subdural effusion. Thiamphenicol concentrations were determined in the serum and CSF 2 h after administration. The mean serum levels were between 10-12 mcg/ml, the mean CSF levels varied from 5.4 mcg/ml at the beginning to 1-1.9 mcg/ml at the end of meningitis. The MIC of H. influenzae was 0.6-12 mcg/ml. A significant, acute, and dose related bone marrow toxicity of thiamphenicol could be documented, but was always rapidly fully reversible. We conclude that thiamphenicol cannot replace chloramphenicol in the treatment of pyogenic meningitis as single systemic antibiotic. Special indications for thiamphenicol in this disease are discussed.