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Cefuroxime versus ampicillin plus chloramphenicol in childhood bacterial meningitis: a multicenter randomized
Insights
Cefuroxime showed similar clinical cure rates to ampicillin plus chloramphenicol for bacterial meningitis in children. Shorter 7-day antimicrobial courses did not increase complications or relapses.
Area of Science:
- Pediatric Infectious Diseases
- Clinical Microbiology
- Pharmacology
Background:
- Bacterial meningitis remains a significant cause of childhood morbidity and mortality.
- Optimal antimicrobial therapy and duration for bacterial meningitis require ongoing evaluation.
- Cefuroxime is a broad-spectrum cephalosporin with activity against common meningitis pathogens.
Purpose of the Study:
- To compare the efficacy and safety of cefuroxime versus ampicillin plus chloramphenicol for treating bacterial meningitis in children.
- To evaluate the impact of 7-day versus 10-day antimicrobial courses on treatment outcomes.
- To assess the rate of delayed cerebrospinal fluid (CSF) sterilization and its clinical implications.
Main Methods:
- A multicenter randomized trial involving 107 children with bacterial meningitis.
- Patients were assigned to receive either cefuroxime or ampicillin plus chloramphenicol for 7 or 10 days.
- Cerebrospinal fluid (CSF) isolates included Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis.
Main Results:
- Clinical cure rates were similar (95%) in both treatment groups.
- Haemophilus influenzae was cultured from CSF in 4/39 patients on cefuroxime, versus 0/40 on ampicillin/chloramphenicol (P=0.11).
- No significant increase in in-hospital complications or relapses was observed with 7-day treatment courses.
Conclusions:
- Cefuroxime demonstrated comparable clinical efficacy to ampicillin plus chloramphenicol for pediatric bacterial meningitis.
- Seven-day antimicrobial courses appear safe and effective, without increasing complications or relapses.
- Further research is needed to confirm regimen equivalence and understand the impact of delayed CSF sterilization.
Abstract:
In a multicenter randomized trial, 107 children with bacterial meningitis were initially given either cefuroxime or ampicillin plus chloramphenicol. Patients were alternately assigned to 7- or 10-day courses of the designated antimicrobial regimen. CSF isolates included Haemophilus influenzae type b (89, of which 25% were beta-lactamase positive), Streptococcus pneumoniae, and Neisseria meningitidis. Although mean CSF bactericidal titers against Haemophilus isolates were 1:6 in each treatment group, H. influenzae was cultured from CSF in four of 39 patients receiving cefuroxime, 24 to 48 hours after initiation of therapy, compared with none of 40 patients given ampicillin plus chloramphenicol (P = 0.11). Clinical cure rates were similar (95%); one death occurred in each group. One child given cefuroxime had persistent meningitis after 5 days of therapy, and mastoiditis with secondary bacteremia developed in one on day 10. Three patients had relapse or reinfection. One patient who received cefuroxime for 10 days had a relapse of epiglottitis 17 days later, and of the patients given ampicillin plus chloramphenicol, one had a relapse of meningitis 1 week after 7 days of therapy, and bacteremia developed in one 42 days after completion of 10 days of therapy. No increase in either in-hospital complications or relapses occurred with a 7-day treatment course. Proof of the equivalence of the antibiotic regimens and the efficacy of 7-day courses of treatment, as well as the consequences of delayed CSF sterilization, will require additional investigation.