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Efficacy of Antibiotic Regimens for Meningitis in Young Infants Aged 0-59 Days: A Systematic Review
Sitarah Mathias1,2, Krysten North2,3, Alexandra Santana2,4
1Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts.
Insights
Limited data exist on optimal antibiotic regimens for infant meningitis. More rigorous randomized controlled trials (RCTs) are urgently needed to guide treatment for this vulnerable population, especially with rising antimicrobial resistance.
Area of Science:
- Pediatrics
- Infectious Diseases
- Clinical Pharmacology
Background:
- Meningitis poses a significant mortality risk in young infants.
- Optimal antibiotic treatment regimens for infant meningitis remain unclear.
Purpose of the Study:
- To systematically evaluate the efficacy of antibiotic regimens for treating meningitis in infants aged 0 to 59 days.
- To assess critical clinical outcomes associated with different antibiotic treatments.
Main Methods:
- Searched multiple databases including MEDLINE, Embase, CINAHL, WHO Global Index Medicus, and Cochrane Central Registry of Trials.
- Included randomized controlled trials (RCTs) comparing antibiotic regimens in young infants with meningitis.
- Extracted data and assessed risk of bias; used GRADE for certainty of evidence.
Main Results:
- Only 2 RCTs involving 168 infants were identified from studies conducted between 1976 and 2015.
- Neither trial compared current World Health Organization-recommended regimens.
- No significant differences in mortality or adverse events were found between compared regimens or treatment durations, though evidence certainty was very low.
Conclusions:
- There is a scarcity of high-quality trial data on antibiotic regimens for infant meningitis.
- Rigorous RCTs are essential to establish optimal treatment guidelines for this vulnerable group.
- Urgent research is needed, considering evolving epidemiology and antimicrobial resistance patterns.
Context:
Meningitis is associated with high mortality risk in young infants, yet the optimal treatment regimen is unclear.
Objectives:
To systematically evaluate the efficacy of antibiotic regimens to treat meningitis in young infants aged 0 to 59 days on critical clinical outcomes.
Data Sources:
MEDLINE, Embase, CINAHL, WHO Global Index Medicus, and Cochrane Central Registry of Trials.
Study Selection:
We included randomized controlled trials (RCTs) of young infants with meningitis (population) comparing the efficacy of antibiotic regimens (interventions) with alternate regimens (control) on clinical outcomes.
Data Extraction:
We extracted data on study characteristics and assessed risk of bias in duplicate. Grading of Recommendations Assessment, Development, and Evaluation was used to assess certainty of evidence.
Results:
Of 1088 studies screened, only 2 RCTs were identified. They included 168 infants from 5 countries and were conducted between 1976 and 2015. Neither study compared current World Health Organization-recommended regimens. One multisite trial from 4 countries compared intrathecal gentamicin plus systemic ampicillin/gentamicin to systemic ampicillin/gentamicin and found no difference in mortality (relative risk, 0.88; 95% confidence interval, 0.41-1.53; 1 trial, n = 98, very low certainty of evidence) or adverse events (no events in either trial arm). Another trial in India compared a 10-day versus 14-day course of antibiotics and found no difference in mortality (relative risk, 0.88; 95% confidence interval, 0.41-1.53; 1 trial, n = 98, very low certainty of evidence) or other outcomes.
Conclusions:
Trial data on the efficacy of antibiotic regimens in young infant meningitis are scarce. Rigorous RCTs are needed to inform recommendations for optimal antibiotic regimens for meningitis treatment in this vulnerable population, particularly within the context of changing epidemiology and increasing antimicrobial resistance.
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