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Kanamycin and gentamicin treatment of neonatal sepsis and meningitis
Abstract:
Mortality from neonatal meningitis due to gram-negative microorganisms remains 50% despite use of aminoglycoside antibiotics. Blood was obtained on 238 occasions from 77 neonates with putative or documented sepsis; paired blood and cerebrospinal fluid (CSF) samples were obtained on 14 occasions from ten neonates with meningitis. Kanamycin and gentamicin were measured by a radioisotopic assay procedure. Kanamycin was administered at 15 mg/kg/day in three divided doses intravenously; serum concentrations peaked at one hour (mean, 7.77mug/ml). Gentamicin was administered at 7.5 mg/kg/day in three divided doses intravenously; serum concentrations peaked at two hours (mean, 5.34mug/ml). Both aminoglycosides generally were nondetectable within the CSF; survival of neonates with gram-negative meningitis correlated specifically with the sensitivity of their isolates to ampicillin which was administered concurrently. This study suggests that alternative approaches to the treatment of neonatal sepsis should be explored; administration of an antibiotic which crosses the blood-cerebrospinal fluid barrier more readily should be considered.
Insights
Aminoglycoside antibiotics show limited efficacy in treating neonatal meningitis, failing to reach cerebrospinal fluid (CSF). Neonatal survival depends on ampicillin sensitivity, suggesting new treatment strategies are needed for gram-negative meningitis.
Area of Science:
- Neonatal Medicine
- Infectious Diseases
- Pharmacology
Background:
- Neonatal meningitis mortality remains high at 50% despite aminoglycoside use.
- Gram-negative microorganisms are a significant cause of neonatal meningitis.
Purpose of the Study:
- To evaluate aminoglycoside (kanamycin, gentamicin) concentrations in neonates with sepsis and meningitis.
- To determine the relationship between antibiotic levels and treatment outcomes.
Main Methods:
- Radioisotopic assays were used to measure kanamycin and gentamicin levels in serum and cerebrospinal fluid (CSF).
- Blood and CSF samples were collected from neonates with sepsis and meningitis.
- Antibiotic administration details and patient outcomes were recorded.
Main Results:
- Aminoglycosides (kanamycin, gentamicin) were generally undetectable in the CSF.
- Peak serum concentrations for kanamycin and gentamicin were achieved within 1-2 hours post-administration.
- Neonatal survival correlated with the sensitivity of Gram-negative isolates to ampicillin.
Conclusions:
- Current aminoglycoside antibiotic regimens are ineffective for neonatal meningitis due to poor CSF penetration.
- Alternative treatments or antibiotics with better blood-CSF barrier penetration are necessary for neonatal sepsis and meningitis.