Cerebrospinal fluid penetration of amikacin in children with community-acquired bacterial meningitis

Abstract

The penetration of amikacin into the cerebrospinal fluid (CSF) was studied with 16 children (mean age, 1 year and 9 months; range, 4 months to 8 years) with community-acquired bacterial meningitis. Amikacin was given intravenously at a dose of 7.5 mg/kg of body weight twice daily. CSF was collected on day 1, at the expected peak concentration of amikacin in CSF. The mean (standard deviation) concentration of amikacin in CSF was 1.65 (1.6) mg/liter. Concentrations of amikacin in CSF correlated significantly with CSF glucose levels on admission. The mean concentrations of amikacin in CSF were 2.9, 1.1, and 0.20 mg/liter in patients with CSF glucose levels of <1, 1 to 2, and >2 mmol/liter, respectively. Thus, amikacin penetrates the blood-brain barrier substantially in children with bacterial meningitis and achieves particularly high concentrations when CSF glucose level is <1 mmol/liter on admission.

Cerebrospinal Fluid Compartmental Pharmacokinetics of Amikacin in Neonates

“…Such an approach allowed investigation of amikacin disposition at the anticipated low concentrations. Based on this HPLC method, a median amikacin CSF concentration of 1.08 mg/liter (range, 0.34 to 2.65 mg/liter) was documented in neonates, but the absence of any correlation between markers of CSF inflammation and the T eq are in contrast to other reports in children and adults where CSF amikacin concentrations appear to be increased in the presence of meningitis (7,8,13,24,26,28). We did note a correlation between the amikacin CSF concentration and the CSF protein content (Fig.…”

“…Using this WBC threshold (21 cells/mm 3 ) as a dichotomous variable, we were unable to show any significant difference in amikacin CSF concentration in this cohort of neonates (1.16 versus 1.15, P ϭ 0.95). Gaillard et al documented amikacin CSF concentrations in a cohort of 16 children (range, 4 months to 8 years old) with community-acquired bacterial meningitis given intravenous amikacin (7.5-mg/kg twice daily) (13). An inverse correlation with CSF glucose level, but not with the CSF protein concentration or leukocyte count was demonstrated.…”

“…Access of aminoglycosides to the central nervous compartment is limited in healthy children and adults (8,26,28), but cerebrospinal fluid (CSF) aminoglycoside exposure after systemic administration is more extended in children with meningitis than in those without meningitis (24). Correlations between antibiotic concentration and CSF glucose content, CSF leukocytosis, or CSF protein concentrations have been investigated (12,13,15,26,27). Ototoxicity relates to the mean aminoglycoside concentration in the central nervous system compartment, but a genetic predisposition to develop aminoglycoside-related ototoxicity has also been documented (4,10,17,23).…”

A Novel Mouse Model of Aminoglycoside-Induced Hyperacusis and Tinnitus

“…A limitation of this study is that we did not investigate cochlear or brain inflammation, but previous studies have shown that AGs do lead to transient inflammatory states (Jiang et al, 2017). Additionally, AGs may cross the blood-labyrinth (Kalinec et al, 2017) and blood-brain barriers in children (Gaillard et al, 1995) and in elderly adults (Mattappalil and Mergenhagen, 2014). Thus, future animal studies might refine the doses and compare different AGs to further detail the otoprotective effects of ebselen on ototoxin-induced cochlear inflammation.…”

Aminoglycoside Antibiotics

“…The concentrations of aminoglycosides achieved in the CSF as a result are variable (Lutsar et al, 1998), but appear to be sufficiently high for excellent therapeutic results (Gaillard et al, 1995). While the highly polar nature of aminoglycosides suggests that they would not be able to cross the blood-brain barrier, and this is usually the case, this membrane is compromised and more permeable when inflammed in bacterial meningitis.…”