No abstract

The incidence of early-onset bacterial infection in the neonate varies from 0.5 to 1% of the total number of deliveries but is significantly higher in preterm neonates, where infection is causally linked with premature delivery in ca. 50% of cases (14). Late-onset, nosocomial bacterial infections occur in a significant number of preterm and term neonates during their stay in the neonatal intensive care unit. Bacteremia, pneumonia, necrotizing enterocolitis, and meningitis are the most frequent loci for infection in neonates. Empirical treatment for suspected infection in early neonatal life consists of combination therapy based on a time-dependent (beta-lactamase) and a concentration-dependent (aminoglycoside) antibiotic coverage (e.g., Streptococcus agalactiae and Escherichia coli), whereas in late neonatal life coagulase-negative Staphylococcus should also be covered.The bactericidal effectiveness of amikacin is linked to intermittent, discontinuous peak concentrations, whereas renal side effects and ototoxicity relate to the average serum concentration that contributes to the saturation of renal and cochlear cell binding sites. The combination of bactericidal effect and toxicity data has resulted in the concept of administration of relative larger doses with extended dosing intervals between consecutive doses. The safety and effectiveness of extended interval dosing of aminoglycosides in neonates has been reviewed (19). After the first few days of postnatal life, size, postmenstrual age (PMA), renal function, and ventilation contribute to renal drug clearance variability in neonates and subsequent serum concentration (1, 2, 3).The effectiveness of amikacin for treating meningitis depends on the concentrations in the central nervous system, and this compartment is separated from the blood by the bloodbrain barrier (BBB). 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).Observations on maturational amikacin CSF disposition in neonates are therefore of relevance (17,19). However, data on amikacin CSF concentrations are limited in neonates, and amikacin CSF time-concentration profiles in preterm neonates have not been reported (9). In the present study, time-concentration profiles of amikacin in serum and single CSF samples were collected to evaluate the relationship between serum and CSF concentration and to explore the impact of CSF inflammatory markers (leuko-, gluco-, and protidorhachia) on this relationship du...