High Gentamicin Trough Concentrations in Neonates of Less than 28 Weeks Gestational Age

Abstract

77 newborns, ranging from 25.5 to 43 weeks gestational age (GA) and receiving gentamicin, were studied prospectively over 4 months. Peak and trough serum concentrations were obtained on days 1, 3, and 5 of therapy. Gentamicin, 2.5 mg/kg/dose, was given at intervals according to GA. 63% of newborns of < 28 weeks on doses of gentamicin of 2.5 mg/kg every 24 h (q24h), 75% of < 28 weeks on gentamicin q18h, 90% of newborns of 23-34 weeks (on q18h), and 82 % of those of > 34 weeks GA (on q12h) had serum gentamicin trough concentrations ≤ 2.0 pg/ml on day 1. By day 3, 5/5 newborns of < 28 weeks (q18h) had trough concentrations > 2.0 μg/ml, whereas only 20% of those on the q24h regimen had high trough concentrations (p < 0.05). Possible risk factors associated with altered gentamicin disposition in neonates are discussed.

Time Course of Trough Serum Gentamicin Concentrations in Preterm and Term Neonates

“…The high Cmin observed in preterm neonates, and especially in preterm neonates of low gestational age, is in agreement with the results of other investigators (Assael et al 1977;Faura et al 1991;Lambert-Zechovskyet al 1982;Miranda et al 1985;Mulhall et al 1983;Szefler et al 1980;Zarowitz et al 1982). The correlation of the ratio Cmin/D with gestational age was linear, similar to that observed by others (ltsarayoungyuen et al 1982).…”

“…Data on gentamicin Cmin after 24h are scarce since most studies have collected samples after 2 or 3 days of treatment (Assael et al 1977;Itsarayoungyuen et aI. In 2 studies in which samples were obtained at 1 and 1.5 days of treatment, gentamicin was administered every 18 or every 24h (Watterberg et al 1989;Zarowitz et al 1982). 1971Mulhall et al 1983;Szefler et al 1980).…”

“…Differences in Cmin between neonates ~3 days and> 3 days of postnatal age were observed after 48 and 72h but not after 96h. Some investigators did not find a significant rise in gentamicin Cmin values (Itsarayoungyuen et al 1982;Mc- Other investigators sampling at I, 3 and 5 days of treatment found an increased risk of toxic Cmin values after 3 days compared with after I day of treatment in preterm neonates <28 weeks of gestational age treated with 2.5 mgfkg every 18h (Zarowitz et al 1982). Serum creatinine concentration may be used to estimate the glomerular filtration rate in neonates (Brion et al 1986), but most of our patients were younger than 5 days of postnatal age and, therefore, the serum creatinine concentration was not at steady-state.…”

“…Pharmacokinet. Therefore, although studies in neonates are not available, it seems possible to recommend an increase in the dosage interval of gentamicin when the risk of potentially toxic concentrations is increased, as has been suggested in preterm neonates in general (Lambert-Zechovsky et al 1982;Mulhall et al 1983), those <35 weeks of gestational age (Besunder et al 1988;Miranda et al 1985;Szefler et al 1980), <31 weeks of gestational age (Assael et al 1977) and <28 weeks of gestational age (Zarowitz et al 1982). The postantibiotic effect of the aminoglycosides allows the dosage interval to be increased from 8 to 24h without a reduction in efficacy (LeBel & Spino 1988;Powell et al 1983;Schentag 1989).…”

“…A higher risk of potentially toxic trough serum concentrations (Cmin) of gentamicin (>2 mg/L) has been demonstrated in neonates with low bodyweight (Assael et al 1977;Koren et al 1985), low gestational age (Assael et al 1977;Lambert-Ze-chovsky et al 1982;Miranda et al 1985;Mulhall et al 1983;Szefler et al 1980;Zarowitz et al 1982), low postnatal age (McCracken et al 1971;Paisley et al 1973;Pons et al 1988) or low postconceptional age (Kasik et al 1985). However, data on the time course of gentamicin Cmin during treatment and the influence of gestational age or postnatal age on that time course are almost lacking.…”