"Random" gentamicin concentrations do not predict trough levels in neonates receiving once daily fixed dose regimens

随机测得的庆大霉素浓度不能预测接受每日一次固定剂量治疗方案的新生儿的谷浓度。

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Abstract

BACKGROUND: Monitoring plasma gentamicin concentrations in neonates 24 hours after a once daily dose (4 mg/kg) often necessitates additional blood sampling. In adults a nomogram has been developed enabling evaluation of gentamicin doses by sampling concentrations with other blood tests, 4-16 hours after administration. We attempted to develop a similar nomogram for neonates. METHODS: In addition to standard 24 hour sampling to monitor trough concentrations, one additional "random" gentamicin concentration was measured in each of 50 neonates < 4 days of age (median gestation 33 weeks [28-41]), when other blood samples were clinically necessary, 4-20 hours after gentamicin administration. 24 hour concentrations of > 1 mg/L were considered high, and an indication to extend the dosing interval. RESULTS: Highest correlation (r2 = 0.51) of plasma gentamicin concentration against time (4 to 20 hours) was with logarithmic regression. A line drawn 0.5 mg/L below the true regression line resulted in all babies with 24 hr gentamicin concentrations > 1 mg/L having the additional "random" test result above that line, i.e. 100% sensitivity for 24 hour concentrations > 1 mg/L, though only 58% specificity. Having created the nomogram, 39 further babies (median gestation 34 weeks [28-41]), were studied and results tested against the nomogram. In this validation group, sensitivity of the nomogram for 24 hr concentrations > 1 mg/L was 92%; specificity 14%, positive predictive value 66%, and negative predictive value 50%. Prematurity (< or = 37 weeks) was a more sensitive (94%) and specific (61%) indicator of high 24-hour concentrations. 62 (87%) of 71 preterm babies had high 24-hour concentrations. CONCLUSION: It was not possible to construct a nomogram to predict gentamicin concentrations at 24 hours in neonates with a variety of gestational ages. Dosage tailored to gestation with monitoring of trough concentrations remains management of choice.

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