Plasma concentration and eGFR in preterm and term neonates receiving gentamicin or successive amikacin therapy

BackgroundGentamicin and amikacin are aminoglycoside antibiotics which are renally excreted and known to be nephrotoxic. Estimate of glomerular filtration rate (eGFR) per body surface area is lower in neonates than in adults and exposure to these drugs could lead to more suppression in kidney function. The aim of this study was to determine maximum and minimum plasma concentrations (C-max and C-min), time to reach C-min levels of gentamicin and amikacin, and to assess eGFR in preterm and term neonates.MethodsTwo groups of patients were recruited, 44 neonates receiving gentamicin (5 mg/kg/24 h) and 35 neonates receiving amikacin (15 mg/kg/24 h) by slow intravenous injection. Patients on amikacin had been on gentamicin before being switched to amikacin. Two blood samples were drawn for the determination of the maximum and minimum plasma concentration. Primary outcomes were determination of C-max, C-min, and the time it took to clear the aminoglycoside to a plasma concentration below the toxicity threshold (gentamicin: < 1 mcg/mL; amikacin: < 5 mcg/mL.ResultsTherapeutic range for C-max of gentamicin (15-25 mcg/mL) or amikacin (30-40 mcg/mL) was achieved in only 27.3 and 2.9% of neonates, respectively. Percentage of neonates reaching plasma concentrations below the toxicity threshold within the 24-hour dosing interval was 72.7% for gentamicin and 97.1% for amikacin. Positive correlation between gentamicin clearance and postnatal age borderline statistical significance (p = 0.007), while the correlation between amikacin clearance and postnatal age was poor and not statistically significant (r(2) = - 0.30, p = 0.971).ConclusionAlthough eGFR decreased significantly as a function of postnatal age in neonates receiving amikacin, the majority (91.4%) of these neonates were able to clear the drug to < 5 mcg/mL within a 24-hour dosing interval.

Automated summary

This study aimed to determine the maximum and minimum plasma concentrations of gentamicin and amikacin in neonates, and assess their glomerular filtration rate (eGFR). The results showed that only a minority of neonates reached the therapeutic range of these drugs, but the majority were able to clear the drugs to below the toxicity threshold within 24 hours. Although amikacin led to a decrease in eGFR, most neonates were still able to clear the drug within the dosing interval.