Amikacin use tied to significant reduction of Kidney function among neonates

"In neonates receiving amikacin, eGFR (estimated glomerular filtration rate) decreased significantly as a function of postnatal age, but about 97.1% of these neonates were able to clear the drug to less than five mcg/mL within an interval of 24-hour dosing," the researchers wrote in their study.

Amikacin and gentamicin are aminoglycoside antibiotics excreted renally and are known to be nephrotoxic. In neonates, the eGFR per body surface is lower than in adults, and exposure to these drugs could lead to more suppression of kidney function. Considering this, Bonifasius Siyuka Singu from the University of Namibia in Windhoek, Namibia, and colleagues aimed to determine the minimum and maximum plasma concentrations (Cmin and Cmax), to assess eGFR in preterm and term neonates and the time to reach Cmin levels of amikacin and gentamicin.

For this purpose, the researchers recruited two groups of patients; 44 neonates received gentamicin at a dose of 5 mg/kg/24 h and 35 neonates received amikacin at a dose of 15 mg/kg/24 h by slow IV (intravenous) injection. Before being switched to amikacin, patients on amikacin had been on gentamicin. Two blood samples were drawn to determine the maximum and minimum plasma concentrations. Cmin, Cmax, and the time it took for aminoglycoside to clear to a plasma concentration below the toxicity threshold (amikacin: < 5 mcg/mL; gentamicin: < 1 mcg/mL) were determined (primary outcomes).

The authors reported the following:

· 2.9% and 27.3 of neonates, respectively, achieved a therapeutic range for Cmax of amikacin (30–40 mcg/mL) or gentamicin (15–25 mcg/mL).

· 72.7% for gentamicin and 97.1% for amikacin of neonates reached plasma concentrations below the toxicity threshold within the 24-hour dosing interval.

· Positive correlation between gentamicin clearance and postnatal age had borderline statistical significance, while the correlation between amikacin clearance and postnatal age was poor and not statistically significant (r2 = − 0.30).

"The study's findings indicate that neonates successively exposed to gentamicin and amikacin as first- and second-line therapy, respectively, could result in nephrotoxicity, as shown by the significant eGFR decline in patients who had been exposed to aminoglycoside therapy longer," the researchers wrote.

However, the study showed that a considerably high proportion of patients (72.7% for gentamicin and 97.1% for amikacin) could clear the drug to reach concentrations below the toxicity threshold within the dosage interval of 24 hours.

"To improve the safety and efficacy of gentamicin and amikacin in newborns, eGFR should be monitored, and the dose can be adjusted using the pharmacokinetic approach," they concluded.

Reference:

Singu, B.S., Ndeunyema, M.N., Ette, E.I. et al. Plasma concentration and eGFR in preterm and term neonates receiving gentamicin or successive amikacin therapy. BMC Pediatr 23, 24 (2023). https://doi.org/10.1186/s12887-023-03834-4