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. 2023 Jan 16;23(1):24.
doi: 10.1186/s12887-023-03834-4.

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

Bonifasius Siyuka Singu  1 , Milka Ndapandula Ndeunyema  2 , Ene I Ette  2 , Clarissa Hildegard Pieper  3 , Roger Karel Verbeeck  2
Affiliations

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

Bonifasius Siyuka Singu et al. BMC Pediatr. .

Abstract

Background: Gentamicin 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 (Cmax and Cmin), time to reach Cmin levels of gentamicin and amikacin, and to assess eGFR in preterm and term neonates.

Methods: Two 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 Cmax, Cmin, 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.

Results: Therapeutic range for Cmax 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 (r2 = - 0.30, p = 0.971).

Conclusion: Although 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.

Keywords: Amikacin; Gentamicin; Kidney function; Neonates; Nephrotoxicity.

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Conflict of interest statement

The authors have no conflicts of interest to declare that are relevant of the content of this article.

Figures

Fig. 1
Fig. 1
The time it took for aminoglycoside concentrations to reach the recommended Trough concentrations, the horizontal line marks 24 hours. a gentamicin: n = 44, Trough < 1 mcg/mL), and b amikacin: n = 35, Trough < 5 mcg/mL
Fig. 2
Fig. 2
Correlations of clearance for gentamicin (in A) and amikacin (in B) with eGFR
Fig. 3
Fig. 3
Correlation of CL with gestational age (A and C), postnatal age (B and D), in neonates while receiving gentamicin and amikacin. In D, a negative correlation can be observed between CL and postnatal age in newborns while receiving amikacin and had previously been exposed to gentamicin. Exclusion of outliers (gentamicin: one neonate with a PNA of 14 days; amikacin: two neonates with eGFR values of 0.4 and 64.9 mL/min/1.73 m2) does not produce statistically significant in both correlations of CL vs PNA
See this image and copyright information in PMC

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