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Acute and delayed adverse effects of gentamicin in the treatment of premature neonates with sepsis during the first postnatal week – an open prospective study (part II)


Authors: P. Pokorná 1;  J. Záhora 3;  V. Vobruba 1;  O. Černá 1;  P. Srnský 1;  D. Lorenčík 1;  P. Klement 1;  L. Blažková 4;  J. Martinková 2;  J. Chládek 2
Authors‘ workplace: Jednotka intenzivní a resuscitační péče Kliniky dětského a dorostového lékařství UK 1. LF a VFN, Prahapřednosta prof. MUDr. J. Zeman, DrSc. 1;  Ústav farmakologie, Lékařská fakulta Univerzity Karlovy, Hradec Královépřednosta doc. MUDr. S. Mičuda, Ph. D. 2;  Ústav lékařské biofyziky, Lékařská fakulta Univerzity Karlovy, Hradec Královépřednosta doc. ing. J. Hanuš, Ph. D. 3;  StatSoft CR s. r. o., Praha 4
Published in: Čes-slov Pediat 2014; 69 (4): 213-227.
Category: Original Papers

Overview

Aim:
To evaluate the adverse effects of an aminoglycoside antibiotic gentamicin in the treatment of premature neonates with sepsis during the first postnatal week and their relationship to pharmacokinetics and clinical characteristics of neonates.

Methods:
Neonates were stratified according to gestational age (GA) into the groups of very preterm (the group S1, GA=25–33 weeks, N=32) and preterm (the group S2, GA=34–38 weeks, N=22). Each of the two groups was further divided in two subgroups of neonates with and without persistent ductus arteriosus (PDA, 18 in S1 a 4 in S2). Biochemical markers of an acute glomerular and tubular dysfunction were evaluated before the initiation of pharmacotherapy with Ge and thereafter. The follow-up investigations performed during the first year and between the 2nd and 5th year of age included the examinations for cochlear ototoxicity using transient otoacoustic emission and nephrocalcinosis with the help of ultrasonography.

Results:
The proportion of neonates with glomerular dysfunction was higher in the group S1 than S2 (16/32 vs. 4/22; p<0.05). Serum concentrations of creatinine and urea and fractional sodium excretion in urine raised with decreasing GA (P<0.001), whereas PDA exerted no influence. In all four groups, pharmacotherapy with Ge resulted in the elevation of the ratio of calcium to creatinine urinary concentrations and of the fractional urinary excretion of magnesium (2- to7-fold, P<0.01). The correlation between the biochemical parameters under the study and Ge concentrations were weak. Nephrocalcinosis was detected in two out of 46 children undergoing sonography and cochlear toxicity was absent.

Conclusions:
Acute renal dysfunction is relatively modest and transient in most of premature neonates treated in the intensive care unit. Pharmacotherapy with Ge results, among other effects, in the increase of calcium excretion in urine. This hypercalciuric adverse effect contributes to other risk factors for nephrocalcinosis. Long-term follow-up of kidney function seems warranted because chronic renal dysfunction can develop in a minority of children.

Key words:
preterm neonate, sepsis, gentamicin, renal dysfunction, nephrocalcinosis, perzistent ductus arteriosus P.


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