Gentamicin in Newborn Sepsis: Once Daily Dose versus Twice Daily Dose

Abstract

Gentamicin is commonly used as first line drug in neonatal sepsis. It is usually used in combination with other drugs. It is a nephrotoxic and an ototoxic drug. Long term use causes renal failure and hearing impairment. Its efficacy depends on the peak concentration, and its toxicity is related to the trough concentration. There is no set protocol of using gentamicin in neonate in Bangladesh, whether it should be used once daily or twice, it is till debatable in this perspective. In daily practice, it is not followed up trough and peak concentration of gentamicin, so it is not known the renal and hearing status of the baby treated with aminoglycosides. In this regard, primary objectives were to measure the peak level (to observe efficacy) and trough (to observe toxicity) level of gentamicin in once-daily dose (ODD) and in twice-daily dose (TDD) of gentamicin in neonates treated for suspected or culture proven sepsis and finally to assess the renal status and hearing status. This was an open label clinical trial, conducted in the Neonatal Intensive Care Unit, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, during the period of March, 2012 to November, 2012. A total of 50 neonates were included in the study, 25 in ODD group and 25 in TDD group of gentamicin. Serum gentamicin peak and trough were measured in both groups. Mean gestational age were 38.85±1.21Wk and 38.83±1.16Wk in ODD and TDD respectively, and their corresponding mean weights were 2341.66±377 gram and 2307±363 gram. Only a fraction (12 % in ODD group 20% in TDD group) of patients had culture positive sepsis. The mean peak concentration of gentamicin was significantly higher (p value < 0.001) among neonates who received once-daily dose (7.19±1.7 microgram/ml) compare to patients who received the twice-daily dose (4.81±1.8 microgram/ml). The mean trough concentration of gentamicin was significantly lower (p value = 0.04) among neonates who received once-daily dose (1.5±0.78) compared to patients who received the twice-daily dose (2.00±0.9). Serum creatinine concentration raise was statistically non-significant in both group. Only 4% in ODD and 8% in TDD had ototoxicity which was non-significant finding. It may be concluded that ODD of gentamicin had significant higher concentration of peak and lower trough concentration, but no significant difference was in serum creatinine concentration and ototoxicity.