Incidence and Risk Factors for Nephrotoxicity Associated With Aminoglycoside Therapy Among Hospitilized Children at Kenyatta National Hospital, Kenya.

Abstract

Background. Aminoglycoside antibiotics are routinely used in neonates for treatment of neonatal sepsis, meningitis and burns in synergy with beta lactam antibiotics and in older children for treatment of acute respiratory tract infections, intra-abdominal infections and complicated urinary infections. They are effective against a wide range of Gram-positive and Gramnegative bacteria like Staphylococcus and Enterococcus, in synergy with β-lactam antibiotics. However, they have a narrow therapeutic window and are nephrotoxic. The risk of nephrotoxicity is increased by other factors such as age, birth weight, other illnesses, and concurrent use of nephrotoxic medications among others. Main objective To determine the incidence and risk factors of nephrotoxicity associated with aminoglycosides use among children aged 5 years and below admitted at (KNH), and describe the short term outcomes of therapy. Methodology This was a hospital based prospective cohort study that targeted all children, age five years and below, who were treated with aminoglycosides for the period of July 2018 to September 2018. The study was conducted at the Kenyatta National Hospital general pediatric wards, and the newborn unit. They were recruited consecutively until a sample size of 195 was reached. Their baseline urea, electrolyte and serum creatinine levels were measured before initiating aminoglycoside treatment. Follow up urea, electrolyte and creatinine levels were measured at termination of the aminoglycoside therapy. Results Of the 195 (100%) children, 20 (10.25%) developed nephrotoxicity. Of these, 13 (65%) developed nephrotoxicity that was mild and reversible (P=0.001), while 4 (20%) of them developed acute kidney injury and 3(15%) developed kidney failure. The neonates who constituted 58 (28.7%) of the study population, were 3.54 (95% CI 1.6- 8.21) times more likely to develop nephrotoxicity compared to older children (P=0.003). Low birth weight neonates were 4.73 (95% CI: 1.8-12.5) times more likely to develop nephrotoxicity than those who weighed >2500gms at birth (P=0.002). Neonates with neonatal sepsis were 4.91 (95% CI: 2.07-11.62) times more likely to develop nephrotoxicity than those treated for other conditions (P=0.001). Most patients who developed nephrotoxicity, 13(65%) were switched to cephalosporin antibiotics, while 5 (25%), and continued on aminoglycoside treatment with dose adjustments. Most patients who developed nephrotoxicity were switched to cephalosporin antibiotics and there was no mortality reported during the study period. Conclusion and recommendations. Aminoglycosides should be used with caution in high-risk populations like the neonates, especially the low birth-weight, asphyxiated and those suffering from sepsis. Routine monitoring of kidney functions should be considered within 72 hours of initiating aminoglycoside use in all neonates since they are at a higher risk of developing nephrotoxicity. Larger studies need to be conducted to assess for correlation between maternal factors and other patient related risk factors with nephrotoxicity, and to assess the long-term outcomes of the patients who develop aminoglycoside-associated nephrotoxicity