Prevalence of abnormal aminoglycoside trough levels in children with clinically suspected gram negative infections at the Aga Khan University Hospital, Nairobi
Date of Award
8-2010
Document Type
Dissertation
Degree Name
Master of Medicine (MMed)
First Supervisor/Advisor
Admani B
Second Supervisor/Advisor
Macharia William M
Department
Paediatrics and Child Health (East Africa)
Abstract
Background: Aminoglycosides are commonly used in the treatment of severe gram-negative infections. Their use is associated with substantial risk of toxicity and hence need to monitor therapeutic drug levels. The prevalence of abnormal aminoglycoside trough levels in hospitalized children in our local setting has not been determined thus putting into question the cost benefits of providing therapeutic drug monitoring services in our resource poor settings.
Objective: To determine the prevalence of abnormal aminoglycoside trough levels in children below the age of 12 years with clinically suspected gram negative infections at the Aga Khan University Hospital, Nairobi. The secondary objective was to determine if glomerular filtration rate (GFR) estimation using Schwartz formula correlates with drug trough levels in children on aminoglycoside therapy.
Methods: Children aged 1 day up to 12 years started on aminoglycoside therapy with either gentamicin or amikacin were identified in this hospital based cross-sectional survey that was undertaken at the Aga Khan University Hospital, Nairobi over a period of six months. Aminoglycoside drug trough levels and serum creatinine measurements were done in 81 patients at 24hours after initiation of aminoglycoside therapy. GFR was calculated using Schwartz formula for all the serum creatinine values obtained.
Data analysis: Data accrued were analysed using Stata Data Analysis and Statistical software. The prevalence of abnormal aminoglycoside trough levels was calculated. The Pearson correlation coefficient was calculated between the drug trough levels and estimated GFR. The prevalence, sensitivity, specificity, positive and vi negative predictive values as well as likelihood ratios, and hence accuracy of estimated GFR in predicting for abnormal aminoglycoside trough levels was also calculated. The area under the receiver operating characteristic (ROC) curve was also determined.
Results: A total of eighty one participants were recruited into this study with a median age of three days, 48.2% of whom were males and 51.8% female. The prevalence of abnormal aminoglycoside trough levels in children below the age of 12 years with clinically suspected gram negative infections admitted at the Aga Khan University Hospital, Nairobi was 4.9% (95% CI 1.4% to 12.2%). There were no reported adverse outcomes in any of the children with abnormal drug trough levels upon follow-up. The strength of the association between aminoglycoside trough levels and glomerular filtration rate was found to be weak with Pearson correlation co-efficient of -0.342. The sensitivity and specificity of estimated GFR in predicting for abnormal aminoglycoside trough levels was 25.0% and 98.7% respectively. The positive and negative predictive values of estimated GFR in predicting for abnormal aminoglycoside trough levels were 50.0% and 96.2%. The positive and negative likelihood ratios were 19.3 and 0.76. The area under the receiver operating characteristic (ROC) curve was 0.6185.
Conclusion: The prevalence of abnormal drug trough levels in children on aminoglycoside treatment in this study is low and therefore the routine screening of patients on aminoglycoside therapy for toxicity using drug trough levels may not be justified. This is further supported by the lack of adverse clinical outcomes in the children found with toxic drug trough levels in this study.
Recommended Citation
Kihurani, I. N. (2010). Prevalence of abnormal aminoglycoside trough levels in children with clinically suspected gram negative infections at the Aga Khan University Hospital, Nairobi (Unpublished master's dissertation). Aga Khan University, East Africa.