Predictive model for aminoglycoside induced ototoxicity.

Abstract

Background: Irreversible hearing loss is a well-known adverse effect of aminoglycosides, however, inability to accurately predict ototoxicity is a major limitation in clinical care. We addressed this limitation by developing a prediction model for aminoglycoside ototoxicity applicable to the general population.

Methods: We employed a prospective non-drug-resistant tuberculosis (TB), non-HIV/AIDS cohort of 153 adults on Streptomycin based anti-TB therapy. High frequency pure-tone audiometry was done at regular intervals throughout the study. Clinical and audiological predictors of ototoxicity were collated and ototoxic threshold shift from the baseline audiogram computed. The prediction model was developed with logistic regression method by examining multiple predictors of ototoxicity. Series of models were fitted sequentially; the best model was identified using Akaike Information Criterion and likelihood ratio test. Key variables in the final model were used to develop a logit model for ototoxicity prediction.

Results: Ototoxicity occurred in 35% of participants. Age, gender, weight, cumulative Streptomycin dosage, social class, baseline pure tone average (PTA) and prior hearing symptoms were explored as predictors. Multiple logistic regression showed that models with age, cumulative dosage and baseline PTA were best for predicting ototoxicity. Regression parameters for ototoxicity prediction showed that yearly age increment raised ototoxicity risk by 5% (AOR = 1.05; CI, 1.01-1.09), and a gram increase in cumulative dosage increased ototoxicity risk by 7% (AOR = 1.05; CI, 1.05-1.12) while a unit change in baseline log (PTA) was associated 254% higher risk of ototoxicity (AOR = 3.54, CI: 1.25, 10.01). Training and validation models had area under the receiver operating characteristic curve as 0.84 (CI, 0.76-0.92) and 0.79 (CI, 0.62-0.96) respectively, showing the model has discriminatory ability.

Conclusion: This model can predict aminoglycoside ototoxicity in the general population.