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Risk factors for the development of auditory toxicity in patients receiving aminoglycosides
Abstract:
Risk factors for the development of auditory toxicity in patients receiving aminoglycosides were determined from the analysis of 135 patients enrolled in three prospective, randomized, double-blind clinical trials of gentamicin, tobramycin, and amikacin. Auditory toxicity, defined as a decrease in auditory acuity of greater than or equal to 15 dB, occurred in 30 patients (22.3%). Patients with auditory toxicity underwent therapy for a longer period, were more likely to be bacteremic, and had, on the average, a higher temperature (P less than 0.05). Using stepwise discriminant analysis, we selected these factors with liver dysfunction and the serum urea nitrogen:serum creatinine ratio in a function that accurately discriminates between toxic and nontoxic patients. Factors not adding significantly to the predictive accuracy of the equation were plasma aminoglycoside levels, aminoglycoside type, furosemide use, diabetes, age, sex, renal function, initial auditory acuity, hematocrit value, and shock. This analysis may be important both for determining the pathophysiology of auditory toxicity and for the prognostic stratification of patients receiving aminoglycosides in clinical trials.
Insights
Longer aminoglycoside therapy, bacteremia, and higher fever increase auditory toxicity risk. These factors, along with liver dysfunction and BUN:creatinine ratio, predict hearing loss in patients.
Area of Science:
- Pharmacology and Toxicology
- Ototoxicity Research
- Clinical Trial Analysis
Background:
- Aminoglycoside antibiotics are crucial for treating severe bacterial infections.
- Auditory toxicity is a significant adverse effect associated with aminoglycoside use.
- Identifying predictive risk factors for ototoxicity is essential for patient safety.
Purpose of the Study:
- To determine risk factors associated with aminoglycoside-induced auditory toxicity.
- To develop a predictive model for identifying patients at higher risk of hearing loss.
Main Methods:
- Analysis of 135 patients from three prospective, randomized, double-blind clinical trials.
- Utilized stepwise discriminant analysis to identify significant risk factors.
- Defined auditory toxicity as a decrease in auditory acuity of ≥15 dB.
Main Results:
- Auditory toxicity occurred in 22.3% of patients.
- Prolonged therapy duration, bacteremia, and higher body temperature were significant risk factors (P < 0.05).
- Liver dysfunction and elevated serum urea nitrogen:serum creatinine ratio also contributed to the predictive model.
Conclusions:
- A discriminant function incorporating therapy duration, bacteremia, temperature, liver dysfunction, and BUN:creatinine ratio accurately predicts aminoglycoside-induced auditory toxicity.
- Factors like plasma drug levels, drug type, and patient demographics did not significantly improve predictive accuracy.
- Findings aid in understanding ototoxicity pathophysiology and stratifying patient risk in clinical settings.