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Back to the future: using aminoglycosides again and how to dose them optimally
George L Drusano1, Paul G Ambrose, Sujata M Bhavnani
1Ordway Research Institute, Albany, NY 12208, USA. gdrusano@ordwayresearch.org
Summary
Aminoglycoside antibiotics are increasingly used due to resistance to other drugs. Optimal dosing and infrequent administration minimize toxicity and maximize efficacy for Gram-negative infections.
Area of Science:
- Pharmacology
- Infectious Diseases
- Clinical Pharmacy
Background:
- Growing resistance of Gram-negative bacteria to beta-lactam antibiotics and fluoroquinolones necessitates alternative treatments.
- Aminoglycoside antibiotics are experiencing a resurgence in clinical use due to their efficacy against resistant Gram-negative pathogens.
- Historical avoidance of aminoglycosides due to toxicity concerns is being re-evaluated with new data.
Purpose of the Study:
- To review the relationship between aminoglycoside exposure and clinical outcomes, including efficacy and nephrotoxicity.
- To provide evidence-based recommendations for optimizing aminoglycoside dosing and administration schedules.
- To guide empirical therapy with aminoglycosides for improved efficacy and reduced toxicity.
Main Methods:
- Analysis of existing literature and clinical data on aminoglycoside pharmacokinetics and pharmacodynamics.
- Evaluation of minimum inhibitory concentration (MIC) values in relation to treatment success.
- Assessment of dosing frequency and its impact on nephrotoxicity and clinical outcomes.
Main Results:
- Minimum inhibitory concentration (MIC) values of 2.0 mg/L or higher are associated with poor clinical outcomes.
- Infrequent administration, specifically 24-hour or longer intervals, is crucial for minimizing aminoglycoside-induced nephrotoxicity.
- Understanding the exposure-toxicity-efficacy relationship allows for safer aminoglycoside use.
Conclusions:
- Optimizing aminoglycoside dosing and scheduling is essential for effective treatment of Gram-negative infections.
- Therapeutic drug monitoring and individualized dosing strategies can enhance efficacy and reduce adverse events.
- Evidence-based guidelines for aminoglycoside use can improve patient outcomes in the era of increasing antibiotic resistance.
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