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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

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
|August 23, 2007
PubMed

Insights

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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