Aminoglycosides for the Treatment of Severe Infection Due to Resistant Gram-Negative Pathogens

Area of Science:

• Pharmacology
• Infectious Diseases
• Critical Care Medicine

Background:

• Aminoglycosides are bactericidal antibiotics effective against Gram-negative bacteria.
• Concerns regarding renal and cochleovestibular toxicity have limited their use in sepsis and septic shock.
• Multidrug-resistant (MDR) Gram-negative infections pose a significant clinical challenge.

Purpose of the Study:

• To review the spectrum of activity and mode of action of aminoglycosides.
• To discuss methods for optimizing aminoglycoside efficacy in clinical practice.
• To highlight current indications for aminoglycosides, particularly against MDR Gram-negative pathogens.

Main Methods:

• Literature review of aminoglycoside activity, toxicity, and clinical applications.
• Analysis of evidence for aminoglycoside use in treating specific MDR Gram-negative infections.
• Examination of data supporting the use of nebulized aminoglycosides.

Main Results:

• Aminoglycosides retain activity against challenging MDR Gram-negative bacteria, including extended-spectrum β-lactamase-producing Enterobacterales, carbapenemase-producing Enterobacterales, MDR Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii.
• Optimizing dosing strategies can enhance efficacy while mitigating toxicity.
• Nebulized aminoglycoside administration shows promise for specific applications.

Conclusions:

• Aminoglycosides remain essential for treating severe infections caused by MDR Gram-negative bacteria.
• Careful patient selection and therapeutic drug monitoring are crucial to balance efficacy and toxicity.
• Further research into novel administration routes, such as nebulization, may expand their utility.