Aminoglycosides in critically ill patients: which dosing regimens for which pathogens?

Area of Science:

• Pharmacology
• Critical Care Medicine
• Infectious Diseases

Background:

• Antibiotic pharmacokinetic parameters are altered in critically ill patients, increasing the risk of treatment failure.
• Aminoglycosides like amikacin, gentamicin, and tobramycin are essential for treating severe infections but require careful dosing.

Purpose of the Study:

• To determine optimized intravenous dosing regimens for amikacin, gentamicin, and tobramycin in critically ill patients.
• To improve the probability of target attainment for these antibiotics in a challenging patient population.

Main Methods:

• A parametric population pharmacokinetic approach was used.
• Monte Carlo simulations calculated the probability of target attainment using Cmax/MIC and trough concentrations.
• Data from 117 critically ill patients treated with amikacin, gentamicin, or tobramycin were analyzed.

Main Results:

• Clearance and volume of distribution varied significantly between antibiotics and patient groups (e.g., cystic fibrosis).
• Dosing adjustments for amikacin and gentamicin should consider actual body weight and creatinine clearance.
• Tobramycin dosing should be based on creatinine clearance and the presence of cystic fibrosis.

Conclusions:

• Recommended initial doses: amikacin 35 mg/kg, tobramycin 10 mg/kg (CF and non-CF).
• Gentamicin (5 mg/kg) showed optimal target attainment for Staphylococcus aureus infections.
• Conflicting efficacy and safety targets necessitate therapeutic drug monitoring for aminoglycosides in critically ill patients.