Once daily aminoglycoside dosing: maintained efficacy with reduced nephrotoxicity?

Area of Science:

• Pharmacology
• Infectious Diseases
• Nephrology

Background:

• Animal studies suggest variable efficacy for once-daily aminoglycoside dosing.
• Human pharmacokinetic variability complicates direct extrapolation of animal data.
• Existing human data indicate comparable efficacy between once-daily and multiple-daily aminoglycoside regimens.

Purpose of the Study:

• To evaluate the efficacy and nephrotoxicity of once-daily versus multiple-daily aminoglycoside dosing.
• To synthesize findings from human studies on aminoglycoside dosing strategies.
• To identify limitations and areas for future research in aminoglycoside therapy.

Main Methods:

• Review of nine human studies comparing once-daily and multiple-daily aminoglycoside dosing.
• Analysis of efficacy and nephrotoxicity data, primarily focusing on non-immunocompromised patients with urinary tract infections.
• Assessment of various aminoglycosides, with a focus on netilmicin, gentamicin, amikacin, and sisomicin.

Main Results:

• Eight of nine trials found no significant difference in serum creatinine levels between dosing regimens.
• Preliminary data suggest equal efficacy and nephrotoxicity for once-daily dosing in the studied population.
• Netilmicin, at 4-6 mg/kg once daily, was frequently studied.

Conclusions:

• Once-daily aminoglycoside dosing appears equally effective and safe regarding nephrotoxicity in non-immunocompromised patients.
• Efficacy in immunocompromised patients, renal dysfunction, or for extended durations (>8 days) remains unproven.
• Further studies are required for infections beyond intra-abdominal and urinary tracts.