Once-daily dosing of gentamicin in obstetrics and gynecology

Abstract

Gentamicin, an aminoglycoside with broad antimicrobial activity, is commonly used in both obstetrics and gynecology. Traditional dosing regimens for gentamicin have called for 3 times daily dosing, but recent insights into the pharmacodynamics of the drug have led to multiple studies of once-daily dosing regimens. Many studies have demonstrated efficacy, safety, and economy of the 24-hour dosing interval, resulting in recommendations that this become the standard for aminoglycoside administration. However, because of the unique considerations for drug administration in pregnant and postpartum women, the once-daily dosing regimens have not been widely adopted. Additional studies in pregnant and postpartum women have demonstrated therapeutic noninferiority, no increase in adverse events, and significant cost savings with once-daily dosing versus 3 times daily dosing of gentamicin. We review the literature and present rationale based on multiple controlled studies supporting single-daily dosing of gentamicin, 5 mg/kg/d actual body weight, for many common obstetrics-gynecology infections.

FIGURE 1

Plasma concentrations of 5λmg/kg of gentamicin as single-daily dosing or q8 hours. As peak levels increase, bactericidal activity increases. Notice the peak is nearly 3 times greater in once-daily dosing. The horizontal line represents 2λμg/mL, the trough level above which the risk of toxicity is increased. Note that with every 24-hour dosing, the time above the maximum trough is decreased. Also notice that the PAE (postantibiotic effect) overlaps the next dose of gentamicin in the every 8-hour regimen. (Adapted from Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 10th edn. NY: McGraw Hill; 2001:1219–1238).