Once‐Daily dosing of gentamicin

Gentamicin remains one of the most effective and commonly used antimicrobials in the armamentarium of clinicians treating pelvic infections. It continues to reliably cover the aerobic gram-negative rods seen within polymicrobial infections. Available in its generic form, it becomes the low-cost drug of choice in these settings. So why mess with success? As Wiesenfield et al point out in this issue of the Journal, you can and should teach an old dog new tricks. The bactericidal activity of gentamicin is characterized by concentration-dependent killing. The higher the drug concentration, the greater the rate and extent of bactericidal activity. More over, prolonged postantibiotic effects (PAE) are observed in gram-negative bacilli following exposure to antimicrobials that are inhibitors of protein synthesis, such as gentamicin. PAE refers to the persistent suppression of bacterial growth following exposure to an antimicrobial. This PAE is further prolonged, almost doubled in fact, by the presence of leukocytes. In clinical trials correlating pharmacokinetic/pharmacodynamic parameters of aminoglycosides with therapeutic efficacy, a clinical response of > 90% required the peak level to exceed the minimum inhibition concentration (MIC) by eightfold to 10-fold. Once-daily dosing with aminoglycosides is designed to enhance peak serum concentrations. Peak concentrations that are eight to 10 times higher than the MIC can reduce the rate of emergence of aminoglycoside-resistant mu-