Compared with other patients with IE, in general, patients with enterococcal IE are older; are often debilitated; may have complicated, underlying urological conditions, including pre-existing renal failure; may have healthcare-associated infections; and have significant other underlying comorbidities common in older In these patients, gentamicin-associated neph- rotoxicity may significantly complicate a standard 4- to 6-week course of therapy and could result in serious, possibly life-threatening, complications such as renal failure requiring hemodialysis. In these situations, the potential risk of attempt- ing to complete a 4- to 6-week course of gentamicin therapy may exceed the benefit.193 In patients with VGS IE treated with multiple divided doses of gentamicin, single daily-dose therapy with genta- micin resulted in similar response rates and was well tol- erated (see treatment of VGS IE above). Studies of single daily dosing of gentamicin compared with divided doses in enterococcal experimental IE and in humans have yielded conflicting results. These results may reflect different PK of aminoglycosides in animals compared with humans. Studies in humans of the dosing interval of gentamicin were not controlled or standardized. Dosing of gentamicin ranged from once daily to 3 times daily; therefore, the data were insufficient to compare the efficacy of once-daily doses with divided doses. Until more convincing data demonstrate that once-daily dosing of gentamicin is as effective as multiple dosing, in patients with normal renal function, gentami- cin should be administered in daily multiple divided doses ) rather than a daily single dose to patients with enterococcal IE. In patients with normal renal function, it is reasonable to administer gentamicin every 8 hours with the dose adjusted to achieve a 1-hour serum con- centration of 3 g/mL and a trough concentration of <1 g/ mL. 