Ototoxic effects of single-dose versus 19-day daily-dose gentamicin

Gentamicin is one of the most extensively studied aminoglycoside antibiotics. The dogma of gentamicin ototoxicity theorizes that (1) the toxic effects of the drug are cumulative and dose dependent, despite clinical observations of ototoxicity after a single dose, and (2) gentamicin's ototoxic effects are irreversible, although clinicians have observed improvement in hearing over time. The objective of this study was to evaluate this basic dogma by examining the ototoxic differences between single-dose and 19-day daily dosing of gentamicin over a 60-day period.

Thirty-six C57 mice were randomly assigned to one of three treatment groups: (1) 19-day daily normal saline intraperitoneal injections (control; n = 10), (2) single-dose intraperitoneal 120 mg/kg gentamicin (n = 12), and (3) 19-day daily intraperitoneal 120 mg/kg gentamicin (n = 14). Pure-tone testing using auditory brainstem response was performed at frequencies of 6, 8, 12, 20, and 30 kHz. Hearing threshold was determined at each frequency by presenting stimuli from 90 dB to 5 dB using 10 dB decrements. Pure-tone testing was performed at days 1, 35, and 60 +/- 2 days.

The results showed that hearing (1) improved between days 35 and 60 (p = .023) and (2) was not significantly different between a single dose versus 19 daily doses of gentamicin (p = .285).

This study concurs with clinical observations that a single large dose of gentamicin may have ototoxic effects similar to those of multiple doses of gentamicin and that, over time, there is the potential for hearing recovery from gentamicin ototoxicity.