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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Gooi
Adrian
A
Department of Otolaryngology, University of Manitoba, Winnipeg, Manitoba.
Hochman
Jordan
J
Wellman
Mark
M
Blakley
Laura
L
Blakley
Brian W
BW
D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005839:Gentamicins / Q000494:pharmacology* / Q000633:toxicity*; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced*; D007274:Injections, Intraperitoneal; D016014:Linear Models; D051379:Mice; D008810:Mice, Inbred C57BL; D011336:Probability; D011897:Random Allocation; D020127:Recovery of Function; D012307:Risk Factors; D012680:Sensitivity and Specificity
D005839:Gentamicins