Program Schedule

405
Risk of gentamicin vestibulotoxicity with different dosing regimens:  a retrospective cohort study

Session: Poster Abstract Session: PK/PD Studies
Thursday, October 9, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
Background: Gentamicin is used for the treatment of resistant gram-negative bacterial infections.  Studies comparing single-daily dosing (SDD) to multiple-daily dosing (MDD) show similar efficacy and less nephrotoxicity.  Less is known about the effects of different dosing regimens on the development of ototoxicity.  Among patients referred to our Multidisciplinary Neurotology Clinic (MNC), we compared the impact of SDD versus MDD of gentamicin in patients without acute kidney injury (AKI) on the development of vestibulotoxicity.

Methods: Data was collected for consecutive patients referred to our MNC between 1993 and 2012, including patient demographics, medical co-morbidities, concurrent medications, gentamicin dosing regimen, indications for use, cumulative dose and duration of therapy-to-time of diagnosis of vestibulotoxicity, and presence of AKI, determined by history or 1.5-fold elevation in serum creatinine. 

Results: Forty-six patients were identified of whom 19 (43.1%) had no evidence of AKI.  Eighteen (94.7%) had imbalance, 10 (52.6%) had oscillopsia (visual blurring with head movement), while only 1 (5.3%) and 2 (10.5%) complained of tinnitus and deafness, respectively.  Vestibulotoxicity was confirmed through audiovestibular testing.  Twelve patients had received SDD and 5 patients had received MDD; 2 were excluded from analysis because of incomplete dosing documentation.  The median cumulative dose resulting in vestibulotoxicity in SDD compared to MDD patients was 4.8g (interquartile range (IQR) = 2.2-8.1g) versus  8.2g (IQR = 6.4-9.4g) (p=0.009) and the median duration of therapy-to-time of diagnosis of vestibulotoxicity was 15d (IQR = 5-22d) versus 34.5d (IQR = 24.3-40.3d) (p=0.03). 

Conclusion: In patients referred to our MNC without AKI, gentamicin vestibulotoxicity occurred at a lower cumulative dose and with a shorter duration of therapy if they had received SDD versus MDD.  As vestibulotoxicity may result in permanent impairment, including an inability to return to work, prospective safety evaluation for both dosing regimens is warranted.

Jerome Leis, MD, MSc, David Pothier, MBChB, MSc, Wayne Gold, MD and John Rutka, MD, University of Toronto, Toronto, ON, Canada

Disclosures:

J. Leis, None

D. Pothier, None

W. Gold, None

J. Rutka, None

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