1 / 25

Introduction:Aminoglycosides

SYSTEMIC GENTAMICIN OTOTOXICITY: DOSING REGIMENS, RISK FACTORS AND MEDICO-LEGAL CONCERNS Prepageran Narayanan FRCS, Vitaly Kisilevsky MD, A.R. Scott FRCS John A Rutka MD, FRCSC. Introduction:Aminoglycosides . commonly used : gram negative infections,some gram positive

amaris
Download Presentation

Introduction:Aminoglycosides

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. SYSTEMIC GENTAMICIN OTOTOXICITY: DOSING REGIMENS, RISK FACTORS AND MEDICO-LEGAL CONCERNSPrepageran Narayanan FRCS, Vitaly Kisilevsky MD, A.R. Scott FRCS John A Rutka MD, FRCSC

  2. Introduction:Aminoglycosides • commonly used : gram negative infections,some gram positive • wide spectrum, low resistance, • Unique mode of action-ribosomal binding

  3. Aminoglycosides • reservations over prolonged use • potential nephrotoxic and ototoxic

  4. Dosage regimes • Single daily dose(SDD) vs multiple daily doses regimens(MDD) • animal studies: SDD consistently less toxic (mainly nephrotoxicity) • Human studies: • SDD: greater efficacy, less toxicity? • SDD vs MDD: no significant difference?

  5. CONCERN? • failure to appreciate the ototoxic potential of SDD regimen? • false sense of security for SDD? Outpatient therapy, need for monitoring?

  6. OBJECTIVE • To compare and contrast the ototoxicity effects due to single daily dose (SDD) Gentamicin (aminoglycoside) therapy from those induced by multiple daily dosage(MDD) regimens.

  7. METHODS AND MATERIAL • retrospective review of patients with documented ototoxicity • Systemic Aminoglycosides • 1992 till present

  8. REVIEW • indications & duration of treatment • pre-existing co-morbidity • ototoxicity: clinical presentation,investigations • serum level monitoring • therapeutic induced renal impairment

  9. RESULTS • 29 patients: confirmed aminoglycoside induced ototoxicity by ENG and rotational chair studies. • female : 13 , male : 16 • age: 34-78 years

  10. Results • SDD :9 patients (31%) • MDD:20 patients (69%)

  11. Indications

  12. Clinical manifestations

  13. ANTIBIOTICS:SINGLE OR COMBINATION

  14. Serum monitoring • 14 had documented serum gentamycin monitoring • 10(71.4%) adequately monitored • 4(29.6%) inadequately monitored

  15. Serum monitoring • Normal : 9/14 (64.3%) • Elevated:5/14 (35.7%)

  16. concomitant nephrotoxicity • 21 pts had sufficient documentation • 8/21(38.1%) developed nephrotoxicity

  17. onset of nephrotoxicity vs ototoxicity • 2 prior to ototoxicity • 3 at the same time • 2 after ototoxicity • 1 could not be determined

  18. Discussion • Aminoglycosides ototoxicity, irreversible damage : end organ sensory hair cells in cochlea & vestibular labyrinth • Incidence : 2-3%, • gentamicin: 8% cochlear toxicity , 14% vestibular • higher incidence with objective testing. • 50% permanent threshold shift with ultrahigh frequency audiogram • Most cochlear toxicity: 9 to 15kHz, not routinely tested

  19. Otoxicity • Cochlear toxicity:organ of corti • Starts at basal turn, progressive • Outer hair cells, inner row of outer hair cells most sensitive • Similar microscopic findings to noise induced hearing loss • Vestibulotoxicity: crista ampularis more sensitive • Type I hair cell more sensitive • Exact mechanism unknown: ?gentamicin-iron complex

  20. SDD Vs MDD • Studies :conflicting results? Reasons? • Inherent bias of criteria,difference in study groups and doses of antibiotics • Discrepancy in diagnosis, measuring outcome, use of laboratory tools

  21. SDD Vs MDD • Ototoxicity occurs in both SDD & MDD • SDD toxicity appears earlier; 77% less than 3 weeks. • Accumulation of aminoglycosides in labyrinth related to prolonged exposure/ cumulative doses, not dosing regimes • related to transient elevated serum levels(peak) in SDD? • Animal studies: ototoxicity related to total daily dosing not frequency

  22. Serum Monitoring • Serum monitoring doesn’t prevent ototoxicty; 64.3% had normal levels. • Levels not adequately monitored in some instances • May be important from medicolegal point of view • No safe gentamicin level or dose, genetic susceptibilty

  23. the way ahead? • Awareness of clinical features of vestibulotoxicity • Imbalance, unsteadiness not vertigo • Gait ataxia, Rhomberg, oscillopsia and post head shake nystagmus • 5 out of 29 cases(16.3%) have medicolegal suits ongoing

  24. Conclusion • SDD can result in ototoxicity, earlier than MDD • Toxicity depends on cumulative dose and duration not frequency. • High index of suspicion important

More Related