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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

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Introduction:Aminoglycosides

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  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

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