Factors Associated with Ototoxicity among TB Patients Treated with Aminoglycosides translation missing: zh.hyrax.visibility.files_restricted.text

Smith, Gillian (Spring 2018)

Permanent URL: https://etd.library.emory.edu/concern/etds/t148fh15c?locale=zh
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Abstract

Multi-resistant tuberculosis (MDR TB) has become a persistent threat to the elimination of TB and requires lengthy, expensive and often toxic treatment. There were an estimated 600,000 cases of MDR TB worldwide in 2016. Aminoglycosides are an important class of drugs in MDR TB treatment, but are known to be highly nephrotoxic and ototoxic (hearing loss). The association between aminoglycoside treatment for TB and ototoxicity is not well studied and this paper seeks to fill in this knowledge gap.

This paper is a secondary analysis of patients hospitalized for TB treatment at the Tuberculosis Unit of the University of Texas Health Science Center (UTHSCT), Texas Center for Infectious Diseases (TCID) and A.G. Holley Hospital (AGHH), Lantana, Florida. The dataset for this study included all patients with therapeutic drug monitoring and at least 2 audiograms. Serial audiogram measurements were used to conduct a longitudinal multivariate analysis of the association between cumulative dosage of aminoglycosides and ototoxicity, using generalized estimating equations.

We report an incidence of ototoxicity of 33.3% (n = 27) in the study population. The odds of ototoxicity was 3.75 times higher among patients with a cumulative dosage of any aminoglycoside greater than 131 grams compared to a cumulative dosage less than or equal to 131 grams (95% CI 1.42,9.96, p = 0.01). Gender, history of TB and total duration of aminoglycoside treatment were also associated with an increased odds of ototoxicity (p = 0.03, p = 0.09, p = 0.04). The odds of ototoxicity was 6.23 times higher among patients at UTHSCT than patients at TCID/AGHH (95% CI 1.5, 25.77, p = 0.02).

Cumulative dosage of aminoglycosides greater than 131 grams is associated with increased odds of ototoxicity. The threshold may biologically represent a threshold of accumulation of aminoglycosides in cochlear cells where cell death is inevitable. Providers should consider carefully and routinely monitoring the level of total exposure to aminoglycosides among patients and perform regular hearing evaluations. However, further study of aminoglycoside-induced ototoxicity is necessary to understand the risk for patients receiving TB treatment before treatment guidelines can be changed.

Table of Contents

TABLE OF CONTENTS

Background................................................................1

   TB Treatment and Drug-Resistant TB....................1

   Aminoglycosides .................................................3

       Mechanisms of Action............................................3

       Application to non-TB Diseases................................3

       Application to TB.............................................4

       Adverse Effects of Aminoglycosides................................4

  Ototoxicity ..........................5

      Ototoxicity in non-TB Diseases........................5

      Ototoxicity in TB..................................................8

      Risk Factors for Ototoxicity....................................10

  Justification for Study....................................................12

  Objectives ...............................................................................12

Methods ........................................................................13

  Data Source.................................................13

  Study Population......................................................13

    Outcome: Ototoxicity ............................................................14

     Exposure: Aminoglycosides........................................14

     Other Sociodemographic and Clinical Characteristics.....................15

  Descriptive Analysis...........................................16

  Bivariate Analysis.........................................16

  Multivariate Analysis..........................................17

Results........................................................19

  Descriptive analysis......................................................19

      Aminoglycoside Exposure.....................................................20

      Ototoxicity......................................................22

      Other Adverse Events and TB Treatment Outcome ...........................23

  Bivariate Analysis...............................................23

     Aminoglycoside Exposure.............................24

    Other adverse Events and TB Treatment Outcome.........................26

 Multivariate analysis..................................................26

    Exposure: Cumulative dosage of Aminoglycosides ............................27

    Exposure: Total Duration ................................................29

   Model Fit........................................31

Discussion.........................................................32

  Strengths and limitations.....................................................35

  Future Directions and Impact on Public Health..........................................35 References............................................................37

Tables............................................................................46

Figures ...............................................66

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