title: Successful MDR-TB treatment regimens including amikacin are associated with high rates of hearing loss.
abstract: BACKGROUND
  Aminoglycosides are a critical component of multidrug-resistant tuberculosis (MDR-TB) treatment but data on their efficacy and adverse effects in Botswana is scarce. We determined the effect of amikacin on treatment outcomes and development of hearing loss in MDR-TB patients.
  
  
  METHODS
  Patients started on MDR-TB treatment between 2006 and 2012 were included. Multivariate analysis was used to determine the effect of amikacin on treatment outcomes and development of hearing loss.
  
  
  RESULTS
  437 MDR-TB patients were included, 288 (66%) of whom were HIV co-infected. 270 (62%) developed hearing loss, of whom 147 (54%) had audiometry. Of the 313 (72%) patients who completed treatment, 228 (73%) had a good outcome (cure or treatment completion). Good outcome was associated with longer amikacin treatment (adjusted OR [aOR] 1.13, 95% CI 1.06 - 1.21) and higher dosage (aOR 1.90, 95% CI 1.12 - 2.99). Longer amikacin duration (aOR 1.98, 95% CI 1.86 - 2.12) and higher dosage per weight per month (aOR 1.15, 95% CI 1.04 - 1.28) were associated with development of hearing loss. Amikacin treatment duration modified the effect of the dosage on the risk of hearing loss, increasing this risk as the duration increased.
  
  
  CONCLUSIONS
  Amikacin was effective for MDR-TB treatment, but was associated with a high incidence of hearing loss especially in our study population. Total treatment duration and average monthly amikacin dose were associated with improved outcomes; however these were also associated with development of hearing loss.
authors.forename: Chawangwa
authors.initials: C
authors.lastname: Modongo
authors.forename: Rafal S
authors.initials: RS
authors.lastname: Sobota
authors.forename: Boikobo
authors.initials: B
authors.lastname: Kesenogile
authors.forename: Ronald
authors.initials: R
authors.lastname: Ncube
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sirugo
authors.forename: Scott M
authors.initials: SM
authors.lastname: Williams
authors.affiliation: Division of Infectious Diseases, University of Pennsylvania, Philadelphia, Pennsylvania, USA. nzetola@gmail.com.
authors.forename: Nicola M
authors.initials: NM
authors.lastname: Zetola
mesh_terms: D000293:Adolescent; D000328:Adult; D000583:Amikacin / Q000008:administration & dosage / Q000009:adverse effects*; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005260:Female; D034381:Hearing Loss / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012306:Risk; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D000583:Amikacin