title: Frequency of adverse reactions to first- and second-line anti-tuberculosis chemotherapy in a Korean cohort.
abstract: OBJECTIVE
  To determine the frequency of and risk factors for major adverse drug reactions (MADRs) associated with anti-tuberculosis treatment at a tuberculosis (TB) referral hospital in the Republic of Korea.
  
  
  METHODS
  Data from an ongoing natural history cohort study were analyzed  for permanent regimen changes due to adverse drug reactions and confirmed by chart review.
  
  
  RESULTS
  Among 655 subjects, there were 132 MADRs in 112 (17%) subjects. The most common MADRs were gastrointestinal (n = 53), musculoskeletal (n = 22), psychiatric (n = 10),  visual (n = 9) and peripheral neuropathic (n = 8). MADRs were more frequent in subjects being treated with second-line regimens (16%) compared to first-line regimens (2.5%). Drugs frequently associated with MADRs were amikacin (3/10, 30%), linezolid (8/29, 28%), para-aminosalicylic  acid (47/192, 24%), pyrazinamide (31/528, 5.8%), macrolides (2/44, 4.5%) and cycloserine (12/272, 4.4%). Fluoroquinolones accounted for a single MADR (1/377, 0.003%), despite widespread usage. In multivariate analysis, infection with multi- or extensively drug-resistant disease and previous  history of anti-tuberculosis treatment were risk factors for MADR, with adjusted hazard ratios of respectively 2.2 (P = 0.02) and 1.6 (P = 0.04).
  
  
  CONCLUSIONS
  MADRs are common during anti-tuberculosis chemotherapy in this population, occurring in more than one in six subjects.  New and less toxic agents to treat drug-resistant TB are urgently needed.
authors.affiliation: International Tuberculosis Research Center, Masan, Republic of Korea.
authors.forename: M W
authors.initials: MW
authors.lastname: Carroll
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: Y
authors.initials: Y
authors.lastname: Cai
authors.forename: C W
authors.initials: CW
authors.lastname: Hallahan
authors.forename: P A
authors.initials: PA
authors.lastname: Shaw
authors.forename: J H
authors.initials: JH
authors.lastname: Min
authors.forename: L C
authors.initials: LC
authors.lastname: Goldfeder
authors.forename: V
authors.initials: V
authors.lastname: Alekseyev
authors.forename: S
authors.initials: S
authors.lastname: Grinkrug
authors.forename: H S
authors.initials: HS
authors.lastname: Kang
authors.forename: S
authors.initials: S
authors.lastname: Hwang
authors.forename: H-M
authors.initials: HM
authors.lastname: Park
authors.forename: E
authors.initials: E
authors.lastname: Kang
authors.forename: S-Y
authors.initials: SY
authors.lastname: Lee
authors.forename: B
authors.initials: B
authors.lastname: Jin
authors.forename: H-E
authors.initials: HE
authors.lastname: Park
authors.forename: S
authors.initials: S
authors.lastname: Min
authors.forename: S K
authors.initials: SK
authors.lastname: Park
authors.forename: D S
authors.initials: DS
authors.lastname: Jeon
authors.forename: L E
authors.initials: LE
authors.lastname: Via
authors.forename: C E
authors.initials: CE
authors.lastname: Barry
mesh_terms: D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D056910:Republic of Korea; D012307:Risk Factors; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents