title: Predictors of multidrug- and extensively drug-resistant tuberculosis in a high HIV prevalence community.
abstract: BACKGROUND
  Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) have emerged in high-HIV-prevalence settings, which generally lack laboratory infrastructure for diagnosing TB drug resistance. Even where available, inherent delays with current drug-susceptibility testing (DST) methods result in clinical deterioration and ongoing transmission of MDR and XDR-TB. Identifying clinical predictors of drug resistance may aid in risk stratification for earlier treatment and infection control.
  
  
  METHODS
  We performed a retrospective case-control study of patients with MDR (cases), XDR (cases) and drug-susceptible (controls) TB in a high-HIV-prevalence setting in South Africa to identify clinical and demographic risk factors for drug-resistant TB. Controls were selected in a 1:1:1 ratio and were not matched. We calculated odds ratios (OR) and performed multivariate logistic regression to identify independent predictors.
  
  
  RESULTS
  We enrolled 116, 123 and 139 patients with drug-susceptible, MDR, and XDR-TB. More than 85% in all three patient groups were HIV-infected. In multivariate analysis, MDR and XDR-TB were each strongly associated with history of TB treatment failure (adjusted OR 51.7 [CI 6.6-403.7] and 51.5 [CI 6.4-414.0], respectively) and hospitalization more than 14 days (aOR 3.8 [CI 1.1-13.3] and 6.1 [CI 1.8-21.0], respectively). Prior default from TB treatment was not a risk factor for MDR or XDR-TB. HIV was a risk factor for XDR (aOR 8.2, CI 1.3-52.6), but not MDR-TB. Comparing XDR with MDR-TB patients, the only significant risk factor for XDR-TB was HIV infection (aOR 5.3, CI 1.0-27.6).
  
  
  CONCLUSIONS
  In this high-HIV-prevalence and drug-resistant TB setting, a history of prolonged hospitalization and previous TB treatment failure were strong risk factors for both MDR and XDR-TB. Given high mortality observed among patients with HIV and drug-resistant TB co-infection, previously treated and hospitalized patients should be considered for empiric second-line TB therapy while awaiting confirmatory DST results in settings with a high-burden of MDR/XDR-TB.
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Andrews
authors.forename: N Sarita
authors.initials: NS
authors.lastname: Shah
authors.forename: Darren
authors.initials: D
authors.lastname: Weissman
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Moll
authors.forename: Gerald
authors.initials: G
authors.lastname: Friedland
authors.forename: Neel R
authors.initials: NR
authors.lastname: Gandhi
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003140:Communicable Disease Control; D054908:Extensively Drug-Resistant Tuberculosis / Q000150:complications* / Q000175:diagnosis*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000175:diagnosis*; D006801:Humans; D008297:Male; D016017:Odds Ratio; D015995:Prevalence; D012189:Retrospective Studies; D012306:Risk; D012307:Risk Factors; D013019:South Africa; D018088:Tuberculosis, Multidrug-Resistant / Q000150:complications* / Q000175:diagnosis*