title: Treatment of tuberculosis in a region with high drug resistance: outcomes, drug resistance amplification and re-infection.
abstract: BACKGROUND
  Emerging antituberculosis drug resistance is a serious threat for tuberculosis (TB) control, especially in Eastern European countries.
  
  
  METHODS
  We combined drug susceptibility results and molecular strain typing data with treatment outcome reports to assess the influence of drug resistance on TB treatment outcomes in a prospective cohort of patients from Abkhazia (Georgia). Patients received individualized treatment regimens based on drug susceptibility testing (DST) results. Definitions for antituberculosis drug resistance and treatment outcomes were in line with current WHO recommendations. First and second line DST, and molecular typing were performed in a supranational laboratory for Mycobacterium tuberculosis (MTB) strains from consecutive sputum smear-positive TB patients at baseline and during treatment.
  
  
  RESULTS
  At baseline, MTB strains were fully drug-susceptible in 189/326 (58.0%) of patients. Resistance to at least H or R (PDR-TB) and multidrug-resistance (MDR-TB) were found in 69/326 (21.2%) and 68/326 (20.9%) of strains, respectively. Three MDR-TB strains were also extensively resistant (XDR-TB). During treatment, 3/189 (1.6%) fully susceptible patients at baseline were re-infected with a MDR-TB strain and 2/58 (3.4%) PDR-TB patients became MDR-TB due to resistance amplification. 5/47 (10.6%) MDR- patients became XDR-TB during treatment. Treatment success was observed in 161/189 (85.2%), 54/69 (78.3%) and 22/68 (32.3%) of patients with fully drug susceptible, PDR- and MDR-TB, respectively. Development of ofloxacin resistance was significantly associated with a negative treatment outcome.
  
  
  CONCLUSIONS
  In Abkhazia, a region with high prevalence of drug resistant TB, the use of individualized MDR-TB treatment regimens resulted in poor treatment outcomes and XDR-TB amplification. Nosocomial transmission of MDR-TB emphasizes the importance of infection control in hospitals.
authors: Clinical Research department, Epicentre, Geneva, Switzerland. maryline.bonnet@geneva.msf.org
authors: Maryline
authors: M
authors: Bonnet
authors: Manuela
authors: M
authors: Pardini
authors: Francesca
authors: F
authors: Meacci
authors: Germano
authors: G
authors: Orrù
authors: Hasan
authors: H
authors: Yesilkaya
authors: Thierry
authors: T
authors: Jarosz
authors: Peter W
authors: PW
authors: Andrew
authors: Mike
authors: M
authors: Barer
authors: Francesco
authors: F
authors: Checchi
authors: Heinz
authors: H
authors: Rinder
authors: Graziella
authors: G
authors: Orefici
authors: Sabine
authors: S
authors: Rüsch-Gerdes
authors: Lanfranco
authors: L
authors: Fattorini
authors: Marco Rinaldo
authors: MR
authors: Oggioni
authors: Juliet
authors: J
authors: Melzer
authors: Stefan
authors: S
authors: Niemann
authors: Francis
authors: F
authors: Varaine
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use; D015331:Cohort Studies; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D005260:Female; D005846:Georgia (Republic) / Q000453:epidemiology; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents