title: Impact of drug resistance on clinical outcome in children with tuberculous meningitis.
abstract: BACKGROUND
  Tuberculous meningitis (TBM) is associated with delayed diagnosis and poor outcome in children. This study investigated the impact of drug resistance on clinical outcome in children with TBM.
  
  
  METHODS
  All children (0-13 years) were included if admitted to Tygerberg Children's Hospital, Cape Town, South Africa, from January 2003 to April 2009 with a diagnosis of either confirmed TBM, or probable TBM with mycobacterial isolation from a site other than cerebrospinal fluid. Mycobacterial samples underwent drug susceptibility testing to rifampin and isoniazid. Children were treated with isoniazid, rifampin, pyrazinamide and ethionamide according to local guidelines.
  
  
  RESULTS
  One hundred twenty-three children were included; 13% (16 of 123) had any form of drug resistance, and 4% (5 of 123) had multidrug-resistant tuberculosis. Time from start of symptoms to appropriate treatment was longer in children with any drug resistance (median: 31 days versus 9 days; P=0.001). In multivariable analysis, young age (P=0.013) and multidrug-resistant tuberculosis (adjusted odds ratio: 12.4 [95% confidence interval: 1.17-132.3]; P=0.037) remained risk factors for unfavorable outcome, and multidrug-resistant tuberculosis remained a risk for death (adjusted odds ratio: 63.9 [95% confidence interval: 4.84-843.2]; P=0.002). We did not detect any difference in outcome between those with isolates resistant to only isoniazid and those with fully susceptible strains (adjusted odds ratio: 0.22 [confidence interval: 0.03-1.87]; P=0.17).
  
  
  CONCLUSIONS
  Multidrug-resistant TBM in children has poor clinical outcome and is associated with death. We did not find any difference in the outcomes between children with isoniazid monoresistant TBM and those with drug-susceptible TBM. One explanation could be the local treatment regimen. Further investigation of this regimen is indicated.
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa. jseddon@sun.ac.za
authors.forename: James A
authors.initials: JA
authors.lastname: Seddon
authors.forename: Douwe H
authors.initials: DH
authors.lastname: Visser
authors.forename: Margaux
authors.initials: M
authors.lastname: Bartens
authors.forename: Annemie M
authors.initials: AM
authors.lastname: Jordaan
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Victor
authors.forename: A Marceline
authors.initials: AM
authors.lastname: van Furth
authors.forename: Johan F
authors.initials: JF
authors.lastname: Schoeman
authors.forename: H Simon
authors.initials: HS
authors.lastname: Schaaf
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002675:Child, Preschool; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013019:South Africa; D016019:Survival Analysis; D016896:Treatment Outcome; D014390:Tuberculosis, Meningeal / Q000188:drug therapy* / Q000382:microbiology* / Q000401:mortality
chemical_list: D000995:Antitubercular Agents