Impact of Drug Resistance on Clinical Outcome in Children with Tuberculous Meningitis.

Seddon, JA; Visser, DH; Bartens, M; Jordaan, AM; Victor, TC; van Furth, AM; Schoeman, JF; Schaaf, HS; (2012) Impact of Drug Resistance on Clinical Outcome in Children with Tuberculous Meningitis. The Pediatric infectious disease journal. ISSN 0891-3668 DOI:

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: 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: 123 children were included; 13% (16 of 123) had any form of drug resistance and 4% (5 of 123) had multidrug-resistant (MDR)-TB. Time from start of symptoms to appropriate treatment was longer in children with any drug resistance (median: 31 days vs. 9 days; p=0.001). In multivariable analysis young age (p=0.013) and MDR-TB (adjusted OR: 12.4 [95%CI: 1.17-132.3]; p=0.037) remained risk factors for unfavorable outcome, and MDR-TB remained a risk for death (adjusted OR: 63.9 [95%CI: 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 stains (OR: 0.22 [CI: 0.03-1.87]; p=0.17). CONCLUSION: MDR-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 mono-resistant TBM and those with drug-susceptible TBM. One explanation could be the local treatment regimen. Further investigation of this regimen is indicated.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
PubMed ID: 22411053
Web of Science ID: 305708300010


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