Seddon J.A., Visser D.H., Bartens M., Jordaan A.M., Victor T.C., Van Furth A.M., Schoeman J.F., Schaaf H.S.
Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, PO Box 19063, Cape Town, South Africa; Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom; Department of Paediatrics, VU University Medical Centre, Amsterdam, Netherlands; Division of Molecular Biology and Human Genetics, Department of Biomedical Science, Stellenbosch University, Tygerberg, South Africa; Tygerberg Children's Hospital, Cape Town, South Africa
Seddon, J.A., Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, PO Box 19063, Cape Town, South Africa, Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom; Visser, D.H., Department of Paediatrics, VU University Medical Centre, Amsterdam, Netherlands; Bartens, M., Department of Paediatrics, VU University Medical Centre, Amsterdam, Netherlands; Jordaan, A.M., Division of Molecular Biology and Human Genetics, Department of Biomedical Science, Stellenbosch University, Tygerberg, South Africa; Victor, T.C., Division of Molecular Biology and Human Genetics, Department of Biomedical Science, Stellenbosch University, Tygerberg, South Africa; Van Furth, A.M., Department of Paediatrics, VU University Medical Centre, Amsterdam, Netherlands; Schoeman, J.F., Tygerberg Children's Hospital, Cape Town, South Africa; Schaaf, H.S., Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, PO Box 19063, Cape Town, South Africa, Tygerberg Children's Hospital, Cape Town, South Africa
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). Conclusion: 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. © 2012 by Lippincott Williams ∧ Wilkins.
ethionamide; isoniazid; pyrazinamide; quinolone derivative; rifampicin; terizidone; adolescent; antibiotic sensitivity; article; bacterial strain; bacterium isolate; bacterium isolation; cerebrospinal fluid; child; death; disease severity; drug resistance; drug sensitivity; female; health status; hospital admission; human; Human immunodeficiency virus infection; infant; major clinical study; male; multidrug resistant tuberculosis; newborn; priority journal; risk factor; tuberculous meningitis; Antitubercular Agents; Child, Preschool; Drug Resistance, Bacterial; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Mycobacterium tuberculosis; South Africa; Survival Analysis; Treatment Outcome; Tuberculosis, Meningeal
