Abstract
BackgroundIndia has a high burden of drug resistant TB, although there are few data on XDR-TB. Although XDR-TB has existed previously in India, the definition has not been widely applied, and surveillance using second line drug susceptibility testing has not been performed. Our objective was to analyze clinical and demographic risk factors associated with isolation of MDR and XDR TB as compared to susceptible controls, at a tertiary center.Methodology/FindingsRetrospective chart review based on positive cultures isolated in a high volume mycobacteriology laboratory between 2002 and 2007. 47 XDR, 30 MDR and 117 susceptible controls were examined. Drug resistant cases were less likely to be extrapulmonary, and had received more previous treatment regimens. Significant risk factors for XDR-TB included residence outside the local state (OR 7.43, 3.07-18.0) and care costs subsidized (OR 0.23, 0.097-0.54) in bivariate analysis and previous use of a fluoroquinolone and injectable agent (other than streptomycin) (OR 7.00, 95% C.I. 1.14-43.03) and an initial treatment regimen which did not follow national guidelines (OR 5.68, 1.24-25.96) in multivariate analysis. Cavitation and HIV did not influence drug resistance.Conclusions/SignificanceThere is significant selection bias in the sample available. Selection pressure from previous treatment and an inadequate initial regimen increases risk of drug resistance. Local patients and those requiring financial subsidies may be at lower risk of XDR-TB.
Highlights
India has the greatest burden of Tuberculosis (TB) disease in the world, with 1.8 million new cases annually and an estimated prevalence of 3.8 million bacteriologically proven cases in 2000.[1]
Significant risk factors for XDR-TB included residence outside the local state and care costs subsidized in bivariate analysis and previous use of a fluoroquinolone and injectable agent and an initial treatment regimen which did not follow national guidelines in multivariate analysis
Inclusion in the study was limited to specimens growing Mycobacterium tuberculosis which were tested for first and second line drug susceptibility test (DST) by request of the physician, and which were available for our evaluation
Summary
India has the greatest burden of Tuberculosis (TB) disease in the world, with 1.8 million new cases annually and an estimated prevalence of 3.8 million bacteriologically proven cases in 2000.[1]. Multidrug resistant TB (MDR-TB) is defined as resistance to the two most important first-line drug treatments, isoniazid and rifampicin. Drug resistant TB (XDR-TB) is resistant to these first line agents, as well as to at least one fluoroquinolone and at least one injectable agent.[3] This phenotype emerges from MDRTB, with the acquisition of further drug resistance mutations, and was first described in the United States[4], followed by the Tugela Ferry outbreak.[5] XDR-TB is associated with a significantly worse clinical outcome,[6,7] and risk factors for poor treatment response have been defined.[8] MDR and XDR represent distinct phenotypes and are considered separately in this paper and other publications. Our objective was to analyze clinical and demographic risk factors associated with isolation of MDR and XDR TB as compared to susceptible controls, at a tertiary center
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