Clinical features, resistance patterns and treatment outcomes of drug-resistant extra-pulmonary tuberculosis: A scoping review

Background: Drug-resistant tuberculosis (DR-TB) is a threat to tuberculosis (TB) control. Extra-pulmonary forms of DR-TB (DR-epTB) are not well characterized. This review summarizes the clinical features, resistance patterns and treatment outcomes of DR-epTB. Methods: We searched EMBASE to identify studies that reported drug-resistance among extra-pulmonary TB sites. All age groups were included in this review. Studies which did not describe drug-resistance patterns at extra-pulmonary TB sites were excluded. We summarized the proportion of resistance to individual anti-TB drugs as well as multi-drug resistant (MDR), pre-extensively drug resistant (pre-XDR) and extensively drug-resistant (XDR) TB. Results: Eighteen studies with a total of 10,222 patients with extra-pulmonary TB of whom 1,236 (12.0%) had DR-epTB, were included in this review. DR-epTB was mostly reported in young people aged 28 to 46 years. While TB meningitis is the most commonly studied form, adenitis is the commonest form of DR-epTB reported in 21% to 47%. Central nervous system TB (3.8% to 51.6%), pleural TB (11.3% to 25.9%), skeletal TB (9.4% to 18.1%), abdominal TB (4.3% to 6.5%), and disseminated TB (3.8%) are also encountered. The HIV co-infection rate is reported to be 5.0% to 81.3% while 2.6% to 25.4 % have diabetes mellitus. Clinical symptoms of DR-epTB are consistent with morbidity in the affected body system. Among patients with DR-epTB, the proportion of MDR TB was 5% to 53% while that for pre-XDR TB and XDR TB was 3% to 40% and 4% to 33%, respectively. Treatment success is achieved in 26% to 83% of patients with DR-epTB while death, treatment loss-to-follow up, and treatment failure occur in 2% to 76%, 7% to 15%, and 0% to 4% respectively. Patients with DR-epTB were reported to have poorer outcomes than those with pulmonary DR-TB and extra-pulmonary drug-susceptible TB. Conclusion: Clinical features of DR-epTB are similar to those observed among people with drug-susceptible EPTB but patients with DR-epTB post worse treatment outcomes