Adverse Events Associated With the Treatment of Multidrug-Resistant Tuberculosis: A Systematic Review and Meta-analysis

Multidrug-resistant tuberculosis (MDR-TB) is a growing public health problem. Due to long durationof therapy and concurrent use of multiple second-line drugs, adverse drug events (ADEs) are re-garded as the most important clinical consideration in patients undergoing anti-MDR-TB treatment.To evaluate the frequency and type of treatment-related ADEs owing to MDR-TB therapy. TheCochrane Library, MEDLINE, and EMBASE were searched from inception through October 1,2012, with additional manual search of International Journal of Tuberculosis and Lung Disease. Studieswith available ADEs were selected if MDR-TB patients were treated with regimen including second-line drugs. Pooled estimations of incidence for each specific type of ADEs were calculated with 95%confidence intervals using random-effects model. Of the 5346 patients included, 2602 (57.3%) expe-rienced at least 1 kind of ADE. The 3 most common side effects were gastrointestinal disorders(32.1%), ototoxicity (14.6%), and psychiatric disorders (13.2%). Subgroup analyses based on eachcharacteristic (study population, previous tuberculosis treated, human immunodeficiency virusprevalence, and length of treatment) did not show any significant difference between groups. Addi-tionally, among 1519 patients who developed ADEs with available data of impact on MDR-TBtherapy, 70.4% required change of MDR-TB treatment. Adverse events were common amongMDR-TB cases, occurring in more than half of the cases, with over two-thirds requiring change ofanti-MDR-TB treatment. MDR-TB patients should be monitored closely and managed aggressivelyfor side effects during therapy, especially for ototoxicity and psychiatric disorders.Keywords: adverse events, MDR-TB, tuberculosis, meta-analysis