Adverse effects induced by second-line antituberculosis drugs: an update based on last WHO treatment recommendations for drug-resistant tuberculosis

Tuberculosis (TB), a common condition worldwide, is still among the main infectious diseases with high mortality rates, both in adults and infants. Drug-resistant tuberculosis (DR-TB) drugs, revised by the World Health Organization (WHO) in 2018, are a prolonged and complex therapy associated with many adverse drug effects (ADEs). To systematically review the ADEs of second-line anti-TB drugs reported in multicentric studies published after the latest WHO guidelines, compared with those from clinical trials published before 2018. A PubMed search, using keywords (TB OR DR-TB) AND (adverse effects) AND “second-line anti-TB drugs”, resulted in 56 studies. Only two studies, published after the last update of WHO guidelines in 2018, reported ADEs. A total of 223 participants were included in the two selected studies. The use of multidrug regimens has been associated with an increased incidence of ADEs: 42 ADEs were recorded in 30 patients (26.3%) in the first study, while all patients had at least one ADE that occurred or worsened during treatment; and 19 (17%) had severe ADEs in the second study. However, both studies had a good favourable outcome rate (90% and 79.8%, respectively). Gastrointestinal disturbances, hepatotoxicity, headache and dizziness are the most common ADEs induced by a majority of second-line DR-TB treatments. A special attention should be given in the case of association of drugs determining QT interval (QT) prolongation on electrocardiogram, or psychiatric disorders. Proper strategies about ADE management have to be planned for timely detection of the possible ADEs that can be induced by second-line anti-TB therapy.