Adverse Events Associated With the Treatment of Multidrug-Resistant Tuberculosis

Abstract

Multidrug-resistant tuberculosis (MDR-TB) is a growing public health problem. Due to long duration of therapy and concurrent use of multiple second-line drugs, adverse drug events (ADEs) are regarded 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. The Cochrane Library, MEDLINE, and EMBASE were searched from inception through October 1, 2012, with additional manual search of International Journal of Tuberculosis and Lung Disease. Studies with 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%) experienced 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 each characteristic (study population, previous tuberculosis treated, human immunodeficiency virus prevalence, and length of treatment) did not show any significant difference between groups. Additionally, among 1519 patients who developed ADEs with available data of impact on MDR-TB therapy, 70.4% required change of MDR-TB treatment. Adverse events were common among MDR-TB cases, occurring in more than half of the cases, with over two-thirds requiring change of anti-MDR-TB treatment. MDR-TB patients should be monitored closely and managed aggressively for side effects during therapy, especially for ototoxicity and psychiatric disorders.

Discordance between patient and clinician reports of adverse reactions to MDR-TB treatment

“…First, insomnia was the most common ADR and one of the most bothersome, yet sleep disturbances were rarely documented in previous studies on MDR-TB ADRs. 9 Another noteworthy finding was that neither depression nor anxiety was ever documented in the medical records. Even though both depression and anxiety are common ADRs during MDR-TB treatment, 30 psychiatric symptoms are often overlooked by clinicians.…”

“…8 The majority of studies on MDR-TB treatment-related ADRs have been retrospective cohorts utilizing medical record data abstraction of clinician report of ADRs. 9 Several studies outside the MDR-TB context have shown a lack of concordance between patient report and clinician medical record documentation. 10–14 …”

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

“…334,335 However, high-quality, prospective studies of adverse effects in children on MDR tuberculosis treatment are rare. Additionally, adverse effects are more difficult to assess in children, and could therefore be underestimated.…”

Dilemma of managing asymptomatic children referred with ‘culture-confirmed’ drug-resistant tuberculosis

“…Serious drug-related adverse effects associated with DR-TB therapy include irreversible hearing loss, hypokalaemia, renal damage, hypothyroidism, depression and psychosis, while unpleasant effects include tinnitus, nausea and vomiting, joint pain, vertigo, peripheral neuropathy, anxiety and confusion. 26 In patients with HIV co-infection, adverse events do not appear to be more common, but can be more difficult to diagnose and manage, due to overlapping drug toxicities with ART. 25 27 While adverse effects associated with DR-TB therapy have been well documented in adults, 26 they have been underinvestigated in young children, [28][29][30] although treatment appears to be better tolerated than in adults.…”

“…26 In patients with HIV co-infection, adverse events do not appear to be more common, but can be more difficult to diagnose and manage, due to overlapping drug toxicities with ART. 25 27 While adverse effects associated with DR-TB therapy have been well documented in adults, 26 they have been underinvestigated in young children, [28][29][30] although treatment appears to be better tolerated than in adults. TB-associated stigma, 31 prolonged hospitalisation and repeated painful injections may also leave psychological scars.…”