RT Journal Article SR Electronic T1 A systematic review and meta-analysis of the efficacy and safety of N-acetylcysteine in preventing aminoglycoside-induced ototoxicity: implications for the treatment of multidrug-resistant TB JF Thorax JO Thorax FD BMJ Publishing Group Ltd and British Thoracic Society SP 1070 OP 1077 DO 10.1136/thoraxjnl-2015-207245 VO 70 IS 11 A1 Kranzer, Katharina A1 Elamin, Wael F A1 Cox, Helen A1 Seddon, James A A1 Ford, Nathan A1 Drobniewski, Francis YR 2015 UL http://thorax.bmj.com/content/70/11/1070.abstract AB Background Ototoxicity is a severe side effect of aminoglycoside antibiotics. Aminoglycosides are recommended for the treatment of multidrug-resistant TB (MDR-TB). N-Acetylcysteine (NAC) appears to protect against drug- and noise-induced hearing loss. This review aimed to determine if coadministering NAC with aminoglycoside affected ototoxicity development, and to assess the safety and tolerability of prolonged NAC administration.Methods Eligible studies reported on the efficacy of concomitant NAC and aminoglycoside administration for ototoxicity prevention or long-term (≥6 weeks) administration of NAC regardless of indication. Pooled estimates were calculated using a fixed-effects model. Heterogeneity was assessed using the I2 statistic.Results Three studies reported that NAC reduced ototoxicity in 146 patients with end-stage renal failure receiving aminoglycosides. Pooled relative risk for otoprotection at 4–6 weeks was 0.14 (95% CI 0.05 to 0.45), and the risk difference was −33.3% (95% CI 45.5% to 21.2%). Eighty-three studies (N=9988) described the administration of NAC for >6 weeks. Abdominal pain, nausea and vomiting, diarrhoea and arthralgia were increased 1.4–2.2 times.Discussion This review provides evidence for the safety and otoprotective effect of NAC when coadministered with aminoglycoside. It represents a strong justification for a clinical trial to investigate the effect of concomitant NAC treatment in patients receiving aminoglycosides as part of MDR-TB treatment.