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Thorax. 2015 Nov;70(11):1070-7. doi: 10.1136/thoraxjnl-2015-207245. Epub 2015 Sep 7.

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.

Author information

1
National Mycobacterium Reference Laboratory, Public Health England, London, UK Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
2
National Mycobacterium Reference Laboratory, Public Health England, London, UK.
3
Division of Medical Microbiology and Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
4
Department of Paediatric Infectious Diseases, Imperial College London, St Mary's Hospital, London, UK.
5
Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa.
6
National Mycobacterium Reference Laboratory, Public Health England, London, UK Department of Infectious Diseases, Imperial College, The Hammersmith Campus, London, UK.

Abstract

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 I(2) 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.

KEYWORDS:

Tuberculosis

PMID:
26347391
DOI:
10.1136/thoraxjnl-2015-207245
[Indexed for MEDLINE]

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