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.
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.


CONCLUSIONS
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.
National Mycobacterium Reference Laboratory, Public Health England, London, UK Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
Katharina
K
Kranzer
National Mycobacterium Reference Laboratory, Public Health England, London, UK.
Wael F
WF
Elamin
Division of Medical Microbiology and Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Helen
H
Cox
Department of Paediatric Infectious Diseases, Imperial College London, St Mary's Hospital, London, UK.
James A
JA
Seddon
Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa.
Nathan
N
Ford
National Mycobacterium Reference Laboratory, Public Health England, London, UK Department of Infectious Diseases, Imperial College, The Hammersmith Campus, London, UK.
Francis
F
Drobniewski
D000111:Acetylcysteine / Q000627:therapeutic use*; D000617:Aminoglycosides / Q000009:adverse effects*; D004427:Ear Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006801:Humans; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
D000617:Aminoglycosides; D016166:Free Radical Scavengers; D000111:Acetylcysteine
Tuberculosis