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Aminoglycosides are associated with nephrotoxicity and ototoxicity. Although dosing strategies such as once\u2010daily administration and therapeutic drug monitoring have reduced the incidence of nephrotoxicity, ototoxicity remains unpredictable and may occur at therapeutic concentrations. A strong association between specific mitochondrial DNA variants in\n                    <jats:italic>MT\u2010RNR1<\/jats:italic>\n                    (m.1555A\u2009&gt;\u2009G, m.1494C\u2009&gt;\u2009T and m.1095\u2009T\u2009&gt;\u2009C) and aminoglycoside\u2010induced hearing loss exists. These variants (frequency ~1 in 330 individuals across populations) predispose to irreversible, sensorineural hearing loss following aminoglycoside exposure, sometimes after a single dose. Avoidance of aminoglycosides is recommended at any detectable variant level. In England, laboratory\u2010based\n                    <jats:italic>MT\u2010RNR1<\/jats:italic>\n                    testing is nationally commissioned, whereas point\u2010of\u2010care testing in time\u2010critical settings like neonatal sepsis is delivered in some centres. Approximately 20% of aminoglycoside use is predictable providing opportunities for pre\u2010emptive pharmacogenetic testing. Where\n                    <jats:italic>MT\u2010RNR1<\/jats:italic>\n                    testing results are unavailable and clinical urgency is high, aminoglycoside treatment should not be delayed. Early health economic evidence suggests that point\u2010of\u2010care testing in neonates may be cost\u2010saving by preventing lifelong hearing loss. Regulatory and Health Technology Assessment bodies support targeted implementation of testing alongside further evidence generation. Overall, integration of\n                    <jats:italic>MT\u2010RNR1<\/jats:italic>\n                    pharmacogenetic testing offers a feasible and proportionate strategy to reduce harm while preserving access to life\u2010saving antibiotic therapy. This guideline is grounded in the latest evidence in this field but cannot account for all individual factors relevant to patient care. Therefore, prescribers must conduct a thorough assessment of each patient's risk\u2013benefit profile, ensuring that therapy is optimized to maximize benefits while minimizing potential harms.\n                  <\/jats:p>","DOI":"10.1002\/bcp.70712","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T14:11:56Z","timestamp":1785334316000},"page":"3002-3011","source":"Crossref","is-referenced-by-count":0,"title":["<i>MT\u2010RNR1<\/i>\n                    genotype testing for preventing aminoglycoside\u2010mediated ototoxicity: A guideline developed by the UK Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI\u2010PGx)"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5220-8837","authenticated-orcid":false,"given":"John H.","family":"McDermott","sequence":"first","affiliation":[{"name":"Division of Evolution, Infection and Genomics, School of Biological Sciences University of Manchester  Manchester UK"},{"name":"Manchester Centre for Genomic Medicine, St Mary's Hospital Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sian","family":"Hilton","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, St Mary's Hospital Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Dello Russo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology University of Liverpool  Liverpool UK"},{"name":"Department of Translational Medicine and Surgery, Section of Pharmacology Universit\u00e0 Cattolica del Sacro Cuore \u2013 Fondazione Policlinico Universitario A. Gemelli, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Booth","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, St Mary's Hospital Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Drysdale","sequence":"additional","affiliation":[{"name":"Oxford Vaccine Group, Children's Hospital University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Howard","sequence":"additional","affiliation":[{"name":"NHS England and NHS Improvement \u2013 North East and Yorkshire, NHS England North\u2010East and Yorkshire  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Chelsea and Westminster Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mallinath","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Neonatal Medicine University Hospital of Wales  Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"McDevitt","sequence":"additional","affiliation":[{"name":"Neonatal Unit Royal Hospital for Children  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Alston","sequence":"additional","affiliation":[{"name":"Newcastle Highly Specialised Mitochondrial Diagnostic Service North East and Yorkshire Genomic Laboratory Hub  Newcastle UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9928-866X","authenticated-orcid":false,"given":"Maya","family":"Desai","sequence":"additional","affiliation":[{"name":"Department of Cystic Fibrosis and Respiratory Medicine Birmingham Women's and Children's Hospital  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Beadsworth","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine  Liverpool UK"},{"name":"Specialist and Academic Medicine Royal Liverpool University Hospital  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Royal Jubilee Maternity Hospital Belfast Health and Social Care Trust  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serim","family":"Min","sequence":"additional","affiliation":[{"name":"Manchester Centre for Health Economics, Division of Population Health, Health Services Research and Primary Care, School of Health Sciences University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Payne","sequence":"additional","affiliation":[{"name":"Manchester Centre for Health Economics, Division of Population Health, Health Services Research and Primary Care, School of Health Sciences University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7534-7266","authenticated-orcid":false,"given":"Munir","family":"Pirmohamed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology University of Liverpool  Liverpool UK"},{"name":"The Wolfson Centre for Personalised Medicine, Centre for Drug Safety Science University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6382-4678","authenticated-orcid":false,"given":"William G.","family":"Newman","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, School of Biological Sciences University of Manchester  Manchester UK"},{"name":"Manchester Centre for Genomic Medicine, St Mary's Hospital Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"e_1_2_17_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a027029"},{"key":"e_1_2_17_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214\u2010109X(23)00514\u20104"},{"key":"e_1_2_17_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjoq\u20102024\u2010002847pogu"},{"key":"e_1_2_17_5_1","unstructured":"British National Formulary (BNF).Treatment summary: aminoglycosides. 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