Aims Amikacin is an aminoglycoside antibacterial, associated with both ototoxicity and nephrotoxicity.1 It is used at the Trust first line for many indications, such as sepsis and pre-operative prophylaxis. A mutation in the m1555A>G gene has been linked to an increased risk of aminoglycoside induced ototoxicity2, therefore making these patients susceptible to hearing damage when treated with aminoglycosides.3 The residual effect of this damage is both profound and rapidly progressive with resulting permanent hearing loss occurring even when the doses administered remain in the therapeutic window.4
Trust guidelines containing amikacin advise that genetic testing should consistently be carried out and where this is not possible, clinicians should discuss and receive advice from the microbiology team for an alternative option. Genetic testing can take up to two weeks to be reported causing a logistical problem for patients requiring the medication usually on a more urgent basis.
The aim of this study was to assess whether the Trust routinely provides genetic testing for mitochondrial DNA mutation m.1555A>G abnormality and to determine whether prescribed antibiotics are appropriately following the results of this testing, including any resulting patient safety issues.
Method The data was collected retrospectively from all genetic testing results since 2008 using prescribing data from the implementation of JAC and also an analysis of patient notes to check audiology referrals. The comparative standards used were 100% of positive test results should be recorded on patient prescribing record, this process is currently manual. 100% of patients who have received an aminoglycoside have prior testing for the m1555A>G mutation, 100% of patients who have received an aminoglycoside tested negative for the m1555A>G mutation, 100% of patients who tested positive for the m1555A>G mutation have not received an aminoglycoside, either before or after the test result.
3815 patients were tested for the m.1555A>G mutation between 2008–2018 and included for audit, 12 patients (0.31%) tested positive for the genetic mutation
100% of these patients had their positive result recorded as an aminoglycoside allergy on JAC
5 of these 12 patients had been treated with aminoglycosides at GOSH (42%)
1 of these patients received Amikacin before genetic testing
Conclusion This audit will inform future decisions regarding Trust guidelines containing amikacin. The low incidence of this mutation will be useful in discussion on moving forward in providing testing for patients. It reassures users that the current reporting system is robust and results are reliably recorded. Of the 5 patients who had a positive genetic mutation and received an aminoglycoside it was not clear if this was an intentional, informed risk benefit decision. Further work is being done to ensure these patients have and are followed up.
Estivill X, Govea N, Barceló A, Perelló E, Badenas C, Romero E, et al. Familial Progressive Sensorineural Deafness Is Mainly Due to the mtDNA A1555G Mutation and Is Enhanced by Treatment with Aminoglycosides. The American Journal of Human Genetics. 1998;62:27–35.
Göpel W, Berkowski S, Preuss M, et al. Mitochondrial mutation m.1555A>G as a risk factor for failed newborn hearing screening in a large cohort of preterm infants. BMC Pediatrics. 2014;14:210.
Bitner-Glindzicz M, Pembrey M, Duncan A, Heron J, Ring S, Hall A, et al. Prevalence of Mitochondrial 1555A→G Mutation in European Children. New England Journal of Medicine. 2009;360:640–642.
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