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Rapid Point-of-Care Genotyping to Avoid Aminoglycoside-Induced Ototoxicity in Neonatal Intensive Care

John H McDermott1,2, Ajit Mahaveer3, Rachel A James1

  • 1Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom.

JAMA Pediatrics
|March 21, 2022
PubMed
Abstract

Insights

A rapid point-of-care test (POCT) for the MT-RNR1 m.1555A>G variant effectively identified neonates at risk for aminoglycoside-induced ototoxicity (AIO). This POCT guided antibiotic choices, preventing AIO in affected infants without disrupting clinical practice.

Area of Science:

  • Genetics and Genomics
  • Neonatal Medicine
  • Pharmacogenomics

Background:

  • Aminoglycosides are crucial for treating neonatal sepsis.
  • The MT-RNR1 m.1555A>G variant significantly increases the risk of aminoglycoside-induced ototoxicity (AIO).
  • Current genotyping methods are too slow for acute clinical settings.

Purpose of the Study:

  • To develop and implement a rapid point-of-care test (POCT) for the MT-RNR1 m.1555A>G variant.
  • To guide antibiotic prescribing in neonates and prevent AIO.
  • To assess the feasibility of POCT integration into neonatal intensive care units.

Main Methods:

  • A pragmatic prospective implementation trial was conducted in two UK neonatal intensive care units.
  • Neonates admitted to the NICU were tested for the m.1555A>G variant using the rapid POCT.
  • The study evaluated the proportion of neonates tested, clinical practice impact, and system performance.

Main Results:

  • The MT-RNR1 POCT successfully genotyped the m.1555A>G variant in a median of 26 minutes.
  • Preclinical validation showed 100% sensitivity and specificity.
  • Three neonates with the variant were identified and successfully avoided aminoglycoside antibiotics; 80.6% of infants receiving antibiotics were tested.

Conclusions:

  • The MT-RNR1 POCT can be integrated into clinical practice without disruption.
  • Rapid genotyping guides antibiotic selection, effectively preventing AIO.
  • Widespread adoption of this POCT has the potential to significantly reduce the incidence of AIO in neonates.

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