Same-day genetic testing saved a child's life from sepsis

A same-day genetic test for pediatric sepsis saved a 10-year-old girl's life by finding a hidden, drug-resistant infection. Willow Crowther from Kent was admitted to intensive care at Great Ormond Street Hospital (GOSH) in March after pneumonia triggered a seizure and multiple cardiac arrests. Her mother, Stacey Moore, was told Willow had only a 50% chance of survival, and the family was brought in to say goodbye. With the right treatment, Willow eventually recovered, but she needed several months in hospital.

The game-changing diagnostic tool

Same-day metagenomic testing rapidly identified Willow's rare, drug-resistant infection, enabling precise treatment. The test was used in a study on 122 critically ill children in GOSH's paediatric intensive care unit. It identified that Willow had a drug-resistant bacterial infection which needed a different antibiotic to the one she had been prescribed. Targeted narrow-spectrum antibiotics based on the test results halted the infection and facilitated her recovery. The test was credited with saving Willow's life.

Dr Sam Ray, a consultant in paediatric intensive care medicine at GOSH, explained the test's impact. 'The study has helped us to spot infections we would have missed, get children on the right treatment and stop antibiotics when we know they aren't going to work,' he said. Metagenomic testing at GOSH was able to identify around nine in 10 bacteria and viruses and all fungi in samples. It detected 50 organisms that were not found by routine diagnostics.

How the test works

Metagenomic sequencing analyzes all genetic material in a sample, detecting thousands of pathogens including unculturable ones within hours. This method, called metagenomic next-generation sequencing (mNGS), extracts and sequences all genetic material simultaneously. It identifies the specific pathogen and its resistance genes within hours, a stark contrast to traditional blood cultures which can take 24 to 72 hours. The technique can find unculturable pathogens such as certain fungi, atypical bacteria, and novel viruses.

Traditional methods, like culturing in Petri dishes, have been used since Victorian times and are less effective. PCR testing can identify viruses and some bacteria but requires clinicians to specify what they are looking for. Dr Sam Ray stated that traditional testing required clinicians to make an educated guess. Widespread adoption of mNGS is currently limited by the high costs of sequencing equipment and the need for bioinformatics expertise, though sequencing costs are decreasing.

Impact on treatment and resistance

The test guided immediate antibiotic changes, halted unnecessary broad-spectrum therapy, and reduced antimicrobial resistance risks. In a quarter of cases in the GOSH study, the results directly influenced prescribing decisions, including starting, stopping, or changing antibiotics. This ability to de-escalate treatment is a key tool for antimicrobial stewardship. Physicians often prescribe broad-spectrum antibiotics due to diagnostic delays, but mNGS allows for more precise targeting.

Dr Sam Ray emphasized this benefit. 'Removing unnecessary treatment is incredibly important for the fight against growing antimicrobial resistance,' he added.

Broader implications for care

The technique is expanding across UK intensive care units and could prevent future pandemic threats by detecting novel pathogens quickly. Dr Julianne Brown, head of the GOSH Metagenomics Service, said the new testing was being gradually rolled out to around 30 intensive care units across the UK treating both adults and children. The project builds on earlier trials at Guy's and St Thomas' NHS Trust which used metagenomics to test for respiratory infections in adults.

Dr Brown highlighted its potential for future outbreak detection. 'It could be a powerful tool for identifying new infections that pose a pandemic threat,' she said. 'In the future, if there was to be a new mystery pathogen that could be a cause of the next pandemic, we would detect that very quickly and put the right measures in place.' Health economists are now evaluating the cost-effectiveness of routine mNGS testing, while regulatory bodies work to standardize data interpretation.

Willow's parents are profoundly grateful for the intervention. Stacey Moore said, 'The fact that they had a test there available to her was most important. It saved her life.' Her father, Russ, added, 'It's a miracle she's here and we're extremely grateful for that.' The study detailing this work was published in the Lancet Microbe. Willow's recovery required several months in hospital.