Unexplained Intoxication – A Rare Case? Auto-Brewery Syndrome

A 46-year-old man from North Carolina, pulled over on suspicion of drunk driving, strongly denied driving under the influence. When he refused an alcohol test, he was taken to hospital, where doctors confirmed what police suspected. His blood alcohol level was two and a half times the state's legal limit, and he was charged with driving while intoxicated.

For a year after his arrest, the cause of his "intoxication" remained a mystery. His aunt realized what was happening when she learned of a similar case successfully treated at a clinic in Ohio. He had auto-brewery syndrome (auto brewery syndrome-ABS).

Gut fermentation syndrome

Also known as gut fermentation syndrome, ABS is a rarely diagnosed gastrointestinal (stomach and bowel) condition that causes patients to appear drunk and experience all the medical and social consequences of alcoholism.

Reporting the case in BMJ Gastroenterology, Fahad Malik said, "ABS occurs when ingested carbohydrates are converted into alcohol by fungi in the gastrointestinal tract."

At his aunt's insistence, the patient went to the Ohio clinic, where a complete blood count, comprehensive metabolic panel (tests providing information about the kidneys, blood sugar and electrolytes), immunology panel and urinalysis were performed, all with normal results.

However, a stool test revealed the presence of two yeast species commonly used in making wine, bread and beer: saccharomyces cerevisiae and saccharomyces boulardii.

To confirm the ABS diagnosis, the patient was given a carbohydrate meal and clinicians monitored his blood alcohol level. After 8 hours, it reached 57 mg / dL. He was treated with antifungals (medicines used for fungal infections) for the saccharomyces fungi in his stool and discharged on a strict carbohydrate-free diet with special supplements, including multivitamins and probiotics, but no further antifungal treatment was given.

Malik said probiotics prevent the development of bad bacteria and fungi, but there is currently evidence showing they are beneficial for ABS.

Despite following the treatment regimen, the patient's intermittent flare-ups returned after several symptom-free weeks. During an episode of “intoxication”, he fell and hit his head. This caused an intracranial haemorrhage, and he was transferred to a neurosurgical centre. During his hospital stay, blood alcohol levels ranged from 50 to 400 mg/dL.

Were antibiotics responsible in this case?

Distressed by his continuing symptoms, the patient sought support in an online forum. There, he read about Fahad Malik and gastroenterologist Prasanna Wickremesinghe, who had treated a complex and very similar ABS case. He contacted the two doctors, and they evaluated him.

Malik said, "We examined the patient from A to Z because we were trying to find similar things in his history. We wanted to know exactly when it began and understand when he started experiencing mental confusion".

After speaking to the patient, Malik and Wickremesinghe traced his first symptoms to an antibiotic course prescribed in 2011 for a complicated traumatic thumb injury (250 mg of cefalexin three times daily for 3 weeks).

About a week after finishing the antibiotics, the patient experienced marked behavioural changes, including depression, mental confusion and aggressive outbursts.

In 2014, he visited his family doctor for treatment, was referred to a psychiatrist and was treated with lorazepam (used to treat anxiety and sleep disorders, active seizures, alcohol withdrawal, and chemotherapy-related nausea and vomiting) and fluoxetine (a type of antidepressant). The patient stated that he had previously been healthy, with no significant medical or psychiatric history.

Malik believes the antibiotics prescribed years earlier were responsible. "We hypothesize that the antibiotics altered his gut microbiome and allowed fungi to grow", he said.

Because there are no established diagnostic criteria or treatment regimen for ABS, Malik and Wickremesinghe developed their own approach.

Diagnosis consisted of a standardized carbohydrate challenge test with a carbohydrate meal, giving the patient 200 grams of glucose orally after an overnight fast. They also drew blood at set intervals over 24 hours to test glucose and blood alcohol levels.

Wickremesinghe said, "After this, we need to isolate the fungi by examining intestinal secretions through upper and lower endoscopy." He grew yeast cultures (Candida albicans and C parapsilosis) from upper small bowel and caecal secretions.

Both fungi were sensitive to azoles (antifungal medicines), and the doctors initially prescribed 150 mg of oral itraconazole daily (an antifungal medicine used to treat fungal infection). Because symptoms had not improved after 10 days, the dose was increased to 200 mg daily, and the patient became completely symptom-free.

Malik said, "We had nothing to guide us. We did not know how long to treat the patient; it really was just a process of trial and error". The doctors asked the patient to check his breath alcohol level twice daily during treatment and report any increase immediately. Over time, he received various probiotics to help normalize his gut flora.

An underdiagnosed condition

When the case study was published in the summer of 2019, the patient had been symptom-free for 18 months and could resume a normal diet. However, he still occasionally checks his breath alcohol level.

Malik said, "Before this patient's case, I reviewed all the literature and found only a few cases of ABS". He added that, after the case study was published, 10 different people contacted him with similar histories of antibiotic use and the same symptoms. Malik emphasized that this was important and that ABS was much more common than previously thought.

Wickremesinghe said, "What we were trying to do was create a protocol to identify these patients, confirm a diagnosis and treat them for an adequate period". Emphasizing that the role of probiotics in ABS still needs research, Malik said, "We also wanted to let other doctors know that this could serve as a standard way to treat patients with ABS and encourage further studies".

Malik and Wickremesinghe note that doctors should recognize that mood changes, mental confusion and delirium may be the first symptoms of ABS in patients who deny drinking alcohol.

Wickremesinghe said that he and Malik had received questions from around the world since the case study was published. He added, "The interest in the article is incredible, so if we have made the medical community and the general public aware of this condition and how to treat it, we have done something great for medicine".