By Carol A. Kemper, MD, FACP

Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases, Santa Clara Valley Medical Center

Dr. Kemper reports no financial relationships relevant to this field of study.

Urinary Fermentation Syndrome?

SOURCE: Kruckenberg KM, DiMartini AF, Rymer JA, et al. Urinary auto-brewery syndrome: A case report. Ann Intern Med 2020 Feb. 25. doi: 10.7326/L19-0661.

A case of intestinal fermentation syndrome, often referred to as “auto-brewery syndrome,” was reviewed recently in this column in December 2019.1 In brief, a previously healthy 46-year-old man had several traumatic falls when inebriated, complicated by intracerebral hemorrhage, and he had been arrested for driving under the influence. Despite protestations that he was not a drinker, his blood alcohol levels were repeatedly elevated (50 to 400 mg/dL). After investigation, it was observed that his blood alcohol level increased following a carbohydrate challenge. Both Saccharomyces cerevisiae and Saccharomyces boulardii were isolated in stool cultures; cultures obtained from the upper small gut and cecum grew Candida albicans and Candida parapsilosis. He was treated sequentially with a carbohydrate-free diet, fluconazole 150 mg daily for 14 days, nystatin three times daily for 10 days, and then increasing doses of itraconazole without much success. Finally, treatment with micafungin 150 mg daily for six weeks was successful at eradicating his yeast colonization, and he resumed a fairly normal, inebriate-free life.

In a fascinating twist to this tale, a 61-year-old woman with diabetes was turned down for a renal transplant because her urine ethanol levels were elevated repeatedly, raising suspicions of occult alcohol abuse. She had repeatedly denied alcohol use, and did not appear to be inebriated during any of her clinical evaluations. But the transplant center insisted on referring her for alcohol addiction treatment.

However, a second transplant center astutely observed that although urine tests for alcohol were positive repeatedly, plasma tests for ethanol were negative, and urine studies for ethyl glucuronide and ethyl sulfate, metabolites of ethanol, both were negative. Frequent glycosuria (> 1,000 mg/dL) was observed. Urine culture yielded Candida glabrata. Yeast-rich fractions of urine were incubated over a 24-hour period and measured ethanol levels increased from a baseline of 44 mg/dL to 476 mg/dL and 816 mg/dL at 25°C and 37°C, respectively. At 37°C, her freshly voided urine produced 32 mg/dL of ethanol per hour! Attempts to clear the bladder of yeast with antifungal therapy were unsuccessful, but she was able to be placed on a transplant list.

Clinicians should be aware of the possibility of deceptively elevated ethanol levels in blood and urine specimens from yeast fermentation in either the gut or the bladder.

REFERENCE

  1. Malik F, Wickremesinghe P, Saverimuttu J. Case report and literature review of auto-brewery syndrome: Probably an underdiagnosed medical condition. BMJ Open Gastroenterol 2019;6:e000325.

Residential Legionellosis From Potable Water

SOURCE: Schumacher A, Kocharian A, Koch A, Marx J. Fatal case of Legionnaires’ disease after home exposure to Legionella pneumophila serogroup 3 — Wisconsin, 2018. MMWR Morb Mortal Wkly Rep 2020;69:207-211.

Legionella in residential, potable water is well-described but seldom causes significant infection. In 2018, the Wisconsin Department of Public Health received a report of a positive culture for Legionella pneumophila serogroup 3 that proved fatal in a 70-year-old man with known immunosuppression. He had been diagnosed with combined immunodeficiency syndrome two years earlier, and had just completed a 30-day course of levofloxacin treatment for lower extremity cellulitis and abscess. Toward the end of his treatment course, he developed fever and rash, with progressive mental status changes and shortness of breath. He presented to a local emergency room, where he tested positive for rhinovirus and parainfluenza 1 and had a normal chest radiograph. Because of the fever and immunosuppression, he was admitted.

On his fifth day of hospitalization, the fever persisted, the cough worsened, and the chest radiograph showed a left upper lobe infiltrate. Urinary antigen tests for Legionella pneumophila 1 were negative. He was started on broad-spectrum antibiotics with meropenem, and two days later, he received inhaled tobramycin. He died on the 10th day of hospitalization. Bronchoalveolar lavage fluid cultured for Legionella grew Legionella pneumophila serogroup 3 six days later.

Because of the possibility of nosocomial exposure in the hospital, epidemiologic investigation of the hospital water system was performed the day following this culture result. Nine potential water sources in the hospital were cultured, including inpatient and outpatient sink faucets, a shower, an ice machine, and a warm water pool. None were positive. Additional samples collected about three weeks later and cultured at both the hospital and the state laboratory again were negative.

Specimens collected from two showers in the home, which is served by a municipal water system, both were positive for L. pneumophila serogroup 3. Later studies confirmed that these isolates matched the patient isolate by both PFGE and whole-genome multilocus sequencing. The investigation concluded that the home was the source of the Legionella infection.

A plumber was called in, and following the advice of a home guidance manual, drained the system, shocked it with chlorine, and then ran the system at 148°F for three days, flushing all the pipes. The shower heads were cleaned and soaked in vinegar. Despite this, two cultures obtained from eight different fixtures about one week later were persistently positive, including the sink sprayer and a bathroom sink faucet. The family was counseled to monitor their systems and consult a physician in the event of illness.

This case report highlights the importance of Legionella culture of lower respiratory tract specimens rather than depending on the urinary antigen test, which tests only for serogroup 1. The Centers for Disease Control and Prevention recommends both cultures and urinary antigen for Legionella, although polymerase chain reaction (PCR) testing on lower respiratory specimens also may be useful and faster than culture.

Further, this case demonstrates the difficulty in eradicating home sources for Legionella infection. In my personal experience dealing with mycobacterial illness, I have recommended removing or replacing all sprayers, aerators, and shower heads, before shocking the system with chlorine, rather than attempting to clean them.


Which Treatment for SARS-CoV-2 Is Best?

SOURCE: Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies (letter). BioSci Trends 2020 Feb. 19. doi:10.5582/bst/2020.01047. [Epub ahead of print].

A hot topic of conversation this week is how best to treat our three critically ill SARS-CoV-2 patients in the intensive care unit (ICU). Facilities nearby are using remdesivir, and another is using hydroxychloroquine.

Chloroquine has been found to block SARS-CoV-2 infection, with cytotoxic activity demonstrated in vitro by increasing the endosomal pH, interfering with viral fusion, and interfering with glycosylation of cellular receptors. The National Health Commission of the People’s Republic of China has been quickly conducting several clinical trials of various agents, including hydroxychloroquine and chloroquine. In a comparison of chloroquine to a “control” treatment of more than 100 patients, researchers found active treatment was superior to the control in “inhibiting the exacerbation of pneumonia, improved lung findings, and shortening the disease course,” and in promoting clearance of the virus in respiratory specimens. It was fairly well tolerated, with no severe adverse reactions. Chloroquine will be included in the upcoming version of China’s treatment guidelines.