Home Medizin Ursache für falsch-positive Testergebnisse?

Ursache für falsch-positive Testergebnisse?

von NFI Redaktion

A case of false positive alcohol toxicology tests, believed to be related to treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors, raises concerns that widely used diabetes medications may be a cause of countless false positive test results – with a lack of proper sample cooling being a major contributing factor.

The case, described in a letter in the New England Journal of Medicine, involved a man in his sixties who had been treated for diabetes with the SGLT2 inhibitor Empagliflozin for five months.

The patient reported to his primary care practice fearing he would be sent to jail because up to four recent toxicological urine tests conducted by the city’s probation office tested positive for alcohol, despite him not consuming alcohol for ten months. Other than that, the samples showed no traces of illegal or non-prescription substances.

When the clinic conducted further lab tests, a new sample showed no detectable ethanol or ethylglucuronide; however, glycosuria was present, indicating that the patient was adhering to the Empagliflozin therapy (20 mg once daily) prescribed to him five months prior for the treatment of his diabetes mellitus.

Additionally, the sample showed no elevated levels of nitrite or leukocyte esterase, and a urine culture revealed less than 50,000 colony-forming units per milliliter of mixed gram-positive organisms.

Key Note: Inadequate Cooling of Urine Sample

A call to the city’s probation office to inquire about the urine collection protocol revealed that the probation office’s urine samples, sent for testing to an external lab only once daily, were not cooled before transport.

This crucial insight led to the patient’s new urine sample being taken from the refrigerator at the primary care center.

While the new test originally tested negative for ethanol, a repeat test conducted after the sample was stored at room temperature for 24 hours actually showed the sample to be positive, indicating a main culprit – the microbial fermentation of urinary glucose.

„This class of medications induces glucosuria even in euglycemia and increases the presence of microbes in the urinary tract – two ingredients necessary for microbial fermentation,“ said author Aaron L. Schwartz, MD, PhD, from the Corporal Michael J. Crescenz Department of Veterans Affairs Medical Center, Philadelphia, Pennsylvania, in his report.

„In this case, urine sample collection and storage by the criminal justice system did not appear sufficient to ensure the stability of the samples,“ he said.

While there have been several reports of false positive alcohol urine tests under similar circumstances, such as with chronically elevated urine sugar levels, „to my knowledge, this is the first report of this phenomenon related to this type of medication,“ Schwartz told Medscape Medical News.

This does not mean there may not be many more.

Schwartz pointed out that several reports described false positive alcohol urine toxicology tests not involving SGLT2 inhibitors but involving similar circumstances of chronically elevated urine sugar levels, including three known cases of patients with false positive alcohol urine tests attributed to poorly controlled diabetes causing high glucose levels in the urine.

„In one case, the patient was removed from the liver transplant list due to the false positive alcohol tests [and] in another case, rape victims truthfully claimed they had not consumed alcohol at the time of their assault.

In the current case, two key factors attributed to the false positive results were the presence of sugar in the urine, which can attract microbes over time, and the fermentation of some microbes from sugar for alcohol.

The second factor is the warm conditions under which the urine was stored, contributing to fermentation.

„Previous studies and cases have shown that microbial fermentation does not take very long at room temperature,“ Schwartz said.

In addition to many patients potentially having sugar in their urine, many employers, law enforcement agencies, and even medical facilities at the collection site do not conduct toxicology tests, he noted.

„It is very common for urine or blood samples to be collected at one location and tested at another. In such situations, the integrity of the sample can be compromised.“

Freezing samples or using sodium fluoride preservatives can prevent urine fermentation, Schwartz added.

However, as these measures are far from standard practice, it is difficult to determine how many false positive tests could occur under current circumstances.

„These medications are widely used [and] they clearly induce sugar in the urine and attract microbes into the urine,“ Schwartz said. „Microbes can ferment sugar into alcohol relatively quickly, and toxicology tests are often conducted.“ Thus, the concern that this phenomenon may be widespread is justified.

Given the possibility of such cases occurring, Schwartz urgently advises physicians to be skeptical of positive urine alcohol tests in patients with high urine glucose levels.

Furthermore, „be particularly skeptical if the urine is not tested immediately.“ [and] Consider using confirmation tests like blood tests,“ he said.

The Fermentation of Sugar into Alcohol is Well Known to Brewers

In a prior report describing false positive urine alcohol tests related to glucosuria and bacteria in the urine, Kevin F. Foley, PhD, from the Department of Pathology, Kaiser Permanente, in Portland, Oregon, explained that the connection between bacterial fermentation and alcohol is likely well known to anyone involved in alcohol production – or even just anyone with a passing interest in craft breweries.

„As brewers and winemakers are aware, fermentation is the biochemical process by which sugar is converted into alcohol (and carbon dioxide) in the absence of oxygen,“ he wrote in his report. „Bacteria and yeasts can ferment sugar.“

Similarly, „as a fluid contains a sufficient amount of sugar (> 500 mg/dL of glucose in the case described by him), along with the presence of bacteria and over time, in vitro fermentation can occur.“

Foley’s case involved a 44-year-old man being treated for type 2 diabetes but also prescribed opioids for lumbar radiculopathy, shoulder, and rib pain, who, as a condition of the opioid treatment, had to refrain from alcohol and other recreational drugs and undergo urine tests.

Despite his claim that his last alcohol consumption was a year ago, the man had positive ethanol urine results.

The necessary tests to confirm the results believed to be altered by fermentation were an ethylglucuronid (ETG) and ethyl sulfate (ETS) urine test.

While bacterial contamination due to bacterial breakdown of ETG can also lead to a false negative ETG result, ETS is not affected by these contamination issues, Foley said.

The ETS and ETG results came out negative for the patient, „strongly suggesting that the ethanol was present in the urine due to bacterial fermentation,“ Foley wrote.

Similar to the case with SGLT inhibitors, in Foley’s reported case as well, the urine sample was transported at ambient temperature throughout the day.

„A period of 6.5 hours seems to be sufficient time for fermentation to occur,“ he wrote, emphasizing that freezing or using sodium fluoride as a preservative could prevent such fermentation.

„This case underscores the fact that samples that cannot be tested immediately should be transported and stored chilled to reduce the likelihood of fermentation in the samples,“ Foley said.

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