Proton-Pump Inhibitors Cause False-Negative Results

By Barbara Biedrzycki, RN, MSN, AOCN, CRNP

Summary—Researchers found that 33% (31/93) of the patients in whom Helicobacter pylori (H. pylori) infection was not eradicated had false-negative results while on therapy with a proton-pump inhibitor.1 While 97% (85/88) of the participants in this research study reverted to their previous H. pylori-positive status after discontinuing the proton-pump inhibitor therapy for one week, 100% (88/88) were positive two weeks after therapy was discontinued. Researchers conclude that patients being treated for H. pylori with a positive urea breath test should not take proton-pump inhibitors for two weeks prior to prevent false-negative results.

Thirty to 50% of the American population has chronic Helicobacter pylori (H. pylori) infection with gastritis, although most are asymptomatic. A strong relationship exists between H. pylori infection and duodenal ulcers. Ninety to 95% of all duodenal ulcer patients have H. pylori gastritis, and about 15% (one in every six) with chronic H. pylori infection develop peptic ulcers.

Proton-pump inhibitors may be used alone for treatment of H. pylori infections, although they are most often used in combination with antibiotics. Symptomatic patients welcome the relief proton-pump inhibitors provide, but scientists learn these medications have a downside.

This study recruited 176 adult subjects. Eligible patients had H. pylori infection identified by endoscopy (47 patients/51%) or serology (46 patients/49%), which was confirmed with positive urea breath tests. The characteristics of the patients included:

• mean age 47 years;

• 52 (56%) men;

• 41 (44%) women;

• 74 (80%) reported heartburn as the predominant symptom;

• and nine (20%) dyspepsia as the predominant symptom.1

Research participants were to take 30 mg of lansoprazole, a proton-pump inhibitor, every morning for 30 days. They were asked to return on day 28 for a urea breath test while still on therapy; however, they were still eligible if they returned on days 26-30. Sixty-two (67%) of 93 people showed a positive urea breath test while receiving therapy, which indicated that the H. pylori infection was not eradicated. They were not tested further for this research study.

In this study, with the treatment of daily doses of 30 mg of lansoprazole, a proton-pump inhibitor, only 2% (2/95) of the patients were cured of H. pylori as evidenced by negative urea breath tests at 28 days.

Thirty-one patients who were initially positive for H. pylori tested negative while taking the proton-pump inhibitor. After discontinuing therapy, urea breath tests were repeated at three, seven, and 14 days or until the patients reverted to positive results, thus indicating that the negative urea breath tests while receiving therapy were false negative results. Five patients did not complete the testing.

• At day three, 77% of the patients previously testing negative now had positive urea breath tests.

• At day seven, three additional patients (total 88%) tested negative.

• All who reverted to positive did so by day 14.

Researchers concluded that proton-pump inhibitors through their antisecretory effects suppress H. pylori, which leads to false-negative results by endoscopic biopsy and urea breath tests.

While the majority of patients (77%) with false-negative urea breath tests reverted to positive after stopping proton-pump inhibitor therapy for three days, the researchers recommend no proton-pump inhibitor therapy within two weeks of urea breath tests to ensure accurate results.

How is H. pylori Diagnosed?

H. pylori can be diagnosed by one of the following three methods: endoscopy, serology or whole blood antibody testing, or urea breath testing. Biopsy material obtained during endoscopy can be examined directly under the microscope for H. pylori, or it can be tested for urease activity.2

Serological H. pylori antibody testing has the disadvantage of being unable to distinguish active, past, and previously treated infections.2 Urea breath testing rivals endoscopic biopsy tests in accuracy1 and is favored among the two diagnostic methods due to its convenience, cost effectiveness, and decreased risks. (For additional information, see testing for H. pylori infection, p. 46.)

Table 1 
Proton-Pump Inhibitor Study Subject Data 
108 
initially enrolled 
did not return after therapy 
received antibiotics
uninterpretable test
95 
evaluable patients 
62 
positive urea breath test during therapy 
33 
negative urea breath test during therapy 
20 
previously negative urea breath test, positive three days after therapy discontinued 
previously negative urea breath test, positive seven days after therapy discontinued 
previously negative urea breath test, positive 14 days after therapy discontinued 
remain negative indicating eradication of H. pylori infection 
did not complete the study 

Source: Laine L, Estrada R, Trujillo M, et al. Effect of proton-pump inhibitor therapy on diagnostic testing for Helicobacter pylori. Ann Int Med 1998; 129:547-550. 
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Why Test for H. Pylori?

H. pylori, a gram-negative rod found beneath the gastric mucus layer next to the gastric epithelial cells, is not invasive. The devastating effects of H. pylori are due to gastric mucosal inflammation with polymorphonuclear neutrophils and lymphocytes. It is believed H. pylori spreads from person to person, although the mode of transmission is unknown.

Repeatedly documented in the research-based literature, ulcer recurrence rate is reduced to less than 5% per year with successful eradication of H. pylori. While the exact pathogenetic mechanisms of ulcer formation related to H. pylori are unknown, its association is well-documented.3

Positive identification of serologic or whole blood quantitative IgG antibodies to H. pylori do not indicate active infection and may be positive with latent or previously successfully treated infection. Quantitative laboratory-based testing has sensitivity and specificity greater than 90% with a cost of $50-75. Qualitative office-based testing, which can be done in 10 minutes, has a lower sensitivity of less than 80% and a corresponding lower cost of about $10.3 The focused research study used the qualitative office-based test called FlexSure, from Smith-Kline Diagnostics in San Jose, CA.1

The cost of $60-$300 is the probable reason most find serological testing more desirable for initial screening for H. pylori, although the urea breath would be the test of choice to validate eradication of H. pylori after therapy as it only detects active infection.3 The focused research study used C-urea breath test from Meretek Diagnostics in San Jose.1

References

1. Laine L, Estrada R, Trujillo M, et al. Effect of proton-pump inhibitor therapy on diagnostic testing for Helicobacter pylori. Ann Int Med 1998;129:547-550.

2. McKinney W, Feldman M. Gastric and duodenal ulcers. In: Primary Care Medicine. 2nd edition. St. Louis: Mosby; 1996:598-605.

3. McQuaid K. Alimentary Tract. In: 1999 Current Medical Diagnosis and Treatment. 38th edition. Stamford, CT: Appleton and Lange; 1999:579-589.