Get access

False Negative Urea Breath Tests with H2-Receptor Antagonists: Interactions Between Helicobacter pylori Density and pH


Reprint requests to: David Y. Graham, MD, VAMC Rm 3A-320 (111D), 2002 Holcombe Blvd. Houston, TX 77030, USA.


Background.  We studied the effects of famotidine, sodium bicarbonate, and citric acid on the 13C-urea breath test (UBT).

Methods. Helicobacter pylori-infected volunteers received a UBT, 40 mg of famotidine at bedtime, and a second UBT (pudding test meal, 648 mg NaHCO3 tablet then 125 mg of urea in 200 ml of water containing 650 mg of NaHCO3). Experiment 2 consisted of four UBTs. Two were standard citric acid UBTs with 75 mg of urea and 2 g citric acid and two were sequential bicarbonate-citric acid UBTs. Sequential UBTs consisted of administration of a 648 mg bicarbonate tablet with 50 g of Polycose in 200 ml of water. Five minutes later, 125 mg of 13C-urea was given in 75 ml of water containing 650 mg of NaHCO3. Breath samples were collected after 15 minutes. Then, to acutely acidify the stomach, 4 g of citric acid was given in 200 ml of water. A second breath sample was collected 15 minutes after the citric acid. The standard UBTs were done before and after 6 days of famotidine (40 mg b.i.d.). Sequential UBTs were done after 1 and 6 days of famotidine therapy. Gastric biopsies for histology, culture, and mucosal cytokines were assessed before and after 6 days of famotidine.

Results. Eighteen subjects participated, 10 in each experiment; seven had endoscopy with biopsy. Famotidine/bicarbonate resulted an ∼50% fall in UBT values (p = .021) with 10% becoming negative. The gastric pH increased from 5.1 ± 0.5 to 6.7 ± 0.2 (p = .03) although no pH value predicted the occurrence of false negative results. Under famotidine acid suppression, NaHCO3 reduced the delta over baseline (DOB) by 63% (p = .021). This was reversed with citric acid. Histology showed a H2-receptor antagonist-associated increase in the depth of gastric corpus inflammation.

Conclusions. H2-receptor antagonists differ from proton pump inhibitors as high intragastric pH may cause a reduction in urease activity, unrelated to a reduced bacterial load and reversed by citric acid.

Get access to the full text of this article