False negative urea breath tests with H2-receptor antagonists: interactions between Helicobacter pylori density and pH.
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 approximately 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.
Graham
David Y
DY
Department of Medicine, Veterans Affairs Medical Center, Houston, TX 77030, USA.
Opekun
Antone R
AR
Jogi
Medhavi
M
Yamaoka
Yoshio
Y
Lu
Hong
H
Reddy
Rita
R
El-Zimaity
Hala M T
HM
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D001944:Breath Tests; D019343:Citric Acid / Q000008:administration & dosage; D016099:Endoscopy, Gastrointestinal; D005188:False Negative Reactions; D015738:Famotidine / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000175:diagnosis* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000254:growth & development*; D006635:Histamine H2 Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D017693:Sodium Bicarbonate / Q000008:administration & dosage; D014508:Urea / Q000032:analysis* / Q000378:metabolism
D006635:Histamine H2 Antagonists; D019343:Citric Acid; D015738:Famotidine; D017693:Sodium Bicarbonate; D014508:Urea