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We discuss a meta-analysis that reported on the association between gastric acid suppression and carriage with antibiotic resistant bacteria, with a special focus on the association for carriage with ESBL-producing Gram-negative bacteria in non-hospitalized subjects. Results from a recent population-based study (not included in the meta-analysis) were added to this subgroup of the meta-analysis. The data point to a positive, yet minor, association between gastric acid suppression and carriage with ESBL-producing Gram-negative bacteria in non-hospitalized subjects in the Netherlands.

Although proton pump inhibitors and H2-receptor antagonists are usually prescribed for continuous use by patients with gastro-oesophageal reflux disease, at least 50% of such patients do not take their medication daily and some take it only sporadically. On-demand treatment with proton pump inhibitors or H2-receptor antagonists is safe and cost-effective. Indications are: (a) incidental reflux episodes of short duration, (b) periodic reflux lasting several weeks or months, (c) chronic reflux not requiring continuous treatment. On-demand treatment is unsuitable for patients with reflux disease who either require daily medication or in whom the maximal dosage is insufficient. There are three types of on-demand treatment. Type 1: use of medication only in case of incidental symptoms. Type 2: continuous medication for 2-4 weeks when symptoms appear. Type 3: continuous use because of chronic symptoms, but the interval between doses is determined by the patient on the basis of his symptoms. All antacids can in principle be used for on-demand treatment; for type 3 treatment, antacids with a rapid onset of action are preferred. A favourable response to the two weeks of initial therapy is a good predictor for successful on-demand treatment.

Gastric acid inhibitors are effective and safe drugs for the treatment of gastro-oesophageal reflux disease. Since reflux disease is frequent in Western populations, the use of gastric acid inhibitors leads to a considerable financial burden to the community. However, a large proportion of the patients with reflux symptoms do not take their medication continuously but use the drugs as required by their symptoms. This opens the possibility of a more cost-effective approach in which optimal symptom relief is achieved in combination with cost reduction. The type of on-demand therapy must be based on the individual pattern of reflux symptoms. In this approach, the patient determines the actual therapy whereas the physician functions as advisor. It is presently unknown whether any adverse effects result from the long-term on-demand therapy of reflux disease.

Ghrelin is a hormone produced by endocrine cells in the stomach. Ghrelin stimulates the secretion of growth hormone by the anterior pituitary. This effect is mediated by hypothalamic growth-hormone secretagogue receptors. Binding to these receptors not only stimulates growth hormone secretion, but also has vascular effects (positive inotropic effects), modifies (decreases) insulin sensitivity, affects glucose metabolism (hyperglycaemia) and stimulates gastric-acid production. Antiproliferative effects of ghrelin have been described on experimental tumour models. Ghrelin seems to play a role in stimulating the appetite as well as promoting a more effective storage of food components. Whether or not ghrelin could play any role in the induction of weight gain has yet to be established. This is also true for the role of potential ghrelin antagonists in the induction of weight loss in case of obesity.

Gastric acid stimulates the absorption of nutrients and is the most important non-immunological defence system against the constant bacterial invasion of our digestive tract. Patients with achlorhydria and resected stomachs have excessive growth of bacteria in the digestive tract and a much higher incidence of gastrointestinal infections. Modern treatment of reflux oesophagitis with acid secretion inhibitors creates a similar low acid state. Suppression of gastric acid secretion causes a dose dependent increased risk of a wide variety of intestinal infections especially for people over 65, immune compromised persons, sick patients with a reduced resistance and travellers to tropical areas. The potentially dangerous infections can be reduced by adequate counselling about the importance of gastric acid, the precaution of improved hygiene, on demand use of especially proton pump inhibitors and prescription of antacids and less potent acid inhibitors.

Colonisation with Helicobacter pylori exerts several effects on the production of acid. The bacterium does not play a direct role in the pathogenesis of gastroesophageal reflux disease (GORD). Successful eradication of H. pylori in patients with ulcer disease appears to be followed by an increase in incidence of GORD. It has been postulated that the infection could protect against the development of GORD. H. pylori ulcers and gastritis should be treated by eradication therapy. It is unclear yet what is the best treatment in patients with H. pylori infection without an ulcus or gastritis.

Intravenous acid inhibition is used in the prevention of upper gastrointestinal bleeding in intensive care unit patients and in the treatment of peptic ulcer bleeding. The strongest risk factors for upper gastrointestinal bleeding are mechanical ventilation for more than 48 hours and coagulopathy. However, a subgroup of critically ill patients without these risk factors may still be at risk of upper gastrointestinal bleeding. Stress ulcer prophylaxis with sucralfate is not effective. Patients who receive intravenous ranitidine (50 mg every 8 hours) run a significantly lower risk of gastrointestinal bleeding. In one study stress ulcer prophylaxis with oral omeprazole was more effective than prophylaxis with intravenous ranitidine. Endoscopic therapy is the cornerstone in modern therapy of peptic ulcer bleeding. Addition of acid inhibition may be effective in preventing clot lysis. H2-receptor antagonists do not influence the natural history of peptic ulcer bleeding. In addition to endoscopic therapy acid inhibition with proton pump inhibitors like omeprazole is more effective than acid inhibition with H2-receptor antagonists. However, the optimal dose and way of administration of omeprazole are not known.