David Y. Graham, MD

ABSTRACT: Undiagnosed or persistent Helicobacter pylori infection and surreptitious or unrecognized NSAID use are the most common causes of refractory peptic ulcers. The use of antibiotics, bismuth, or proton pump inhibitors (PPIs) suppresses the H pylori bacterial load and may obscure the diagnosis. H pylori infections have also become more difficult to cure because of increased antibiotic resistance. For refractory infection, select an antibiotic based on in vitro susceptibility testing. When this is not available, combination therapy with a PPI, tetracycline, metronidazole, and bismuth is often effective. To detect surreptitious or inadvertent NSAID use, review the drug history in detail. When there is any doubt about such use, check platelet cyclooxygenase function.