Helicobacter pylori (Hp) infection affects one-half of the human population and produces a variety of diseases from peptic ulcer to cancer. Current eradication therapies achieve modest success rates (around 70%), resistance to the antibiotics of choice is on the rise, and vaccination has not proved to be successful yet. Using an essential Hp protein, flavodoxin, as target, we identified three low-molecular-weight flavodoxin inhibitors with bactericidal anti-Hp properties. To improve their therapeutic indexes, we have now identified and tested 123 related compounds. We have first tested similar compounds available. Then we have designed, synthesized, and tested novel variants for affinity to flavodoxin, MIC for Hp, cytotoxicity, and bactericidal effect. Some are novel bactericidal inhibitors with therapeutic indexes of 9, 38 and 12, significantly higher than those of their corresponding leads. Developing novel Hp-specific antibiotics will help fighting Hp resistance and may have the advantage of not generally perturbing the bacterial flora.

A simple and rapid urease test to detect Campylobacter pylori infection was evaluated with bacterial culture as the "gold standard." The test was compared with the Gram stain and the conventional Christensen urease test. The culture method detected C. pylori in 29 of 49 gastric biopsy specimens. The rapid urease test showed 27 positive samples within 1 h at 55°C (specificity, 100%; sensitivity, 93%) and 18 at room temperature (specificity, 100%; sensitivity, 62%). The Gram stain exhibited a sensitivity of 86% and a specificity of 91%. The conventional Christensen urease test detected C. pylori in only 4, 10, and 18 samples after 24, 48, and 72 h, respectively (sensitivities, 12, 36, and 60%, respectively; specificities, 95, 95, and 83%, respectively). We conclude that the rapid urease test is simple and highly specific for the detection of C. pylori and that it can be performed with small amounts of sample.

These results indicate that despite freezing and greatly reducing the viability of the micro-organism, the urease enzyme remains sufficiently active after six months of freezing to give positive results at 55'C. We conclude that the modified rapid urease test is more accurate than culture in identifying Helicobacter pylori in frozen gastric mucosal specimens and, therefore, it is the most convenient method for retrospective studies.

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