Quantifying gastric Helicobacter pylori infection: a comparison of quantitative culture, urease breath testing, and histology.

Although there are several methods to detect Helicobacter pylori infection, there is no simple validated test to quantify the density of infection, which is believed to play a major role in the pathogenesis of H. pylori-associated gastritis and peptic ulceration. The aim of this study was to evaluate and compare noninvasive and invasive tests for assessing the level of H. pylori infection so as to facilitate the development and clinical testing of new antibiotic treatments. Healthy volunteers (n=323) were screened for H. pylori infection by serology and, if positive (n=86), invited to undergo (13)C urea breath testing (UBT) (n=55). An increase of >2.4 parts per thousand (13)CO(2) at 15 min compared to baseline was considered a positive test. Total cumulative urease activity (mumol) at 60 min was also calculated. UBT-positive subjects underwent endoscopy and nine biopsies were obtained from defined sites for quantitative culture and histological grading using the modified Sydney System. A total of 19 subjects were studied, 4 of whom underwent repeat testing. All subjects were positive for H. pylori by serology, UBT, culture, and histology. The increase in (13)CO(2) at 30 min correlated with the total cumulative urease activity at 60 min (r (2)=0.92, P< 0.0001). Bacterial counts (log cfu/biopsy; mean+/-SD) were 3.9+/-0.5, 3.9+/-0.4, and 3.9+/-0.6 at the lesser curve antrum, greater curve antrum, and corpus, respectively. There was no significant correlation between UBT results and bacterial counts at any biopsy site. Nor was there any significant correlation between the histology grading and either the UBT or the bacterial counts at any site. This study indicates that there is little correlation among the three methods used to measure bacterial burden in H. pylori infection. Thus, decrements in bacterial numbers during single-agent therapy cannot be measured reliably by UBT and therefore cannot be used to evaluate the potential efficacy of novel agents to treat gastric H. pylori infection.

Activities of rifamycin derivatives against wild-type and rpoB mutants of Chlamydia trachomatis.

Rifalazil, a semisynthetic rifamycin, was shown previously to have exceptional potency against Chlamydia trachomatis (MIC of 0.00025 microg/ml). We therefore tested 250 additional rifamycin derivatives and identified 12 with activities that are eightfold more potent than that of rifalazil. These compounds also showed exceptional activities against rifampin-resistant strains that carry missense mutations in the rpoB gene. The antimicrobial potency and intracellular penetration of these agents suggest their potential in treatment of chlamydial infections.