Etest for metronidazole susceptibility in H. pylori: use of the wrong standard may have led to the wrong conclusion.
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Publications and source records attributed to Michael S Osato.
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Helicobacter pylori infection is the most common cause of gastritis with its associated sequelae. Gastritis secondary to other bacteria is rare. This report describes Enterococcus-associated gastritis in a 59-year-old diabetic man. Nine months after receiving treatment for H. pylori-associated gastritis, he underwent endoscopy to confirm H. pylori eradication and to evaluate the status of previously seen ulcers. Mucosal biopsy specimens revealed severe active but focal gastritis adjacent to gram-positive coccobacilli in short to long chains with no H. pylori. Culture grew an Enterococcus similar to E. hirae and E. durans. No treatment was given, and endoscopy done 2 months later showed complete resolution of the gastritis and absence of H. pylori or enterococci. Our patient's gastritis represents a previously undescribed manifestation of Enterococcus infection. It is possible that the presence of NSAID gastric mucosal injury and diabetes predisposed this individual to the development of transient Enterococcus gastritis.
AIM: To compare the short-term (7-day) safety and efficacy of two triple-therapy regimens using pantoprazole with those of two dual-therapy regimens (one with pantoprazole and one without), for Helicobacter pylori eradication in patients with peptic ulcer disease. METHODS: H. pylori infection was identified by rapid urease (CLOtest), and confirmed by histology and culture. Patients were enrolled into one of two randomized, double-blind, multicenter, parallel-group studies. In study A, patients received oral pantoprazole 40 mg, clarithromycin 500 mg, and metronidazole 500 mg (PCM); pantoprazole, clarithromycin and amoxicillin 1000 mg (PCA); or pantoprazole and clarithromycin (PC). In study B, patients received PCM, PCA, PC, or clarithromycin and metronidazole without pantoprazole (CM). Treatments were given twice daily for 7 days. H. pylori status after therapy was assessed by histology and culture at 4 weeks after completing the course of study treatment. Modified intent-to-treat (MITT; each study: n = 424, n = 512) and per-protocol (PP; each study: n = 371, n = 454) populations were analyzed. The MITT population comprised all patients whose positive H. pylori status was confirmed by culture and histology; the PP population comprised patients who also complied with > or = 85% of study medication doses. RESULTS: A total of 1016 patients were enrolled. Cure rates among patients with clarithromycin-susceptible H. pylori strains were 82 and 86% for PCM, and 72 and 71% for PCA, in studies A and B, respectively. Cure rates among patients with metronidazole-susceptible H. pylori strains were 82 and 87% for PCM, and 71 and 69% for PCA, in studies A and B, respectively. The combined eradication rates observed with the PCM regimen were superior to those of all other regimens tested. Side-effects were infrequent and mild. CONCLUSIONS: PCM had the highest overall eradication rate in these two studies examining 7-day treatment regimens. All regimens were safe and well tolerated.
OBJECTIVE: The mechanism of false negative urea breath tests (UBTs) results among proton pump inhibitor (PPI) users is unknown. We studied the time course of PPI-associated negative UBT, the relation to Helicobacter pylori density, and whether gastric acidification would prevent false negative UBT results. METHOD: In the UBT experiment, H. pylori-infected volunteers received omeprazole 20 mg b.i.d. for 13.5 days. UBTs with citric acid were done before, after 6.5 days of PPI, and 1, 2, 4, 7, and 14 days after therapy. In the culture and histology experiment, after a wash-out of >5 months, nine of the original subjects were rechallenged with omeprazole for 6.5 days. Antral and corpus biopsies for histology and culture were done before and 1 day after PPI administration. RESULTS: Thirty subjects (mean age 42 yr) were enrolled. UBTs were significantly reduced on day 6.5 (p = 0.031); 10 subjects (33%) developed transient negative UBTs. The UBT recovered in all but one subject by the fourth day post-PPI and in all subjects by day 14. In the culture and histology experiment, upon PPI rechallenge, three of nine subjects (33%) had negative UBTs. H. pylori density, whether measured by culture or histology, decreased with PPI therapy; antral biopsies became histologically negative in five subjects and corpus biopsies in three subjects. CONCLUSION: PPI-induced negative UBT results were related to the anti-H. pylori effect of the PPI. Acidification of the stomach did not prevent false negative UBT results. Three days is likely the minimum delay from stopping PPI until one should perform a test for active infection. A delay of 14 days is preferred.
We present a molecular epidemiologic study, based on an analysis of vacA, cagA and cag right end junction genotypes from 1042 Helicobacter pylori isolates, suggesting that H. pylori was present in the New World before Columbus. Eight Native Colombian and Alaskan strains possessed novel vacA and/or cagA gene structures and were more closely related to East Asian than to non-Asian H. pylori. Some Native Alaskan strains appear to have originated in Central Asia and to have arrived after strains found in South America suggesting that H. pylori crossed the Bering Strait from Asia to the New World at different times.
BACKGROUND & AIMS: Disease-associated virulence factors of Helicobacter pylori may not be independent of one another. The aim was to determine which H. pylori virulence factor(s) was the most important predictor of severity of gastric inflammation or clinical outcome. METHODS: cag Pathogenicity island (PAI), vacA babA2, and iceA status were determined by polymerase chain reaction (PCR). oipA functionality was based on switch status determined by PCR-based sequencing. A backward stepwise multiple regression analysis was performed to determine which factor(s) was the most discriminating for clinical outcome as well as the relationship to mucosal histology (H. pylori density, neutrophil infiltration, intestinal metaplasia, and gastric atrophy) and mucosal interleukin 8 (IL-8) production. RESULTS: H. pylori were obtained from 247 patients (86 with gastritis, 86 with duodenal ulcer, and 75 with gastric carcinoma). Although oipA status was closely linked to specific cag PAI, vacA, and babA2 genotypes, only oipA status remained in the final model to discriminate duodenal ulcer from gastritis (adjusted odds ratio [OR] = 5 and 95% confidence interval [CI] = 2.1-11.9). Among the factors, only a functional oipA was significantly associated with high H. pylori density, severe neutrophil infiltration, and high mucosal IL-8 levels (P < 0.001). oipA status had no relationship to gastric atrophic changes. CONCLUSIONS: oipA functional status was related to clinical presentation, H. pylori density, and gastric inflammation. cag PAI, babA2, or vacA status appear important only as surrogate markers for a functional oipA gene.
OBJECTIVE: This study investigated the genetic diversity of the cag pathogenicity island (PAI) in Helicobacter pylori (H. pylori) in relation to clinical outcome and interleukin (IL)-8 production. METHODS: Seven genes in the cag PAI (cagA, cagE, cagG, cagM, cagT, open reading frame 13 and 10) were examined by polymerase chain reaction and Southern blot hybridization using H. pylori from 120 patients with different presentations (duodenal ulcer, gastric cancer, gastritis alone). IL-8 production from AGS cells (gastric cancer cell line) cocultured with H. pylori was measured by ELISA. RESULTS: An intact cag PAI was present in 104 (87%) isolates, and five (4%) had deletions within the cag PAI; 11 (9%) lacked the entire cag PAI. Clinical isolates containing the complete cag PAI induced a greater secretion of IL-8 as compared with those without the cag PAI (3048 +/- 263 vs 480 +/- 28 pg/ml, p < 0.001). Deletion of only cagG reduced IL-8 secretion by two thirds. Deletions of more than one locus reduced IL-8 secretion to background. A similar proportion of H. pylori from patients with gastritis, duodenal ulcer, or gastric cancer had intact cag PAI (88%, 88%, and 85%, respectively). Although the presence of cagG was a better predictor of the presence of an intact cag PAI than cagA or cagE, the presence or absence of any of these genes had no association with clinical presentation. CONCLUSION: Although the cag PAI plays an important role in IL-8 production, clinical presentation cannot be predicted by the presence of an intact cag PAI or any of these seven cag PAI genes.
We evaluated a new immunoblot assay (Helicoblot 2.1) for Helicobacter pylori infection and CagA and VacA status by using serum samples from 222 patients. The test accurately detected H. pylori infection and VacA status, but improvements in the interpretation criteria are required before it can be recommended for determination of CagA status.
The BabA, cagA, and vacA statuses of 827 Helicobacter pylori isolates were used in logistic regression models to discriminate duodenal ulcer from gastritis. Only BabA was a candidate for a universal virulence factor, but the low c statistic value (0.581) indicates that none of these factors were helpful in predicting the clinical presentation.
The epidemiology of Helicobacter pylori infection and risk factors associated with its transmission are not well understood. Kazakhstan is country with two ethnic groups, Asian (Kazakhs) and Western (Russians), living under similar socioeconomic conditions. The aim of this study was to examine the seroepidemiologic pattern of H. pylori and hepatitis A among the same individuals from both ethnic groups, with emphasis on water source and household sanitation practices. This was a cross-sectional seroepidemiologic study conducted among unrelated healthy individuals in Kazakhstan. From May through August 1999, individuals between the ages of 10 and 60 years from Almaty, Kazakhstan, were invited to participate. Demographic information, socioeconomic factors, living conditions, and various aspects of the local household environment including access to water were collected. A clean water index (CWI) was created based on combined factors, consistency of boiling water before drinking, frequency of storing and reusing water, and frequency of bathing and showering. H. pylori and hepatitis A antibodies were assessed by enzyme-linked immunosorbent assay. Two hundred eighty-eight individuals between the ages of 10 and 60 years participated. The prevalence of H. pylori infection was almost identical among the two ethnic groups (Russians 79% and Kazakhs 80%). H. pylori infection was inversely correlated with the CWI (i.e., 56%, 79%, and 95% for high, middle, and low, respectively (P < .05). Drinking river water had highest risk of H. pylori infection (OR = 13.6, 95% CI = 1.8-102.4; P < .01, compared with tap water). Crowding showed no significant effect on H. pylori prevalence. Anti-HAV antibodies were found in 86% of the population, 90% among the Russians versus 82% among the Kazakhs (OR = 1.8, 95% CI = 1.1-3.8, P = .05). Although the two infections were highly correlated (P < .001), antibody to both infections were present simultaneously in only 74%. The prevalence of H. pylori infection in Kazakhstan is very high. The data suggest that transmission of H. pylori can be water borne, related to poor sanitary practices, or both. The high prevalence of antibodies to H. pylori and HAV among this population is a marker for poor sanitation and hygienic practices. Reducing the rate of H. pylori transmission will require improvements in overall sanitation including clean water, waste disposal, as well as in household hygienic practices.