Valentina Castelli

Culture-based Selection Therapy for Patients Who Did Not Respond to Previous Treatment for Helicobacter pylori Infection

BACKGROUND & AIMS Eradication of Helicobacter pylori using empiric therapy has become difficult as a result of increasing resistance to antibiotics. We evaluated the efficacy of specific treatments, selected based on response of bacterial samples to culture with clarithromycin, levofloxacin, and metronidazole, for patients infected with resistant strains of H pylori. METHODS We performed a prospective study at a single center of 236 consecutive patients with persistent H pylori infection, despite 1 or more treatment attempts, and documented resistance to at least 1 antimicrobial agent (based on bacterial culture tests). Biopsy samples were collected by endoscopy and cultured in selective media. Patients received either 10 days of levofloxacin (250 mg twice daily for 131 patients with susceptible infections) or 12 days of rifabutin (150 mg once daily for 105 patients resistant to levofloxacin) in combination with amoxicillin (1 g twice daily) and esomeprazole (40 mg twice daily). Efficacy of eradication was determined by the (13)C-urea breath test, 6 to 8 weeks after therapy. Compliance and side effects were determined via personal interviews at the end of therapy. Rifabutin toxicity was monitored by analysis of blood samples. RESULTS H pylori infection was cured in 118 of the patients who received levofloxacin triple therapy (90%; 95% confidence interval, 85%-95%) and 93 of the patients who received rifabutin triple therapy (88.6%; 95% confidence interval, 82%-95%). In each group, the cure rate did not differ significantly between patients infected with H pylori strains resistant to single or multiple antibiotics. Mild side effects occurred in 15.5% and 14.9% of patients resistant to single or multiple antibiotics, respectively, and self-limiting neutropenia was observed in 1 (0.7%) case. CONCLUSIONS Selection of triple therapy with either levofloxacin or rifabutin, based on results from bacterial culture tests, cures H pylori infection in about 90% who did not previously respond to antibiotics.

Newer agents for Helicobacter pylori eradication

Helicobacter pylori infection remains widespread internationally, with a definite morbidity and mortality. The efficacy of standard 7–14 day triple therapies is decreasing, mainly due to increasing primary bacterial resistance to antibiotics. Currently, the most effective treatments are either the sequential regimen or the concomitant therapy. Different patents have been registered showing high bactericidal effects in vitro, some of which are active against clarithromycin- and metronidazole-resistant strains, even at low pH values. Among these novel molecules, benzimidazole-derivatives, polycyclic compounds, pyloricidin, and arylthiazole analogues seem to be the more promising. The identification of essential genes for either bacterial colonization or growth represents a route for potential target therapies in the near future.

Tablet and oral liquid L-thyroxine formulation in the treatment of naïve hypothyroid patients with Helicobacter pylori infection

To compare the clinical efficacy of tablet and oral liquid L-thyroxine (LT4) formulation in naïve hypothyroid subjects with Helicobacter pylori infection. Forty-seven adult naïve hypothyroid subjects with dyspeptic symptoms were investigated with upper endoscopy and divided into: 28 patients with Helicobacter pylori infection (Group A); 15 patients without gastric alterations (group B); 4 patients with autoimmune gastritis were excluded from the study. Subjects were randomly treated with a same dose of LT4 tablet (TAB) or oral liquid formulation (SOL), for 9 months on group A and 6 months on group B. Helicobacter pylori infection was eradicated after 3 months of LT4 treatment. On group A, after 3 months (before Helicobacter pylori eradication), subjects treated with SOL showed a greater thyroid-stimulating hormone reduction (ΔTSH3–0: TAB = −4.1 ± 4.6 mU/L; SOL = −7.7 ± 2.5 mU/L; p = 0.029) and a greater homogeneity in the thyroid-stimulating hormone values (TSH3mo: TAB = 5.7 ± 4.9 mU/L; SOL = 4.1 ± 2.0 mU/L; p = 0.025), compared to LT4 tablet. At 9 months (after 6 months of Helicobacter pylori eradication) mean thyroid-stimulating hormone values were lower in subjects treated with LT4 tablet (TSH9mo: TAB = 1.8 ± 1.2 mU/L; SOL = 3.2 ± 1.7 mU/L; p = 0.006). On group B no difference were observed, at each time point, in the mean thyroid-stimulating hormone values and thyroid-stimulating hormone variations between two LT4 formulations. LT4 liquid formulation may produce a better clinical response compared to the tablet formulation in hypothyroid subjects with Helicobacter pylori infection.

Gastroesophageal reflux disease and Barrett’s esophagus

Gastroesophageal reflux disease is the most common gastrointestinal diagnosis recorded during visits to outpatient clinics. The spectrum of injury includes esophagitis, stricture, the development of columnar metaplasia in place of the normal squamous epithelium (Barrett’s esophagus), and adenocarcinoma. Barrett’s esophagus is a premalignant lesion detected in the majority of patients with esophageal and gastroesophageal adenocarcinoma. The incidence of these cancers has been increasing in the United States and they are associated with a low rate of survival (5-year survival rate, 15–20%). When symptoms of gastroesophageal reflux disease are typical and the patient responds to therapy, no diagnostic tests are necessary to verify the diagnosis. Endoscopy is the primary test in patients whose condition is resistant to empirical therapy but its yield in this setting is low because of the poor correlation between symptoms attributed to the condition and endoscopic features of the disease. Clinical experience suggests that lifestyle modifications may be beneficial for gastroesophageal reflux disease although trials of the clinical efficacy of dietary or behavioral changes are lacking. Abundant data from randomized trials show benefits of inhibiting gastric acid secretion and suggest that proton-pump inhibitors are superior to H2-blockers and that both are superior to placebo. In patients with Barrett’s esophagus, antireflux interventions are intended to control symptoms of reflux and promote healing of the esophageal mucosa. If a patient has symptoms refractory to proton-pump inhibitors or cannot tolerate such therapy, antireflux surgery, most commonly Nissen fundoplication, may be an alternative management approach. In patients with high-grade dysplasia, endoscopic therapies or surgical resection must be considered.

OC.06.3 EFFICACY OF SEQUENTIAL THERAPY IN NEVER BEEN TREATED HELICOBACTER PYLORI PATIENTS WITH MULTI-RESISTANT STRAINS

(2183) subjects reported previous eradication therapy. BMI was ≤18 in 188 (4%), ≥18.1-≤25 in 2322 (50%), ≥25.1-≤30 in 1576 (35%) and ≥30.1 in the remaining 514 (11%) of the cases. H. pylori infection was detected in 1892 (40.7%) with a progressive increasing trend according to BMI (≤18: 36%; ≥18.1-≤25: 34%, ≥25.1-≤30: 46% and ≥30.1: 56%; p 50 years). Conclusions: H. pylori infection is significantly more frequent in obese than in normal weight individuals, irrespective of sex and age. Further studies, aiming to explore the role of hormones involved in the homeostasis food intake/satiety, such as ghrelin and obestatin, in linking H. pylori infection and obesity are needed.