Maria Pina Dore

Effect of pretreatment antibiotic resistance to metronidazole and clarithromycin on outcome of Helicobacter pylori therapy: a meta-analytical approach.

Our purpose was to define the effect of pretreatment Helicobacter pylori resistance to metronidazole or to clarithromycin on the success of antimicrobial therapy. We used 75 key words to perform a literature search in MEDLINE as well as manual searches to identify clinical treatment trials that provided results in relation to H. pylori susceptibility to metronidazole and clarithromycin or both during the period 1984–1997 (abstracts were not included). Meta-analysis was done with both fixed- and random-effect models; results were shown using Galbraiths radial plots. We identified 49 papers with 65 arms for metronidazole (3594 patients, 2434 harboring H. pylori strains sensitive to metronidazole and 1160 harboring resistant strains). Metronidazole resistance reduced effectiveness by an average of 37.7% (95% CI = 29.6–45.7%). The variability in the risk difference for metronidazole was 122.0 to −90.6 and the chi-square value for heterogeneity was significant (P < 0.001). Susceptibility tests for clarithromycin were performed in 12 studies (501 patients, 468 harboring H. pylori strains sensitive to clarithromycin and 33 harboring resistant strains). Clarithromycin resistance reduced effectiveness by an average of 55% (95% CI = 33–78%). We found no common factors that allowed patients to be divided into subgroups with additional factors significantly associated with resistance. In conclusion, metronidazole or clarithromycin pretreatment resistant H. pylori are the main factors responsible for treatment failure with regimens using these compounds. If H. pylori antibiotic resistance continues to increase, pretherapy antibiotic sensitivity testing might become necessary in many regions.

Pretreatment Antibiotic Resistance in Helicobacter pylori Infection: Results of Three Randomized Controlled Studies

Background. Although combinations of antibiotics and antisecretory drugs are useful for treatment of Helicobacter pylori infection, treatment failure is common. The aim of this study was to evaluate the relation between pretreatment antibiotic resistance and outcome by using six different treatment regimens for H. pylori infection.

Isolation of Helicobacter pylori From Sheep—Implications for Transmission to Humans

OBJECTIVES:When and how Helicobacter pylori (H. pylori) originally entered the human population as well as how the infection is transmitted in different communities is unknown. We previously showed that Sardinian shepherds had almost a 100% prevalence of H. pylori and that the prevalence was higher than that of their same-household siblings.Aim:To examine whether H. pylori infection might be transmitted from sheep.METHODS:Milk and gastric tissue were cultured and analyzed by PCR amplification using three sets of primers Helicobacter genus–specific 16S rRNA and two sets of primers specific for H. pylori vacA gene.RESULTS:Helicobacter DNA was demonstrated in 60% (38/63) of milk samples and in 30% (6/20) of sheep tissue samples. H. pylori vacA gene was amplified in five of 38 milk samples, and in two of six sheep tissue samples respectively. H. pylori were cultured from sheep milk and tissue samples and confirmed as H. pylori on the basis of colony morphology, positive biochemical reactions, and negative Gram stain. Sequence analysis of 16S rRNA PCR products from these isolates demonstrated 99% identity with H. pylori.CONCLUSIONS:Together, the presence of H. pylori in sheep stomach in the absence of associated gastritis and recovery of H. pylori from sheep milk and gastric tissue suggest that sheep may be a natural host for H. pylori.

Risk Factors Associated with Helicobacter pylori Infection among Children in a Defined Geographic Area

Factors influencing the pattern of Helicobacter pylori infection among children living in adjacent urban and rural areas of northern Sardinia, Italy, were compared. The seroprevalence of H. pylori infection was 22% (625 of 2810 children) in the study population and was significantly higher among children in rural areas (37%) than in urban areas (13%) (odds ratio [OR], 3.8; 95% confidence interval [CI], 3.2-4.7; P<.005). This difference was consistent within each age group. In rural areas, children who had dogs were at greatest risk for H. pylori infection (OR, 1.8; 95% CI, 1.3-2.6; P<.05). No association was seen between H. pylori seropositivity and a history of breast-feeding. Urban children attending day care centers had a higher prevalence of infection (17%) than did those who never attended (12%) (OR, 1.5; 95% CI, 1.1-2.0; P<.05). The epidemiology of H. pylori infection is complex; even within the same geographic area, different factors influence acquisition of H. pylori infection.

Amoxycillin resistance is one reason for failure of amoxycillin-omeprazole treatment of Helicobacter pylori infection

The efficacy of omeprazole and amoxycillin dual therapy to treat Helicobacter pylori infection has been inconsistent, suggesting the presence of host or bacterial factors influencing treatment success. The aim of this study was to assess the role of pre‐treatment amoxycillin resistance in the efficacy of omeprazole and amoxycillin dual therapy.

Diet, Lifestyle and Gender in Gastro-Esophageal Reflux Disease

Background Studies indicate that gastro-esophageal reflux disease (GERD) is associated with obesity, smoking, esophagitis, diet, and lifestyle. Aim To identify risk factors associated with GERD among patients presenting to a tertiary GI clinic in Italy. Methods Patients with a first diagnosis of GERD based on heartburn and/or regurgitation and/or esophagitis at the endoscopic examination were enrolled. A control group with neither GERD symptoms nor esophagitis was enrolled from the same hospital. Each subject completed a questionnaire including demographic information, lifestyle (e.g., exercise, alcohol, coffee, chocolate, and soda consumption, smoking, having large meals), and frequency of bowel movement. For each participant the body mass index (BMI) was calculated. Results Five hundred subjects were enrolled including 300 GERD patients and 200 controls. Females had significantly higher prevalence of GERD than males (66 vs. 48%, Pxa0=xa00.001, ORxa0=xa02.1, 95% CIxa0=xa01.5–3.1). There was an inverse relationship between the level of education and presence of GERD (76% of GERD patients has completed only elementary school (ORxa0=xa02.1, 95% CIxa0=xa01.7–4.9). Obesity (BMI of ≥95th percentile for their age/gender specific) was significantly related to GERD (ORxa0=xa01.8, Pxa0=xa00.01). None of the other variables studied showed significant associations with GERD. Logistic regression analysis showed that BMI ≥95th percentile, gender, and low education level were significant risk factors for GERD. Conclusions Understanding the epidemiology and risk factors for GERD in a region is the first step in designing prevention and treatment strategies.

Helicobacter pylori in sheep milk

Helicobacter pylori was recovered from sheep milk, suggesting a role for animals in transmission. H. pylori may be a commensal in the sheep, which may be H. pyloris ancestral host.

Colloidal bismuth subcitrate-based twice-a-day quadruple therapy as primary or salvage therapy for Helicobacter pylori infection

OBJECTIVE:Helicobacter pylori (H. pylori) eradication rates in northern Sardinia using standard 1-wk triple therapies (i.e., a proton pump inhibitor and two antibiotics) are typically <60%, primarily because of antibiotic resistance. The aim of this study was to test b.i.d. quadruple therapy as primary and as salvage therapy in this population.METHODS:This was a prospective, single center study of consecutive dyspeptic H. pylori-infected patients. Therapy consisted of omeprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth subcitrate caplets 240 mg, all b.i.d. with the midday and evening meals for 14 days. H. pylori status was evaluated by 13C-urea breath test and histology before and 4–6 wk after therapy. Eradication was defined as no positive test.RESULTS:We enrolled 118 consecutive dyspeptic patients (mean age 46 yr; 73 men, including 15 with peptic ulcer disease). Of the patients, 42 (38%) had failed prior therapy: twice in 21 cases, three times in 12, and four or more times in nine. The intention-to-treat cure rate was 95% (110 of 116) (95% CI = 90–98%) overall, and 98% per protocol, irrespective of diagnosis, age, prior treatment failure, or smoking status. Moderate or severe side effects were experienced by only 5% of patients.CONCLUSIONS:Bismuth subcitrate-based b.i.d. quadruple therapy was an excellent primary and salvage therapy and should be considered as first line therapy.

Different penicillin-binding protein profiles in amoxicillin-resistant Helicobacter pylori.

Background. The β‐lactam group of antibiotics kills bacteria by inhibiting the terminal stages of peptidoglycan metabolism. We have recently identified amoxicillin‐resistant Helicobacter pylori, none of which expressed β‐lactamase. Penicillin‐binding proteins (PBPs) represent a group of target enzymes for the β‐lactam antibiotic family, and alterations in PBPs have been described in other penicillin‐resistant bacteria. The amoxicillin‐resistant phenotype characteristically was lost after freezing but could be restored by consecutive transfers into gradient plates.

Role of bismuth in improving Helicobacter pylori eradication with triple therapy

In most regions of the world, antimicrobial resistance has increased to the point where empirical standard triple therapy for Helicobacter pylori eradication is no longer recommended. The treatment outcome in a population is calculated as the sum of the treatment success in the subpopulation with susceptible infections plus treatment success in the subpopulation with resistant infections. The addition of bismuth (ie, 14-day triple therapy plus bismuth) can improve cure rates despite a high prevalence of antimicrobial resistance. The major bismuth effect is to add an additional 30%–40% to the success with resistant infections. The overall result is therefore dependent on the prevalence of resistance and the treatment success in the subpopulation with resistant infections (eg, with proton-pump inhibitor–amoxicillin dual therapy). Here, we explore the contribution of each component and the mechanisms of how bismuth might enhance the effectiveness of triple therapy. We also discuss the limitations of this approach and provide suggestions how triple therapy plus bismuth might be further improved.