Ustekinumab safety and effectiveness in patients with ulcerative colitis: results from a large real-life study.

BACKGROUND: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist recently approved for treating ulcerative colitis (UC) but with limited real-world data. Therefore, we evaluated the effectiveness and safety of UST in patients with UC in a real-world setting. RESEARCH DESIGN AND METHODS: This is a multicenter, retrospective, observational cohort study. The primary endpoints were the clinical remission rate (partial Mayo score, PMS, ≤1) and the safety of UST. Other endpoints were corticosteroid-free remission (CSFR) rate, clinical response rate (PMS reduction of at least 2 points), and fecal calprotectin (FC) reduction at week 24. RESULTS: We included 256 consecutive patients with UC (M/F 139/117, median age 52). The clinical remission and clinical response rates at eight weeks were 18.7% (44/235) and 53.2% (125/235), respectively, and 27.6% (42/152) and 61.8% (94/152) at 24 weeks, respectively. At 24 weeks, CSFR was 20.3% (31/152), and FC significantly dropped at week 12 (p = 0.0004) and 24 (p = 0.038). At eight weeks, patients naïve or with one previous biologic treatment showed higher remission (p = 0.002) and clinical >response rates (p = 0.018) than patients previously treated with ≥ 2. Adverse events occurred in six patients (2.3%), whereas four patients (1.6%) underwent colectomy. CONCLUSION: This real-world study shows that UST effectively and safely treats patients with UC.

Use of tofacitinib as first or second-line therapy is associated with better outcomes in patients with ulcerative colitis: data from a real-world study.

BACKGROUND: Data regarding the real-world (RW) use of tofacitinib (TOF) in patients with ulcerative colitis (UC) are limited. We aimed to investigate TOF's RW efficacy and safety in Italian UC patients. RESEARCH DESIGN AND METHODS: A retrospective assessment of clinical and endoscopic activity was performed according to the Mayo score. The primary endpoints were to evaluate the effectiveness and safety of TOF. RESULTS: We enrolled 166 patients with a median follow-up of 24 (IQR 8-36) weeks. Clinical remission was achieved in 61/166 (36.7%) and 75/166 (45.2%) patients at 8-week and 24-week follow-ups, respectively. The optimization was requested in 27 (16.3%) patients. Clinical remission was achieved more frequently when TOF was used as a first/second line rather than a third/fourth line treatment (p = 0.007). Mucosal healing was reported in 46% of patients at the median follow-up time. Colectomy occurred in 8 (4.8%) patients. Adverse events occurred in 12 (5.4%) patients and severe in 3 (1.8%). One case of simple Herpes Zoster and one of renal vein thrombosis were recorded. CONCLUSIONS: Our RW data confirm that TOF is effective and safe in UC patients. It performs remarkably better when used as the first/second line of treatment.

Effectiveness and safety of vedolizumab in a matched cohort of elderly and nonelderly patients with inflammatory bowel disease: the IG-IBD LIVE study.

BACKGROUND: Vedolizumab registration trials were the first to include elderly patients with moderate-to-severe ulcerative colitis (UC) or Crohn's disease (CD), but few real-life data have been reported in this population. AIMS: We investigated the effectiveness and safety of vedolizumab in matched cohorts of elderly and nonelderly UC and CD patients. METHODS: The Long-term Italian Vedolizumab Effectiveness (LIVE) study is a retrospective-prospective study including UC and CD patients who started vedolizumab from April 2016 to June 2017. Elderly patients (≥65 years) were matched clinically 1:2 to nonelderly patients (18-64 years); the 2 groups were followed until drug discontinuation or June 2019. RESULTS: The study included 198 elderly (108 UC, 90 CD) and 396 matched nonelderly patients (205 UC, 191 CD). Nonelderly UC patients had a significantly higher persistence on vedolizumab compared to elderly patients (67.6% vs. 51.4%, p = 0.02). No significant difference in effectiveness was observed between elderly and nonelderly CD patients (59.4% vs. 52.4%, p = 0.32). Age ≥65 years was associated with lower persistence in UC; for CD, previous exposure to anti-TNF-α agents, Charlson comorbidity index >2 and moderate-to-severe clinical activity at baseline were associated with lower persistence. There were recorded 130 adverse events, with comparable rates between the two groups. A Charlson comorbidity index >2 was associated with an increased risk of adverse events. CONCLUSION: Vedolizumab can be considered a safe option in elderly IBD patients. Its effectiveness in elderly UC patients may be reduced, while no age-dependent effect on effectiveness was observed in CD.

An Objective Comparison of Vedolizumab and Ustekinumab Effectiveness in Crohn's Disease Patients' Failure to TNF-Alpha Inhibitors.

INTRODUCTION: The use of ustekinumab and vedolizumab as second-line therapies in patients with Crohn's disease (CD) in which tumour necrosis factor alpha inhibitors (TNFi) failed is still debated. The aim of this study was to compare, in a large multicenter observational retrospective cohort, the effectiveness of ustekinumab and vedolizumab as second-line therapies, as assessed by clinical and objective outcomes including endoscopy and gastrointestinal imaging. METHODS: Clinical response, remission, and steroid-free remission at weeks 26 and 52 were evaluated in a retrospective propensity score-weighted and propensity score-matched cohort of patients in which TNFi failed. Objective response and remission were evaluated by 1 or more techniques among endoscopy, magnetic resonance/computed tomography enteroclysis, and small bowel ultrasound. RESULTS: A total of 470 patients with CD (239 treated with ustekinumab and 231 treated with vedolizumab) were included in the study. At week 26, clinical outcomes were similar between the 2 groups. At week 52, clinical remission (ustekinumab 42.5% vs vedolizumab 55.5%, P = 0.01) and steroid-free remission (ustekinumab 40.6% vs vedolizumab 51.1%, P = 0.038) rates were significantly higher in vedolizumab-treated patients. Three hundred two patients (hundred thirty-five treated with ustekinumab and hundred sixty-seven treated with vedolizumab) had an objective evaluation of disease activity at baseline and week 52. At week 52, objective response and remission rates were similar between the 2 groups. Clinical response at week 26 predicted steroid-free remission at week 52 in both ustekinumab-treated and vedolizumab-treated patients. Safety profiles were similar between the 2 groups. DISCUSSION: In patients with CD in which TNFi failed, both ustekinumab and vedolizumab showed similar clinical effectiveness after 26 weeks of treatment. At 1 year, vedolizumab was associated with a higher rate of clinical remission when compared with ustekinumab. However, no difference was observed between the 2 groups when objective outcomes were investigated at this time point.

Influence of the COVID-19 Outbreak on Disease Activity and Quality of Life in Inflammatory Bowel Disease Patients.

Objective: The present preliminary cross-sectional study aimed to investigate the extent to which health-related quality of life of patients with inflammatory bowel disease (IBD) was influenced by the outbreak of Covid-19 while controlling for disease activity. Methods: Two samples of 195 (recruited before Covid-19 outbreak) and 707 patients (recruited during the Covid-19-related lockdown) were included. Psychological distress (Hospital Anxiety and Depression Scale, HADS), quality of life (Inflammatory Bowel Disease Questionnaire, IBDQ), and somatization (Patient Health Questionnaire, PHQ-12) were concurrently assessed. Results: Patients with active IBD were more prevalently affected by ulcerative colitis (60.2%, η2 = 0.12) and, expectedly, showed higher psychological distress (HADS, d = 0.34) and somatization (PHQ-12, d = 0.39), as well as poorer disease-specific health-related quality of life (effect sizes for the total and subscale IBDQ scores in the large range of d > 0.50). Hierarchical regression models revealed that setting (pre-Covid-19 outbreak vs. during lockdown) (p < 0.001) explained only a small portion (8%) of the IBDQ variance. IBD-related factors (ulcerative colitis and disease activity) and psychological factors (psychological distress and somatization) added a significant amount of 25 and 27%, respectively, to the explained IBDQ variance. The final model predicted 59% of the explained IBDQ variance. Conclusion: Clinical and psychological manifestations seem to be major impairments in IBD patients both before and during the Covid-19 outbreak. Furthermore, the quality of life of IBD patients seem to be more influenced by psychological and somatizing distressing symptoms than the pandemic-related living conditions.

Two-year effectiveness and safety of golimumab in ulcerative colitis: An IG-IBD study.

BACKGROUND: Few data exist regarding the long-term effectiveness of golimumab in ulcerative colitis. No data have been reported on real-world continuous clinical response. OBJECTIVE: This study aimed to describe the long-term outcomes in a large cohort of patients on golimumab who had ulcerative colitis. METHODS: Consecutive patients with active ulcerative colitis, started on golimumab, were enrolled and prospectively followed up. The primary end point was to evaluate the long-term persistence on golimumab therapy. RESULTS: A total of 173 patients with ulcerative colitis were studied. Of these, 79.2% were steroid dependent, and 46.3% were naïve to anti-tumour necrosis factor alpha agents. The median duration of golimumab therapy was 52 weeks (range: 4-142 weeks). The cumulative probability of maintaining golimumab treatment was 47.3% and 22.5% at 54 and 108 weeks, respectively. Biological-naïve status (odds ratio [OR] = 3.02, 95% confidence interval [CI]: 1.44-6.29; p = 0.003) and being able to discontinue steroids at Week 8 (OR = 3.32, 95% CI: 1.34-8.30; p = 0.010) and Week 14 (OR = 2.94, 95% CI: 1.08-8.02; p = 0.036) were associated with longer persistence on therapy. At Week 54, 65/124 (52.4%) postinduction responders were in continuous clinical response. A continuous clinical response was associated with a lower likelihood of golimumab discontinuation throughout the subsequent year of therapy (p < 0.01). Overall, 40 (23.1%) patients were in clinical remission at the last follow-up visit. Twenty-six adverse events were recorded, leading to golimumab withdrawal in 9.2% of patients. CONCLUSIONS: Biological-naïve status and not requiring steroids at Weeks 8 and 14 seem to be associated with a longer persistence on golimumab therapy in ulcerative colitis.

Activities related to inflammatory bowel disease management during and after the coronavirus disease 2019 lockdown in Italy: How to maintain standards of care.

BACKGROUND AND AIMS: Restructuring activities have been necessary during the lockdown phase of the coronavirus disease 2019 (COVID-19) pandemic. Few data are available on the post-lockdown phase in terms of health-care procedures in inflammatory bowel disease (IBD) care, and no data are available specifically from IBD units. We aimed to investigate how IBD management was restructured during the lockdown phase, the impact of the restructuring on standards of care and how Italian IBD units have managed post-lockdown activities. METHODS: A web-based online survey was conducted in two phases (April and June 2020) among the Italian Group for IBD affiliated units within the entire country. We investigated preventive measures, the possibility of continuing scheduled visits/procedures/therapies because of COVID-19 and how units resumed activities in the post-lockdown phase. RESULTS: Forty-two referral centres participated from all over Italy. During the COVID-19 lockdown, 36% of first visits and 7% of follow-up visits were regularly done, while >70% of follow-up scheduled visits and 5% of first visits were done virtually. About 25% of scheduled endoscopies and bowel ultrasound scans were done. More than 80% of biological therapies were done as scheduled. Compared to the pre-lockdown situation, 95% of centres modified management of outpatient activity, 93% of endoscopies, 59% of gastrointestinal ultrasounds and 33% of biological therapies. Resumption of activities after the lockdown phase may take three to six months to normalize. Virtual clinics, implementation of IBD pathways and facilities seem to be the main factors to improve care in the future. CONCLUSION: Italian IBD unit restructuring allowed quality standards of care during the COVID-19 pandemic to be maintained. A return to normal appears to be feasible and achievable relatively quickly. Some approaches, such as virtual clinics and identified IBD pathways, represent a valid starting point to improve IBD care in the post-COVID-19 era.

Outcomes of COVID-19 in 79 patients with IBD in Italy: an IG-IBD study.

OBJECTIVES: COVID-19 has rapidly become a major health emergency worldwide. Patients with IBD are at increased risk of infection, especially when they have active disease and are taking immunosuppressive therapy. The characteristics and outcomes of COVID-19 in patients with IBD remain unclear. DESIGN: This Italian prospective observational cohort study enrolled consecutive patients with an established IBD diagnosis and confirmed COVID-19. Data regarding age, sex, IBD (type, treatments and clinical activity), other comorbidities (Charlson Comorbidity Index (CCI)), signs and symptoms of COVID-19 and therapies were compared with COVID-19 outcomes (pneumonia, hospitalisation, respiratory therapy and death). RESULTS: Between 11 and 29 March 2020, 79 patients with IBD with COVID-19 were enrolled at 24 IBD referral units. Thirty-six patients had COVID-19-related pneumonia (46%), 22 (28%) were hospitalised, 7 (9%) required non-mechanical ventilation, 9 (11%) required continuous positive airway pressure therapy, 2 (3%) had endotracheal intubation and 6 (8%) died. Four patients (6%) were diagnosed with COVID-19 while they were being hospitalised for a severe flare of IBD. Age over 65 years (p=0.03), UC diagnosis (p=0.03), IBD activity (p=0.003) and a CCI score >1 (p=0.04) were significantly associated with COVID-19 pneumonia, whereas concomitant IBD treatments were not. Age over 65 years (p=0.002), active IBD (p=0.02) and higher CCI score were significantly associated with COVID-19-related death. CONCLUSIONS: Active IBD, old age and comorbidities were associated with a negative COVID-19 outcome, whereas IBD treatments were not. Preventing acute IBD flares may avoid fatal COVID-19 in patients with IBD. Further research is needed.

Real-Life Effectiveness and Safety of Golimumab and Its Predictors of Response in Patients with Ulcerative Colitis.

BACKGROUND: Golimumab is a new anti-TNF-alpha monoclonal antibody for patients with ulcerative colitis. AIMS: To assess the short- and long-term effectiveness and safety of golimumab in daily clinical practice and to identify predictors of response. METHODS: Consecutive patients treated with golimumab in 22 Italian centers were enrolled. Clinical, laboratory, and endoscopic data were prospectively collected before and during treatment. A subgroup of patients completed a questionnaire to assess personal satisfaction with a golimumab autoinjector system. RESULTS: A total of 196 patients were included. After 3 months, 130 patients were responders (66.3%) and showed significant reductions in mean partial, total, and endoscopic Mayo scores and in mean ESR, C-reactive protein, and fecal calprotectin levels (p < 0.001). Multivariate analysis revealed that a higher total Mayo score (p < 0.001, OR 1.5, 95% CI 1.2-1.8) and naïve status to anti-TNF-alpha (p = 0.015, OR 3.0, 95% CI 1.2-7.5) were predictive of a favorable response. Seventy-seven (39.3%) of the 130 responders maintained a response at month 12 of therapy. There were 17 adverse events, 28 patients needed hospitalization, and 15 patients underwent surgery. Self-administration of the drug was appreciated by most patients. CONCLUSIONS: The efficacy and safety of golimumab in daily clinical practice were confirmed for the short- and long-term treatment of patients with active ulcerative colitis. Patients naïve to the anti-TNF-alpha monoclonal antibody and those with a higher total Mayo score were more likely to respond to golimumab.

Fabric phase sorptive extraction-high performance liquid chromatography-photo diode array detection method for simultaneous monitoring of three inflammatory bowel disease treatment drugs in whole blood, plasma and urine.

This paper reports a novel fabric phase sorptive extraction-high performance liquid chromatography-photodiode array detection (FPSE-HPLC-PDA) method for the simultaneous extraction and analysis of three drug residues (ciprofloxacin, sulfasalazine, and cortisone) in human whole blood, plasma, and urine samples, generally administered in human patients to treat inflammatory bowel disease (IBD). The drugs of interest were well resolved using a Luna C18 column (250 mm × 4.6 mm; 5 µm particle size) in gradient elution mode within 20 min. The analytical method was optimized and validated in the range 0.05-10 µg/mL for whole blood, 0.25-10 µg/mL for human plasma, and 0.10-10 µg/mL for human urine. Blank human whole blood, plasma, and urine were used as the sample matrix for the method development and validation; while methyl-p-hydroxybenzoate was used as the internal standard (IS). Weighted-matrix matched standard calibration curves showed a good linearity up to a concentration of 10 µg/mL. The intra- and inter-day accuracy values (precision and trueness) were found in the range from -10.9% to 12.3%, and the performances of the validated FPSE-HPLC-PDA were further tested on real IBD patient samples. This is the first FPSE procedure applied simultaneously to whole blood, plasma, and urine samples for the determination of residual IBD drugs, which possess a wide range of polarity (logP values ranging from 2.30 for Ciprofloxacin, to 1.66 for Cortisone, and 2.92 for Sulfasalazine). The new approach exhibits high potential for immediate adoptation as a rapid, robust and green analytical tool for future clinical and pharmaceutical applications.

Esophagitis and its causes: Who is "guilty" when acid is found "not guilty"?

Esophagitis is mainly a consequence of gastroesophageal reflux disease, one of the most common diseases affecting the upper digestive tract. However the esophageal mucosa can also be targeted by some infectious, systemic or chemical conditions. Eosinophilic esophagitis (EoE) is an immune-mediated inflammatory disease, characterized by eosinophilic infiltration in the mucosa. Esophageal localization of Crohn's disease is not very common, but it should always be considered in patients with inflammatory bowel disease complaining of upper digestive tract symptoms. There are also forms of infectious esophagitis (e.g., Herpes simplex virus or Candida albicans) occurring in patients with a compromised immune system, either because of specific diseases or immunosuppressive therapies. Another kind of damage to esophageal mucosa is due to drug use (including oncologic chemotherapeutic regimens and radiotherapy) or caustic ingestion, usually of alkaline liquids, with colliquative necrosis and destruction of mucosa within a few seconds. Dysphagia is a predominant symptom in EoE, while infectious, drug-induced and caustic damages usually cause chest pain and odynophagia. Endoscopy can be useful for diagnosing esophagitis, although no specific pattern can be identified. In conclusion when a patient refers upper gastrointestinal tract symptoms and the diagnosis of gastro-esophageal reflux disease is not convincing we should always carefully investigate the patient's clinical history to consider possibilities other than the gastric refluxate.

Clinical and economic impact of infliximab one-hour infusion protocol in patients with inflammatory bowel diseases: A multicenter study.

AIM: To assess the impact of short infliximab (IFX) infusion on hospital resource utilization and costs. METHODS: All inflammatory bowel diseases (IBD) patients who received IFX 1 h infusion from March 2007 to September 2014 in eight centers from Southern Italy were included in the analysis. Demographic, clinical and infusion related data were collected. The potential benefits related to the short infusion protocol were assessed both in terms of time saving and increased infusion unit capacity. In addition, indirect patient-related cost savings were evaluated. RESULTS: One hundred and twenty-five patients were recruited (64 with ulcerative colitis and 61 with Crohn's disease). Median duration of disease was of 53 mo and mean age of pts at diagnosis was of 34 years (SD: ± 13). Adverse infusion reactions were reported in less than 4% both before and after short infusion. The total number of infusions across the selected centers was of 2501 (30.5% short infusions). In the analyzed cohort, 1143 h were saved (762 in the infusion and 381 in observation phases) through the rapid IFX infusion protocol. This time saving (-15% compared to the standard protocol in infusion phase) represents, from the hospital perspective, an opportunity to optimize infusion unit capacity by allocating the saved time in alternative cost-effective treatments. This is the case of opportunity cost that represents the value of forgone benefit which could be obtained from a resource in its next-best alternative use. Hence, an extra hour of infusion in the case of standard 2-h IFX represents a loss in opportunity to provide other cost effective services. The analysis showed that the short infusion increased the infusion units capacity up to 50% on days when the IFX infusions were scheduled (infusion phase). Furthermore, the analysis showed that the short IFX infusion protocol leads to time savings also in the post-infusion phase (observation) leading to a time saving of 10% on average among the analyzed centers. Finally, the short infusion protocol has been demonstrated to lead to indirect cost savings of €138/patient (average -€17.300 on the whole cohort). CONCLUSION: A short IFX infusion protocol can be considered time and cost saving in comparison to the standard infusion protocol both from the hospital's perspective, as it contributes to increase infusion units capacity, and the patients' perspective, as it reduces indirect costs and the impact of treatment on everyday life and work productivity.

Rifabutin Containing Triple Therapy and Rifabutin with Bismuth Containing Quadruple Therapy for Third-Line Treatment of Helicobacter pylori Infection: Two Pilot Studies.

AIM: To evaluate the therapeutic gain of the addition of bismuth to a rifabutin containing triple therapy with amoxicillin and pantoprazole at standard dosages for the treatment of third-line Helicobacter pylori infection after a preliminary susceptibility test. METHODS: Two separate groups of patients in two pilot studies which were carried out simultaneously. One group was treated with rifabutin 150 mg b.i.d., pantoprazole 20 mg b.i.d., and amoxicillin 1 g b.i.d. for 10 days and the other group with rifabutin 150 mg b.i.d., pantoprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and bismuth subcitrate 240 mg b.i.d. for 10 days. All patients underwent to culture and susceptibility testing prior to their inclusion in the study. A successful outcome was confirmed with an Urea Breath test performed 8 weeks after the end of treatment. A blood cell count was performed for all patients at the start and after 5 days of treatment since rifabutin has been shown to inhibit the growth of leucocytes. RESULTS: Twenty-nine patients were recruited in the pantoprazole, amoxicillin, rifabutin group and 30 in the pantoprazole, amoxicillin, rifabutin, and bismuth subcitrate group. All patients had a positive H. pylori culture and the susceptibility test used showed H. pylori sensitivity to rifabutin and amoxicillin. H. pylori eradication during follow-up was 18/27 (66.7%, 95% CI: 47.7-85.7%) in the pantoprazole, amoxicillin, rifabutin group and 28/29 (96.6%, 95% CI: 89.5-100.0%) in the pantoprazole, amoxicillin, rifabutin, and bismuth subcitrate group. Both treatments were well-tolerated with no reported side effects. Blood cell count remained normal in all patients. CONCLUSION: The addition of bismuth subcitrate to a triple therapy that includes proton pump inhibitors, amoxicillin, and rifabutin in patients who are treated for the third time for H. pylori infection resulted in a 30% therapeutic gain.

In vitro antimicrobial susceptibility of Helicobacter pylori to nine antibiotics currently used in Central Italy.

OBJECTIVE: Helicobacter pylori expresses an increased resistance in respect to antimicrobials currently used in therapy. The aim of this study was to evaluate the antimicrobial profiles of H. pylori isolates to nine conventional antibiotics used in a Central Region (Abruzzo) of Italy. MATERIALS AND METHODS: Biopsies were taken from antrum and fundus of 112 adult and 3 children with Urea Breath Test positive with dyspeptic symptoms and analyzed for H. pylori culture and antibacterial activity. Antimicrobial susceptibility tests were performed for clarithromycin, metronidazole, levofloxacin, moxifloxacin, ciprofloxacin, tetracycline, amoxicillin, ampicillin, and rifabutin by a modified agar dilution susceptibility test. RESULTS: Bacterial culture was successful in 100 out of 115 patients. Helicobacter pylori strains were isolated from 98 antrum and 83 fundus samples. The rate of recovery of H. pylori strains was 90.50% (181/200). The percentages of resistance were as follows: clarithromycin 72.44% antrum, 72.28% fundus; metronidazole 34.69% antrum, 42.16% fundus; levofloxacin 42.85% antrum, 53.01% fundus; moxifloxacin 37.35% antrum, 46.57% fundus; ciprofloxacin 39.47% antrum, 44.28% fundus; tetracycline 2.63% antrum, 2.85% fundus; amoxicillin 1.02% antrum, 1.20% fundus; ampicillin 0% antrum and fundus and rifabutin 0% antrum, 1.20% fundus. A total of 35 subjects harbored multi-resistant strains. CONCLUSIONS: This study underlines the high rate of resistance to clarithromycin, metronidazole and quinolones, which may reflect an overuse of them. Culture and susceptibility test, should be performed to prevent the emergence of multi-resistance and to assess an efficacious regimen.

Typical and atypical symptoms of gastro esophageal reflux disease: Does Helicobacter pylori infection matter?

AIM: To analyze whether the presence of Helicobacter pylori (H. pylori) infection could affect the quality of symptoms in gastro-esophageal reflux disease (GERD) patients. METHODS: one hundred and forty-four consecutive patients referred to our Unit for suspected GERD were recruited for the study. All patients underwent esophageal pH-metric recording. For those with a positive test, C13 urea breath test was then performed to assess the H. pylori status. GERD patients were stratified according to the quality of their symptoms and classified as typical, if affected by heartburn and regurgitation, and atypical if complaining of chest pain, respiratory and ears, nose, and throat features. H. pylori-negative patients were also asked whether they had a previous diagnosis of H. pylori infection. If a positive response was given, on the basis of the time period after successful eradication, patients were considered as "eradicated" (E) if H. pylori eradication occurred more than six months earlier or "recently eradicated" if the therapy had been administered within the last six months. Patients without history of infection were identified as "negative" (N). χ (2) test was performed by combining the clinical aspects with the H. pylori status. RESULTS: one hundred and twenty-nine of the 144 patients, including 44 H. pylori-positive and 85 H. pylori-negative (41 negative, 21 recently eradicated, 23 eradicated more than 6 mo before), were eligible for the analysis. No difference has been found between H. pylori status and either the number of reflux episodes (138 ± 23 vs 146 ± 36, respectively, P = 0.2, not significant) or the percentage of time with pH values < 4 (6.8 ± 1.2 vs 7.4 ± 2.1, respectively, P = 0.3, not significant). The distribution of symptoms was as follows: 13 typical (30%) and 31 atypical (70%) among the 44 H. pylori-positive cases; 44 typical (52%) and 41 atypical (48%) among the 85 H. pylori-negative cases, (P = 0.017 vs H. pylori+; OR = 2.55, 95%CI: 1.17-5.55). Furthermore, clinical signs in patients with recent H. pylori eradication were similar to those of H. pylori-positive (P = 0.49; OR = 1.46, 95%CI: 0.49-4.37); on the other hand, patients with ancient H. pylori eradication showed a clinical behavior similar to that of H. pylori-negative subjects (P = 0.13; OR = 0.89, 95%CI: 0.77-6.51) but different as compared to the H. pylori-positive group (P < 0.05; OR = 3.71, 95%CI: 0.83-16.47). CONCLUSION: Atypical symptoms of GERD occur more frequently in H. pylori-positive patients than in H. pylori-negative subjects. In addition, atypical symptoms tend to decrease after H. pylori eradication.

A Triple and Quadruple Therapy with Doxycycline and Bismuth for First-Line Treatment of Helicobacter pylori Infection: A Pilot Study.

BACKGROUND: Tetracycline-containing triple therapy has been suggested as an alternative first-line therapy for H. pylori infection. AIM: To evaluate the effect of two dosages of doxycycline (DOX) associated with amoxicillin and esomeprazole with and without bismuth subcitrate as first-line treatment of H. pylori infection. METHODS: Helicobacter pylori-positive patients underwent a 10-day therapy randomized into four groups: Group A received esomeprazole, amoxicillin, and DOX-100 mg b.i.d. (EAD-100), Group B a quadruple therapy with esomeprazole, amoxicillin, DOX-100 mg b.i.d. and bismuth subcitrate (EADB-100), Group C a triple therapy with esomeprazole, amoxicillin, and DOX-200 mg b.i.d. (EAD-200) and Group D a quadruple therapy with esomeprazole, amoxicillin, DOX-200 mg b.i.d., and bismuth subcitrate (EADB-200). Success was accessed by (13)C urea breath test 2 months after the end of treatment. The number of patients to be recruited for each group had to be at least 50 subjects. Treatment success of 80% or less was considered unacceptable. Stopping rules therefore were anytime six failures had occurred. RESULTS: In the EAD-100 group and in EAD-200 group, the recruitment was stopped at the 14th and 15th patient, respectively. Fifty-two patients entered in the EADB-100 group and 51 in the EADB-200 group. Intention to treat eradication was in EADB-100 group 46/52 (88.5%, 95% CI 76.6-95.6); in the EADB-200 group 47/51 (92.1%, 95% CI: 81.1-97.8) (n.s.). Side effects were absent. CONCLUSION: The adjunction of bismuth subcitrate to a triple therapy that includes esomeprazole, amoxicillin, and DOX in patients who are treated for the first time for the H. pylori infection potentiates the therapeutic effect. This regimen, however, deserves to be optimized in terms of duration and dose of DOX.

Quadruple therapy with moxifloxacin and bismuth for first-line treatment of Helicobacter pylori.

AIM: To compare triple therapy vs quadruple therapy for 10 d as first-line treatment of Helicobacter pylori (H. pylori) infection. METHODS: Consecutive H. pylori positive patients never treated in the past for this infection were randomly treated with triple therapy of pantoprazole (PAN) 20 mg bid, amoxicillin (AMO) 1 g bid and moxifloxacin (MOX) 400 mg bid for 10 d (PAM) or with quadruple therapy of PAN 20 mg bid, AMO 1 g bid, MOX 400 mg bid and bismuth subcitrate 240 mg bid for 10 d (PAMB). All patients were found positive at 13 C-Urea breath test (UBT) performed within ten days prior to the start of the study. A successful outcome was confirmed with an UBT performed 8 wk after the end of treatment. χ(2) analysis was used for statistical comparison. Per protocol (PP) and intention-to-treat (ITT) values were also calculated. RESULTS: Fifty-seven patients were enrolled in the PAM group and 50 in the PAMB group. One patient in each group did not return for further assessment. Eradication was higher in the PAMB group (negative: 46 and positive: 3) vs the PAM group (negative: 44 and positive: 12). The H. pylori eradication rate was statistically significantly higher in the PAMB group vs the PAM group, both with the PP and ITT analyses (PP: PAMB 93.8%, PAM 78.5%, P < 0.02; ITT: PAMB 92%, PAM 77.1 %, P <0.03). CONCLUSION: The addition of bismuth subcitrate can be considered a valuable adjuvant to triple therapy in those areas where H. pylori shows a high resistance to fluoroquinolones.

Helicobacter pylori isolates from proximal and distal stomach of patients never treated and already treated show genetic variability and discordant antibiotic resistance.

INTRODUCTION: The treatment failure of Helicobacter pylori (H. pylori) infection may be mainly because of antibiotic resistance and the presence of a mixed infection in the same patient. AIM: To investigate the incidence of mixed infection and discordant antibiotic resistance in patients never treated and already treated. MATERIALS AND METHODS: Susceptibility test to amoxicillin, rifabutin, tinidazole, clarithromycin, levofloxacin, and moxifloxacin was conducted on H. pylori strains culture from 76 patients never treated and 72 patients already treated unsuccessfully. DNA fingerprinting was determined on H. pylori strains harboring in the same patient with a discordant resistance to the same antibiotic. RESULTS: Forty percent of patients never treated and 53% of patients already treated showed a pangastric infection. The overall resistance to amoxicillin, clarithromycin, and tinidazole was significantly higher in patients with pangastric infection in comparison with those with the infection in the antrum (P<0.05). Discordant resistance was present in 33% of patients never treated, and 21% of patients already treated. DNA fingerprinting showed substantial differences among DNA patterns suggesting a mixed infection. CONCLUSION: Culture and susceptibility test should be performed when necessary not only in the antrum but also in the fundus of patients with H. pylori infection.

Role of the preliminary susceptibility testing for initial and after failed therapy of Helicobacter pylori infection with levofloxacin, amoxicillin, and esomeprazole.

BACKGROUND: Levofloxacin has been proposed as an alternative to classic therapy in secondary resistance to Helicobacter pylori. AIM: To evaluate primary and secondary resistance of H. pylori to levofloxacin, and to test the role of susceptibility test on the efficacy of levofloxacin-based triple therapy. METHODS: Eighty consecutive dyspeptic patients with positive (13)C-urea breath test never treated were randomly allocated into group A(1) (40 patients) and group B(1) (39 patients). Eighty-three patients already treated unsuccessfully with positive (13)C-urea breath test were divided into group A(2) (51 patients) and group B(2) (32 patients). Patients in group A(1) and group A(2) underwent upper gastrointestinal endoscopy for H. pylori susceptibility test to amoxicillin, clarithromycin, tinidazole, rifabutin, and levofloxacin. These patients were treated with levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.) and esomeprazole (20 mg b.i.d.) for 10 days if sensitive to these two antibiotics. If H. pylori was found resistant to amoxicillin and/or levofloxacin the treatment was based on the indications of the susceptibility test. Patients in group B(1) and group B(2) were treated empirically with levofloxacin, amoxicillin, and esomeprazole at the same dose and duration as group A. All patients underwent (13)C-urea breath test 2 months after the end of therapy. RESULTS: The antibiotic resistance of H. pylori strains in group A(1) and group A(2) was (%): amoxicillin: 2.4, 10; clarithromycin: 21.9, 43.1; tinidazole: 31.7, 70; rifabutin: 2.4, 4; and levofloxacin: 9.7, 12.2, respectively. In group A(1) with susceptibility test-driven therapy, eradication was 97.2%, and in group B(1) with empirical treatment, 94.1% (n.s.). In group A(2) with susceptibility test, eradication was 97.5%, whereas in group B(2) with empirical treatment 81.2% (p < .01). CONCLUSION: Primary and secondary resistance of H. pylori to levofloxacin is approximately 10% of the tested strains. The susceptibility test does not influence therapeutic outcome of triple therapy with amoxicillin and levofloxacin in patients never treated, while it is determinant for patients who were previously treated without success.