Rifabutin for the treatment of helicobacter pylori infection: A review

Nowadays, apart from having to know first-line Helicobacter pylori eradication regimens well, we must also be prepared to face treatment failures. The aim of this review is to summarize the role of rifabutin in the management of H. pylori infection. Bibliographical searches were performed in PubMed. Data on resistance and efficacy of rifabutin-containing regimens on H. pylori eradication were meta-analyzed. Mean H. pylori rifabutin resistance rate (39 studies, including 9721 patients) was 0.13%; when studies only including patients naïve to H. pylori eradication treatment were considered, this figure was even lower (0.07%). Mean H. pylori eradication rate (by intention-totreat) with rifabutin-containing regimens (3052 patients) was 73%. Respective cure rates for second-, third-, fourth-and fifth-line therapies, were 79%, 69%, 69% and 72%. Most studies administered rifabutin 300 mg/day, which seemed to be more effective than 150 mg/day. The ideal length of treatment remains unclear, but 10–12-day regimens are generally recommended. Adverse events to rifabutin treatment in H. pylori studies were relatively infrequent (15%), and severe adverse events were exceptional (myelotoxicity was the most significant, although always reversible). In summary, rifabutin-containing therapy represents an encouraging strategy generally restricted, at present, to patients where previous (usually multiple) eradication regimens have failed

Rescue Therapy for Helicobacter pylori Infection 2012

Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. After 30 years of experience in H. pylori treatment, however, the ideal regimen to treat this infection has still to be found. Nowadays, apart from having to know well first-line eradication regimens, we must also be prepared to face treatment failures. In designing a treatment strategy, we should not only focus on the results of primary therapy alone but also on the final—overall—eradication rate. The choice of a “rescue” treatment depends on which treatment is used initially. If a first-line clarithromycin-based regimen was used, a second-line metronidazole-based treatment (quadruple therapy) may be used afterwards, and then a levofloxacin-based combination would be a third-line “rescue” option. Alternatively, it has recently been suggested that levofloxacin-based “rescue” therapy constitutes an encouraging 2nd-line strategy, representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure, with the advantage of efficacy, simplicity and safety. In this case, quadruple regimen may be reserved as a 3rd-line “rescue” option. Even after two consecutive failures, several studies have demonstrated that H. pylori eradication can finally be achieved in almost all patients if several “rescue” therapies are consecutively given

Anti‑TNF agents and new biological agents (Vedolizumab and Ustekinumab) in the prevention and treatment of postoperative recurrence after surgery in crohn’s disease

Surgery for Crohn’s disease (CD) is not curative, as postoperative recurrence (POR) after ileocolonic resection is the rule in the absence of prophylactic treatment. In the present article, we critically review available data on the role of anti-tumour necrosis factor (TNF) agents and new biologics (including vedolizumab and ustekinumab) in the prevention and treatment of POR after surgery in CD. Several studies (summarised in various meta-analyses) have confrmed the efcacy of anti-TNFs in the prevention of POR. We identifed 37 studies, including 1863 CD patients, with mean endoscopic POR at 6–12 months of 29%. Only few randomised controlled trials (RCTs) have directly compared thiopurines and anti-TNFs, with controversial results, although the superiority of the latter is supported by several meta-analyses. Infiximab and adalimumab seem equally efective. The combination of anti-TNFs and immunosuppressives should be considered in patients previously exposed to anti-TNFs. Several studies have shown that anti-TNFs remain an efective option to prevent POR also in patients with anti-TNF failure before surgery. In fact, the use of the same anti-TNF before and after surgery might be efective for the prevention of POR. Prophylactic anti-TNF treatment, once started, should be continued long term. Anti-TNFs are also efective for the treatment of established POR. Retreatment with anti-TNFs for POR is a valid strategy even after their preoperative failure. In six studies (including 156 patients) evaluating vedolizumab, mean endoscopic POR at 6–12 months was 41%. The non-randomised comparison of anti-TNFs and vedolizumab has provided controversial results. One placebo-controlled RCT confrmed that vedolizumab is quite efective in preventing POR in CD patients with increased risk of recurrence. Seven studies (including 162 patients) evaluated ustekinumab, with a mean endoscopic POR at 6–12 months of 41%. The comparative efcacy of ustekinumab and anti-TNFs is still unclear. Ustekinumab and vedolizumab seem to be equally efective, although the experience is very limited. In conclusion, to date, anti-TNFs are the most efective agents in preventing and treating POR in CD. Anti-TNFs remain an efective option to prevent POR also in patients with anti-TNF failure before surgery. Vedolizumab seems to be quite efective in the prevention of POR in patients with increased risk of recurrence. Ustekinumab is probably also efective in the postoperative setting, although the comparative efcacy with anti-TNFs or vedolizumab is still unclea

Adverse event profile during the treatment of Helicobacter pylori: A real-world experience of 22,000 patients from the European Registry on H. pylori Management (Hp-EuReg)

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si lo hubiere, y los autores pertenecientes a la UAMThe safety of Helicobacter pylori eradication treatments and to what extent adverse events (AEs) influence therapeutic compliance in clinical practice are hardly known. Our aim was to assess the frequency, type, intensity, and duration of AEs, and their impact on compliance, for the most frequently used treatments in the “European Registry on Helicobacter pylori management.” Methods: Systematic prospective noninterventional registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H. pylori infection in routine clinical practice. All prescribed eradication treatments and their corresponding safety profile were recorded. AEs were classified depending on the intensity of symptoms as mild/moderate/severe and as serious AEs. All data were subject to quality control. Results: The different treatments prescribed to 22,492 patients caused at least 1 AE in 23% of the cases; the classic bismuth-based quadruple therapy was the worst tolerated (37% of AEs). Taste disturbance (7%), diarrhea (7%), nausea (6%), and abdominal pain (3%) were the most frequent AEs. The majority of AEs were mild (57%), 6% were severe, and only 0.08% were serious, with an average duration of 7 days. The treatment compliance rate was 97%. Only 1.3% of the patients discontinued treatment due to AEs. Longer treatment durations were significantly associated with a higher incidence of AEs in standard triple, concomitant, bismuth quadruple, and levofloxacin triple or quadruple therapies. Discussion: Helicobacter pylori eradication treatment frequently induces AEs, although they are usually mild and of limited duration. Their appearance does not interfere significantly with treatment complianc

European Registry on Helicobacter pylori management (Hp-EuReg): Patterns and trends in first-line empirical eradication prescription and outcomes of 5 years and 21 533 patients

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMObjective The best approach for Helicobacter pylori management remains unclear. An audit process is essential to ensure clinical practice is aligned with best standards of care. Design International multicentre prospective non-interventional registry starting in 2013 aimed to evaluate the decisions and outcomes in H. pylori management by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables included demographics, previous eradication attempts, prescribed treatment, adverse events and outcomes. Data monitoring was performed to ensure data quality. Time-trend and geographical analyses were performed. Results 30 394 patients from 27 European countries were evaluated and 21 533 (78%) first-line empirical H. pylori treatments were included for analysis. Pretreatment resistance rates were 23% to clarithromycin, 32% to metronidazole and 13% to both. Triple therapy with amoxicillin and clarithromycin was most commonly prescribed (39%), achieving 81.5% modified intention-to-treat eradication rate. Over 90% eradication was obtained only with 10-day bismuth quadruple or 14-day concomitant treatments. Longer treatment duration, higher acid inhibition and compliance were associated with higher eradication rates. Time-trend analysis showed a region-dependent shift in prescriptions including abandoning triple therapies, using higher acid-inhibition and longer treatments, which was associated with an overall effectiveness increase (84%-90%). Conclusion Management of H. pylori infection by European gastroenterologists is heterogeneous, suboptimal and discrepant with current recommendations. Only quadruple therapies lasting at least 10 days are able to achieve over 90% eradication rates. European recommendations are being slowly and heterogeneously incorporated into routine clinical practice, which was associated with a corresponding increase in effectivenessThis project has been funded by the European Helicobacter and Microbiota Study Group (EHMSG), the Asociación Española de Gastroenterología (AEG) and the Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd

Systematic review: The gut microbiome and its potential clinical application in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic relapsing-remitting systemic disease of the gastrointestinal tract. It is well established that the gut microbiome has a profound impact on IBD pathogenesis. Our aim was to systematically review the literature on the IBD gut microbiome and its usefulness to provide microbiome-based biomarkers. A systematic search of the online bibliographic database PubMed from inception to August 2020 with screening in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. One-hundred and forty-four papers were eligible for inclusion. There was a wide heterogeneity in microbiome analysis methods or experimental design. The IBD intestinal microbiome was generally characterized by reduced species richness and diversity, and lower temporal stability, while changes in the gut microbiome seemed to play a pivotal role in determining the onset of IBD. Multiple studies have identified certain microbial taxa that are enriched or depleted in IBD, including bacteria, fungi, viruses, and archaea. The two main features in this sense are the decrease in beneficial bacteria and the increase in pathogenic bacteria. Significant differences were also present between remission and relapse IBD status. Shifts in gut microbial community composition and abundance have proven to be valuable as diagnostic biomarkers. The gut microbiome plays a major role in IBD, yet studies need to go from casualty to causality. Longitudinal designs including newly diagnosed treatment-naïve patients are needed to provide insights into the role of microbes in the onset of intestinal inflammation. A better understanding of the human gut microbiome could provide innovative targets for diagnosis, prognosis, treatment and even cure of this relevant disease.This work is supported by Sara Borrell contract CD19/00247 from the Instituto de Salud Carlos III (ISCIII) to L.A.-G

Frequency and effectiveness of empirical anti-tnf dose intensification in inflammatory bowel disease: Systematic review with meta-analysis

Loss of response to antitumor necrosis factor (anti-TNF) therapies in inflammatory bowel disease occurs in a high proportion of patients. Our aim was to evaluate the loss of response to anti-TNF therapy, considered as the need for dose intensification (DI), DI effectiveness and the possible variables influencing its requirements. Bibliographical searches were performed. Selection: prospective and retrospective studies assessing DI in Crohn’s disease and ulcerative colitis patients treated for at least 12 weeks with an anti-TNF drug. Exclusion criteria: studies using anti-TNF as a prophylaxis for the postoperative recurrence in Crohn’s disease or those where DI was based on therapeutic drug monitoring. Data synthesis: effectiveness by intention-to-treat (random effects model). Data were stratified by medical condition (ulcerative colitis vs. Crohn’s disease), anti-TNF drug and follow-up. Results: One hundred and seventy-three studies (33,241 patients) were included. Overall rate of the DI requirement after 12 months was 28% (95% CI 24–32, I2 = 96%, 41 studies) in naïve patients and 39% (95% CI 31–47, I2 = 86%, 18 studies) in non-naïve patients. The DI requirement rate was higher both in those with prior anti-TNF exposure (p = 0.01) and with ulcerative colitis (p = 0.02). The DI requirement rate in naïve patients after 36 months was 35% (95% CI 28–43%; I2 = 98%; 18 studies). The overall short-term response and remission rates of empirical DI in naïve patients were 63% (95% CI 48–78%; I2 = 99%; 32 studies) and 48% (95% CI: 39–58%; I2 = 92%; 25 studies), respectively. The loss of response to anti-TNF agents—and, consequently, DI—occurred frequently in inflammatory bowel disease (approximately in one-fourth at one year and in one-third at 3 years). Empirical DI was a relatively effective therapeutic option

Empirical vs. Susceptibility-Guided Treatment of Helicobacter pylori Infection: A Systematic Review and Meta-Analysis

Background: Treating Helicobacter pylori infection according to antibiotic resistance has been frequently recommended. However, information on its real effectiveness is scarce. Aim: The aim of this study is to perform a meta-analysis comparing empirical vs. susceptibility-guided treatment of H. pylori. Methods: Selection of studies: Studies comparing empirical versus susceptibility-guided treatment were selected. Search strategy: electronic and manual up to August 2021. Data synthesis: by intention-to-treat (random-effects model). Results: Overall, 54 studies were included (6,705 patients in the susceptibility-guided group and 7,895 in the empirical group). H. pylori eradication rate was 86 vs. 76%, respectively (RR: 1.12; 95% CI: 1.08–1.17; I2: 83%). Similar results were found when only RCTs were evaluated (24 studies; RR: 1.16; 95% CI: 1.11–1.22; I2: 71%) and when susceptibility testing was assessed by culture (RR: 1.12; 95% CI: 1.06–1.18) or PCR (RR: 1.14; 95% CI: 1.05–1.23). For first-line treatments (naïve patients; 30 studies), better efficacy results were obtained with the susceptibility-guided strategy (RR: 1.15; 95% CI: 1.11–1.20; I2: 79%). However, for empirical first-line quadruple regimens, in particular (both with and without bismuth, excluding the suboptimal triple therapies), not based on CYP2C19 gene polymorphism, no differences in efficacy were found compared with the susceptibility-guided group (RR: 1.04; 95% CI: 0.99–1.09); this lack of difference was confirmed in RCTs (RR: 1.05; 95% CI: 0.99–1.12). For rescue therapies (13 studies, most 2nd-line), similar results were demonstrated for both strategies, including all studies (RR: 1.09; 95% CI: 0.97–1.22; I2: 82%) and when only RCTs were considered (RR: 1.15; 95% CI: 0.97–1.36). Conclusion: The benefit of susceptibility-guided treatment over empirical treatment of H. pylori infection could not be demonstrated, either in first-line (if the most updated quadruple regimens are prescribed) or in rescue therapie

Update on non-bismuth quadruple (concomitant) therapy for eradication of Helicobacter pylori

Background: Traditional standard triple therapy for Helicobacter pylori (H. pylori) infection (proton pump inhibitor-clarithromycin-amoxicillin) can easily be converted to non-bismuth quadruple (concomitant) therapy by the addition of a nitroimidazole twice daily. Aim: To critically review evidence on the role of non-bismuth quadruple therapy (proton pump inhibitor-clarithromycin-amoxicillin-nitroimidazole) in the treatment of H. pylori infection. Methods: Bibliographical searches were performed in MEDLINE and relevant congresses up to December 2011. We performed a meta-analysis of the studies evaluating the concomitant therapy, and of the randomized controlled trials comparing the concomitant and the standard triple therapy. Results: A meta-analysis of 19 studies (2070 patients) revealed a mean H. pylori cure rate (intention-to-treat) of 88% (95% confidence interval from 85% to 91%) for non-bismuth quadruple therapy. We performed a meta-analysis of the randomized controlled studies comparing the concomitant (481 patients) and the standard triple therapy (503 patients). The formerwas more effective than the latter: 90% versus 78% (intention-to-treat analysis). Results were homogeneous (I = 0%). The odds ratio for this comparison was 2.36 (95% confidence interval from 1.67 to 3.34). A tendency toward better results with longer treatments (7-10 days versus 3-5 days) has been observed, so it seems reasonable to recommend the length of treatment achieving the highest cure rates (10 days). Clarithromycin resistance may reduce the efficacy of non-bismuth quadruple therapy, although the decrease in eradication rates seems to be farlower than in standard triple therapy. Experience with the non-bismuth quadruple therapy in patients with metronidazole-resistant strains is still very limited. Conclusion: Non-bismuth quadruple (concomitant) therapy appears to be an effective, safe, and well-tolerated alternative to triple therapy and is less complex than sequential therapy. Therefore, this regimen appears well suited for use in settings where the efficacy of triple therapy is unacceptably low