David Olivares

Third-Line Rescue Therapy with Levofloxacin After Two H. pylori Treatment Failures

AIM:Eradication therapy with proton pump inhibitor, clarithromycin and amoxicillin fails in a considerable number of cases. A rescue therapy still fails in more than 20% of the cases. Our aim was to evaluate the efficacy and tolerability of a third-line levofloxacin-based regimen in patients with two consecutive Helicobacter pylori eradication failures.METHODS:Design: Prospective multicenter study. Patients: In whom a first treatment with omeprazole-clarithromycin-amoxicillin and a second with omeprazole-bismuth-tetracycline-metronidazole (or ranitidine bismuth citrate with these antibiotics) had failed. Intervention: A third eradication regimen with levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.), and omeprazole (20 mg b.i.d.) was prescribed for 10 days. Outcome: Eradication was confirmed with 13C-urea breath test 4–8 wk after therapy.RESULTS:One-hundred patients were initially included, and nine were lost for follow-up. All patients but five took all the medications correctly. Per-protocol and intention-to-treat eradication rates were 66% (95% CI = 56–75%) and 60% (50–70%). Adverse effects were reported in 25% of the patients, mainly including metallic taste (8%), nausea (8%), myalgia/arthralgia (5%), and diarrhea (4%); none of them were severe.CONCLUSION:Levofloxacin-based rescue therapy constitutes an encouraging empirical third-line strategy after multiple previous H. pylori eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, and tetracycline.

Helicobacter pylori first-line treatment and rescue options in patients allergic to penicillin

Background : Helicobacter pylori eradication is a challenge in patients allergic to penicillin, especially those who have failed a first‐eradication trial.

Long-term follow-up of 13C-urea breath test results after Helicobacter pylori eradication: frequency and significance of borderline δ13CO2 values

Background  The precise choice of cut‐off point for the 13C‐urea breath test to define whether it is positive or negative represents a controversial issue.

Need for infliximab dose intensification in Crohn's disease and ulcerative colitis

AIM To compare the need for infliximab dose intensification in two cohorts of patients with Crohns disease (CD) or ulcerative colitis (UC). METHODS Single centre, uncontrolled, observational study. Consecutive patients with CD and UC who responded to infliximab induction doses were included. Data collected in a prospectively maintained database were retrospectively analysed. Differences in the rates of dose intensification per patient-month and the intensification-free survival time were compared. We also evaluated the interval between the first infliximab induction dose and the first infliximab escalated dose. The weight-adjusted infliximab administration costs were also calculated. RESULTS Fifty nine patients with CD and 38 patients with UC were enrolled. The rate of intensification per patient-month was 3.9% for UC and 1.4% for CD (P = 0.005). The median time from baseline to intensification was significantly shorter in UC compared to CD [6.6 mo (IQR: 4.2-9.5 mo) vs 10.7 mo (IQR: 8.9-11.7 mo), P = 0.005]. In the survival analysis, the cumulative probability of avoiding infliximab dose intensification was significantly higher in CD (P = 0.002). In the multivariate analysis, disease (UC vs CD) was the only factor significantly associated with dose intensification. The infiximab administration costs during the first year were significantly higher for UC compared to CD (mean ± SD 234.9 ± 53.3 Euros/kg vs 212.3 ± 15.1 Euros/kg, P = 0.03). CONCLUSION The rate of infliximab dose intensification per patient-month is significantly higher in UC patients. The infliximab administration costs are also significantly higher in patients with UC.

Factors involved in the pathogenesis of Helicobacter pylori infection.

Helicobacter pylori is a bacterium that chronically colonizes the gastric epithelium and infects approximately half of the human population worldwide. This pathogen is responsible for chronic gastritis and a high percentage of peptic ulcers, and its presence has been correlated to gastric cancer development (1-4). Several factors have been associated with this germ’s aggressiveness and hence implicated in epithelial damage, including vacuolizing cytotoxin (VacA), cytotoxinassociated gene A (cagA), surface lipopolysaccharide (LPS), bacterial urease, flagella, surface adhesins, oxidizing radicals, and citokines produced by leukocytes in response to infection. On the other hand, there is increasing evidence that H. pylori species are genetically diverse, that such diversity is associated with different aggresiveness degrees on the mucosa, and hence with gastric mucosal inflammation to different extents and a variety of clinical prognoses for infected patients (5). H. pylori genoma includes more than 1,000 preserved genes and strain-specific genes. This bacterium may acquire or lose exogenous DNA, and thus follows an ongoing microevolution model allowing high genetic variability, which may result in strains adapted to multiple adverse environments. Such variability also results from a high recombination rate during colonization of one host by non-related H. pylori species, in addition to a high frequency of mutation (6-11). The objective of this paper is to review the characteristics, and both the in vivo and in vitro effects, of major bacterial factors related to H. pylori virulence on human epithelial cells, as well as the effects deriving from H. pylori’s intrinsic genetic variability.

Helicobacter pylori infection and gastric mucosal epithelial cell apoptosis.

NF-κB: nuclear factor κB; TNF-α: tumor necrosis factor α; DD: death domain; FADD: Fas-associated death domain; FasL: Fas receptor ligand; TNFR: TNF receptor; TRADD: TNFR-associated death domain; TRAF: TNFR-associated factor; COX: cyclooxygenase; PG: prostaglandin; iNOS: inducible nitric oxide synthase; NO: nitric oxide; MDR-1: multiple drug resistance gene; IL: interleukin; EGF: epithelial growth factor; IGF: insulin-like growth factor; HGF: hepatocyte growth factor; PI-3 kinase: phosphoinositol-3 kinase, RIP: receptor interactive protein, SOD: superoxide dismutase, MTP: mitochondrial transition pore, Apaf-1: apoptotic protease activation factor, MHC: major histocompatibility complex, TGF-α: transforming growth factor α, ROS: reactive oxygen species, MAPK: mitogen-activated protein kinase, NSAID: non-steroidal anti-inflammatory drug.

Clinical Outcomes of Golimumab as First, Second or Third Anti-tnf Agent in Patients with Moderate-to-severe Ulcerative Colitis

Background: Golimumab efficacy data in ulcerative colitis (UC) are limited to anti–tumor necrosis factor &agr; (TNF)-naive patients. The aim of this study was to assess the short-term and long-term efficacy of golimumab used as first, second, or third anti-TNF in UC in a real-life clinical setting. Methods: This retrospective multicenter cohort study included patients with moderate-to-severe UC treated with golimumab. The primary efficacy endpoints were short-term partial Mayo score response, long-term golimumab failure-free survival, and colectomy-free survival. Results: In 142 patients with UC, golimumab was administered as first (40%), second (23%), or third anti-TNF (37%). Ninety-two patients (65%, 95% confidence interval 56.6–73) achieved short-term clinical response. Forty-five patients (32%, 95% confidence interval 23.7–39.7) achieved clinical remission. Response rates for golimumab were 75% as first anti-TNF, 70% as second anti-TNF (ns versus first anti-TNF), and 50% as third anti-TNF (P = 0.007 versus first anti-TNF). After 12 months median follow-up (interquartile range 6–18), 60 patients (42%, 95% confidence interval 34–51) had golimumab failure, and 15 patients (11%) needed colectomy. Thirty-one patients (22%) needed golimumab dose escalation, and 71% of these regained response after escalation. Starting maintenance with 100 mg golimumab doses and short-term nonresponse were independent predictors of golimumab failure. Conclusions: In this real-life cohort of patients with UC, golimumab therapy was effective for inducing and maintaining clinical response. Although anti-TNF–naive patients had better outcomes, golimumab was also effective in anti-TNF–experienced patients. Only the patients given golimumab after previous failure of 2 anti-TNF agents had significantly worse outcomes. Golimumab dose escalation was beneficial and safe.

7-day rescue therapy with ranitidine bismuth citrate after Helicobacter pylori treatment failure

Background : Quadruple rescue therapy requires a complex scheme with four drugs.

How frequently do tuberculosis screening tests convert in inflammatory bowel disease patients on anti-tumour necrosis factor-alpha? A pilot study.

BACKGROUND Tuberculosis reactivation can lead to severe complications in patients treated with anti-tumour necrosis factor-alpha. AIM To assess the usefulness of repeat tuberculosis screening tests in inflammatory bowel disease patients on stable anti-TNF therapy. METHODS Cross-sectional study, in patients on prolonged anti-TNF treatment (≥ 12 months) and basal negative screening for latent tuberculosis. Quantiferon(®)-TB Gold In-tube test was performed and then, tuberculin skin test was administered. RESULTS 74 patients were included, median duration of anti-TNF treatment was 30 months (IQR 19-54); 47 patients on infliximab and 27 on adalimumab; no patient was on glucocorticoids. Previous BCG vaccination was present in 5 cases. After anti-TNF was started, 4 patients suffered from potential tuberculosis exposure and two cases travelled to endemic areas. The cumulative incidence of tuberculin skin test conversion was 2.7% (95% CI 0.3-9.4%, 2/74), and the incidence rate of tuberculin skin test conversion was 0.83% (95% CI 0.1-2.9%) per patient-year of treatment with anti-TNF drugs. All Quantiferon tests but one (a patient with an indeterminate result and a negative tuberculin skin test) were negative. CONCLUSIONS The incidence rate of conversion of tuberculosis screening tests among patients on anti-TNF treatment seems to be low and these conversions were diagnosed based on a positive tuberculin skin test and were discordant with Quantiferon testing.

Clinical trial evaluating amoxicillin and clarithromycin hydrogels (Chitosan-polyacrylic acid polyionic complex) for H. pylori eradication.

Aim It has been suggested that enhancement of amoxicillin or clarithromycin concentration at the gastric tissue may improve the anti-Helicobacter pylori effect of these drugs. This could be achieved by allowing the drug to remain longer in the stomach using dried hydrogels. Our aim was to evaluate the efficacy of an H. pylori eradication regimen including both amoxicillin and clarithromycin hydrogels. Methods Design: prospective clinical trial. Patients: with peptic ulcer or functional dyspepsia. Intervention: 7-day rabeprazole-amoxicillin-clarithromycin regimen. In addition, amoxicillin and clarithromycin hydrogels were administered twice daily during the 7 days. The polyionic complex hydrogel was prepared with Chitosan and polyacrylic acid. Outcome: H. pylori eradication was defined as a negative 13C-urea breath test 8 weeks after completing therapy. Results Forty patients were included. One patient did not return for follow-up. Ninety percent of the patients took all the medications correctly. Per-protocol and intention-to-treat eradication rates were 74% (95% CI=58%–86%) and 70% (55%–82%). Mild adverse effects were reported in 4 (10%) patients (diarrhea in 3, and nausea/heartburn in 1). Conclusions Although dried polyionic complexes could serve as suitable candidates for amoxicillin and clarithromycin site-specific delivery in the stomach, its addition does not increase the eradication efficacy of the generally prescribed proton pump inhibitor plus amoxicillin and clarithromycin regimen.