Non-bismuth Quadruple Regimens Research Articles

10-Day Versus 14-Day Quadruple Concomitant Nonbismuth Therapy for the Treatment of Helicobacter pylori Infection: Results From a Randomized Prospective Study in a High Clarithromycin Resistance Country.

The aim of this study was to investigate the implementation of a 14-day quadruple nonbismuth concomitant regimen, as proposed by recent Guidelines and Consensus Statements. In Greece, a region with >20% clarithromycin resistance where bismuth is unavailable, the 10-day quadruple concomitant scheme has already been adopted as the accepted first-line Helicobacter pylori eradication treatment. Our prospective randomized study included 364 patients with newly diagnosed H. pylori infection, randomized to receive a 10-day or a 14-day nonbismuth quadruple concomitant scheme. Treatment outcome was assessed by C-urea breath test and/or histology at least 4 weeks after therapy. Intention to treat and per protocol analyses of the eradication rates were performed. Secondary endpoints included patient adherence, safety, and the impact of prior antibiotic exposure in treatment efficacy. The overall eradication rates of the 2 treatments were 87.9% versus 87.4% in the intention to treat analysis, P=1.000, and 93% versus 94.1%, P=0.859, in the per protocol analysis for the 10-day and the 14-day treatment group, respectively. Both groups displayed excellent compliance rates (99.5% for the 10-day vs. 96.2% for the 14-day treatment duration, P=0.067). As regards treatment safety, serious adverse events that led to the discontinuation of both regimens were few, with no statistical difference between the 2 groups (0.5% in the 10-day group and 2.2% in the 14-day group, P>0.05). Previous antibiotic exposure was not significant with regard to treatment efficacy. In Greece, the 10-day concomitant nonbismuth quadruple regimen for first-line treatment remains the most efficient strategy for H. pylori eradication.

Treatment of Helicobacter pylori infection 2017.

This review summarizes important studies regarding Helicobacter pylori therapy published from April 2016 to April 2017. The main themes that emerge involve studies assessing the efficacy of bismuth and nonbismuth quadruple regimens. While in recent years, much of the emphasis on the use of bismuth has focussed on its utility in a second-line setting, an increasing number of studies this year have shown excellent efficacy in first-line therapy. The efficacy of bismuth as a second-line after sequential and concomitant therapy was particularly noteworthy. Antibiotic resistance was more intensely studied this year than for a long time, and definite trends are presented regarding an increase in resistance, including the fact that clarithromycin resistance in particular is now at a level where the continued use of clarithromycin triple therapy first-line as a mainstream treatment is not recommended. Another exciting trend to emerge this year is the utility of vonoprazan as an alternative to PPI therapy, especially in resistant and difficult-to-treat groups.

Efficacy and Safety of Quinolone-Containing Rescue Therapies After the Failure of Non-Bismuth Quadruple Treatments for Helicobacter pylori Eradication: Systematic Review and Meta-Analysis.

Anti-Helicobacter pylori eradication treatment fails in a significant percentage of cases. Although this percentage has been reduced to 5-15% with the use of non-bismuth quadruple therapies, limited data exist regarding rescue after failure of these treatments. The aim of this study was to systematically review the efficacy and safety of quinolone-containing therapies after the failure of non-bismuth quadruple regimens. Studies evaluating the efficacy of second-line quinolone-containing therapies after the failure of non-bismuth sequential or concomitant regimens were selected. Efficacy (by intention to treat) was analyzed using the inverse variance method; safety data were recorded as the occurrence of any adverse event. The risk of bias of each primary study was evaluated using the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) tool. The quality of the evidence was summarized using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Sixteen studies were included. The 10-day levofloxacin/amoxicillin/proton pump inhibitor (PPI) triple therapy (LT) achieved eradication rates of 80% (95% CI 71-88). Regarding the moxifloxacin/amoxicillin/PPI triple therapy (MT), its efficacy was higher when administered for 14 days instead of 7 days (80 vs 63%). Two studies investigated the levofloxacin/bismuth-containing quadruple therapies (LBQ) obtaining eradication rates over 90%. Safety was similar in all treatments. The sensitivity analyses showed that results for LT were robust, but MT had weak evidence. Quinolone-containing triple therapies reported eradication rates ≤80%, but LBQ therapies showed encouraging rates. However, the strength of the evidence was very low. The efficacy of LBQ should be corroborated in more studies, and the usefulness of quinolones needs to be evaluated in areas with moderate to high bacterial resistances.

Treatment of Helicobacter pylori infection 2014.

This review summarizes important studies regarding H.pylori therapy published from April 2013 to April 2014. The main themes that emerge are assessing the efficacy of standard triple therapy, as well as exploring new first-line treatments, predominantly optimized triple therapies and non-bismuth quadruple schemes. Regarding newer non-bismuth quadruple regimens, the compliance and tolerance seem to be similar for sequential and concomitant regimens. Notably, no study yet has demonstrated a clear statistical superiority for either, and a systematic review and meta-analysis may be warranted. Other studies examined the role of levofloxacin and bismuth based therapies in H. pylori eradication. The efficacy of bismuth as a second-line after sequential therapy was particularly noteworthy. Levofloxacin-based therapies also appear to be useful and versatile as part of different antibiotic combinations and in first-, second-, and third-line therapies. The emerging problem of quinolone resistance remains a worry. Individualized therapy, based on factors such as antimicrobial information, resistance data, and CYP2C19 metabolism, may well be the most notable future trend to emerge this year.

Optimal treatment strategy forHelicobacter pylori: Era of antibiotic resistance

Standard triple therapy, consisting of a proton pump inhibitor, plus amoxicillin and clarithromycin, has been the most commonly used first-line treatment regimen for Helicobacter pylori (H. pylori) eradication for many years worldwide. However, as a result of increased resistance to antibiotics, H. pylori eradication rates with use of standard triple therapy have been declining and recently reached < 80% in many countries. Several new strategies to enhance the eradication rate of H. pylori have been studied. Currently, among the alternative first-line eradication regimens, concomitant and hybrid regimens have shown excellent results and could be the optimal treatment option. Although clinical usefulness of rescue therapy for patients in whom eradication of H. pylori with non-bismuth quadruple regimen has failed is unclear, levofloxacin-based quadruple therapy has shown promise as a rescue treatment. The choice of third-line therapy depends on factors such as the local pattern of antibiotic resistance, drug availability, and previous treatment. We hope that a simple method for detection of antibiotic susceptibility using polymerase chain reaction would be a possible alternative to administration of "tailored treatment" in the era of increasing prevalence of antimicrobial resistance.

Optimizing clarithromycin-containing therapy for Helicobacter pylori in the era of antibiotic resistance.

The efficacy of triple therapy for Helicobacter pylori infection has dramatically declined over the last decade, largely related to increasing clarithromycin resistance rates. From a microbiological standpoint, bismuth quadruple therapy is the ideal replacement since it combines drugs for which resistance does not impair its efficacy. Nonetheless, several obstacles such as availability, complexity or tolerance prevent a general implementation of bismuth quadruple therapy, so non-bismuth quadruple regimens remain the best first-line treatment in clinical practice in many geographical areas. We review the rationale and efficacy of several optimization tools (increasing the length of duration, high-dose acid suppression, probiotics), which have been largely evaluated over the last 5 years to increase the effectiveness of standard triple therapy. Then, we update available evidence on the effectiveness of several non-bismuth quadruple therapies (sequential, concomitant, hybrid, miscellaneous therapy), which have gained interest lately. We also revise evidence on the efficacy of the aforementioned optimization tools for non-bismuth quadruples schemes and, finally we provide a novel regionalized therapeutic algorithm, based on novel formulas recently developed for predicting the outcome of non-bismuth quadruple regimens, upon local antibiotic resistance rates.

Treatment of Helicobacter pylori Infection 2013

This review summarizes important studies regarding Helicobacter pylori therapy published from April 2012 up to March 2013. To begin with, the updated European Consensus Guidelines were published last year, highlighting the role of bismuth and nonbismuth quadruple regimen as first-line treatments. Cure rates for standard triple therapy remain acceptable in quite a few settings nowadays, and some reports on innovative triple therapies look promising. One study evaluating bismuth quadruple therapy as first-line therapy was reported. Regarding nonbismuth quadruple regimens, there is a trend of superiority emerging for the "concomitant" therapy over the "sequential" regimen. "Hybrid" therapy, a combination of sequential and concomitant therapy, has also shown advantage over sequential therapy. Levofloxacin-based therapies appear to be useful and versatile in second- and third-line therapies, with interesting results for newer generation quinolones, which may partially overcome antibiotic resistance. Some promising works have been reported for bismuth-based rescue therapy, using individualized therapies upon antimicrobial information, as well as for rifabutin fourth-line therapy. Probiotics appear to have an effect in terms of reducing side effects and improving compliance, but data on improvement of eradication rates remain controversial.

Second-line rescue triple therapy with levofloxacin after failure of non-bismuth quadruple “sequential” or “concomitant” treatment to eradicate H. pylori infection

Background. Non-bismuth quadruple “sequential” and “concomitant” regimens, including a proton pump inhibitor (PPI), amoxicillin, clarithromycin and a nitroimidazole, are increasingly used as first-line treatments for Helicobacter pylori infection. Eradication with rescue regimens may be challenging after failure of key antibiotics such as clarithromycin and nitroimidazoles. Aim. To evaluate the efficacy and tolerability of a second-line levofloxacin-containing triple regimen (PPI–amoxicillin–levofloxacin) in the eradication of H. pylori after non-bismuth quadruple-containing treatment failure. Methods. Design: prospective multicenter study. Patients: in whom a non-bismuth quadruple regimen, administered either sequentially (PPI + amoxicillin for 5 days followed by PPI + clarithromycin + metronidazole for 5 more days) or concomitantly (PPI + amoxicillin + clarithromycin + metronidazole for 10 days) had previously failed. Intervention: levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.) and PPI (standard dose b.i.d.) for 10 days. Outcome: eradication was confirmed with 13C-urea breath test 4–8 weeks after therapy. Compliance and tolerance: compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. Results. 100 consecutive patients were included (mean age 50 years, 62% females, 12% peptic ulcer and 88% dyspepsia): 37 after “sequential”, and 63 after “concomitant” treatment failure. All patients took all medications correctly. Overall, per-protocol and intention-to-treat H. pylori eradication rates were 75.5% (95% CI 66–85%) and 74% (65–83%). Respective intention-to-treat cure rates for “sequential” and “concomitant” failure regimens were 74.4% and 71.4%, respectively. Adverse effects were reported in six (6%) patients; all of them were mild. Conclusion. Ten-day levofloxacin-containing triple therapy constitutes an encouraging second-line strategy in patients with previous non-bismuth quadruple “sequential” or “concomitant” treatment failure.

Optimized Nonbismuth Quadruple Therapies Cure Most Patients With Helicobacter pylori Infection in Populations With High Rates of Antibiotic Resistance

Strategies to eradicate Helicobacter pylori infection could be improved by suppressing acid and extending the duration of therapy (optimization). We compared the efficacy of 2 different optimized nonbismuth quadruple regimens in areas of high resistance to antimicrobial agents. We performed a prospective noninferiority multicenter trial in which 343 consecutive individuals with H pylori infection were assigned randomly to groups given hybrid therapy (40 mg omeprazole and 1 g amoxicillin, twice daily for 14 days; 500 mg clarithromycin and 500 mg nitroimidazole were added, twice daily for the final 7 days) or concomitant therapy (same 4 drugs taken concurrently, twice daily for 14 days). We assessed bacterial resistance to these drugs in a subset of patients using the E-test. Efficacy, side effects, and compliance were determined. In per-protocol analysis, rates of eradication for hybrid and concomitant therapies were 92% (95% confidence interval [CI], 87%-95%) and 96.1% (95% CI, 93%-99%), respectively (P = .07). In intention-to-treat analysis, rates were 90% (95% CI, 86%-93%) and 91.7% (95% CI, 87%-95%), respectively (P = .35). Almost all patients (95.5%) were fully compliant; 23.5% of patients had H pylori strains that were resistant to clarithromycin (Italy, 26%; Spain, 19.5%), 33% were resistant to metronidazole (Italy, 33%; Spain, 34%), and 8.8% were resistant to both drugs (Italy, 7.1%; Spain, 11.5%). Side effects (only mild) were reported in 51.5% of patients (47% hybrid vs 56% concomitant; P = .06). Compliance greater than 80% was the only significant predictor of eradication (odds ratio, 12.5; 95% CI, 3.1-52; P = .001). Significantly more patients were compliant with hybrid therapy (98.8%) than concomitant therapy (95.2%; P = .05). Optimized nonbismuth quadruple hybrid and concomitant therapies cured more than 90% of patients with H pylori infections in areas of high clarithromycin and metronidazole resistance. ClinicalTrials.gov number NCT01464060.

Should quinolones come first in Helicobacter pylori therapy?

New generations of fluoroquinolones, like levofloxacin and moxifloxacin, exhibit a broad-spectrum activity against Gram-positive and Gram-negative bacteria, and have been successfully introduced into the treatment of Helicobacter pylori infection. Based on a large body of evidence, current guidelines recommend the use of levofloxacin- or moxifloxacin-containing proton-pump inhibitor (PPI) triple therapies in second-line or rescue treatment of H. pylori infection. The efficacy of standard PPI triple therapies has substantially declined during the last decade, mainly due to increasing resistance against the key antibiotics clarithromycin and metronidazole. Therefore, alternative strategies for first-line therapy of H. pylori infection have been evaluated in a considerable number of clinical trials including sequential regimens, nonbismuth quadruple regimens, and quinolone-containing PPI triple therapy regimens. The aim of this paper is to summarize the current body of evidence of levofloxacin- and moxifloxacin-containing regimens in first-line treatment of H. pylori infection, and to discuss the risks and benefits of these strategies in the light of increasing resistance of H. pylori to quinolones.