Non-bismuth Quadruple Research Articles

Su1171 Second-Line Rescue Triple Therapy With Levofloxacin After Failure of Non-Bismuth Quadruple “Sequential” or “Concomitant” Treatment to Eradicate H. pylori Infection

Su1171 Second-Line Rescue Triple Therapy With Levofloxacin After Failure of Non-Bismuth Quadruple “Sequential” or “Concomitant” Treatment to Eradicate H. pylori Infection

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: meeting the challenge of antimicrobial resistance.

Treatment of Helicobacter pylori (H. pylori) infection is paramount for the management of prevalent gastrointestinal disorders including peptic ulcer disease and gastric cancer. Due to the wide increase in prevalence of H. pylori resistance to antibiotics, clarithromycin-based triple therapies are not any more suitable for unconditional empiric use, and should not be recommended, unless local resistance to this antibiotic is low (< 20%). Alternative strategies have been proposed to overcome the issue of increasing clarithromycin resistance, and some of them are already implemented in clinical practice. These comprise: (1) adoption of novel, more effective, empirical treatments: bismuth quadruple, sequential, non-bismuth quadruple (concomitant), dual-concomitant (hybrid), and levofloxacin-based regimens, the latter mainly designated as second-line/rescue options; (2) perspectives for a susceptibility-guided (tailored) therapeutic approach based on culture-free molecular testing methods; and (3) adjunct use of probiotics to improve eradication rates. The present article is aimed to provide a comprehensive overview of current and emerging strategies in the treatment of H. pylori infection, focusing on the challenge of antimicrobial resistance.

Sa1916 Second-Line Rescue Triple Therapy With Levofloxacin After Failure of Non-Bismuth Quadruple “Sequential” or “Concomitant” Treatment to Eradicate H. pylori Infection

Sa1916 Second-Line Rescue Triple Therapy With Levofloxacin After Failure of Non-Bismuth Quadruple “Sequential” or “Concomitant” Treatment to Eradicate H. pylori Infection

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.

Nonbismuth Quadruple “Concomitant” Therapy Versus Standard Triple Therapy, Both of the Duration of 10 Days, for First-Line H. Pylori Eradication

To compare the efficacy, compliance, and tolerability of a quadruple, nonbismuth-containing concomitant therapy with standard triple therapy, both of the duration of 10 days, for Helicobacter pylori eradication. Eradication rates obtained with standard therapies are declining as antibiotic resistance becomes more prevalent worldwide. New first-line treatment strategies are needed. Two hundred fifty-seven patients with H. pylori infection were included in the study. Patients were randomized to receive 10-day concomitant therapy comprising esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg, all bid, or 10-day standard triple therapy comprising of esomeprazole 40 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, all bid. Cure rates were defined as a negative 13C urea breath test 8 weeks after the start of treatment. Two hundred forty-six patients completed the study. The intention-to-treat cure rates were 90.5% [95% confidence interval (CI): 84.1%-95%] and 73.8% (95%CI, 65.6%-80.7%), whereas the per protocol cure rates were 93.3% (95%CI, 87.2% -97.1%) and 78.5% (95%CI, 70.3%-84.9%), respectively. The eradication rate was significantly higher in the concomitant group compared with the triple therapy group in both the intention-to-treat (P=0.0006) and per protocol (P=0.0014) populations. Adverse events were generally of mild/moderate intensity and did not interfere significantly with compliance, which was excellent for both treatment groups (96.6% and 98.5%, respectively, P=0.44). Performance of a 10-day conventional triple regimen is suboptimal. A 10-day concomitant regimen achieved a significantly higher eradication rate and seems to be an effective, safe, and well-tolerated treatment option for H. pylori eradication.

Nonbismuth Quadruple (Concomitant) Therapy: Empirical and Tailored Efficacy versus Standard Triple Therapy for Clarithromycin‐Susceptible Helicobacter pylori and versus Sequential Therapy for Clarithromycin‐Resistant Strains

Using quadruple clarithromycin-containing regimens for Helicobacter pylori eradication is controversial with high rates of macrolide resistance. To evaluate antibiotic resistance rates and the efficacy of empirical and tailored nonbismuth quadruple (concomitant) therapy in a setting with cure rates <80% for triple and sequential therapies. 209 consecutive naive H. pylori-positive patients without susceptibility testing were empirically treated with 10-day concomitant therapy (proton pump inhibitors (PPI), amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg; all drugs b.i.d.). Simultaneously, 89 patients with positive H. pylori culture were randomized to receive triple versus concomitant therapy for clarithromycin-susceptible H. pylori, and sequential versus concomitant therapy for clarithromycin-resistant strains. Eradication was confirmed with ¹³C-urea breath test or histology 8 weeks after completion of treatment. Per-protocol (PP) and intention-to-treat eradication rates after empirical concomitant therapy without susceptibility testing were 89% (95%CI:84-93%) and 87% (83-92%). Antibiotic resistance rates were: clarithromycin, 20%; metronidazole, 34%; and both clarithromycin and metronidazole, 10%. Regarding clarithromycin-susceptible H. pylori, concomitant therapy was significantly better than triple therapy by per protocol [92% (82-100%) vs 74% (58-91%), p = 0.05] and by intention to treat [92% (82-100%) vs 70% (57-90%), p = 0.02]. As for antibiotic-resistant strains, eradication rates for concomitant and sequential therapies were 100% (5/5) vs 75% (3/4), for clarithromycin-resistant/metronidazole-susceptible strains and 75% (3/4) vs 60% (3/5) for dual-resistant strains. Empirical 10-day concomitant therapy achieves good eradication rates, close to 90%, in settings with multiresistant H. pylori strains. Tailored concomitant therapy is significantly superior to triple therapy for clarithromycin-susceptible H. pylori and at least as effective as sequential therapy for resistant strains.

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

BackgroundTraditional 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.AimTo critically review evidence on the role of non-bismuth quadruple therapy (proton pump inhibitor-clarithromycin-amoxicillin-nitroimidazole) in the treatment of H. pylori infection.MethodsBibliographical 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.ResultsA 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 former was more effective than the latter: 90% versus 78% (intention-to-treat analysis). Results were homogeneous (I2 = 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 far lower than in standard triple therapy. Experience with the non-bismuth quadruple therapy in patients with metronidazole-resistant strains is still very limited.ConclusionNon-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.

Review article: non-bismuth quadruple (concomitant) therapy for eradication of Helicobater pylori

Traditional standard triple therapy for Helicobacter pylori infection (PPI-clarithromycin-amoxicillin) can easily be converted to non-bismuth quadruple (concomitant) therapy by the addition of a nitroimidazole twice daily. To critically review evidence on the role of non-bismuth quadruple therapy (PPI-clarithromycin-amoxicillin-nitroimidazole) in the treatment of H. pylori infection. Bibliographical searches were performed in MEDLINE and relevant congresses. The first randomised comparison of the non-bismuth quadruple therapy and the sequential (PPI-amoxicillin 5days plus PPI-clarithromycin-nitroimidazole 5days) regimens recently concluded that both were similar in terms of efficacy and safety and that the sequential administration protocol may be unnecessarily complex. Several randomised controlled trials (and one meta-analysis) have demonstrated that non-bismuth quadruple therapy is more effective than and is equally well tolerated as standard triple therapy. A meta-analysis of 15 studies (1723 patients) revealed a mean H. pylori cure rate (intention-to-treat) of 90% for non-bismuth quadruple therapy. A tendency towards better results with longer treatments (7-10days vs. 3-5days) has been observed, so it seems reasonable to recommend the length of treatment by achieving maximal cure rates (10days). Clarithromycin resistance may reduce the efficacy of non-bismuth quadruple therapy, although the decrease in eradication rates seems to be far lower than in standard triple therapy. Experience with the non-bismuth quadruple therapy in patients with metronidazole-resistant strains is still very limited. 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.

Efficacy of Non-Bismuth Quadruple “Concomitant” Therapy for H. pylori Infection in a Setting With High Clarithromycin Resistance

Efficacy of Non-Bismuth Quadruple “Concomitant” Therapy for H. pylori Infection in a Setting With High Clarithromycin Resistance

Sequential Therapy for Helicobacter pylori Eradication

Alternative treatment regimens for standard triple therapy are urgently needed. To critically review the evidence on the role of "sequential" regimen for the treatment of Helicobacter pylori infection. Bibliographical searches were performed in MEDLINE and international congresses. Several pooled-data analyses and meta-analyses have demonstrated that sequential regimen is more effective than standard triple therapy. Sequential therapy is not affected by bacterial (CagA status, infection density) and host factors (underlying disease, smoking). Clarithromycin resistance seems to be the only factor reducing their efficacy. However, even in these patients, an acceptable >75% eradication rate can be achieved. Unfortunately, almost all the studies have been performed in Italy. Whether it is necessary to provide the drugs sequentially or if the 4 components of sequential therapy can be given concurrently is unclear. Nonbismuth quadruple therapy seems to be an effective and safe alternative to triple therapy and is less complex than sequential therapy. Sequential therapy is a novel promising treatment approach that deserves consideration as a treatment strategy for H. pylori infection. However, further robust assessment across a much broader range of patients is required before sequential therapy could supplant existing treatment regimens and be generally recommended in clinical practice.

A prospective study of a one-week nonbismuth quadruple therapy for childhood Helicobacter pylori infection

Purpose: In the eradication of Helicobacter pylori infection, a 1-week therapy improves patient compliance, but drug resistance may limit its efficacy. The effectiveness of the 1-week nonbismouth quadruple therapy was studied prospectively in children with proven H pylori infection in a population with a high rate of metronidazole resistance. Methods: All pediatric patients who presented to our institutions with acute and chronic upper gastrointestinal conditions requiring endoscopy from June 1997 to February 2000 were investigated prospectively for H pylori infection. Gastric biopsy specimens were analyzed with rapid urease test and histopathology, H pylori–positive children were treated with omeprazole, clarithromycin, amoxicillin, and metronidazole for 7 days. The result of treatment was assessed 1 month after treatment with endoscopy and biopsy. The same treatment was repeated for 2 weeks if H pylori was still present. In patients who needed a third endoscopy, their biopsy specimens were cultured to determine antibiotic sensitivity. Results were correlated with patients' symptoms and endoscopic findings. Results: Thirty-three children with acute (severe epigastric pain, n = 14; gastrointestinal bleeding, n = 9) and chronic (recurrent abdominal pain, n = 7; anemia, n = 3) conditions were treated for H pylori. Thirty-one (94%) were confirmed to have H pylori eradicated by a 1-week therapy, whereas 1 patient had eradication after a further 2-we`ek therapy (3.3%). The only unresponsive patient had H pylori resistant to both clarithromycin and metronidazole. All ulcers and erosions healed after the eradication of H pylori. Three patients had persistent recurrent abdominal pain despite H pylori eradication. Conclusions: The 1-week therapy with omeprazole, clarithromycin, amoxicillin, and metronidazole is an effective treatment of H pylori in children in a population with a high incidence of metronidazole resistant strain of H pylori. Peptic ulcers and erosions healed with the eradication of the bacteria. J Pediatr Surg 36:1008-1011. Copyright © 2001 by W.B. Saunders Company.