Gastritis

Sequential Helicobacter pylori eradication therapy

With emerging resistance to H pylori, investigators are searching for alternative approaches to treatment, including the use of sequential H pylori eradication therapy.[85][86][87][88][89] Sequential therapy is defined as use of a proton-pump inhibitor (PPI) plus an antibiotic for 5 days, followed by an additional 5 days of treatment using 2 or 3 different agents. Sequential therapy for 5 days with a PPI and amoxicillin, followed by a PPI, clarithromycin, and tinidazole for a further 5 days, has been shown to have eradication rates >90% in Italy.[88][89] This also shows higher efficacy in patients with clarithromycin-resistant infection.[90] One randomized, multicenter trial compared 10 days of standard triple therapy with sequential therapy.[91] Gastric mucosal biopsies were tested for resistance to amoxicillin, clarithromycin, and metronidazole.[91] The authors found no statistically significant difference in regard to eradication rates.[91] Clarithromycin and metronidazole resistance both independently predicted treatment failure in the sequential therapy group.[91] Another study compared sequential therapy (i.e., a PPI plus amoxicillin for 5 days, followed by clarithromycin and metronidazole for an additional 5 days) with quadruple therapy (i.e., the same four drugs for 10 days) and found eradication rates of 87% versus 81%, respectively.[92] The authors point out that antibiotic resistance was not studied in this population.[92] One meta-analysis found that geography may have an impact on the effectiveness of eradication therapy.[93] Sequential therapy was compared with a 14-day course of triple therapy, and evaluated by areas of low and high resistance to metronidazole/clarithromycin. In areas with high resistance to clarithromycin, sequential therapy was superior to 14-day triple therapy. In areas with high resistance to metronidazole, sequential and 14-day triple therapy were equivalent.[93] The eradication rate of fluoroquinolone-based sequential therapy (5-7 days of PPI and amoxicillin therapy, followed by 5-7 days of PPI, fluoroquinolone, and metronidazole or tinidazole or furazolidone) was similar to that of standard sequential therapy (5 days of PPI plus amoxicillin, followed by 5 days of PPI, clarithromycin, and metronidazole or tinidazole) in one meta-analysis of six randomized trials.[94] The authors concluded that fluoroquinolone-based sequential therapy is a reasonable treatment alternative to first-line eradication therapy.[94] One meta-analysis demonstrated declining efficacy of sequential therapy and suggested that sequential therapy is not currently a valid alternative to standard therapy.[95]

High-dose dual therapy

High-dose dual therapy comprises high-dose amoxicillin with either a high-dose PPI or a high-dose potassium-competitive acid blocker.[3] Although not routinely recommended for persistent H pylori infection, it may be considered in certain situations such as when other therapies are not feasible, when antibiotic susceptibility testing is unavailable or yields inconclusive results, or when the H pylori strain is only sensitive to amoxicillin.[3][96]

Levofloxacin-based quadruple therapy

This comprises treatment with levofloxacin, omeprazole, nitazoxanide, and doxycycline (LOAD). One open-label, randomized trial, in treatment-naive patients compared 7-10 days of the LOAD regimen versus standard triple therapy: intention-to-treat analysis revealed significantly higher H pylori eradication rates with the LOAD regimen.[97]H pylori eradication was confirmed by stool antigen testing at least 4 weeks after cessation of therapy. A larger randomized controlled trial is warranted to further evaluate the efficacy of this regimen.

H pylori vaccines

One double-blind, placebo-controlled trial randomized healthy children, ages 6-15 years, to an oral recombinant H pylori vaccine (n = 2232) or to placebo (n = 2232) in Jiangsu Province, China.[98] There were 64 events of H pylori infection within the first year: 14 events in the vaccine group and 50 events in the placebo group (vaccine efficacy of 71.8%; 95% CI 48.2 to 85.6). The authors concluded that the vaccine may decrease the incidence of H pylori infection, but longer follow-up is required.[98]

Vitamin C

One randomized controlled trial was performed to evaluate the effect of vitamin C supplementation on serum reactive oxygen species (ROS) in 244 Japanese subjects with atrophic gastritis.[99] Subjects were randomized to take a daily supplement of vitamin C at different doses. Compared with baseline, a statistically significant difference in ROS at the end of 5 years of supplementation was demonstrated. In addition, a greater reduction in ROS was observed in the group receiving the higher dose compared with the group receiving the lower dose.

Addition of probiotic to H pylori eradication therapy

One systematic review and network meta-analysis found that probiotic-supplemented eradication regimens (7 days of triple therapy supplemented with probiotic, and 7 days of levofloxacin-based triple therapy supplemented with probiotic) had a lower proportion of adverse events compared with other H pylori eradication regimens.[100]

Periodontal therapy

One systematic review and meta-analysis suggests that periodontal therapy may improve the efficiency ofH pylori eradication and prevent the recurrence of gastric H pylori infection.[101] [ ]

Polaprezinc (zinc L-carnosine)

Polaprezinc, a chelated form of zinc and L-carnosine, is a free radical scavenger that is purported to have wound-healing properties. It is approved in Japan for the treatment of gastric ulcers. In one study, the addition of polaprezinc to a 14-day regimen for the eradication of H pylori (omeprazole, amoxicillin, and clarithromycin) resulted in improved eradication (77.0% and 75.9%, respectively) compared with placebo (58.9%, p<0.01).[102]