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.[62][63][64][65][66] 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.[65][66] This also shows higher efficacy in patients with clarithromycin-resistant infection.[67] A randomised, multicenter trial compared 10 days of standard triple therapy to sequential therapy.[68] Gastric mucosal biopsies were tested for resistance to amoxicillin, clarithromycin, and metronidazole.[68] The authors found no statistically significant difference in regard to eradication rates.[68] Clarithromycin and metronidazole resistance both independently predicted treatment failure in the sequential therapy group.[68] 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 4 medications for 10 days) and found eradication rates of 87% versus 81%, respectively.[69] The authors point out that antibiotic resistance was not studied in this population.[69] One meta-analysis found that geography may have an impact on the effectiveness of eradication therapy.[70] 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.[70] 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 a meta-analysis of 6 randomised trials.[71] The authors concluded that fluoroquinolone-based sequential therapy is a reasonable treatment alternative to first-line eradication therapy.[71] One meta-analysis demonstrated declining efficacy of sequential therapy and suggested that sequential therapy is not currently a valid alternative to standard therapy.[72]

Levofloxacin-based triple therapy

This has been studied mainly as second- and third-line therapy in patients with persistent H pylori infection. A meta-analysis of 4 randomised controlled trials found that a 10-day regimen of levofloxacin triple therapy resulted in a superior eradication rate and fewer adverse effects compared with a 7-day course of bismuth-based quadruple therapy.[73]

Rifabutin-based therapy

Another rescue therapy that includes PPI plus amoxicillin and rifabutin for 10 days. This has been shown to have eradication rates ranging from 38% to 91% as a salvage regimen in patients with persistent H pylori infection.[74]

High-dose dual therapy

High-dose dual therapy with amoxicillin and omeprazole is another option as a salvage regimen for persistent H pylori infection.[75]

Levofloxacin-based quadruple therapy

This comprises treatment with levofloxacin, omeprazole, nitazoxanide, and doxycycline (LOAD). One open-label randomised 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.[76]H pylori eradication was confirmed by stool antigen testing at least 4 weeks after cessation of therapy. A larger randomised controlled trial is warranted to further evaluate the efficacy of this regimen.

H pylori vaccines

A double-blind, placebo-controlled trial randomised healthy children, aged 6-15 years, to an oral recombinant H pylori vaccine (n = 2232) or to placebo (n = 2232) in Jiangsu Province, China.[77] 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 48.2-85.6). The authors concluded that the vaccine may decrease the incidence of H pylori infection, but longer follow-up is required.[77]

Vitamin C

A randomised 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.[78] Subjects were randomised to take a daily supplement of either 50 mg or 500 mg of vitamin C. 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 500 mg dose compared with the group receiving the 50 mg dose.

Addition of probiotic to H pylori eradication therapy

A 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.[79]

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.[80] [ ]

Polaprezinc

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 to placebo (58.9%, p<0.01).[81]