By: Dr. Geoffrey Modest
Most of the cure rates for H. pylori infections are in the 80-90% range, leaving many people with persistent infections. There have been several articles on rescue therapy, including a recent one with a relatively easy regimen and 90% efficacy (see Aliment Pharmacol Ther 2015; 41: 768–775). This Spanish/Italian study looked at 200 patients who failed several different initial therapies. details:
–17 hospitals involved in study (15 Spanish, 2 Italian)
–200 patients (mean age 47, 67% women, 13% had ulcers), having had the following prior therapies: 131 patients had standard PPI-clarithromycin-amoxacillin, 32 with sequential (PPI-amoxacillin x 5 days, then PPI-clarithromycin-metronidazole x 5 days), 37 with quad therapy of PPI-amoxacillin-clarithromycin-metronidazole for 10 days. Failure was defined as a positive 13C-urea breath test 4-8 weeks after therapy.
–all were put on esomeprazole 40mg bid, amoxicillin 1gm bid, levofloxacin 500 mg in the evening, and bismuth subcitrate 240mg bid for 14 days
–primary outcome: eradication rate confirmed by breath test, as above
–results: 180/200 patients (90%), in intention-to-treat analysis, and 175/192 (91%), on per-protocol anaylsis, had cures. Similar results in Spain and Italy, whether diagnosis was peptic ulcer or dyspepsia, or with the type of prior treatment (eg: success in 88.5% on standard triple therapy, 93.8% on sequential therapy, and 91.9% on quad therapy)
–adverse events in 46% (mostly nausea in 17%, diarrhea in 16%, abdominal pain in 15%, metallic taste in 15%), but these were time-limited to the 14 days of treatment and only 6 (3%) felt the adverse effects were “intense”, though none were considered serious.
So, why did this therapy work so well?
–The role of bismuth is likely a major part: bismuth is not itself associated with bacterial resistance, is synergistic with antibiotics, overcomes clarithromycin and levofloxacin resistance, and has efficacy in setting of metronidazole resistance. Purported additional mechanisms of action: decreases mucin viscosity, binds to toxins produced by h pylori, is adherent to gastric epithelium and prevents bacterial colonization, and reduces the bacterial load.
–Although H pylori resistance to fluoroquinolones is increasing (up to 24% in Europe and 13% in Spain), other studies have found that the addition of bismuth dramatically increased eradication rates to a regimen of PPI, amoxacillin, and levofloxacin for 14 days, finding no difference when the h pylori was sensitive to levofloxacin (85%), but when levofloxacin-resistance was present, adding bismuth increased eradication from 37% to 71%.
–The longer 14-day regimen, which has been found in several studies to improve eradication rates
–The use of high dose esomeprazole. ??the role of the high dosage of 40mg (some studies have found 6-10% higher cure rates with higher doses of PPI). ??the role of the newer PPI (some data that esomeprazole and rabeprazole are better than the first-generation PPIs)
So, this was a large study of patients with documented primary treatment failure and very high response rates to a 14-day course of quadruple-therapy containing bismuth. Although there were no data presented on resistance patterns of the h pylori, it seems very likely that there were many resistant bacteria (given prevailing resistance patterns). Unfortunately, in the US we have very little data (none I can find in Boston), where h pylori is basically an imported infection from many different parts of the world with differing resistance patterns. Clinically, i have had good success with the sequential therapy noted above. But this bismuth therapy seems to be a good one for treatment failure. Although it makes sense to use the regimen they prescribe above in order to get their results, I would opt for high dose pantoprazole or omeprazole, given the difficulty in getting esomeprazole through insurance.