h pylori rescue therapy

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 hpylori rescue rx alimentpharm2015​ in dropbox, or 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.