Treatment of Helicobacter pylori.

PURPOSE OF REVIEW: Helicobacter pylori eradication has become more challenging over the past decade due to increasing antimicrobial resistance, especially to clarithromycin and levofloxacin. We identified 508 recent publications on H. pylori treatment (published between January 2018 and June 2019), focusing on the most highly clinically relevant for this review. RECENT FINDINGS: Declining H. pylori eradication rates with clarithromycin triple therapy have led to most guidelines recommending 14 days bismuth-based quadruple therapy or concomitant therapy as the best initial empiric regimen. Substituting amoxicillin for tetracycline or metronidazole in quadruple therapy, and a three-in-one pill version of the regimen, also appear effective. Vonoprazan, a potent acid inhibitor, can overcome much clarithromycin resistance in triple therapy. High-dose dual therapy (proton pump inhibitor with amoxicillin) is a promising alternative approach. Reviewing resistance patterns to select suitable first-line empiric therapies is important in high resistance regions. Molecular methods to evaluate H. pylori antimicrobial susceptibility promise to be simpler than standard microbiological culture. The cost-effectiveness of antimicrobial susceptibility testing in refractory cases remains unproven. SUMMARY: Updating clinicians treating H. pylori is important to combat the emerging problems of multidrug antimicrobial resistance in H. pylori strains. Truly novel approaches to H. pylori eradication are needed.

Reconciliation of Recent Helicobacter pylori Treatment Guidelines in a Time of Increasing Resistance to Antibiotics.

Increasing resistance to antibiotics worldwide has adverse effects on the effectiveness of standard therapies to eradicate Helicobacter pylori infection. We reviewed guidelines developed by expert groups in Europe, Canada, and the United States for the treatment of H pylori infection. We compared the recommendations of these guidelines, reconciled them, and addressed the increasing resistance of H pylori to antibiotic therapy regimens. The guidelines recommend bismuth quadruple therapy for first-line treatment, replacing clarithromycin-based triple therapy. There is consensus for concomitant 4-drug therapy as an alternative, especially when bismuth is not available. When therapy is unsuccessful, it is likely due to resistance to clarithromycin, levofloxacin, and/or metronidazole; these drugs, if used previously, should be avoided in subsequent eradication attempts. Second-line therapies should be bismuth quadruple therapy or levofloxacin triple therapy, depending on suspected resistance, reserving rifabutin-based triple and high-dose dual amoxicillin proton pump inhibitor therapy for subsequent treatment attempts. The increasing resistance of H pylori to antibiotic therapy necessitates local availability of susceptibility tests for individuals, and establishment of regional and national monitoring programs to develop evidence-based locally relevant eradication strategies. Further studies into the development of more easily accessible methods of resistance testing, such as biomarker analysis of stool samples, are required. Options under investigation include substituting vonoprazan for proton pump inhibitors, adding probiotics, and vaccine development. Narrow-spectrum antibiotics and new therapeutic targets could be identified based on genomic, proteomic, and metabolomic analyses of H pylori.

Non-steroidal anti-inflammatory drugs have bacteriostatic and bactericidal activity against Helicobacter pylori.

BACKGROUND: Helicobacter pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs) are each associated with gastrointestinal mucosal damage, but the extent and direction of their interactions remain controversial. Therefore, the purpose of the present paper was to examine whether specific NSAIDs inhibit the growth of Helicobacter pylori in vitro. METHODS: Sodium salicylate, ibuprofen, indomethacin, the selective cyclooxygenase-2 inhibitor NS-398 and two derivatives of sulindac sulfoxide were tested against two laboratory strains of H. pylori, the mouse-adapted Sydney strain, and against seven fresh clinical isolates of Helicobacter pylori. Possible effects on Campylobacter jejuni, Staphyloccoccus aureus, Escherichia coli, Salmonella typhimurium, and Shigella boydii were also examined. RESULTS: Certain NSAIDs possess antibacterial activity against Helicobacter pylori at therapeutically achievable doses; an effect that appears to be independent of cyclooxygenase enzymes inhibition. For Helicobacter pylori, >90% growth inhibition and bactericidal activity were observed consistently for sulindac sulfide at < or =70 microg/mL and sulindac sulfone at < or =175 microg/mL. The minimal inhibitory concentration against Helicobacter pylori was 125 microg/mL for ibuprofen, 100 microg/mL for indomethacin and 300 microg/mL for NS-398 but much higher concentration of sodium salicylate (4000 microg/mL) and sulindac sulfoxide (> or =1250 microg/mL) were required to inhibit the growth of Helicobacter pylori. CONCLUSIONS: The decreased prevalence of Helicobacter pylori in specimens from some NSAID users and the chemopreventive effects of NSAIDs in gastric cancer may be related to inhibition of Helicobacter pylori growth.

Colonic epithelial cell proliferation decreases with increasing levels of serum 25-hydroxy vitamin D.

Epidemiological evidence suggests a potential role for vitamin D in colon cancer prevention. Vitamin D, absorbed from the intestine or derived from solar ultraviolet light, is metabolized in the liver to 25-hydroxyvitamin D (25-OH D(3)). Previous studies examining effects of vitamin D upon carcinogenesis have focused upon the active metabolite 1,25-dihydroxyvitamin D [1,25-(OH)(2) D(3)], which interacts with nuclear vitamin D receptors in several organs. Until recently, the metabolism of 25-OH D(3) to 1,25-(OH)(2) D(3) was believed to occur only in the kidney, but more recent studies have shown that 25-OH D(3) conversion to 1,25-(OH)(2) D(3) can occur in other tissues. We examined the association between fasting levels of 25-OH D(3), 1,25-(OH)(2) D(3), and BsmI polymorphism of the vitamin D receptor (VDR) gene with indices of colonic epithelial cell proliferation and differentiation in a chemoprevention study, after giving vitamin D or calcium and taking rectal biopsies that were incubated with bromodeoxyuridine. Vitamin D receptor polymorphism was determined by genotyping of the 3' BsmI polymorphism in intron eight of the VDR gene. No significant changes in cell proliferation or in differentiation were found in subjects between study start and end. However, fasting serum levels of 25-OH D(3) showed a highly significant decrease with whole crypt labeling index and the size of the proliferative compartment (phi h). There was no correlation between serum levels of 1,25-(OH)(2) D(3) and the proliferative parameters. Calcium supplementation induced a significant effect upon the relationship between serum 25-OH D(3) and rectal epithelial cell labeling index and phi h when studied by covariance analysis without a relationship with 1,25-(OH)(2) D(3) levels. VDR genotype did not influence the effects of serum 25-OH D(3) or serum 1,25-(OH)(2) D(3) levels upon proliferation. These data suggest that there might be a local effect of 25-OH D(3) on colonic epithelial cells through conversion of 25-OH D(3) to 1,25-(OH)(2) D(3). Subsequent studies have demonstrated the presence of 1alpha-hydroxylase mRNA in normal colorectal epithelium and in colorectal cancer. Thus, vitamin D may have an important role in determining the effects of calcium on colorectal epithelial proliferation and may explain some of the discrepancies found previously in studies that examine the direct role of calcium on the colorectal epithelium.