New concepts of resistance in the treatment of Helicobacter pylori infections

Abstract

SummaryThe prevalence of antimicrobial resistance is now such that all patients should be considered as having resistant infections. Ideally therapy is based on pretreatment susceptibility testing. Empiric therapies should assume antimicrobial resistance and use higher doses for 14 days. Acceptable results are 90-94% cure intention to treat (Grade B) or greater. Clarithromycin-containing triple therapies now typically produce ≤80% cure ITT (Grade F) and are no longer acceptable empiric therapy. Current initial therapy options are between sequential therapy, concomitant therapy, and bismuth containing quadruple therapy. Sequential therapy has the potential to be improved to ≥95% cure ITT (Grade A) by continuing the amoxicillin through the second and/or by increasing the duration. Better appreciation of the role of acidity in phenotypic resistance has resulted in high cure rates with high dose PPI plus amoxicillin dual therapy; additional studies to devise better dual-based multidrug regimes are still needed. Antimicrobial choices following treatment failure is best approached by susceptibility testing. If not available, we recommended a bismuth containing quadruple therapy substituting a new drug for metronidazole/tinidazole and/or clarithromycin if they have been used previously. The alternate would be to use a 14 day high dose PPI, amoxicillin-based triple therapy with rifabutin, a fluoroquinolone, or furazolidone. KeywordsHelicobacter pylori; therapy; resistance; antibiotics; anti-secretory drugs; phenotypic drug resistance; cytochrome P450 "To read without reflecting is like eating without digesting". -86-462-1111-86-462- , FAX 81-86-464-1195 Review criteria: We searched the relevant papers by using computer-assisted bibliographic searches of PubMed through November 30, 2007 using combinations of the following terms: H. pylori combined with resistance, therapy, eradication, second, triple, quadruple, sequential, or rescue. We also reviewed the recent literature on pharmacokinetics and pharmacodynamics in relation to the drugs used in H. pylori therapy and the relation to host cytochrome P450 genotypes to treatment outcome. We did not perform meta-analyses. We reviewed only articles published in English.

Non-steroidal anti-inflammatory drugs and risk of gastric and oesophageal adenocarcinomas: results from a cohort study and a meta-analysis

“…However, recent studies suggest that H. pylori may have health benefits, such as preventing asthma (Blaser et al, 2008) or oesophageal adenocarcinoma (Islami and Kamangar, 2008). Beyond the direct benefits and risks of eradication to the individual, the methods and consequences of attempted widespread eradication, such as increasing antibiotic resistance, must also be considered (Graham and Shiotani, 2008). A single trial has tested the effect of the NSAID rofecoxib on subjects with gastric pre-neoplastic lesions over 24 months and found no evidence of benefit, but this study was small and did not use cancer as an end point (Leung et al, 2006).…”

Clarithromycin-resistant Helicobacter pylori in Recife, Brazil, directly identified from gastric biopsies by polymerase chain reaction

“…The worldwide increase in antibiotic resistance to infection by H. pylori necessitates that therapy be devised on the basis of the testing of antibiotic susceptibility (4) . This is advocated particularly for clarithromycin, the most effective drug used in the eradication of the organism, resistance to which is the main factor responsible for treatment failure (3,7,9) .…”

Antimicrobial resistance in Helicobacter pylori: current situation and management strategy in Vietnam

“…Surveillance of H. pylori antibiotic resistance is therefore mandatory in order to adapt the antibiotic combination to local resistance patterns [10]. This issue is of particular relevance with regard to clarithromycin, which can induce virtually a 70% loss of effectiveness in the standard triple therapy (proton pump inhibitor, PPI + clarithromycin + amoxicillin) in patients infected with clarithromycin resistant strains versus susceptible strains [11].…”

“…This approach is generally unavailable for H. pylori, and decisions about the choice of antibiotic treatment is therefore based on the knowledge of antibiotic use in the population, resistance development in the region, and history of H. pylori eradication of patients [10].…”