title: Metronidazole resistance reduces efficacy of triple therapy and leads to secondary clarithromycin resistance.
abstract: There has been a significant increase in the prevalence of H. pylori resistance to metronidazole in recent years, while clarithromycin resistance is still relatively rare. In this study we assessed: (1) the effect of primary H. pylori resistance to metronidazole and clarithromycin on the clinical efficacy of a one-week regimen consisting of omeprazole, metronidazole, and clarithromycin; and (2) the rate of acquisition of secondary antimicrobial resistance after treatment failure. Eighty-seven patients with duodenal ulceration or nonulcer dyspepsia were included in the study. The primary metronidazole and clarithromycin resistance rates were 35.6% and 3.4%, respectively (all three pretreatment clarithromycin resistant strains had concurrent metronidazole resistance). H. pylori was eradicated in 81.6% of patients. The eradication rate for fully sensitive isolates was 98.2% (55/56) but was significantly reduced to 57.1% (16/28) for isolates that were resistant to metronidazole alone and 0% (0/3) in cases of dual resistance (P < 0.001). Secondary resistance to clarithromycin was acquired in 58.3% of cases of treatment failure. In areas of high prevalence of primary metronidazole resistance, this is a significant cause of treatment failure with this triple therapy regimen. This leads to the selection of strains with dual resistance that are difficult to eradicate and may contribute to an increase in the prevalence of clarithromycin resistance. In such areas an alternative first-line treatment should be prescribed.
authors.affiliation: Department of Gastroenterology, Meath/Adelaide Hospitals, Dublin, Ireland.
authors.forename: M J
authors.initials: MJ
authors.lastname: Buckley
authors.forename: H X
authors.initials: HX
authors.lastname: Xia
authors.forename: D M
authors.initials: DM
authors.lastname: Hyde
authors.forename: C T
authors.initials: CT
authors.lastname: Keane
authors.forename: C A
authors.initials: CA
authors.lastname: O'Morain
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D017291:Clarithromycin / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D004359:Drug Therapy, Combination; D004381:Duodenal Ulcer / Q000188:drug therapy / Q000382:microbiology; D004415:Dyspepsia / Q000188:drug therapy / Q000382:microbiology; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D008795:Metronidazole / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D008795:Metronidazole; D017291:Clarithromycin; D009853:Omeprazole