The importance of the level of metronidazole resistance for the success of Helicobacter pylori eradication.
OBJECTIVE
To evaluate the role of antibiotic susceptibility for the treatment outcome of proton pump inhibitor-dependent and independent Helicobacter pylori eradication regimens.


METHODS
In a placebo-controlled clinical study of peptic ulcer patients with H. pylori infection, patients were randomized to receive lansoprazole, clarithromycin and tinidazole twice-daily, clarithromycin and tinidazole once-daily with lansoprazole or with placebo. Helicobacter pylori status was assessed by culture and antibiotic susceptibility by E-test minimal inhibitory concentration (MIC) in 205 clinical isolates.


RESULTS
Primary resistance to clarithromycin and metronidazole was 1 and 76%, respectively. In metronidazole susceptible strains eradication rates were similar at > 90% for all treatment groups (P = 0.49). With low-level metronidazole resistance (4 microg/mL < MIC < 256 microg/mL), eradication rates were similar at >75% (P = 0.80). The major difference was found at high-level metronidazole resistance (MIC >or= 256 microg/mL) with 95%, 58% and 21% eradication in the lansoprazole, clarithromycin and tinidazole twice-daily, lansoprazole, clarithromycin and tinidazole once-daily and placebo, clarithromycin and tinidazole once-daily groups, respectively (P < 0.001).


CONCLUSIONS
In the absence of antibiotic resistance, a once-daily therapy of only clarithromycin and tinidazole can achieve a high rate of H. pylori eradication. Such a combination could offer a simpler and cheaper treatment option for developing countries. The standard, twice-daily proton pump inhibitor-based triple therapy was shown to be efficient in H. pylori eradication even in the presence of high-level metronidazole resistance.
Wheeldon
T-U
TU
Department of Medicine, Unit of Infectious Diseases, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden. wheeldon@tiscali.se
Granström
M
M
Hoang
T T H
TT
Phuncarg
D C
DC
Nilsson
L E
LE
Sörberg
M
M
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D017291:Clarithromycin / Q000627:therapeutic use; D004334:Drug Administration Schedule; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D064747:Lansoprazole; D008795:Metronidazole / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010437:Peptic Ulcer / Q000382:microbiology; D054328:Proton Pump Inhibitors; D014011:Tinidazole / Q000627:therapeutic use; D016896:Treatment Outcome
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; D014011:Tinidazole; D064747:Lansoprazole; D008795:Metronidazole; D017291:Clarithromycin; D009853:Omeprazole