Effect of antibiotic resistance to metronidazole and clarithromycin on outcome of Helicobacter pylori therapy: a Meta-Analytical approach.

Our purpose was to define the effect of pretreatment Helicobacter pylori resistance to
metronidazole or to clarithromycin on the success of antimicrobial therapy. We used 75
key words to perform a literature search in MEDLINE as well as manual searches to
identify clinical treatment trials that provided results in relation to H. pylori susceptibility
to metronidazole and clarithromycin or both during the period 1984 –1997 (abstracts were
not included). Meta-analysis was done with both fixed- and random-effect models; results
were shown using Galbraith’s radial plots. We identified 49 papers with 65 arms for
metronidazole (3594 patients, 2434 harboring H. pylori strains sensitive to metronidazole
and 1160 harboring resistant strains). Metronidazole resistance reduced effectiveness by
an average of 37.7% (95% CI 5 29.6 – 45.7%). The variability in the risk difference for
metronidazole was 122.0 to 290.6 and the chi-square value for heterogeneity was
significant (P , 0.001). Susceptibility tests for clarithromycin were performed in 12
studies (501 patients, 468 harboring H. pylori strains sensitive to clarithromycin and 33
harboring resistant strains). Clarithromycin resistance reduced effectiveness by an average
of 55% (95% CI 5 33–78%). We found no common factors that allowed patients to
be divided into subgroups with additional factors significantly associated with resistance.
In conclusion, metronidazole or clarithromycin pretreatment resistant H. pylori are the
main factors responsible for treatment failure with regimens using these compounds. If H.
pylori antibiotic resistance continues to increase, pretherapy antibiotic sensitivity testing
might become necessary in many regions