Effect of pretreatment 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 re sistance to metronidazole or to clarithromycin on the success of antimicrob ial therapy. We used 75 key words to perform a literature search in MEDLINE as well as manual searches to identify clinical treatment trials that prov ided results in relation to H, pylori susceptibility to metronidazole and c larithromycin or both during the period 1984-1997 (abstracts were not inclu ded). Meta-analysis was done with both fixed- and random-effect models; res ults were shown using Galbraith's radial plots. We identified 49 papers wit h 65 arms for metronidazole (3594 patients, 2434 harboring H. pylori strain s sensitive to metronidazole and 1160 harboring resistant strains). Metroni dazole resistance reduced effectiveness by an average of 37.7% (95% CI = 29 .6-45.7%). The variability in the risk difference for metronidazole was 122 .0 to -90.6 and the chi-square value for heterogeneity was significant (P < 0.001). Susceptibility tests for clarithromycin were performed in 12 studi es (501 patients, 468 harboring H. pylori strains sensitive to clarithromyc in and 33 harboring resistant strains). Clarithromycin resistance reduced e ffectiveness by an average of 55% (95% CI = 33-78%). We found no common fac tors that allowed patients to be divided into subgroups with additional fac tors significantly associated with resistance. In conclusion, metronidazole or clarithromycin pretreatment resistant Pi. pylori are the main factors r esponsible 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.