Combined activity of azithromycin and lansoprazole against Helicobacter pylori

Background. Due to its unique pharmacokinetic properties, azithromycin may be an attractive combination partner for H. pylori eradication regimens. Ho wever, up to 15% of clinical isolates are primarily resistant to azithromyc in as well as to other macrolide antibiotics. Combination therapy with lans oprazole, a proton pump inhibitor known to have intrinsic antibacterial act ivity against H. pylori, may be useful to counteract such resistance. We th erefore evaluated the combined effects of azithromycin and lansoprazole in vitro. Materials and Methods. Minimal inhibitory concentrations (MICs) of azithrom ycin and lansoprazole alone and in combination were determined for 106 clin ical H. pylori isolates by means of an agar dilution technique. Killing kin etics of seven isolates were also studied in fluid medium. Results. MIC values for 50 and 90% of the isolates (MIC50, MIC90) were 0.19 and 0.5 mg/l for azithromycin, and 44.5 and 104 mg/l for lansoprazole. Nin e strains (8.5%) had an MIC of azithromycin greater than or equal to 16 mg/ l and were regarded as resistant. An additive interaction between the two d rugs was found in 72 (68%), and indifferent effects in 24 strains (23%). Th ree of 9 azithromycin-resistant strains regained sensitivity in the presenc e of lansoprazole. In fluid culture, synergism between the two drugs occurr ed in 6 out of 7 strains tested. Conclusion. In the majority of strains, lansoprazole and azithromycin inter acted in an additive or synergistic manner depending on the test method emp loyed. Addition of lansoprazole restored in vitro sensitivity to azithromyc in in 3 out of 9 azithromycin-resistant strains. Such effects may enhance t he elimination of H. pylori during clinical eradication therapy.