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. However, up to 15% of clinical isolates are primarily resistant to azithromycin as well as to other macrolide antibiotics. Combination therapy with lansoprazole, a proton pump inhibitor known to have intrinsic antibacterial activity against H. pylori, may be useful to counteract such resistance. We therefore evaluated the combined effects of azithromycin and lansoprazole in vitro.


METHODS
Minimal inhibitory concentrations (MICs) of azithromycin and lansoprazole alone and in combination were determined for 106 clinical H. pylori isolates by means of an agar dilution technique. Killing kinetics 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. Nine strains (8.5%) had an MIC of azithromycin > or = 16 mg/l and were regarded as resistant. An additive interaction between the two drugs was found in 72 (68%), and indifferent effects in 24 strains (23%). Three of 9 azithromycin-resistant strains regained sensitivity in the presence of lansoprazole. In fluid culture, synergism between the two drugs occurred in 6 out of 7 strains tested.


CONCLUSIONS
In the majority of strains, lansoprazole and azithromycin interacted in an additive or synergistic manner depending on the test method employed. Addition of lansoprazole restored in vitro sensitivity to azithromycin in 3 out of 9 azithromycin-resistant strains. Such effects may enhance the elimination of H. pylori during clinical eradication therapy.
Trautmann
M
M
Department of Medical Microbiology, University Hospital Ulm, Germany. matthias.trautmann@medizin.uni-ulm.de
Riediger
C
C
Möricke
A
A
Vogt
K
K
Bohr
U
U
Glasbrenner
B
B
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017963:Azithromycin / Q000494:pharmacology*; D004357:Drug Synergism; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D064747:Lansoprazole; D008826:Microbial Sensitivity Tests; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D054328:Proton Pump Inhibitors
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000900:Anti-Bacterial Agents; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D017963:Azithromycin; D009853:Omeprazole