Antibiotic MICs and short time-killing against Helicobacter pylori: therapeutic potential of kanamycin

We compared the susceptibility of Helicobacter pylori to several antibiotics, expressed as MICs and as bactericidal effectiveness in short (3 h) time-killing studies. Of the antimicrobial agent tests, clarithromycin and amoxycillin had the lowest MIC50, 0.063 and 0.125 mg/L respectively, for 24 strains of H. pylori. Minocycline, levofloxacin and lansoprazole followed, with MIC50s of 0.5, 1, and 2 mg/L, respectively. Three-hour time-killing studies using a standard strain demonstrated a different pattern. At 4 x MIC, kanamycin, metronidazole and clarithromycin produced 4.4, 2.6 and 2.1 log decreases in viability, whereas the remaining seven antibiotics (including amoxycillin) were less bactericidal. Amoxycillin's lack of bactericidal activity during brief incubations was confirmed by examining several different clinically isolated H. pylori strains. Clarithromycin's effect, on the other hand, was strain- and concentration-dependent. Kanamycin was the most potent antibiotic in short time-killing studies, with concentrations of 1 x MIC and 4 x MIC producing a reduction of more than 2 and 4 log respectively in all ten strains. Our data suggest that the MIC of antimicrobial agents against H. pylori does not necessarily predict their activity in short time-killing studies. Furthermore, our short time-kill data suggest kanamycin as a potential therapeutic choice for H. pylori infection, even though this agent's MIC would suggest limited activity.