Are new generation fluoroquinolones useful for the treatment Helicobacter pylori infection?
Turlough Heffernan1, Denise Brennan2, Joseph Omorogbe2, Grainne Holleran2, Mary Hussey2, Colm O’Morain2, Deirdre McNamara2, Sinead Smith1,2.
1School of Pharmacy and 2Trinity Academic Gastroenterology Group, Trinity College Dublin.
Fluoroquinolones exert their antimicrobial effect by preventing bacterial DNA from unwinding and duplicating. H. pylori fluoroquinolone resistance results from point mutations in the gyrA gene, which encodes the A subunit of the DNA gyrase enzyme involved in regulating DNA strain during bacterial replication. Consensus guidelines currently recommend levofloxacin-based triple therapy for the treatment of H. pylori infection following failure of standard first-line triple therapy. However, H. pylori levofloxacin resistance has emerged with a prevalence of 11.7% in Irish patients1. New generation fluoroquinolone antibiotics have been suggested as a more potent alternative to levofloxacin with the potential to overcome fluoroquinolone resistance.
To compare the minimum inhibitory concentration (MIC) of levofloxacin required to inhibit the growth of H. pylori with that of the new generation fluoroquinolone moxifloxacin, and (ii) evaluate the efficacy of moxifloxacin against H. pylori strains bearing gyrA DNA mutations.
Following ethical approval and informed consent, antrum biopsies of adult patients with a positive Campylobacter-like organism test were used to inoculate Columbia blood agar plates (Oxoid) for H. pylori culture. Antibiotic susceptibility testing was performed using E-test strips (Biomerieux) and isolates were deemed sensitive or resistant using MIC cut-off guidelines outlined by the European Committee on Antimicrobial Susceptibility Testing (levofloxacin >1 mg/L, moxifloxacin >1 mg/L). H. pylori DNA was analysed using the GenoType HelicoDr assay (Hain Life Sciences).
In all, cultures from 23 patients (mean age 45.6 ± 17.8 years, 52% male) were analysed. Culture and antimicrobial susceptibility testing revealed that the rates of levofloxacin and moxifloxacin resistance were 13% (N=3) and 9% (N=2) respectively. Two of the 3 levofloxacin- resistant strains were resistant to moxifloxacin. In susceptible strains, the average MIC required to inhibit H. pylori growth was lower for moxifloxacin than levofloxacin (0.07 versus 0.09 mg/L), although this did not reach statistical significance at the numbers tested (p=0.4). DNA analysis indicated that all 3 levofloxacin-resistant strains were positive for a gyrA DNA mutation. One strain with a gyrA mutation was susceptible to moxifloxacin.
The prevalence of moxifloxacin resistance was lower than that of levofloxacin resistance in our patient cohort. Additionally, a levofloxacin-resistant strain bearing a gyrA mutation was susceptible to moxifloxacin. These findings provide a rationale for further investigations into the use of moxifloxacin as an alternative to levofloxacin in rescue therapy for H. pylori.