Clinical Role of gyrA Mutations in Levofloxacin-Based Rescue Therapy for Helicobacter pylori Infection in Japan

Abstract

Purpose: Levofloxacin is the focus of the recent concern to provide an excellent efficacy for Helicobacter pylori (H. pylori) infection. The association between molecular testing and treatment outcomes was not well studied. This study evaluated the frequency of gyrA/B mutations after unsuccessful standard therapy in Japan and confirmed whether molecular genetic approach will be useful in levofloxacin-based rescue therapy in comparison with the E test MICs. Methods: Seventy-five H. pylori culture-positive patients after standard therapy who received 7- or 10-day-rescue therapy with lansoprazole (30 mg b.d.), amoxicillin (1000 mg b.d.), and levofloxacin (200 mg or 300 mg b.d.) were analyzed. The E test was performed using gastric biopsy samples. The quinolone resistance-determining regions of H. pylori gyrA/B gene were amplified by PCR and directly sequenced. The impacts of clinical backgrounds (age, gender, disease, levofloxacin dosage, treatment duration, the E test MICs to clarithromicin and levofloxacin, gyrA mutations) on treatment outcomes were calculated by multivariate logistic regression analysis. Results: Twenty- four (32%) of 75 strains showed gyrA mutations. No gyrB mutations were observed. Fifteen and 9 strains respectively showed point mutations in the gyrA gene at amino acid (aa) 87 (Asn to Lys or Ile) and at aa 91 (Asp to Asn or Gly). Seven out of 14 strains with MIC values to levofloxacin of >1ug/mL, and 16 out of 61 strains with those of <1ug/mL, were not successfully eradicated. Sixteen out of 23 refractory strains to rescue therapy showed gyrA mutations. Forty- one out of 51 strains without gyrA mutations were successfully eradicated. The existence of gyrA mutations showed a tendency toward worse results regardless of the MICs and levofloxacin dosage. No other clinical factors have a significant impact on treatment outcomes. Longer treatment duration brought about better response in wild type strains. Conclusions: H. pylori gyrA mutations were common after failed standard therapy in Japan. In levofloxacin-based therapy for H. pylori infection, molecular genetic approach appeared to be a useful indicator for treatment outcomes.