Levofloxacin-based quadruple therapy not superior to bismuth-based quadruple in second-line H pylori treatment

A new trial found that levofloxacin-based quadruple therapy is not superior to bismuth-based quadruple therapy in the second-line treatment of H pylori infection. The trial results were published in the journal, The Lancet Gastroenterology and Hepatology. 

After unsuccessful attempts with clarithromycin-based therapy, levofloxacin-based therapy or bismuth-based quadruple therapy are the recommended second-line regimens for Helicobacter pylori eradication. But in the recent past resistance to levofloxacin has increased enormously in the last decade.  As there is little data on the long-term effects of H pylori eradication on the antibiotic resistome, researchers carried out a trial to compare these second-line eradication therapies for efficacy, tolerability, and short-term and long-term effects on the gut microbiota, antibiotic resistome, and metabolic parameters. 

A multicentre, open-label, parallel-group, randomized controlled trial was carried out at eight hospitals in Taiwan between Feb 25, 2015, and Dec 11, 2020. Adult patients aged ≥20 years with persistent H pylori infection after first-line clarithromycin-based therapy were randomly assigned (1:1, permuted block sizes of four) to receive levofloxacin-based sequential quadruple therapy for 14 days or bismuth-based quadruple therapy for 10 days. Nearly 560 patients were randomly assigned to receive EAML14 or BQ10 with 280 patients per group. Out of which there were 261 [47%] men and 299 [53%] women.

All investigators were masked to the randomization sequence. H pylori eradication rate measured by 13C urea breath test 6 weeks after second-line treatment according to both intention-to-treat (ITT) and per-protocol analysis was the primary endpoint. Shotgun metagenomic sequencing and 16S rRNA gene sequencing were used to profile the microbiota composition and antibiotic resistome of fecal samples collected at baseline (before treatment) and 2 weeks, 8 weeks, and 1 year after eradication therapy. Using the available data, the frequency of adverse effects and changes in the gut microbiota and antibiotic resistome were assessed in all participants.  

Key findings of the study: 

• The Mean age was 55·9 years in the EAML14 group and 54·9 years in the BQ10 group.
• As per the ITT analysis, H pylori was eradicated in 246 (88%) of 280 participants in the EAML14 group and 245 (88%) of 280 in the BQ10 group. 
• H pylori could be eradicated in 246 (90%) of 273 participants in the EAML14 group and 245 (93%) of 264 participants in the BQ10 group as per the per-protocol analysis. 
• Transient perturbation of fecal microbiota diversity at week 2 was largely restored to basal state 1 year after EAML14 or BQ10.
• When compared with EAML14, diversity recovery was slower with BQ10, and recovery in species abundance was partial after both therapies.
• Shotgun sequencing showed a significant increase in total resistome after EAML14 (p=0·0002) and BQ10 (p=4·3 × 10–10) at week 2, which were restored to pretreatment level by week 8.
• The resistance rates of Escherichia coli and Klebsiella pneumonia to levofloxacin, ciprofloxacin, ampicillin (ampicillin–sulbactam for K pneumonia), and various cephalosporins were significantly increased in the EAML14 group compared with in the BQ10 group at week 2, which were restored to pretreatment levels and showed no significant differences at week 8 and 1 year.
• BQ10 therapy (211 [77%] of 273 participants) showed a significantly high frequency of adverse effects than after EAML14 therapy (134 [48%] of 277; p<0·0001). 

Thus, no significant difference was observed between levofloxacin-based quadruple therapy and bismuth-based quadruple therapy in the second-line treatment of H pylori infection. 

Further reading: Liou JM, Jiang XT, Chen CC, et al. Second-line levofloxacin-based quadruple therapy versus bismuth-based quadruple therapy for Helicobacter pylori eradication and long-term changes to the gut microbiota and antibiotic resistome: a multicentre, open-label, randomised controlled trial [published online ahead of print, 2022 Dec 19]. Lancet Gastroenterol Hepatol. 2022;S2468-1253(22)00384-3. doi: 10.1016/S2468-1253(22)00384-3