Letter: levofloxacin resistance – a challenge for the treatment of Helicobacter pylori infection

SIRS, We read with great interest the systematic review and meta-analysis by Chen et al., reviewing the trend of efficacy of levofloxacin-based triple therapy (including a proton pump inhibitor (PPI), levofloxacin and amoxicillin) in the treatment of Helicobacter pylori worldwide since 2000–2016. The authors addressed most of the issues related to the topic of their article, however, we have some comments on their review. Chen et al.’s article did not mention a randomized trial by Molina-Infante (2008–2009), in which it was reported that triple regimen therapy (containing levofloxacin, amoxicillin and omeprazole), as the first-line treatment, had intention-to-treat and per-protocol cure rates of 80% and 82.6%, respectively. The authors declared that higher dosage of PPIs does not affect the eradication rate of levofloxacin-based triple therapy. This statement needs to be discussed. To our knowledge, efficacy of antibiotics in acidic environments is low and it increases using acid suppression drugs, such as PPIs. It has also been revealed that some patients are resistant to PPIs due to the rapid PPIs metabolism. Therefore, it would be better the authors considered this issue in their method and analysis, to give more precise results. But if we assume that the authors’ finding is acceptable, one of the appropriate suggestions can be substitution of PPIs by other drugs, such as H2 blockers, in the triple therapy regimen with levofloxacin. Chen et al. discussed the rate of primary resistance of levofloxacin against H. pylori in different countries as subgroup analyses – for example, Belgium, France and Japan. There are other studies such as Spain (14.5%, 2010), China (55.7%, 2007–2009), Ireland (11.7%, 2008–2009), Senegal (15%, 2007–2009), and Poland (5.85%, 2006–2012). A study by Phan et al. in Vietnam (2012–2014), showed a primary resistance rate of 35.6%, which was significantly higher in females (55.8%) than in males (28.6%). In addition, an investigation in South Korea indicated that the primary resistance rate to levofloxacin increased from 4.7% to 28.1% during 2003– 2012. Moreover, some studies showed that the rate of resistance increases with age. 9, 10 So far, no meta-analysis has been published assessing the exact rate of primary levofloxacin resistance and we suggest such study, especially considering the potential effect of age on the resistance. Also, because of the differences in the rate of levofloxacin resistance between countries, it is proposed that the treatment guidelines for H. pylori infection should be geographically designed.