Since the emergence of falling eradication rates and the need for new medications, the use of levofloxacin has been recommended. Resistance to metronidazole and clarithromycin, which are the cornerstones of traditional triple treatments, makes it difficult to find an effective alternative [14]. One of the suggested salvage regimens in second-line treatment is 10–14 day levofloxacin-based triple therapy. When compared to clarithromycin-based treatment, our study showed that levofloxacin-based treatment was linked with a higher incidence of treatment success (74.5 vs. 62%). Similar results were confirmed by Haji-Aghamohammadi et al. who reported the superiority of levofloxacin triple regimen to clarithromycin-based regimen (75 vs. 51.7% and 80.4 vs. 57.4%) according to intention- to-treat and per protocol analyses, respectively [16]. Another large randomized trial of 300 patients who were treated with either a standard clarithromycin regimen or a levofloxacin triple therapy showed a higher eradication rate of 87% with levofloxacin-containing therapy compared to standard regimens with eradication rates of 72 and 75% (clarithromycin with esomeprazole and either amoxicillin or metronidazole, respectively) [11].

Discrepancies between trial results could be also attributed to ethnic differences, although drug dosage and treatment duration should also be considered. Such impact was suggested by Silva et al. who conducted a study on 66 Brazilian patients who had H. pylori infection, did not receive prior treatment, and were treated with levofloxacin triple-based regimen (levofloxacin, amoxicillin, and lansoprazole) showed an eradication rate of 73% (95% CI, 62–84%) compared with 82.7% (95% CI, 79–86%) reported with classic regimen of clarithromycin, amoxicillin, and a PPI [17]. This finding could be explained by an earlier Brazilian study that found higher rates of resistance by H. pylori to levofloxacin (23%) than to clarithromycin (8%) [18].

In terms of duration of therapy, the present study found that the eradication rate of H. pylori who failed the first-line was 62.7% and 80.9% for 10-day and 14-day levofloxacin-based regimen, respectively. On the other hand, the use of a clarithromycin-based regimen for 10 or 14 days resulted in eradication rates of 41.2% and 66.3%, respectively (P = 0.02). These differences suggest that the 14-day levofloxacin-based triple therapy is more effective in eradicating H. pylori infection than clarithromycin-based therapy for either 10 or 14 days treatment course. Regarding the optimal duration of levofloxacin triple salvage treatment, Di Caro et al. compared two types of 10-day and two types of 7 day PAL regimens in Italy and found significantly higher efficacy with longer duration (88 vs. 78%) [14]. This finding was confirmed by an RCT from Turkey which reported significantly higher efficacy with longer duration of PAL as first-line treatment (72% with 14 day regimen vs. 34% with 7 day regimen) [19]. Furthermore, according to Gisbert et al. systemic review and meta-analysis, when levofloxacin– amoxicillin–PPI combination was given for 7 and 10 days, the mean eradication rate was 68% (95% CI, 62–75%) and 80% (95% CI, 77–83%) (P < 0.001) [15].

Our findings revealed that the presence of diabetes as a comorbid condition had no effect on H. pylori eradication. These findings are consistent with those reported by Kato et al., where the eradication failure was reported in 3.7% of diabetic patients and 2.5% of patients without diabetes. Although patients with diabetes were more likely to have eradication failure, the difference was not statistically significant (1.2%; 95% CI, − 0.8–3.2%) [19]. On the other hand, Horikawa et al. showed a significantly higher risk of H. pylori eradication failure in patients with diabetes compared with non-diabetic patients (P < 0.001) in a meta-analysis of 693 patients, of whom 273 had diabetes) [9]. Therefore, the authors recommended that diabetic patients should be treated for an extended duration or to use a new regimen for H. pylori eradication. Several studies explained the potential mechanisms that explain the low rate of effective H. pylori eradication among diabetic patients [20, 21] .

Similar to our findings with diabetes, the presence or absence of any GI condition had no impact on the successful eradication of H. pylori. Nonetheless, Kalkan et al. demonstrated that treatment failure was higher in the presence of gastric atrophy and intestinal metaplasia [22]. Due to a lack of data on the relationship between the existence and grade of intestinal metaplasia/atrophy and H. pylori eradication success, we were unable to explain the specific mechanism behind this outcome.

Based on our results, the eradication rate of H. pylori was improved in the presence of amoxicillin plus esomeprazole in the clarithromycin-based regimen patients (P = 0.02). In the levofloxacin-based regimens, however, the type of PPI and the inclusion or exclusion of amoxicillin within the regimen had no change on the eradication rate. The use of esomeprazole had a higher cure rate when compared to pantoprazole in a study published by Graham et al. This is a finding they attributed to the greater relative potency of esomeprazole compared to pantoprazole; an observation that was not directly assessed in this present study [23]. However, the finding that esomeprazole-treated patients had high eradication rates in our study (in the clarithromycin-based regimens) is consistent with the findings of Graham et al. and most likely attributable to the high potency of esomeprazole compared to pantoprazole.

The findings of this study must be seen in light of some limitations. Patient compliance was not assessed, though there is no reason to assume a difference in compliance between these two regimens. This is a single center study with low rates of levofloxacin resistance in the region, possibly limiting the generalizability of the results. The choice of PPI was not compared based on the relative potency; possibly skewing the results as some studies state esomeprazole has greater potency than pantoprazole requiring a dose-adjustment for comparison based on equal-potency dosages. Our study favors real-life practice with physicians prescribing typical dosages of each PPI. Lastly, the levofloxacin-based regimen was used as salvage therapy, whereas the clarithromycin group was more likely to be treatment-naïve.