Five alternative Helicobacter pylori antibiotics to counter high levofloxacin and metronidazole resistance in the Dominican Republic

Abstract

The prevalence of Helicobacter pylori resistance to levofloxacin and metronidazole was high in the Dominican Republic. We used two-fold agar dilution method to determine the minimum inhibitory concentration of five alternative antibiotics in 63 Dominican strains. We also assessed the genetic mutations associated with the antibiotic resistance using next-generation sequencing. We revealed that all 63 strains were sensitive towards sitafloxacin, furazolidone, and rifabutin. In contrast, the prevalence of rifaximin and garenoxacin resistance were high (82.5% and 34.9%, respectively). Patients more than or equal to 60 years old had the highest risk of double-antibiotic resistance (7/9, 77.8%, OR = 31.5, P = 0.009) and garenoxacin resistances (8/9, 88.9%, OR = 45.33, P = 0.002) with an increasing risk simultaneously by age (P = 0.004, r = 0.357). Almost all rifaximin resistant strains possessed multiple mutations with more than three mutations within rpoB including the most frequent novel mutations of S352L, I2726L, and V2465A. There was a significant association between vacA genotype and rifaximin resistance (P = 0.042). Among 23 levofloxacin-resistant strains, 82.6% (19/23, P <0.001) were also resistant to garenoxacin, and 39.1% (9/23) had a high minimal inhibitory concentration ≥8 μg/mL with positive trend correlation (P = <0.001, r = 0.84). Among 19 garenoxacin resistant strains, 16 (84.2%) contained mutations at D91 and N87 of gyrA . In conclusion, sitafloxacin, rifabutin, and furazolidone might be considered as alternative antibiotics to be included in H . pylori eradication regimen in regions with high prevalence of levofloxacin and metronidazole resistance, such as the Dominican Republic.

Rifabutin for the Treatment of Helicobacter pylori Infection: A Review

“…Finally, for the present review of the most up to date literature, we summarized in Table 1 all the studies that have evaluated H. pylori rifabutin resistance rates [ 3 , 24 , 25 , 27 , 28 , 38 , 41 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 ]. From these 39 studies, including a total of 9721 patients, an overall rifabutin resistance rate of 0.13% was calculated ( Figure 1 ); however, when only studies including pre-treatment patients (that is, naïve to H. pylori eradication treatment) were considered, this figure was even lower (0.07%), as is summarized in Figure 2 .…”

Therapeutic Potential of Sitafloxacin as a New Drug Candidate for Helicobacter Eradication in Korea: An In Vitro Culture-Based Study

“…According to the study results, 95.2% of H. pylori strains from Nepal and 98.2% of strains from Bangladesh showed high susceptibility to sitafloxacin. Korea, Nepal, and Bangladesh are classified as regions with a high prevalence of H. pylori infection (Bangladesh at 60.2% prevalence), and high antibiotic resistance, including that of clarithromycin, metronidazole, and levofloxacin (39.3%, 94.6%, and 66.1%, respectively), resulting in eradication failure [30]. Second, Miftahussurur et al reported the possibility of sitafloxacin in H. pylori infection using 63 H. pylori strains from Dominican patients [31].…”

“…Further investigation should be guaranteed. Sixth, H. pylori can acquire double mutations in the gyrA gene at the A87 and D91 positions, which results in drug resistance against sitafloxacin [30]. Furthermore, because H. pylori also has traits of cross-resistance with other quinolone series drugs such as ciprofloxacin, careful clinical antibiotic use of sitafloxacin for appropriate indications, as well as the use of antibiotic sensitivity test-based regimens rather than empirical use, are still imperative to reduce the possibility of antibiotic resistance.…”

Review – Treatment of Helicobacter pylori infection 2020

“…An unprecedented number of studies last year reported on the important topic of antimicrobial resistance of H pylori strains 24‐60 . These are outlined in Table 1.…”