TY - JOUR
T1 - Five alternative Helicobacter pylori antibiotics to counter high levofloxacin and metronidazole resistance in the Dominican Republic
AU - Miftahussurur, Muhammad
AU - Cruz, Modesto
AU - Doohan, Dalla
AU - Subsomwong, Phawinee
AU - Jiménez Abreu, José A.
AU - Hosking, Celso
AU - Waskito, Langgeng Agung
AU - Yamaoka, Yoshio
N1 - Funding Information:
This report is based on work supported in part by grants from the National Institutes of Health (DK62813) (YY), and Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (26640114, 221S0002, 16H06279, 15H02657 and 16H05191) (YY). This work was also supported by the Japan Society for the Promotion of Science Institutional Program for Young Researcher Overseas Visits and the Strategic Funds for the Promotion of Science and Technology Agency (JST) for YY and The Ministries of Research, Technology and Higher Education of Indonesia for World Class Professor Program (no. 123.4/D2.3/ KP/2018) to MIL and MM. LAW and DD are PhD students supported by the Japanese Government (MEXT) scholarship program for 2015, 2016, and 2017, respectively. In addition, it was supported in part by a grant from The National Fund for Innovation and Development of Science and Technology (FONDOCYT) from the Ministry of Higher Education Science and Technology (MESCyT) of the Dominican Republic (2012-2013-2A1-65 and 2015-3A1-182) (MC).
Publisher Copyright:
© 2019 Miftahussurur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2019/3
Y1 - 2019/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85063586660&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0213868
DO - 10.1371/journal.pone.0213868
M3 - Article
C2 - 30917150
AN - SCOPUS:85063586660
SN - 1932-6203
VL - 14
JO - PLoS ONE
JF - PLoS ONE
IS - 3
M1 - e0213868
ER -