TY - JOUR
T1 - Effective therapeutic regimens in two South Asian countries with high resistance to major Helicobacter pylori antibiotics
AU - Miftahussurur, Muhammad
AU - Aftab, Hafeza
AU - Shrestha, Pradeep Krishna
AU - Sharma, Rabi Prakash
AU - Subsomwong, Phawinee
AU - Waskito, Langgeng Agung
AU - Doohan, Dalla
AU - Fauzia, Kartika Afrida
AU - Yamaoka, Yoshio
N1 - Funding Information:
This study was funded by grants from the National Institutes of Health (DK62813) and Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of (221S0002, 16H06279, 16H05191 and 18KK0266) (YY). It was also supported by the Japan Society for the Promotion of Science (JSPS) Institutional Program for Core-to-Core Program; B. Africa-Asia Science Platform (YY). LAW, DD, and KAF are doctoral students supported by the MEXT Scholarship Program for 2015, 2016, and 2017, respectively. In addition, the Ministries of Research, Technology, and Higher Education in the World Class Professor Program (123.4/D2.3/KP/2018) also supported this research (MM and MIL). All authors have read and approved the final version of the manuscript.
Publisher Copyright:
© The Author(s). 2019.
PY - 2019/2/15
Y1 - 2019/2/15
N2 - Background: Nepal and Bangladesh have a high prevalence of Helicobacter pylori with high resistance rates to clarithromycin, metronidazole, and levofloxacin. Here, we evaluated the susceptibility and genetic mutations of 5 alternative antibiotics against isolates from both countries to obtain an effective treatment regimen for H. pylori eradication. Methods: We used the agar dilution method to determine the minimal inhibitory concentration of 5 alternative antibiotics against 42 strains from Nepal and 56 from Bangladesh and performed whole genome mutation analysis. Results: No resistance to furazolidone or rifabutin and a high susceptibility of sitafloxacin (95.2% in Nepal and 98.2% in Bangladesh) were observed. In contrast, resistance to rifaximin (52.4% in Nepal and 64.3% in Bangladesh) was high. Moreover, resistance to garenoxacin was higher in Bangladesh (51.6%) than in Nepal (28.6%, P = 0.041), most likely due to its correlation with levofloxacin resistance (P = 0.03). Garenoxacin and rifaximin were significantly correlated in Bangladesh (P = 0.014) and occurred together with all sitafloxacin-resistant strains. Mutations of gyrA could play a significant role in garenoxacin resistance, and double mutations of A87 and D91 were associated with sitafloxacin resistance. Analysis of the rpoB gene demonstrated well-known mutations, such as V657I, and several novel mutations, including I2619V, V2592 L, T2537A, and F2538 L Conclusions: Rifabutin can be cautiously implemented as therapy for H. pylori infection due to its interaction with the tuberculosis endemic in Bangladesh. The high susceptibility of furazolidone and sitafloxacin suggests their possible future application in Nepal and Bangladesh.
AB - Background: Nepal and Bangladesh have a high prevalence of Helicobacter pylori with high resistance rates to clarithromycin, metronidazole, and levofloxacin. Here, we evaluated the susceptibility and genetic mutations of 5 alternative antibiotics against isolates from both countries to obtain an effective treatment regimen for H. pylori eradication. Methods: We used the agar dilution method to determine the minimal inhibitory concentration of 5 alternative antibiotics against 42 strains from Nepal and 56 from Bangladesh and performed whole genome mutation analysis. Results: No resistance to furazolidone or rifabutin and a high susceptibility of sitafloxacin (95.2% in Nepal and 98.2% in Bangladesh) were observed. In contrast, resistance to rifaximin (52.4% in Nepal and 64.3% in Bangladesh) was high. Moreover, resistance to garenoxacin was higher in Bangladesh (51.6%) than in Nepal (28.6%, P = 0.041), most likely due to its correlation with levofloxacin resistance (P = 0.03). Garenoxacin and rifaximin were significantly correlated in Bangladesh (P = 0.014) and occurred together with all sitafloxacin-resistant strains. Mutations of gyrA could play a significant role in garenoxacin resistance, and double mutations of A87 and D91 were associated with sitafloxacin resistance. Analysis of the rpoB gene demonstrated well-known mutations, such as V657I, and several novel mutations, including I2619V, V2592 L, T2537A, and F2538 L Conclusions: Rifabutin can be cautiously implemented as therapy for H. pylori infection due to its interaction with the tuberculosis endemic in Bangladesh. The high susceptibility of furazolidone and sitafloxacin suggests their possible future application in Nepal and Bangladesh.
KW - Antibiotics
KW - Bangladesh
KW - Drug resistance
KW - Helicobacter pylori
KW - Nepal
UR - http://www.scopus.com/inward/record.url?scp=85062410577&partnerID=8YFLogxK
U2 - 10.1186/s13756-019-0482-x
DO - 10.1186/s13756-019-0482-x
M3 - Article
C2 - 30815255
AN - SCOPUS:85062410577
SN - 2047-2994
VL - 8
JO - Antimicrobial Resistance and Infection Control
JF - Antimicrobial Resistance and Infection Control
IS - 1
M1 - 40
ER -