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Effective therapeutic regimens in two South Asian countries with high resistance to major Helicobacter pylori antibiotics.

ABSTRACT: 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.

SUBMITTER: Miftahussurur M

PROVIDER: S-EPMC6377755 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Effective therapeutic regimens in two South Asian countries with high resistance to major <i>Helicobacter pylori</i> antibiotics.

Miftahussurur Muhammad M Aftab Hafeza H Shrestha Pradeep Krishna PK Sharma Rabi Prakash RP Subsomwong Phawinee P Waskito Langgeng Agung LA Doohan Dalla D Fauzia Kartika Afrida KA Yamaoka Yoshio Y

Antimicrobial resistance and infection control 20190215

<h4>Background</h4>Nepal and Bangladesh have a high prevalence of <i>Helicobacter pylori</i> 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 <i>H. pylori</i> eradication.<h4>Methods</h4>We used the agar dilution method to determine the minimal inhibitory concentration of 5 alternative antibiotics ...[more]

PMID: 30815255

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Project description:Helicobacter pylori, a Gram-negative bacterium, is associated with a wide range of gastric diseases such as gastritis, duodenal ulcer, and gastric cancer. The prevalence of H pylori and risk of disease vary in different parts of the world based on the prevailing bacterial lineage. Here, we present a contextual and comparative genomics analysis of 20 clinical isolates of H pylori from patients in Bangladesh. Despite a uniform host ethnicity (Bengali), isolates were classified as being part of the HpAsia2 (50%) or HpEurope (50%) population. Out of twenty isolates, eighteen isolates were cagA positive, with two HpEurope isolates being cagA negative, three EPIYA motif patterns (AB, AB-C, and ABC-C) were observed among the cagA-positive isolates. Three vacA genotypes were observed with the s1m1i1dic1 genotype observed in 75% of isolates; the s1m2i1d1c2 and s2m2i2d2c2 genotypes were found to be 15% and 10% of isolates, respectively. The non-virulent genotypes s2m2i2d2c2 was only observed in HpEurope population isolates. Genotypic analysis of oipA gene, present in all isolates, revealed five different patterns of the CT repeat; all HpAsia2 isolates were in "ON" while 20% of HpEurope isolates were genotypically "OFF." The three blood group antigen binding adhesins encoded genes (bab genes) examined and we observed that the most common genotype was (babA/babB/-) found in eight isolates, notably six were HpAsia2 isolates. The babA gene was found in all HpAsia2 isolates but present in only half of the HpEurope isolates. In silico antibiotic susceptibility analysis revealed that 40% of the strains were multi-drug resistant. Mutations associated with resistance to metronidazole, fluoroquinolone, and clarithromycin were detected 90%, 45%, and 5%, respectively, in H pylori strain. In conclusion, it is evident that two populations of H pylori with similar antibiotic profiles are predominant in Bangladesh, and it appears that genotypically the HpAisa2 isolates are potentially more virulent than the HpEurope isolates.

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Effective therapeutic regimens in two South Asian countries with high resistance to major Helicobacter pylori antibiotics.

Publications

Effective therapeutic regimens in two South Asian countries with high resistance to major <i>Helicobacter pylori</i> antibiotics.

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