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

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. © 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

Overview of Helicobacter pylori Infection in Indonesia: What Distinguishes It from Countries with High Gastric Cancer Incidence?

Helicobacter pylori infects more than half the human population. However, the prevalence in Indonesia is low, as is the prevalence of gastric cancer. Hence, it could be instructive to compare these prevalence rates and their determining factors with those of countries that have high gastric cancer incidence. Ethnicity and genetic characteristics of H. pylori are important determinants of the H. pylori infection rate in Indonesia. The infection rate is higher in Bataknese, Papuans and Buginese than in Javanese, the predominant ethnic group. Ethnicity is also an important determinant of the genetic characteristics of H. pylori. Analysis of CagA in the EPIYA segment showed that the predominant genotypes in Papuans, Bataknese and Buginese are ABB-, ABD- and ABC-type CagA, respectively. Meanwhile, in the countries with high gastric cancer incidence, almost all strains had East Asian type CagA. An antibiotic susceptibility evaluation showed that the standard triple therapy can still be used with caution in several cities. There is a very high rate of resistance to second-line regimens such as levofloxacin and metronidazole. Recent studies have shown that furazolidone, rifabutin and sitafloxacin are potential alternative treatments for antibiotic-resistant H. pylori infection in Indonesia. Rather than focusing on early detection and eradication as in countries with high gastric cancer prevalence, countries with low gastric cancer prevalence should focus on screening the several groups that have a high risk of gastric cancer

E-test versus agar dilution for antibiotic susceptibility testing of Helicobacter pylori: A comparison study

Objective: For evaluating the antibiotic resistance of Helicobacter pylori, the agar dilution method is the gold standard; however, using this method in daily practice is laborious. E-test has been proposed to be an uncomplicated method. This study was aimed at validating the E-test and detecting the presence of any bias between the agar dilution method and E-test. Results: The agar dilution method and E-test were performed using five antibiotics for 72 strains of H. pylori obtained from clinical patients in Indonesia. The E-test's results showed a higher prevalence of resistance to all the antibiotics tested but the difference was not significant. Results showed high essential agreement (> 90.0) for all the antibiotics, but only 84.7 for metronidazole. The agreement for MIC value was acceptable for levofloxacin, clarithromycin, and metronidazole. For amoxicillin, it showed only fair agreement (0.25) by the Kappa analysis and significant difference by Passing-Bablok regression. Even though some discrepancies were found, the E-test has an acceptable agreement for levofloxacin, metronidazole, tetracycline, and clarithromycin but further confirmation may be necessary for amoxicillin. © 2020 The Author(s)

Gastroesophageal reflux disease in an area with low Helicobacter pylori infection prevalence

The association between gastroesophageal reflux disease (GERD) prevalence and its risk factors in an area with low Helicobacter pylori prevalence is important to clarify. We analyzed the prevalence of GERD and risk factors in an area of Indonesia with low prevalence of H. pylori infection. We recruited 104 dyspeptic patients who underwent endoscopy in Surabaya. Patients were diagnosed with GERD based on the Los Angeles classification. We evaluated gastric biopsy specimens and measured serum pepsinogen levels. Interleukin polymorphisms were evaluated by polymerase chain reaction-restriction fragment length polymorphism. Of 104 patients, 56 (53.8) were endoscopically found to have GERD, with most categorized as grade A; 48 (46.2) were classified as non-GERD. Higher economic status, smoking, and a history of proton-pump inhibitor use significantly increased the risk of GERD. GERD Questionnaire scores showed a positive correlation with GERD (P < 0.001). An association was found between antral atrophic gastritis and GERD (P = 0.030), and patients with GERD more frequently had severe antral atrophy than nonerosive reflux disease (P = 0.018). We found an association between pepsinogen I/II levels and GERD (P = 0.047), but with low accuracy. IL-1β -511 TT and CT were predominant among the IL-1β -511 genotypes, and IL-8-251 AT and TT were predominant among the IL-8-251 genotypes. In conclusion, we found a high prevalence of GERD in an area with low prevalence of H. pylori infection, which could be associated with acid reflux. Smoking, history of proton-pump inhibitor use, and higher economic group significantly increased the risk of GERD. Copyright: © 2018 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

Gastric microbiota and Helicobacter pylori in Indonesian population

Background The profile of gastric mucosal microbiota has not yet been described in the Indonesian population where the prevalence of Helicobacter pylori is low. Methods This is a cross-sectional study analyzing 16S rRNA of 137 gastric biopsy specimens. We analyzed the association between gastric microbiota, H. pylori infection, and gastric mucosal damage. Result Among 137 analyzed samples, 27 were H. pylori-positive and 110 were H. pylori -negative based on culture, histology, and 16S rRNA gene analysis. Significantly lower α-diversity parameters, including Pielou's index, was observed in H. pylori-infected individuals compared with noninfected individuals (all P < .001). Among H. pylori-negative individuals, the permutational analysis of variance of Bray-Curtis dissimilarity distances showed a significant association with different ethnicities, suggesting some ethnic groups had specific microbiota profiles based on the presence of different operational taxonomic units. The linear discriminant analysis effect size (LEfSe) of the H. pylori-negative group showed significant associations between the presence of Micrococcus luteus and Sphingomonas yabuuchiae with Timor and Papuan ethnicities, respectively. The presence of Bulledia sp and Atopobium sp was associated with the Javanese ethnicity. We observed lower α-diversity scores in individuals with gastric mucosal damage and profiles with high abundances of Paludibacter sp and Dialister sp based on LEfSe analysis. Conclusion Our findings suggest the presence of H. pylori is more correlated with a distinct microbiome profile than ethnic precedence

Characterization of a novel Helicobacter pylori East Asian-type CagA ELISA for detecting patients infected with various cagA genotypes

Currently, Western-type CagA is used in most commercial Helicobacter pylori CagA ELISA kits for CagA detection rather than East Asian-type CagA. We evaluated the ability of the East Asian-type CagA ELISA developed by our group to detect anti-CagA antibody in patients infected with different cagA genotypes of H. pylori from four different countries in South Asia and Southeast Asia. The recombinant CagA protein was expressed and later purified using GST-tag affinity chromatography. The East Asian-type CagA-immobilized ELISA was used to measure the levels of anti-CagA antibody in 750 serum samples from Bhutan, Indonesia, Myanmar, and Bangladesh. The cutoff value of the serum antibody in each country was determined via Receiver-Operating Characteristic (ROC) analysis. The cutoff values were different among the four countries studied (Bhutan, 18.16 U/mL; Indonesia, 6.01 U/mL; Myanmar, 10.57 U/mL; and Bangladesh, 6.19 U/mL). Our ELISA had better sensitivity, specificity, and accuracy of anti-CagA antibody detection in subjects predominantly infected with East Asian-type CagA H. pylori (Bhutan and Indonesia) than in those infected with Western-type CagA H. pylori predominant (Myanmar and Bangladesh). We found positive correlations between the anti-CagA antibody and antral monocyte infiltration in subjects from all four countries. There was no significant association between bacterial density and the anti-CagA antibody in the antrum or the corpus. The East Asian-type CagA ELISA had improved detection of the anti-CagA antibody in subjects infected with East Asian-type CagA H. pylori. The East Asian-type CagA ELISA should, therefore, be used in populations predominantly infected with East Asian-type CagA. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature

Helicobacter pylori BabA–SabA Key Roles in the Adherence Phase: The Synergic Mechanism for Successful Colonization and Disease Development

Helicobacter pylori is a pathogenic microorganism that successfully inhabits the human stomach, colonizing it by producing several virulence factors responsible for preventing host self-defense mechanisms. The adherence mechanism to gastric mucosal tissue is one of the most important processes for effective colonization in the stomach. The blood group antigen-binding adhesion (BabA) and sialic acid-binding adherence (SabA) are two H. pylori outer membrane proteins able to interact with antigens in the gastroduodenal tract. H. pylori possesses several mechanisms to control the regulation of both BabA and SabA in either the transcriptional or translational level. BabA is believed to be the most important protein in the early infection phase due to its ability to interact with various Lewis antigens, whereas SabA interaction with sialylated Lewis antigens may prove important for the adherence process in the inflamed gastric mucosal tissue in the ongoing-infection phase. The adherence mechanisms of BabA and SabA allow H. pylori to anchor in the gastric mucosa and begin the colonization process

Hubungan Antara Tingkat Pendapatan dan Aktivitas Fisik Terhadap Kejadian Obesitas Sentral pada Kelompok Usia 49 – 59 Tahun di RW VIII Desa Randuagung Kecamatan Singosari Kabupaten Malang

Obesitas merupakan kondisi dimana terjadi akumulasi lemak pada jaringan adiposa. Obesitas dipengaruhi oleh banyak faktor, diantaranya faktor genetik, usia, jenis kelamin, aktivitas fisik dan konsumsi tinggi kalori. Berdasarkan survey pendahuluan pada tanggal 22 April 2013 di Desa Randuagung, Kecamatan Singosari, Kabupaten Lawang diketahui bahwa 62,5% dari 32 responden acak memiliki lingkar perut melebihi batas normal. 40% diantaranya berusia 49-59 tahun, 40% berusia 28-48 tahun, dan 20% sisanya berusia di atas 60 tahun. Dari hasil tersebut diketahui bahwa obesitas masih menjadi masalah kesehatan. Karena itu, peneliti berupaya membuktikan adanya hubungan antara pendapatan dan tingkat aktivitas fisik terhadap kejadian obesitas sentral. Penelitian ini merupakan penelitian analitik observasional dengan desain cross sectional. Populasinya adalah penduduk usia 49-59 tahun di RW VIII Dusun Karang Kunci sebanyak 176 orang. Besar sampel pada penelitian ini adalah 75 responden yang sesuai dengan kriteria inklusi. Teknik pengambilan sampel yang digunakan adalah simple random sampling. Dengan demikian, setiap unit populasi memiliki kesempatan yang sama untuk dipilih sebagai sampel. Berdasarkan pengolahan data, didapatkan proporsi sampel yang menderita obesitas sebesar 69,33%. Hasil Chi-Square Test menggunakan SPSS 17 menggambarkan tidak terdapat hubungan anatara tingkat pendapatan dengan kejadian obesitas sentral (p=0,101, p>α,α=0,05). Terdapat hubungan antara aktivitas fisik dengan kejadian obesitas sentral (p=0,001, p<α,α=0,05). Berdasarkan uji Koefisien Cramer, kuat hubungan antara aktivitas fisik dengan kejadian obesitas sentral sebesar 0,481 (sedang). Berdasarkan uji regresi logistik, didapatkan aktivitas fisik mempengaruhi kejadian obesitas sentral sebesar 21,3% dan aktivitas fisik kategori inactive memiliki resiko menderita obesitas sentral sebesar 8,708 kali lebih besar dibanding aktivitas fisik kategori active

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

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

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