Increased resistance of Helicobacter pylori to clarithromycin and metronidazole has resulted in recommendation to substitute fluoroquinolones for eradication therapy. The aims of the study were to determine the prevalence and changes in primary levofloxacin resistance related to H. pylori gyrA sequences. The study utilized H. pylori strains isolated from patients undergoing gastroscopy in Bogotá, Colombia from 2009 to 2014. Levofloxacin susceptibility was assessed by agar dilution. Mutations in gyrA sequences affecting the quinolone resistance-determining region (QRDR) were evaluated by direct sequencing. Overall, the mean prevalence of primary levofloxacin resistance was 18.2% (80 of 439 samples). Resistance increased from 11.8% (12/102) in 2009 to 27.3% (21/77) in 2014 (p = 0.001). gyrA mutations in levofloxacin resistant strains were present in QRDR positions 87 and 91. The most common mutation was N87I (43.8%, 35/80) followed by D91N (28.8%, 23/80) and N87K (11.3%, 9/80). Levofloxacin resistance increased markedly in Colombia during the six-year study period. Primary levofloxacin resistance was most often mediated by point mutations in gyrA, with N87I being the most common QRDR mutation related to levofloxacin resistance.
The clinical outcome of Helicobacter pylori infection has been particularly associated with virulence genotypes. These genotypes are useful as molecular markers in the identification of patients that are infected and at high risk for developing more severe gastric pathologies. Our main objective was to determine the prevalence of virulence genotypes cagA, vacA, iceA and babA2 of H. pylori, in patients with functional dyspepsia who are infected with the bacteria. H. pylori genotypes babA2 and cagA as well as vacA and iceA allelic variants were identified by PCR in 122 isolates resulting from 79 patients with functional dyspepsia. A high prevalence of genes cagA+ (71%), vacAs1am1 (34%), babA2 (57%) and iceA1 (87%) was found. The most frequent combined genotype found were cagA+/vacAs1am1/babA2+/iceA1 and cagA-/vacAs1am1/babA2+/iceA1, regardless of any family history of gastric cancer or MALT lymphoma. The very virulent genotype cagA+/vacAs1am1/babA2+/iceA1 prevailed in the studied patients with functional dyspepsia. Our results provide information about the prevalence of four of the more important virulent factors and constitute new evidence on the prevalence of the most virulent H. pylori genotype in patients with functional dyspepsia.
Background Helicobacter pylori is a human gastric carcinogen that is highly prevalent in Latin American. The prophages of H. pylori show a structured population and contribute to the diversity of this bacterium. However, H. pylori prophages present in American strains have not been described to date. In this study, we identified, characterized, and present the phylogenetic analysis of the prophages present in Colombian H. pylori strains. Methods To characterize Colombian H. pylori strains and their prophages, a Multilocus Sequences Typing (MLST) and a Prophage Sequences Typing (PST), using the integrase and holin genes, were performed. Furthermore, five Colombian H. pylori had their full genome sequenced, and six Colombian H.pylori retrieved from databases, allowing to determine the prophage complete genome and insertion site. Results The integrase gene frequency was 12.6% (27/213), while both integrase and holin genes were present in 4.2% (9/213) of the samples analyzed. The PST analysis showed that Colombian prophages belong to different populations, including hpSWEurope, hpNEurope, hpAfrica1, and a new population, named hpColombia. The MLST analysis classified most of the Colombia strains in the hpEurope population. Conclusions The new H. pylori prophage population revealed that Colombian prophages follow a unique evolutionary trajectory, contributing to bacterial diversity. The global H. pylori prophage phylogeny highlighted five phylogenetic groups, one more than previously reported. After the arrival of Europeans, the Colombian H. pylori bacteria and their prophages formed an independent evolutionary line to adapt to the new environment and new human hosts.
Introduction Proton pump inhibitors (PPIs) are a group of drugs that are essential for the treatment of acid-related disorders, such as gastroesophageal reflux (GERD), dyspepsia, gastric ulcers and Helicobacter pylori (H. pylori) infection. PPIs such as omeprazole, esomeprazole, pantoprazole and lansoprazole are metabolized by the CYP2C19 enzyme, which is encoded by a polymorphic gene. Four polymorphisms have an impact on the speed of PPI metabolism: CYP2C19*1/*1 (extensive metabolizers), CYP2C19*2/*2 (intermediate metabolizers), CYP2C19*3/*3 (poor metabolizers) and CYP2C19*17/*17 (ultrarapid metabolizers). Extensive and ultrarapid metabolizers inactivate PPIs quickly, which consequently causes low plasma concentrations of PPIs, while intermediate or poor metabolizers have higher plasma concentrations of PPIs and, therefore, PPIs have greater therapeutic efficacy in individuals with these polymorphisms. Objective To determine the frequency of genetic polymorphisms of the CPY2C19 enzyme in Bogotá, Colombia. Methods This observational study was conducted in Bogotá between 2012 and 2015 and was part of a clinical trial (ID: NCT03650543). It included 239 subjects with dyspepsia, H. pylori infection, or GERD symptoms. CYP2C19 genotyping was performed on gastric biopsy samples. Polymorphisms *1, *2, and *3 were analyzed by real-time PCR (Roche®), and PCR-RFLP was used to determine the presence of polymorphism *17. Results The distribution of different types of PPI metabolizers was as follows: extensive (70.7%), ultrarapid (12.9%), intermediate (8.8%) and poor (0.8%). Conclusion The population studied consisted mainly of extensive and ultrarapid PPI metabolizers. These findings show that it is necessary to increase PPI doses in this group of subjects or to use PPIs that are not metabolized by CYP2C19 (rabeprazole). This is the first Colombian work to identify ultrarapid metabolizers.
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