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1.
Int J Infect Dis ; 97: 102-107, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32474200

RESUMO

OBJECTIVES: Bhutan suffers from a high prevalence of Helicobacter pylori (H. pylori) infection and gastric cancer-related mortality. In preparation for a countrywide H. pylori eradication program, the antibiotic resistance patterns of H. pylori infection were surveyed in different geographical regions. METHODS: Dyspeptic patients in 6 districts including Thimphu, Punakha, Wangdue, Trongsa, Bumthang, and Haa underwent upper gastrointestinal endoscopy during GASTROCAMP and were enrolled between December 2010 and April 2015. Gastric biopsies were obtained for rapid urease test, histopathology, and H. pylori culture. Antimicrobial susceptibility testing was later performed if the culture was positive. RESULTS: A total of 1178 patients were surveyed. The overall H. pylori infection in Bhutan was 66.2%. Punakha had the highest prevalence of H. pylori infection (85.6%). Thimphu and Punakha (city areas) had higher prevalence of H. pylori infection than rural districts (73.5% vs 63.3%, OR=1.61, 95% CI 1.22-2.13, p=0.0008). There were 357 patients (30.3%) with positive H. pylori culture completed antimicrobial susceptibility testing. The mean age was 40.5 years with female predominance (57.1%). No amoxicillin resistant strains were found. Metronidazole resistance was 81% followed by levofloxacin resistance (8.1%). Clarithromycin (2%) and tetracycline (0.6%) resistance was rare except in Thimphu, the capital city (10%) vs 0% in rural areas, p<0.001. The metronidazole resistance rate remained stable at approximately 80% during the past 5 years of study. Levofloxacin-resistant strains gradually rose from 5.3% in 2010 to 9.9% in 2015. CONCLUSIONS: Bhutan had a high prevalence of H. pylori infection. Metronidazole resistance was extremely high, whereas clarithromycin resistance was quite low in this specific area. Antibiotic resistance pattern could be good evidence for guiding a proper treatment regimen for H. pylori infection in Bhutan.


Assuntos
Farmacorresistência Bacteriana , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/efeitos dos fármacos , Adulto , Amoxicilina/farmacologia , Antibacterianos/farmacologia , Butão/epidemiologia , Claritromicina/farmacologia , Feminino , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Levofloxacino/farmacologia , Masculino , Metronidazol/farmacologia , Pessoa de Meia-Idade , Prevalência , Tetraciclina/farmacologia
2.
Int J Infect Dis ; 97: 270-277, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32526389

RESUMO

OBJECTIVES: A standard treatment regimen against Mycobacteroides abscessus complex (MABC) infections has not yet been established, making MABC difficult to treat successfully. In this study, we sought to develop an active ingredient for the clinical treatment of MABC infections. METHODS: We screened 102 MABC strains isolated from clinical specimens using DNA sequence analysis with the housekeeping genes hsp65 and rpoB. Drug susceptibility testing was performed against two subspecies-Mycobacteroides abscessus subsp. abscessus (M. abscessus) and Mycobacteroides abscessus subsp. massiliense (M. massiliense)-using eight antimicrobial agents (clarithromycin, amikacin, doxycycline, imipenem, linezolid, moxifloxacin, faropenem, and rifampicin). The combined efficacy of the antimicrobial agents was investigated using a checkerboard method. RESULTS: We identified 51 isolates as M. abscessus, 46 as M. massiliense, and five as others. Most of the M. abscessus isolates (83.0 %) exhibited inducible resistance to clarithromycin via the expression of the erm(41) gene. Combinations of imipenem with linezolid, moxifloxacin, and rifampicin exhibited additive effects against 81.0 %, 40.7 %, and 26.9 % of M. abscessus, respectively, and against 54.5 %, 69.2 %, and 30.8 % of M. massiliense, respectively. CONCLUSIONS: These results demonstrated the potential efficacy of a regimen containing imipenem against M. abscessus and M. massiliense infections.


Assuntos
Antibacterianos/farmacologia , Mycobacteriaceae/efeitos dos fármacos , Infecções por Actinomycetales/microbiologia , Amicacina/farmacologia , Claritromicina/farmacologia , Doxiciclina/farmacologia , Humanos , Imipenem/farmacologia , Linezolida/farmacologia , Testes de Sensibilidade Microbiana , Moxifloxacina/farmacologia , Mycobacteriaceae/classificação , Mycobacteriaceae/crescimento & desenvolvimento , Análise de Sequência de DNA , beta-Lactamas/farmacologia
3.
Biochemistry ; 59(12): 1217-1220, 2020 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-32157864

RESUMO

The identification of proteins that bind selectively to nucleic acid sequences is an ongoing challenge. We previously synthesized nucleobase amino acids designed to replace proteinogenic amino acids; these were incorporated into proteins to bind specific nucleic acids predictably. An early example involved selective cell free binding of the hnRNP LL RRM1 domain to its i-motif DNA target via Watson-Crick-like H-bonding interactions. In this study, we employ the X-ray crystal structure of transcriptional regulator Rob bound to its micF promoter, which occurred without DNA distortion. Rob proteins modified in vivo with nucleobase amino acids at position 40 exhibited altered DNA promoter binding, as predicted on the basis of their Watson-Crick-like H-bonding interactions with promoter DNA A-box residue Gua-6. Rob protein expression ultimately controls phenotypic changes, including resistance to antibiotics. Although Rob proteins with nucleobase amino acids were expressed in Escherichia coli at levels estimated to be only a fraction of that of the wild-type Rob protein, those modified proteins that bound to the micF promoter more avidly than the wild type in vitro also produced greater resistance to macrolide antibiotics roxithromycin and clarithromycin in vivo, as well as the ß-lactam antibiotic ampicillin. Also demonstrated is the statistical significance of altered DNA binding and antibiotic resistance for key Rob analogues. These preliminary findings suggest the ultimate utility of nucleobase amino acids in altering and controlling preferred nucleic acid target sequences by proteins, for probing molecular interactions critical to protein function, and for enhancing phenotypic changes in vivo by regulatory protein analogues.


Assuntos
Aminoácidos/química , Proteínas de Ligação a DNA/metabolismo , Farmacorresistência Bacteriana Múltipla/genética , Proteínas de Escherichia coli/metabolismo , Escherichia coli/genética , Fatores de Transcrição/metabolismo , Ampicilina/farmacologia , Claritromicina/farmacologia , Cristalografia por Raios X , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Proteínas de Ligação a DNA/química , Escherichia coli/efeitos dos fármacos , Proteínas de Escherichia coli/química , Regulação Bacteriana da Expressão Gênica , Guanina/química , Testes de Sensibilidade Microbiana , Regiões Promotoras Genéticas/genética , RNA Interferente Pequeno/genética , Roxitromicina/farmacologia , Fatores de Transcrição/química
4.
Vet Microbiol ; 242: 108568, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32122582

RESUMO

Mainstay therapy for rhodococcosis in foals is the combination of rifampicin and a macrolide. While emergence of resistance to rifampicin and macrolides has been reported, studies demonstrating the development of resistance to such drugs is limited in necropsied foals with rhodococcosis. In this study, the foal necropsy records between 01/01/2011 and 08/30/2019 were reviewed for culture-positive R. equi with MICs and, whether or not the affected foals received any mainstay dual therapy before their deaths. Resistance to antimicrobials in the R. equi isolates from necropsied foals were then compared between treated foals with dual therapy and untreated foals to determine the association between the administration of antimicrobials and development of the drug resistance. In a total of 256 R. equi isolates from each of the 256 necropsied foals with rhodococcosis, rifampicin, azithromycin, clarithromycin and erythromycin showed high rates of resistance, 22.65 %, 16.01 %, 14.84 % and 15.23 %, respectively. The most active antimicrobials exhibiting MIC50/90 values were imipenem, doxycycline, amikacin and gentamicin including in the rifampicin- and macrolides-resistant R. equi isolates. Based on the treatment histories available for the 114 necropsied foals with rhodococcosis, R. equi isolates resistant to rifampicin, and macrolides were significantly more isolated from treated foals with mainstay dual therapy compared to untreated foals. Despite dual therapy, development of resistance against rifampicin and macrolides warrants evaluation of new treatment protocols in foals.


Assuntos
Infecções por Actinomycetales/veterinária , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Doenças dos Cavalos/microbiologia , Rhodococcus equi/efeitos dos fármacos , Infecções por Actinomycetales/tratamento farmacológico , Infecções por Actinomycetales/microbiologia , Animais , Azitromicina/farmacologia , Claritromicina/farmacologia , Eritromicina/farmacologia , Doenças dos Cavalos/tratamento farmacológico , Cavalos/microbiologia , Testes de Sensibilidade Microbiana
5.
J Infect Public Health ; 13(4): 497-501, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31839585

RESUMO

BACKGROUND: Haemophilus influenzae strains with reduced susceptibilities to antimicrobial agents have emerged in Japan. Here, we aimed to investigate H. influenzae non-susceptibility to ß-lactams and non-ß-lactams. METHODS: A total of 260 H. influenzae isolates from patients in 2013-2016 were analysed. Antimicrobial susceptibilities were assessed by determining the minimum inhibitory concentration. Additionally, isolates with reduced susceptibility were analysed by both genetic and statistical methods. RESULTS: ß-Lactamase-non-producing ampicillin-resistant H. influenzae (BLNAR) strains increased significantly and accounted for more than 50% of all isolates from 2014. Additionally, the proportion of quinolone-low-susceptibility isolates increased significantly (P<0.05). Among these, three quinolone-non-susceptible isolates showed minimum inhibitory concentrations higher than the susceptibility breakpoint of levofloxacin. Moreover, one of the three isolates showing multidrug resistance was resistant to macrolides, ß-lactams, and quinolones. Low susceptibilities to non-ß-lactams were significantly associated with BLNAR. CONCLUSIONS: The present study indicates that BLNAR strains are increasing and tend to show multidrug resistance. Additionally, multidrug-resistant H. influenzae (MDRHI) has emerged. To prevent the further spread of MDRHI, the proportions of BLNAR strains should be evaluated.


Assuntos
Infecções por Haemophilus/tratamento farmacológico , Haemophilus influenzae/efeitos dos fármacos , Resistência a Ampicilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/enzimologia , Haemophilus influenzae/genética , Humanos , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Testes de Sensibilidade Microbiana , Análise de Sequência de DNA , beta-Lactamases/metabolismo
6.
APMIS ; 128(1): 25-34, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31628820

RESUMO

Eradication failure of Helicobacter pylori infection could play a causal role in progression of gastric disorders. In this study, infection with H. pylori was followed in gastric biopsies of symptomatic adult patients at two phases during 1-year period. Analyses were done to show association of therapeutic regimens with the refractory infection, changes in sequence types (STs) and minimum inhibitory concentration (MIC) values, and progression of histopathological changes. Infection with H. pylori was confirmed in 32.3% (57/170) of the patients. Persistent infection with H. pylori was confirmed in 14 out of the 25 patients (56%) who participated at the second phase of the study. A difference between primary and secondary resistance rates to clarithromycin (49% vs 64.3%), metronidazole (76.36% vs 100%), and ciprofloxacin (45% vs 57.1%) was detected. Although the re-emerged strains in patients with refractory infection did not show alteration in STs, their MIC50 values showed twofold increases for clarithromycin and ciprofloxacin. While ciprofloxacin containing regimens were more successful, failure of metronidazole containing regimens was detected in 77% of the patients. Consequently, inappropriate medication has an impact on refractory H. pylori infection, which could cause to a rise in resistance levels to antibiotics and progression of pathological disorders.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/patologia , Helicobacter pylori/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Técnicas de Tipagem Bacteriana , Biópsia , Ciprofloxacino/farmacologia , Claritromicina/farmacologia , Feminino , Seguimentos , Técnicas Histológicas , Humanos , Concentração Inibidora 50 , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Estômago/microbiologia , Estômago/patologia
7.
PLoS One ; 14(12): e0224356, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31841502

RESUMO

It has become critical to detect Helicobacter pylori (H. pylori) infection due to the link to gastric cancer with some strains. These strains are also increasing in resistance to antibiotics with clarithromycin leading the way as the first line treatment. Resistance to clarithromycin has been shown to correlate with the A2142G, A2142C, and A2143G mutations on the rrl gene. In the last few decades, non-invasive specimens, such as stool, have been a reliable alternate to gastric biopsy for immunoassay tests. More recently, it has been proven feasible for stool to be used in molecular based tests. Many of the core laboratories in the United States need a high throughput sample preparation to run this test. Here, a high throughput assay is compared to a previously published manual sample prep H. pylori molecular based assay. Using the Magna Pure 96 (Roche), at least 96 stool species and 96 biopsy specimens can be tested in an 8-hour shift of a clinical lab. The high throughput sample prep had a positive percent agreement (PPA) of 87% compared to the manual sample prep using the same testing configuration. The genotype predictions from the high throughput assay matched genotype predictions from the manual sample prep with the same stool sample 92% of the time. A concordance rate of 89% was observed with genotype predictions from the high throughput assay of the same patient stool and biopsy. In stool samples from the high throughput assay, there was 100% concordance between the quantitative polymerase chain reaction (qPCR)-derived genomic prediction and DNA sequencing data. The high throughput workflow can get more patients tested faster in addition to detection of mutations associated with clarithromycin resistance.


Assuntos
Fezes/microbiologia , Helicobacter pylori/metabolismo , Ensaios de Triagem em Larga Escala/métodos , Antibacterianos/farmacologia , Líquidos Corporais/química , Claritromicina/farmacologia , Claritromicina/uso terapêutico , DNA Bacteriano/genética , Farmacorresistência Bacteriana/genética , Fezes/química , Genótipo , Infecções por Helicobacter/complicações , Helicobacter pylori/genética , Helicobacter pylori/patogenicidade , Humanos , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase/métodos
8.
Arq Gastroenterol ; 56(4): 361-366, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31721972

RESUMO

BACKGROUND: Helicobacter pylori infection in Chile remains as a public and private health-care system's challenge, with a prevalence of the infection over 70%. Nowadays, antibiotic treatment of the infection is mandatory to prevent the arising of severe associated diseases but failures in the eradication therapy mainly due to clarithromycin resistance has been observed worldwide and first line eradication therapy seems to be not effective anymore in several geographical areas. Thus, health-care systems are committed to maintain an epidemiological surveillance upon the evolution of the antibiotic resistance of this priority 2 pathogen. OBJECTIVE: This work reports a 10 years surveillance of the primary antibiotic resistance of H. pylori clinical isolates at the Biobío region-Chile, and the evolution of resistance toward amoxicillin, clarithromycin, levofloxacin, metronidazole, and tetracycline among the species. METHODS: H. pylori strains were investigated during the periods 2005-2007 (1435 patients analysed) and 2015-2017 (220 patients analysed) by inoculating a saline homogenate biopsy onto the surface of Columbia agar (Oxoid, Basingstoke, UK) - supplemented with 7% horse red blood cells plus DENT inhibitor (Oxoid, Basingstoke, UK) - following by incubation at 37ºC under 10% CO2 atmosphere for five days. Antibiotic resistance pattern of the isolates was assessed using the disk diffusion test in Müeller-Hinton agar supplemented with 7% horse red blood cells followed by incubation for further three days under 10% CO2 atmosphere. Statistical analysis was done using the SPSS v22 software and P values <0.05 were considered statistically significant. RESULTS: A total of 41% of 1435 patients were detected to be infected with H. pylori by bacteriological culture in 2005-2007 period, meanwhile 32.7% from 220 patients were also infected in 2015-2017 period. The clinical isolates of H. pylori are mostly susceptible to amoxicillin and tetracycline (both over 98% of strains), but less susceptible to levofloxacin in both periods analysed (over 79% of the strains). On the other hand, metronidazole continuous showing the highest score of resistant isolates (over 40% of resistant strains), although an 18% fewer resistant strains were observed in 2015-2017 period. Clarithromycin, the key antibiotic in eradication therapies, has an increased frequency of resistant strain isolated in the decade (22.5% in 2005-2007 and 29.2% in 2015-2017). Multidrug resistant strains (two, three and four antibiotics) were also detected in both periods with the highest scores for simultaneous resistance to clarithromycin-metronidazole (18%) and clarithromycin-metronidazole-levofloxacin (12.5%) resistant strains. According to gender, the isolates resistant to amoxicillin, clarithromycin and metronidazole were more frequent in female, with a specific increment in amoxicillin and clarithromycin resistance. CONCLUSION: The frequency of clarithromycin resistance (29.2%) detected in 2015-2017 suggests that conventional triple therapy is no longer effective in this region.


Assuntos
Antibacterianos/farmacologia , Helicobacter pylori/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amoxicilina/farmacologia , Chile , Claritromicina/farmacologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Farmacorresistência Bacteriana Múltipla , Feminino , Infecções por Helicobacter/microbiologia , Humanos , Levofloxacino/farmacologia , Masculino , Metronidazol/farmacologia , Pessoa de Meia-Idade , Vigilância da População , Tetraciclina/farmacologia , Adulto Jovem
9.
J Ovarian Res ; 12(1): 107, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703731

RESUMO

BACKGROUND: Cisplatin-based chemotherapy is the first-line treatment for ovarian cancer. However, acquired resistance to cisplatin treatment often occurs in epithelial ovarian cancer, and effective and practical methods for overcoming this obstacle are urgently needed. The study aimed to demonstrate the synergistic effect of clarithromycin (CAM) with cisplatin to inhibit ovarian carcinoma cells growth in vitro and in vivo. RESULTS: We performed CCK-8 assay to detect apoptosis rates in response to CAM alone or in combination with cisplatin, which were further confirmed by Annexin V and PI staining methods and western blotting. Mechanistically, CAM could reduce endogenous antioxidant enzyme expression and increase the levels of reactive oxygen species (ROS) to augment the cytotoxic effect of cisplatin. Meanwhile, a tumor xenograft model in athymic BALB/c-nude mice demonstrated that CAM combined with cisplatin resulted in reduced tumor growth and weight compared with cisplatin alone. CONCLUSION: Collectively, our results indicate that CAM works synergistically with cisplatin to inhibit ovarian cancer cell growth, which may be manipulated by a ROS-mediated mechanism that enhances cisplatin therapy, and offers a novel strategy for overcoming cisplatin therapy resistance.


Assuntos
Cisplatino/farmacologia , Claritromicina/farmacologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Feminino , Humanos , Camundongos , Neoplasias Ovarianas , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Rev Med Suisse ; 15(667): 1854-1858, 2019 Oct 16.
Artigo em Francês | MEDLINE | ID: mdl-31617972

RESUMO

Helicobacter pylori infection is associated with chronic gastric inflammation, peptic ulcer and an increased risk of gastric cancer. Helicobacter eradication traditionally consists of an empirical therapy combining clarithromycine, amoxicillin and proton pump inhibitors. However, this classic therapy needs to be reassessed because of the raising prevalence of clarithromycine resistance. Various alternative eradication treatments have been studied. This article aims to review the recommended alternatives and the different factors to guide the most appropriate first line eradication therapy.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Amoxicilina/farmacologia , Amoxicilina/uso terapêutico , Antibacterianos/farmacologia , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Quimioterapia Combinada , Humanos , Inibidores da Bomba de Prótons/farmacologia , Inibidores da Bomba de Prótons/uso terapêutico
11.
Molecules ; 24(19)2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591315

RESUMO

Helicobacter pylori infection is a WHO class 1 carcinogenic factor of gastric adenocarcinoma. In the past decades, many studies have demonstrated the increasing trend of antibiotic resistance and pointed out the necessity of new effective treatment. This study was aimed at identifying phytochemicals that can inhibit H. pylori and possibly serve as adjuvant treatments. Here, in silico molecular docking and drug-like properties analyses were performed to identify potential inhibitors of urease, shikimate kinase and aspartate-semialdehyde dehydrogenase. These three enzymes are targets of the treatment of H. pylori. Susceptibility and synergistic testing were performed on the selected phytochemicals and the positive control antibiotic, amoxicillin. The in-silico study revealed that oroxindin, rosmarinic acid and verbascoside are inhibitors of urease, shikimate kinase and aspartate-semialdehyde dehydrogenase, respectively, in which, oroxindin has the highest potency against H. pylori, indicated by a minimum inhibitory concentration (MIC) value of 50 µg/mL. A combination of oroxindin and amoxicillin demonstrated additive effects against H. pylori, as indicated by a fractional inhibitory concentration (FIC) value of 0.75. This study identified phytochemicals that deserve further investigation for the development of adjuvant therapeutic agents to current antibiotics against H. pylori.


Assuntos
Amoxicilina/farmacologia , Antibacterianos/farmacologia , Helicobacter pylori/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Antibacterianos/química , Aspartato-Semialdeído Desidrogenase/antagonistas & inibidores , Cromonas/química , Cromonas/farmacologia , Cinamatos/química , Cinamatos/farmacologia , Claritromicina/farmacologia , Simulação por Computador , Depsídeos/química , Depsídeos/farmacologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Glucosídeos/química , Glucosídeos/farmacologia , Glucuronatos/química , Glucuronatos/farmacologia , Simulação de Acoplamento Molecular , Fenóis/química , Fenóis/farmacologia , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Compostos Fitoquímicos/química , Urease/antagonistas & inibidores
12.
Pak J Pharm Sci ; 32(3 Special): 1321-1326, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31551210

RESUMO

The aim of the study was to compare the effects of three treatment regimens for H. pylori in patients sensitive to clarithromycin and analyze the polymorphism of 23S rRNA gene between patients who were sensitive or resistant to clarithromycin in a Chinese Han population. 204 H. pylori sensitive cases and 45 H. pylori resistant Han patients were selected as subjects of the research. All H. pylori sensitive cases were divided into three groups based on their different therapies. The polymerase chain reaction-ligase detection reaction (PCR) was used to identify the genotype at the A2143G of the 23S rRNA gene. SPSS18.0 software was applied to analyze the data statistically. The success rate of H. pylori eradication in the TTP (TT + probiotic) group was higher when compared with the triple therapy (TT) group, and the difference was statistically significant. The incidence of abdominal pain, headache and diarrhea in TTP group was significantly lower than that in the TT group and the TTB (TT+ bismuth) group. Moreover, patients in the TTP group suffered less taste impairment than patients in the other two groups. In addition, there was significant difference in genotype frequency distribution between the clarithromycin-resistant group and the clarithromycin-sensitive group. It was suggested in the results of Chinese Han population that the TTP regimen was significantly superior to the other two regimens in the treatment of clarithromycin-sensitive H.PYLORI infection. In addition, potential genotypic differences between clarithromycin-sensitive and drug-resistant patients provided a theoretical basis for gene therapy in patients with clarithromycin resistance.


Assuntos
Antibacterianos/farmacologia , Bismuto/farmacologia , Claritromicina/farmacologia , Farmacorresistência Bacteriana/genética , Infecções por Helicobacter/tratamento farmacológico , Probióticos/uso terapêutico , Adulto , Idoso , Amoxicilina/farmacologia , Antibacterianos/efeitos adversos , Grupo com Ancestrais do Continente Asiático/genética , Bismuto/efeitos adversos , Claritromicina/efeitos adversos , Esomeprazol/uso terapêutico , Feminino , Frequência do Gene , Infecções por Helicobacter/genética , Helicobacter pylori/patogenicidade , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , RNA Ribossômico 23S/genética , Resultado do Tratamento
13.
Biomedica ; 39(Supl. 2): 117-129, 2019 08 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31529839

RESUMO

Introduction: Clarithromycin is the first-line antibiotic for the treatment of Helicobacter pylori infection. Bacterial resistance is mainly due to the presence of specific mutations in the 23S ribosomal RNA (rRNA) gene. Objective: To determine the frequency of A2143G and A2142G specific mutations in the 23S rRNA gene associated with clarithromycin resistance of H. pylori in samples from patients with dyspeptic manifestations in Medellín, northwestern Colombia. Materials and methods: DNA was extracted from gastric biopsy samples of patients with dyspeptic manifestations seen at an endoscopy unit in Medellín between 2016 and 2017. PCR was performed to amplify the bacterial s and m vacA regions, and a region in the 23S rRNA gene. The presence of the A2142G and A2143G mutations was determined using the restriction fragment length polymorphism (RFLP) technique with the BbsI and BsaI enzymes, respectively. Results: The prevalence of infection was 44.2% (175/396), according to the histopathology report. The positive samples were analyzed and the three regions of the bacterial genome were amplified in 143 of the 175 samples. The A2143G and A2142G mutations were identified in 27 samples (18.8%, 27/143). The most frequent mutation was A2143G (81.5%, 22/27). Conclusions: We found a high prevalence of H. pylori mutations associated with clarithromycin resistance in the study population. Further studies are required to determine the bacterial resistance in the Colombian population in order to define first line and rescue treatments.


Assuntos
Antibacterianos/farmacologia , Claritromicina/farmacologia , Farmacorresistência Bacteriana/genética , Genes Bacterianos , Genes de RNAr , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Mutação de Sentido Incorreto , Mutação Puntual , RNA Bacteriano/genética , RNA Ribossômico 23S/genética , Adulto , Idoso , Colômbia/epidemiologia , Estudos Transversais , Dispepsia/epidemiologia , Dispepsia/microbiologia , Feminino , Gastrite/epidemiologia , Gastrite/microbiologia , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
14.
Biomedica ; 39(s1): 125-134, 2019 05 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31529855

RESUMO

Introduction: The main cause for Helicobacter pylori infection treatment failure is antibiotic resistance, where clarithromycin and metronidazole play the main role. In Colombia, primary resistance as a consequence of the use of these two antibiotics and excessive levofloxacin use is above the accepted limit (13.6%, 83%, and 16%, respectively). Despite this fact, empirical therapies that include the combination of these antibiotics are used in patients with previous therapeutic failure. Objective: To determine antibiotic resistance in patients previously treated for H. pylori in Bogotá, Colombia. Materials and methods: We conducted a descriptive study that included ten isolates obtained from five patients with three or four previous failed treatments for H. pylori. Antibiotic resistance to amoxicillin, clarithromycin, levofloxacin, and metronidazole was investigated by agar dilution and confirmed by DNA sequencing (Magrogen, Korea). Results: Eight isolates were resistant to two or more antibiotics. All isolates were resistant to levofloxacin. Susceptibility patterns in isolates from the gastric antrum and the body of the stomach were different in three patients. Conclusion: As far as we know, this is the first evidence of multiple H. pylori resistance in Colombia in previously treated patients. Results demonstrated the consequences of using an ineffective antibiotic scheme and the need to assess antibiotic susceptibility in different anatomical sites of the stomach. The consequences of multiple resistance decrease possible antibiotic effectiveness to eradicate H. pylori in the future.


Assuntos
Farmacorresistência Bacteriana Múltipla , Gastrite/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Adulto , Idoso , Amoxicilina/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biópsia , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Colômbia/epidemiologia , DNA Bacteriano/genética , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Gastrite/epidemiologia , Gastroscopia , Genes Bacterianos , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Masculino , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade
15.
Helicobacter ; 24(6): e12660, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31507036

RESUMO

BACKGROUND: Antimicrobial resistance of Helicobacter pylori (H pylori) affects the efficacy of eradication therapy. The aim of this study was to estimate the prevalence of primary and secondary resistance of H pylori isolates to antibiotics in Korea. METHODS: The present study was performed from 2003 to 2018. Primary resistance was evaluated in 591 patients without any history of eradication and secondary resistance in 149 patients from whom Helicobacter pylori was cultured after failure of eradication. A minimal inhibitory concentration test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and rifabutin using the agar dilution method. RESULTS: An increase in the primary resistance rate was found in clarithromycin (P < .001), metronidazole (P < .001), and both levofloxacin (P < .001) during the study period. The primary resistance rates of amoxicillin and tetracycline were low and stable during the study period. The secondary resistance rate significantly increased in metronidazole and levofloxacin (P = .022 and .039, respectively). CONCLUSIONS: The primary and secondary resistance rates of clarithromycin, metronidazole, and levofloxacin for Helicobacter pylori in Korea were high and increased over time. However, the primary and secondary resistance rates of amoxicillin and tetracycline were low and stable over time. These results will help in selecting effective eradication regimens of H pylori in Korea in the future.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Adulto , Idoso , Amoxicilina/farmacologia , Claritromicina/farmacologia , Feminino , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/classificação , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Levofloxacino/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , República da Coreia , Adulto Jovem
16.
Chem Pharm Bull (Tokyo) ; 67(8): 810-815, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366830

RESUMO

Helicobacter pylori (H. pylori) infection is common and can result in gastric and duodenal ulcers, and in some cases, gastric lymphoma and cancer. Omeprazole (OMP)-in combination with clarithromycin (CLR), amoxicillin (AMX), tinidazole (TND), or metronidazole (MET)-is used in double or triple combination therapy for eradication of H. pylori. However, the roles of the drugs other than OMP are not clearly understood. Therefore, in the present study, we aimed to investigate any effects of these drugs on OMP metabolism by wild-type CYP2C19 using spectroscopy and enzyme kinetics. The dissociation constants (Kd) for CYP2C19 with OMP, CLR, AMX, TND, and MET were 8.6, 126, 156, 174, and 249 µM, respectively. The intrinsic clearance of OMP was determined to be 355 mL/min/µmol of CYP2C19. Metabolism of OMP was significantly inhibited by 69, 66, 28, and 40% in the presence of CLR, TND, AMX, and MET, respectively. Moreover, the combination of CLR and TND resulted in 76% inhibition of OMP metabolism, while the combination of AMX and MET resulted in 48% inhibition of OMP metabolism. Both combinations of drugs not only have antibacterial effects, but also enhance the effect of OMP by inhibiting its metabolism by CYP2C19. These results indicate that drug-drug interactions of co-administered drugs can cause complex effects, providing a basis for OMP dose adjustment when used in combination therapy for H. pylori eradication.


Assuntos
Antibacterianos/farmacologia , Citocromo P-450 CYP2C19/metabolismo , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Omeprazol/farmacologia , Amoxicilina/química , Amoxicilina/farmacologia , Antibacterianos/química , Antibacterianos/metabolismo , Cromatografia Líquida de Alta Pressão , Claritromicina/química , Claritromicina/farmacologia , Citocromo P-450 CYP2C19/química , Combinação de Medicamentos , Humanos , Metronidazol/química , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Omeprazol/antagonistas & inibidores , Omeprazol/metabolismo , Tinidazol/química , Tinidazol/farmacologia
17.
Pathog Dis ; 77(4)2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374569

RESUMO

Clarithromycin resistance is the most common cause of Helicobacter pylori treatment failure and it is attributed to three point mutations, A2142G, A2142C and A2143G, within the 23S rRNA gene. We aimed to determine the prevalence of H. pylori clarithromycin resistance using a novel high resolution melt assay. A total of 151 stool samples were collected from treatment-naïve patients with general gastric discomfort who also performed 13CO2 breath tests. Stool antigen tests were also performed on 126 of the 151 stool samples collected. Bacterial DNA was extracted from the stool and analyzed by comparing it with four reference plasmids incorporating the three mutations and the wild type (WT) sequences. The melt assay detected 106 H. pylori positive samples, of which 54 had a WT sequence, and 52 had a point mutation associated with clarithromycin resistance, including A2142G in 10, A2142C in 13, A2143G in 18 and heterozygosity (multiple peaks) in 11. Compared with the gold standards (13CO2 breath and stool antigen tests), the melt assay had a sensitivity of 100% and 99% and a specificity of 82% and 78%, respectively. Therefore, our stool-based molecular assay is able to identify H. pylori infection and clarithromycin resistance. It could be used for screening prior to administration of clarithromycin eradication therapy.


Assuntos
Antibacterianos/farmacologia , Claritromicina/farmacologia , Farmacorresistência Bacteriana , Técnicas de Genotipagem/métodos , Helicobacter pylori/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Reação em Cadeia da Polimerase/métodos , Adolescente , Adulto , Criança , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , DNA Ribossômico/genética , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Humanos , Pessoa de Meia-Idade , Mutação Puntual , RNA Ribossômico 23S/genética , Sensibilidade e Especificidade , Temperatura de Transição , Adulto Jovem
18.
Infect Immun ; 87(10)2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31331959

RESUMO

The soil-dwelling, saprophytic actinomycete Rhodococcus equi is a facultative intracellular pathogen of macrophages and causes severe bronchopneumonia when inhaled by susceptible foals. Standard treatment for R. equi disease is dual-antimicrobial therapy with a macrolide and rifampin. Thoracic ultrasonography and early treatment with antimicrobials prior to the development of clinical signs are used as means of controlling endemic R. equi infection on many farms. Concurrently with the increased use of macrolides and rifampin for chemoprophylaxis and the treatment of subclinically affected foals, a significant increase in the incidence of macrolide- and rifampin-resistant R. equi isolates has been documented. Previously, our laboratory demonstrated decreased fitness of R. equi strains that were resistant to macrolides, rifampin, or both, resulting in impaired in vitro growth in iron-restricted media and in soil. The objective of this study was to examine the effect of macrolide and/or rifampin resistance on intracellular replication of R. equi in equine pulmonary macrophages and in an in vivo mouse infection model in the presence and absence of antibiotics. In equine macrophages, the macrolide-resistant strain did not increase in bacterial numbers over time and the dual macrolide- and rifampin-resistant strain exhibited decreased proliferation compared to the susceptible isolate. In the mouse model, in the absence of antibiotics, the susceptible R. equi isolate outcompeted the macrolide- or rifampin-resistant strains.


Assuntos
Infecções por Actinomycetales/tratamento farmacológico , Antibacterianos/farmacologia , Claritromicina/farmacologia , Macrófagos Alveolares/microbiologia , Rhodococcus equi/efeitos dos fármacos , Rifampina/farmacologia , Infecções por Actinomycetales/imunologia , Infecções por Actinomycetales/microbiologia , Animais , Contagem de Colônia Microbiana , Farmacorresistência Bacteriana , Aptidão Genética/efeitos dos fármacos , Aptidão Genética/fisiologia , Cavalos , Fígado/efeitos dos fármacos , Fígado/microbiologia , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Macrófagos Alveolares/efeitos dos fármacos , Masculino , Camundongos , Camundongos Nus , Testes de Sensibilidade Microbiana , Cultura Primária de Células , Rhodococcus equi/fisiologia , Baço/efeitos dos fármacos , Baço/microbiologia
19.
World J Gastroenterol ; 25(25): 3183-3195, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31333310

RESUMO

Helicobacter pylori (H. pylori) is the causative agent of gastritis, peptic ulcer disease, mucosa associated lymphoid tissue lymphoma and gastric cancer (GC). While this bacterium infects 50% of the world's population, in Africa its prevalence reach as high as 80% as the infection is acquired during childhood. Risk factors for H. pylori acquisition have been reported to be mainly due to overcrowding, to have infected siblings or parent and to unsafe water sources. Despite this high H. pylori prevalence there still does not exist an African guideline, equivalent to the Maastricht V/Florence Consensus Report of the European Helicobacter and Microbiota Study Group for the management of this infection. In this continent, although there is a paucity of epidemiologic data, a contrast between the high prevalence of H. pylori infection and the low incidence of GC has been reported. This phenomenon is the so-called "African Enigma" and it has been hypothesized that it could be explained by environmental, dietary and genetic factors. A heterogeneity of data both on diagnosis and on therapy have been published. In this context, it is evident that in several African countries the increasing rate of bacterial resistance, mainly to metronidazole and clarithromycin, requires continental guidelines to recommend the appropriate management of H. pylori. The aim of this manuscript is to review current literature on H. pylori infection in Africa, in terms of prevalence, risk factors, impact on human health, treatment and challenges encountered so as to proffer possible solutions to reduce H. pylori transmission in this continent.


Assuntos
Antibacterianos/farmacologia , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/patogenicidade , Neoplasias Gástricas/epidemiologia , África/epidemiologia , Antibacterianos/uso terapêutico , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Gastroenterologia/normas , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Humanos , Incidência , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Guias de Prática Clínica como Assunto , Prevalência , Fatores de Risco , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/prevenção & controle
20.
Helicobacter ; 24(5): e12633, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31295754

RESUMO

BACKGROUND: Antimicrobial resistance of Helicobacter pylori reduces the eradication rate. This study aimed to investigate changes in antimicrobial susceptibility of H pylori isolated from children in Taiwan in the past two decades. METHODS: This study enrolled children receiving esophagogastroduodenoscopy for upper gastrointestinal diseases in a national tertiary referring hospital from 1998 to 2018. H pylori infection was diagnosed by culture. The minimal inhibitory concentrations (MICs) of antibiotics were tested using the E test. The antibiotic resistance rates and MICs of amoxicillin, clarithromycin, metronidazole, levofloxacin, and tetracycline were compared between 1998-2008 and 2009-2018. RESULTS: A total of 70 Helicobacter pylori isolates (29 from 1998 to 2008 and 41 from 2009 to 2018) were identified. The esophagogastroduodenoscopy findings included duodenal ulcers (n = 31), gastric ulcers (n = 9), and gastritis (n = 30). The overall antimicrobial resistance rates of clarithromycin and metronidazole were 22.9% and 21.4%, respectively. The dual resistance rate of clarithromycin and metronidazole was 10%. Resistance rates of levofloxacin and amoxicillin were 8.3% and 2.9%, respectively. None of the isolates were resistant to tetracycline. Compared with the isolates from 1998 to 2008, those from 2009 to 2018 had higher MICs and resistance rates of clarithromycin (26.8% vs 17.2%, P = 0.35) and metronidazole (26.8% vs 13.8%, P = 0.19), but not levofloxacin (9.8% vs 5.3%, P = 1.0) or coresistance to clarithromycin and metronidazole (12.2% vs 6.9%, P = 0.69). CONCLUSIONS: The antimicrobial resistance rates of pediatric H pylori isolates to clarithromycin and metronidazole increased during the past decade. The selection of antimicrobial agents other than clarithromycin and metronidazole is crucial to increase pediatric H pylori eradication rates.


Assuntos
Antibacterianos/farmacologia , Claritromicina/farmacologia , Farmacorresistência Bacteriana , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Metronidazol/farmacologia , Adolescente , Criança , Pré-Escolar , Feminino , Helicobacter pylori/isolamento & purificação , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Prevalência , Estudos Retrospectivos , Taiwan/epidemiologia , Centros de Atenção Terciária
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