Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.894
Filtrar
1.
Helicobacter ; 26(6): e12855, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34628694

RESUMO

BACKGROUND AND OBJECTIVES: The present study describes the successful adaptation of an in-house Polymerase Chain Reaction (PCR) for Helicobacter pylori detection coupled with the main mutations associated with resistance to clarithromycin in ready-to-use PCR microwell strips. MATERIALS AND METHODS: These microwell strips can be used on LightCycler® 480, and are delivered with nine microliters of the reaction mixture dispensed into 8-well microwell strips. An extraction control PCR targeting the ß-globin household gene is amplified in the same run as H pylori detection. RESULTS AND CONCLUSION: These microwell strips can be stored at -20°C for 1 year and left at room temperature and in the light for up to 4 h with no impact on the PCR results. Microwell strips can also undergo a thaw and refreeze cycle without impacting the PCR results. These PCR microwell strips are available for purchase from Eurogentec.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Antibacterianos/farmacologia , Claritromicina/farmacologia , Farmacorresistência Bacteriana/genética , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/genética , Humanos , Macrolídeos/farmacologia , Testes de Sensibilidade Microbiana , Mutação , Reação em Cadeia da Polimerase , RNA Ribossômico 23S
2.
PLoS One ; 16(10): e0258694, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34648603

RESUMO

OBJECTIVES: Macrolides are generally considered to be the drugs of choice for treatment of patients with Mycoplasma pneumoniae infection. However, macrolide-resistant M. pneumoniae has been emerging since about 2000. The Smart Gene® system (MIZUHO MEDY Co., Ltd., Tosu, Japan) is a novel fully automated system for detection of pathogens using the method of quantitative polymerase chain reaction (qPCR) with QProbe (QProbe PCR). The entire procedure is completed within 50 min and the size of the instrument is small (15 x 34 x 30 cm). The purpose of this study was to evaluate the usefulness of the Smart Gene® system for detection of M. pneumoniae and detection of a point mutation at domain V of the 23S rRNA gene of M. pneumoniae. MATERIALS: Pharyngeal swab samples were collected from 154 patients who were suspected of having respiratory tract infections associated with M. pneumoniae. RESULTS: Compared with the results of qPCR, the sensitivity and specificity of the Smart Gene® system were 98.7% (78/79) and 100.0% (75/75), respectively. A point mutation at domain V of the 23S rRNA gene was detected from 7 (9.0%) of 78 M. pneumoniae-positive samples by the Smart Gene® system and these results were confirmed by direct sequencing. The minimum inhibitory concentrations of clarithromycin among the 5 isolates of M. pneumoniae with a point mutation at domain V of the 23S rRNA gene were >64 µg/ml and those among the 33 isolates without a mutation in the 23S rRNA gene were <0.0625 µg/ml. CONCLUSION: The Smart Gene® system is a rapid and accurate assay for detection of the existence of M. pneumoniae and a point mutation at domain V of the 23S rRNA gene of M. pneumoniae at the same time. The Smart Gene® system is suitable for point-of-care testing in both hospital and outpatient settings.


Assuntos
Claritromicina/farmacologia , Mycoplasma pneumoniae/isolamento & purificação , Pneumonia por Mycoplasma/diagnóstico , Mutação Puntual , RNA Ribossômico 23S/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , DNA Bacteriano/genética , DNA Ribossômico/genética , Feminino , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Pessoa de Meia-Idade , Mycoplasma pneumoniae/efeitos dos fármacos , Mycoplasma pneumoniae/genética , Faringe/microbiologia , Testes Imediatos , Kit de Reagentes para Diagnóstico , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Adulto Jovem
3.
Clin Lab ; 67(10)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34655183

RESUMO

BACKGROUND: Spontaneous point mutations in genes encoding gyrA/B subunits of DNA gyrase are responsible for fluoroquinolone resistance. We aimed to determine the clarithromycin and levofloxacin resistance phenotypically in H. pylori strains and to investigate the mutations responsible for levofloxacin resistance and the effects of these mutations on dual antibiotic resistance. METHODS: A total of 65 H. pylori isolates were included. The E-test method was used for the clarithromycin and le-vofloxacin antimicrobial susceptibility test. Real-time PCR was used to detect the point mutations. RESULTS: Twenty-four (36.9%) of 65 H. pylori strains were phenotypically resistant to clarithromycin and 14 (21.5%) to levofloxacin. The phenotypic levofloxacin resistance rate of strains with Asn87Lys and Asp91Asn mutations were significantly higher (gyrA gene) (p < 0.05). The phenotypic levofloxacin resistance rate of strains with Arg484Lys and Asp481Glu mutations were significantly higher (gyrB gene) (p < 0.05). The Asn87Lys mutation increased the risk of phenotypes being resistant to levofloxacin 70.156 times and Asp91Asn mutation increased 125,427 times higher. Seven (10.8%) of 65 H. pylori strains showed dual resistance to both levofloxacin and clarithromycin. The rate of being dual resistant with A2143G mutation (clarithromycin resistance) was found to be significantly higher (p < 0.05). CONCLUSIONS: The Asn87Lys and Asp91Asn mutations in the gyrA gene had a phenotypically enhancing effect on levofloxacin resistance, while the presence of Asp481Glu and Arg484Lys mutations in the gyrB gene did not. The existence of dual resistance was developed with the increase in clarithromycin and levofloxacin resistance rates.


Assuntos
Proteínas de Bactérias/genética , Claritromicina , DNA Girase/genética , Farmacorresistência Bacteriana , Helicobacter pylori , Antibacterianos/farmacologia , Claritromicina/farmacologia , Farmacorresistência Bacteriana/genética , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Humanos , Levofloxacino/farmacologia , Testes de Sensibilidade Microbiana , Mutação Puntual
4.
Trop Biomed ; 38(3): 343-352, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34508342

RESUMO

Outbreak of SARS-CoV-2 has been declared a pandemic, which is a serious threat to human health. The disease was named coronavirus disease 2019 (COVID-19). Until now, several vaccines and a few drugs have been approved for the prevention and treatment for COVID-19. Recently, the effect of some macrolides including clarithromycin (CAM) on COVID-19 has attracted attention. CAM is known to have diverse effects including immunomodulatory and immunosuppressive effects, autophagy inhibition, steroid sparing effect, reversibility of drug resistance, antineoplastic effect, antiviral effect as well as bacteriostatic/bactericidal effect. Many patients with COVID-19 died due to an overwhelming response of their own immune system characterized by the uncontrolled release of circulating inflammatory cytokines (cytokine release syndrome [CRS]). This CRS plays a major role in progressing pneumonia to acute respiratory distress syndrome (ARDS) in COVID-19 patients. It is noteworthy that CAM can suppress inflammatory cytokines responsible for CRS and also has anti-SARS-CoV-2 effect. Considering the rapidly progressive global disease burden of COVID 19, the application of CAM for treating COVID-19 needs to be urgently evaluated. Recently, an open-labeled non-randomized trial using CAM for treating COVID-19 (ACHIEVE) was initiated in Greece in May, 2020. Its results, though preprint, indicated that CAM treatment of patients with moderate COVID-19 was associated with early clinical improvement and containment of viral load. Thus, treatment with CAM as a single agent or combined with other anti-SARS CoV-2 drugs should be tried for treating COVID-19. In this article, we discussed the significance and usefulness of CAM in treating COVID-19.


Assuntos
COVID-19/tratamento farmacológico , Claritromicina/uso terapêutico , Reposicionamento de Medicamentos , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2/metabolismo , Azitromicina/uso terapêutico , Claritromicina/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Fatores Imunológicos/farmacologia , SARS-CoV-2/efeitos dos fármacos
5.
Arab J Gastroenterol ; 22(3): 224-228, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34531132

RESUMO

BACKGROUND AND STUDY AIM: Peptic ulcer is one of the most serious diseases in Egypt, affecting more than one-third of the population. Helicobacter pylori is the main organism responsible for peptic ulcer formation. These ulcers can lead to chronic active gastritis and lymphoma. As such, in this study, we evaluate the efficacy of Pelargonium graveolens oil for the treatment of H pylori, as well as its synergistic effects with the antibiotic clarithromycin (CLR). PATIENTS AND METHODS: We evaluated the chemical composition of P. graveolens volatile oil as well as its anti-Helicobacter activities. We assessed the volatile oil components using gas chromatography coupled with mass spectrometry. We determined anti-H. pylori potential using a micro-well dilution method. RESULTS: We identified 92 compounds from the oil. Citronellol, geraniol, citronellyl formate, and isolongifolan-7-α-ol were the predominant components (15.64%, 11.31%, 10.19%, and 7.84%, respectively). The oil exhibited a good activity against H. pylori at an minimal inhibitory concentration of 15.63 µg/ml. Once we combined the volatile oil with CLR, a significant synergistic effect appeared at an fractional inhibitory concentration index of 0.38 µg/ml. CONCLUSION: The in-vitro interaction between the P. graveolens oil and CLR improved the antimicrobial activity of the latter, suggesting that further studies are needed to determine formulations for potential antimicrobial applications in food and pharmaceuticals.


Assuntos
Helicobacter pylori , Óleos Voláteis , Pelargonium , Claritromicina/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Óleos Voláteis/farmacologia
6.
World J Gastroenterol ; 27(24): 3595-3608, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34239272

RESUMO

BACKGROUND: The drug resistance rate of clinical Helicobacter pylori (H. pylori) isolates has increased. However, the mechanism of drug resistance remains unclear. In this study, drug-resistant H. pylori strains were isolated from different areas and different populations of Chinese for genomic analysis. AIM: To investigate drug-resistant genes in H. pylori and find the genes for the early diagnosis of clarithromycin resistance. METHODS: Three drug-resistant H. pylori strains were isolated from patients with gastritis in Bama County, China. Minimal inhibitory concentrations of clarithromycin, metronidazole, and levofloxacin were determined and complete genome sequencing was performed with annotation. Hp1181 and hp1184 genes were found in these strains and then detected by reverse transcription polymerase chain reaction. The relationships between hp1181 or hp1184 and clarithromycin resistance were ascertained with gene mutant and drug-resistant strains. The homology of the strains with hp26695 was assessed through complete genome detection and identification. Differences in genome sequences, gene quantity, and gene characteristics were detected amongst the three strains. Prediction and analysis of the function of drug-resistant genes indicated that the RNA expression of hp1181 and hp1184 increased in the three strains, which was the same in the artificially induced clarithromycin-resistant bacteria. After gene knockout, the drug sensitivity of the strains was assessed. RESULTS: The strains showing a high degree of homology with hp26695, hp1181, and hp1184 genes were found in these strains; the expression of the genes hp1184 and hp1181 was associated with clarithromycin resistance. CONCLUSION: Hp1181 and hp1184 mutations may be the earliest and most persistent response to clarithromycin resistance, and they may be the potential target genes for the diagnosis, prevention, and treatment of clarithromycin resistance.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , China/epidemiologia , Claritromicina/farmacologia , Farmacorresistência Bacteriana/genética , Diagnóstico Precoce , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/genética , Humanos , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , RNA Ribossômico 23S
7.
Sci Rep ; 11(1): 13858, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226601

RESUMO

The disease caused by Enterococcus lacertideformus is multisystemic and ultimately fatal. Since its emergence, the bacterium has significantly impacted the captive breeding programs of the extinct in the wild Christmas Island Lister's gecko (Lepidodactylus listeri) and blue-tailed skink (Cryptoblepharus egeriae). The bacterium's pathogenicity, inability to grow in-vitro, and occurrence beyond the confines of Christmas Island necessitated the development of an experimental infection and treatment model. Asian house geckos (Hemidactylus frenatus) were challenged with a single dose of E. lacertideformus inoculum either by mouth, application to mucosal abrasion or skin laceration, subcutaneous injection, coelomic injection, or via co-housing with an infected gecko. Five healthy geckos acted as controls. Each transmission route resulted in disease in at least 40% (n = 2) geckos, expanding to 100% (n = 5) when E. lacertideformus was applied to skin laceration and mucosal abrasion groups. Incubation periods post-infection ranged between 54 and 102 days. To determine the efficacy of antibiotic treatment, infected geckos were divided into six groups (enrofloxacin 10 mg/kg, per os (PO), every 24 h (q24), amoxicillin-clavulanic acid 10 mg/kg, PO, q24, enrofloxacin 10 mg/kg combined with amoxicillin-clavulanic acid 10 mg/kg, PO, q24, rifampicin 15 mg/kg, PO, q24, clarithromycin 15 mg/kg, PO, q24, and untreated controls) for 21 days. Response to treatment was assessed by the change in lesion size, bacterial dissemination, and histological evidence of a host immune response. Irrespective of the antibiotic given, histology revealed that geckos inoculated by skin laceration were observed to have more extensive disease spread throughout the animal's body compared to other inoculation routes. The reduction in the average surface area of gross lesions was 83.6% for geckos treated with enrofloxacin, followed by the combination therapy amoxicillin-clavulanic acid and enrofloxacin (62.4%), amoxicillin-clavulanic acid (58.2%), rifampicin (45.5%), and clarithromycin (26.5%). Lesions in geckos untreated with antibiotics increased in size between 100 and 300%. In summary, enrofloxacin and amoxicillin-clavulanic acid show promising properties for the treatment of E. lacertideformus infection in geckos. The Asian house gecko E. lacertideformus infection model therefore provides foundational findings for the development of effective therapeutic treatment protocols aimed at conserving the health of infected and at-risk reptiles.


Assuntos
Antibacterianos/farmacologia , Infecções Bacterianas/microbiologia , Enterococcus/patogenicidade , Lagartos/microbiologia , Combinação Amoxicilina e Clavulanato de Potássio/farmacologia , Animais , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/transmissão , Claritromicina/farmacologia , Modelos Animais de Doenças , Enrofloxacina/farmacologia , Humanos
8.
Sci Rep ; 11(1): 12208, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108590

RESUMO

This study aimed to identify effective treatments against rapidly growing mycobacteria (RGM) infections by investigating the minimum inhibitory concentrations (MIC) of 24 antimicrobial agents and their molecular mechanisms of resistance. In total, 509 clinical RGM isolates were identified by analyzing the sequences of three housekeeping genes (hsp65, rpoB, and sodA), and their susceptibilities to 24 antimicrobial agents were tested. We also performed sequencing analysis of antimicrobial resistance genes (rrl, rrs, gyrA, and gyrB). To identify Mycobacteroides abscessus group subspecies, we performed PCR-based typing and determined the sequevar of erm(41). We identified 15 RGM species, most of which were susceptible to amikacin and linezolid. Among these species, arbekacin and sitafloxacin had the lowest MIC among the same class of antimicrobials. The MIC of rifabutin for M. abscessus subsp. abscessus (MAB) was lower than that for M. abscessus subsp. massiliense (MMA). The proportion of MAB isolates with MIC ≤ 2 mg/L for rifabutin was significantly higher than that of MMA [MAB: 50/178 (28.1%) vs. MMA: 23/130 (17.7%); p = 0.041]. In summary, our study revealed the antimicrobial susceptibility profile of 15 RGM species isolated in Japan and indicated that arbekacin, sitafloxacin, and rifabutin may be possible therapeutic options for RGM infections.


Assuntos
Amicacina/farmacologia , Antibacterianos/farmacologia , Claritromicina/farmacologia , Farmacorresistência Bacteriana , Linezolida/farmacologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Micobactérias não Tuberculosas/efeitos dos fármacos , Humanos , Japão/epidemiologia , Testes de Sensibilidade Microbiana , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas/genética , Micobactérias não Tuberculosas/crescimento & desenvolvimento , Micobactérias não Tuberculosas/isolamento & purificação
9.
Diagn Microbiol Infect Dis ; 101(2): 115447, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34192638

RESUMO

A 15-valent conjugate vaccine that provides protection against Streptococcus pneumoniae serotypes 22F and 33F is in development. Here we report on the prevalence, antimicrobial susceptibility, and clonal structure of these serotypes in Canada. From 2011 to 2018, the SAVE study collected 11,044 invasive S. pneumoniae isolates. Of these, 9.3% (1024/11,044) and 3.8% (416/11,044) were 22F and 33F, respectively. Serotype 22F isolates were susceptible to most antimicrobials tested except clarithromycin, where susceptibility significantly decreased over time (2011: 80.4%, 2018: 52.9%, P < 0.0001). Only 1.6% of serotype 22F isolates were multidrug-resistant (MDR), while 96% of typed strains were clonal cluster (CC) 433. Serotype 33F isolates demonstrated low susceptibility to clarithromycin and trimethoprim/sulfamethoxazole (22.4% and 24.6%, respectively) and 4.8% MDR. Most serotype 33F isolates were CC100, CC673 and CC717. CC100 prevalence increased significantly over time (2011: 50.0%, 2018: 84.8%, P < 0.006). Continued surveillance of these serotypes is crucial to identify further changes in prevalence, antimicrobial susceptibility, and clonal spread.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Infecções Pneumocócicas/epidemiologia , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Vacinas Conjugadas/imunologia , Adolescente , Adulto , Idoso , Canadá/epidemiologia , Criança , Pré-Escolar , Claritromicina/farmacologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/tratamento farmacológico , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/prevenção & controle , Sorogrupo , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação , Combinação Trimetoprima e Sulfametoxazol/farmacologia , Adulto Jovem
10.
J Clin Microbiol ; 59(8): e0045521, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-33980653

RESUMO

Mycobacterium abscessus is a rapidly growing nontuberculous mycobacterial species that comprises three subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii. These predominantly environmental microorganisms have emerged as life-threatening chronic pulmonary pathogens in both immunocompetent and immunocompromised patients, and their acquisition of macrolide resistance due to the erm(41) gene and mutations in the 23S rrl gene has dramatically impacted patient outcome. However, standard microbiology laboratories typically have limited diagnostic tools to distinguish M. abscessus subspecies, and the testing for macrolide resistance is often not done. Here, we describe the development of a real-time multiplex assay using molecular beacons to establish a robust, rapid, and highly accurate method to both distinguish M. abscessus subspecies and to determine which strains are susceptible to macrolides. We report a bioinformatic approach to identify robust subspecies sequence targets, the design and optimization of six molecular beacons to identify all genotypes, and the development and application of a 2-tube 3-color multiplex assay that can provide clinically significant treatment information in less than 3 h.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Claritromicina/farmacologia , Farmacorresistência Bacteriana/genética , Humanos , Macrolídeos/farmacologia , Testes de Sensibilidade Microbiana , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium abscessus/genética , Reação em Cadeia da Polimerase em Tempo Real
11.
Antimicrob Agents Chemother ; 65(8): e0273020, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-33972258

RESUMO

For Mycobacterium avium complex pulmonary disease (MAC-PD), current treatment regimens yield low cure rates. To obtain an evidence-based combination therapy, we assessed the in vitro activity of six drugs, namely, clarithromycin (CLR), rifampin (RIF), ethambutol (EMB), amikacin (AMK), clofazimine (CLO), and minocycline (MIN), alone and in combination, against Mycobacterium avium and studied the contributions of individual antibiotics to efficacy. The MICs of all antibiotics against M. avium ATCC 700898 were determined by broth microdilution. We performed kinetic time-kill assays of all single drugs and clinically relevant two-, three-, four-, and five-drug combinations against M. avium. Pharmacodynamic interactions of these combinations were assessed using area under the time-kill curve-derived effect size and Bliss independence. Adding a second drug yielded an average increase of the effect size (E) of 18.7% ± 32.9%, although antagonism was seen in some combinations. Adding a third drug showed a smaller increase in effect size (+12.2% ± 11.5%). The RIF-CLO-CLR (E of 102 log10 CFU/ml · day), RIF-AMK-CLR (E of 101 log10 CFU/ml · day), and AMK-MIN-EMB (E of 97.8 log10 CFU/ml · day) regimens proved more active than the recommended RIF-EMB-CLR regimen (E of 89.1 log10 CFU/ml · day). The addition of a fourth drug had little impact on effect size (+4.54% ± 3.08%). In vitro, several two- and three-drug regimens are as effective as the currently recommended regimen for MAC-PD. Adding a fourth drug to any regimen had little additional effect. In vitro, the most promising regimen would be RIF-AMK-macrolide or RIF-CLO-macrolide.


Assuntos
Complexo Mycobacterium avium , Infecção por Mycobacterium avium-intracellulare , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Quimioterapia Combinada , Etambutol/farmacologia , Etambutol/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico
12.
J Med Microbiol ; 70(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33999797

RESUMO

Introduction. Mycobacterium avium complex (MAC) has been reported as the most common aetiology of lung disease involving nontuberculous mycobacteria.Hypothesis. Antimicrobial susceptibility and clinical characteristics may differ between Mycobacterium avium and Mycobacterium intracellulare.Aim. We aimed to evaluate the differences in antimicrobial susceptibility profiles between two major MAC species (Mycobacterium avium and Mycobacterium intracellulare) from patients with pulmonary infections and to provide epidemiologic data with minimum inhibitory concentration (MIC) distributions.Methodology. Between January 2019 and May 2020, 45 M. avium and 242 M. intracellulare isolates were obtained from Shanghai Pulmonary Hospital. The demographic and clinical characteristics of patients were obtained from their medical records. The MICs of 13 antimicrobials were determined for the MAC isolates using commercial Sensititre SLOWMYCO MIC plates and the broth microdilution method, as recommended by the Clinical and Laboratory Standards Institute (CLSI; Standards M24-A2). MIC50 and MIC90 values were derived from the MIC distributions.Results. M. intracellulare had higher resistance rates than M. avium for most tested antimicrobials except clarithromycin, ethambutol, and ciprofloxacin. Clarithromycin was the most effective antimicrobial against both the M. avium (88.89 %) and M. intracellulare (91.32 %) isolates, with no significant difference between the species (P=0.601). The MIC90 of clarithromycin was higher for M. avium (32 µg ml-1) than M. intracellulare (8 µg ml-1). The MIC50 of rifabutin was more than four times higher for M. intracellulare (1 µg ml-1) than M. avium (≤0.25 µg ml-1). The percentages of patients aged >60 years and patients with sputum, cough, and cavitary lesions were significantly higher than among patients with M. intracellulare infection than M. avium infections.Conclusions. The pulmonary disease caused by distinct MAC species had different antimicrobial susceptibility, symptoms, and radiographic findings.


Assuntos
Antibacterianos/farmacologia , Pneumopatias/microbiologia , Complexo Mycobacterium avium/efeitos dos fármacos , Infecção por Mycobacterium avium-intracellulare/microbiologia , Mycobacterium avium/efeitos dos fármacos , Adulto , Idoso , China , Ciprofloxacina/farmacologia , Claritromicina/farmacologia , Tosse , Doxiciclina/farmacologia , Farmacorresistência Bacteriana , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pneumopatias/fisiopatologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium avium/isolamento & purificação , Complexo Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Infecção por Mycobacterium avium-intracellulare/fisiopatologia , Radiografia , Escarro
13.
Bioorg Med Chem Lett ; 43: 128110, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33991629

RESUMO

A novel series of 3-O-descladinosyl-3-keto-clarithromycin derivatives, including 11-O-carbamoyl-3-O-descladinosyl-3-keto-clarithromycin derivatives and 2',9(S)-diaryl-3-O-descladinosyl-3-keto-clarithromycin derivatives, were designed, synthesized and evaluated for their in vitro antibacterial activity. Among them, some derivatives were found to have activity against resistant bacteria strains. In particular, compound 9b showed not only the most significantly improved activity (16 µg/mL) against S. aureus ATCC43300 and S. aureus ATCC31007, which was >16-fold more active than that of CAM and AZM, but also the best activity against S. pneumoniae B1 and S. pyogenes R1, with MIC values of 32 and 32 µg/mL. In addition, compounds 9a, 9c, 9d and 9g exhibited the most effective activity against S. pneumoniae AB11 with MIC values of 32 or 64 µg/mL as well. Unfortunately, 2',9(S)-diaryl-3-O-descladinosyl-3-keto-clarithromycin derivatives failed to exhibit better antibacterial activity than references. It can be seen that the combined modification of the C-3 and C-11 positions of clarithromycin is beneficial to improve activity against resistant bacteria, while the single modification of the C-2'' position is very detrimental to antibacterial activity.


Assuntos
Antibacterianos/farmacologia , Claritromicina/farmacologia , Staphylococcus/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Claritromicina/síntese química , Claritromicina/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
14.
Bioorg Chem ; 113: 104992, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34051415

RESUMO

Bacterial infections are still the main significant problem of public health in the world, and their elimination will greatly rely on the discovery of antibacterial drugs. In the processes of our searching for novel macrolide derivatives with excellent activity against sensitive and resistant bacteria, three series of novel N11-, C12- and C13-substituted 15-membered homo-aza-clarithromycin derivatives were designed and synthesized as Series A, B and C by creatively opening the lactone ring of clarithromycin (CAM), introducing various 4-substituted phenyl-1H-1,2,3-triazole side chains at the N11, C12 or C13 position of CAM and macrolactonization. The results from their in vitro antibacterial activity demonstrated that compounds 20c, 20d and 20f displayed not only the most potent activity against S. aureus ATCC25923 with the MIC values of 0.5, 0.5 and 0.5 µg/mL, but also greatly improved activity against B. subtilis ATCC9372 with the MIC values of less than or equal to 0.25, 0.25 and 0.25 µg/mL, respectively. In particular, compound 11g exhibited the strongest antibacterial effectiveness against all the tested resistant bacterial strains and had well balanced activity with the MIC values of 4-8 µg/mL. Further study on minimum bactericidal concentration and kinetics confirmed that compound 11g possessed a bacteriostatic effect on bacterial proliferation. Moreover, the results of molecular docking revealed an potential additional binding force between compound 11g and U790 in addition to the normal binding force of macrolide skeleton, which may explain why this compound performed the most potent activity against resistant bacteria. The results of cytotoxic assay indicated that compounds 20c, 20d and 20f were non-toxic to human breast cancer MCF-7 cells at its effective antibacterial concentration.


Assuntos
Antibacterianos/farmacologia , Compostos Aza/farmacologia , Bacillus subtilis/efeitos dos fármacos , Claritromicina/farmacologia , Desenho de Fármacos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Compostos Aza/síntese química , Compostos Aza/química , Claritromicina/síntese química , Claritromicina/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
15.
Nat Commun ; 12(1): 2255, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33859206

RESUMO

Clarithromycin is a macrolide antibiotic widely used for eradication of Helicobacter pylori infection, and thus resistance to this antibiotic is a major cause of treatment failure. Here, we present the results of a retrospective observational study of clarithromycin resistance (Cla-res) in 4744 H. pylori-infected patients from Central Hungary. We use immunohistochemistry and fluorescence in situ hybridization on fixed gastric tissue samples to determine H. pylori infection and to infer Cla-res status, respectively. We correlate this information with macrolide dispensing data for the same patients (available through a prescription database) and develop a mathematical model of the population dynamics of Cla-res H. pylori infections. Cla-res is found in 5.5% of macrolide-naive patients (primary Cla-res), with no significant sex difference. The model predicts that this primary Cla-res originates from transmission of resistant bacteria in 98.7% of cases, and derives from spontaneous mutations in the other 1.3%. We find an age-dependent preponderance of female patients among secondary (macrolide-exposed) clarithromycin-resistant infections, predominantly associated with prior use of macrolides for non-eradication purposes. Our results shed light into the sources of primary resistant cases, and indicate that the growth rate of Cla-res prevalence would likely decrease if macrolides were no longer used for purposes other than H. pylori eradication.


Assuntos
Antibacterianos/farmacologia , Claritromicina/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Adulto , Fatores Etários , Idoso , Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/transmissão , Helicobacter pylori/isolamento & purificação , Humanos , Hungria/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Modelos Biológicos , Prevalência , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Adulto Jovem
16.
Helicobacter ; 26(4): e12804, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33860967

RESUMO

BACKGROUND: Antibiotic resistance is the main cause of Helicobacter pylori (H. pylori) treatment failure. This study aimed to explore the characteristics of antibiotic resistance of H. pylori isolates in Beijing in the last 8 years and to estimate the impact of previous eradication failure on resistance patterns. MATERIALS AND METHODS: This retrospective study included data from a single center in Beijing from 2013 to 2020. Antibiotic susceptibility of 365 clinical H. pylori isolates was tested for amoxicillin, clarithromycin, metronidazole, levofloxacin, moxifloxacin, and tetracycline. The characteristics of the included patients and their previous eradication history were collected. Primary and secondary resistance rates of H. pylori to the six antibiotics and the impact of previous eradication failure on antibiotic resistance patterns were analyzed. RESULTS: The overall primary resistance rates of amoxicillin, clarithromycin, metronidazole, levofloxacin, moxifloxacin, and tetracycline were 0.7%, 55.2%, 68.0%, 49.7%, 64.5%, and 0%, with no significant increase during the observed period; while the secondary resistance rates were 3.2%, 96.7%, 90.7%, 93.1%, 80.0%, and 0%, respectively. The secondary resistance rate of clarithromycin (p < .001), metronidazole (p = .001), and levofloxacin (p < .001) significantly increased to 100% as the number of previous eradication therapies increased and exhibited a linear association. For strains naive to eradication, only 6.8% were susceptible to all the antibiotics, while 32.4% were single resistant, and 60.8% dual or multiple resistant. Clarithromycin+metronidazole+fluoroquinolone multiple resistance was the predominant pattern (0 course: 21.6%, 1 course: 37.5%, 2 courses: 56.1%, ≥3 courses: 71.1%; p < .001) for patients with treatment failure. The prevalence of dual or multiple-resistance patterns increased significantly as the number of previous therapies increased. CONCLUSIONS: The prevalence of primary and secondary resistance rates of clarithromycin, metronidazole, moxifloxacin, and levofloxacin were high in Beijing. Multiple-resistance patterns were common after treatment failure. Resistance rates of amoxicillin and tetracycline remained low and stable.


Assuntos
Farmacorresistência Bacteriana Múltipla , Infecções por Helicobacter , Helicobacter pylori , Amoxicilina/farmacologia , Amoxicilina/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Pequim , Claritromicina/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/efeitos dos fármacos , Humanos , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Estudos Retrospectivos
17.
Bioorg Chem ; 112: 104896, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33901764

RESUMO

Effective and precise eradication of Helicobacter pylori (H. pylori) is the most promising approach to avoid H. pylori-related gastrointestinal disorders. The present study was conducted to demonstrate the efficacy of the co-delivery of hesperidin (Hesp) and clarithromycin (CLR) in nanostructured lipid carriers (NLCs) against H. pylori. We have produced a new delivery system by combining bioflavonoid Hesp and CLR NLCs to address the failure in single antibiotic therapies. Briefly, a blend of solid lipid, liquid lipid, and surfactant was used. Homogeneous NLCs with all the formulations showed a nano size and surface-negative charge and presented high in vitro stability and slow release of the drug even after 24 h. Bioimaging studies by scanning electron microscopy, transmission electron microscopy, and imaging flow cytometry indicated that NLCs interacted with the membrane by adhering to the outer cell membrane and disrupted the membrane that resulted in the leakage of cytoplasmic contents. The prepared NLCs provide sustained and controlled drug release that can be used to increase the rate of H. pylori eradication.


Assuntos
Antibacterianos/farmacologia , Claritromicina/farmacologia , Sistemas de Liberação de Medicamentos , Helicobacter pylori/efeitos dos fármacos , Hesperidina/farmacologia , Lipídeos/química , Nanopartículas/química , Antibacterianos/química , Proteínas da Membrana Bacteriana Externa/análise , Claritromicina/química , Relação Dose-Resposta a Droga , Portadores de Fármacos/química , Hesperidina/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
18.
Methods Mol Biol ; 2283: 45-50, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33765308

RESUMO

Culture-based antimicrobial susceptibility testing is a crucial method for the management of Helicobacter pylori infection . It must follow the European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations for fastidious microaerophilic bacteria, with some possible variation especially for the medium to be used. It is recommended to test six antibiotics by diffusion using strips charged with an antibiotic gradient in order to determine the minimum inhibitory concentrations (MICs). Two of these antibiotics, clarithromycin and levofloxacin, are more important because of frequent resistance which jeopardizes the success of the treatment.


Assuntos
Antibacterianos/farmacologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão/métodos , Helicobacter pylori/crescimento & desenvolvimento , Claritromicina/farmacologia , Meios de Cultura , Farmacorresistência Bacteriana Múltipla , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Humanos , Levofloxacino/farmacologia
19.
Eur J Clin Microbiol Infect Dis ; 40(8): 1599-1608, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33646449

RESUMO

In China, there is a high prevalence of antibiotic-resistant Helicobacter pylori infections in the population. The aim of the study was to assess a new ARMS-PCR test for detection of H. pylori clarithromycin resistance (CR) and quinolone resistance (QR) mutations and evaluate the spectrum of antibiotic resistance in patients from three Chinese provinces. Sanger sequencing and multiplex ARMS-PCR were used to detect H. pylori CR and QR bacteria in gastric biopsy samples. Among the 1,182 patients enrolled with gastritis, 643 (54.4%) were positive for H. pylori. Of these, 371 (57.7%) had antibiotic-resistant strains, comprising 236 (63.6%) with a single drug antibiotic-resistant strain and 135 (36.4%) with multiple drug-resistant strains. Following Sanger sequencing analysis of 23S rRNA and gyrA gene for mutations (antibiotic resistance markers), rates of CR, QR, and multidrug resistance (CR and QR) were 19.9, 12.0, and 25.8%, respectively. The 23S rRNA CR mutation A2143G (286, 96.9%) and the gyrA QR mutations C261A (85, 31.5%) and G271A (71, 26.3%) were common. Benchmarking against Sanger sequencing results, multiplex ARMS-PCR test had a high diagnostic sensitivity and specificity for detection of CR (96 and 93%), QR (95 and 92%) and multidrug resistance (95 and 95%). Based on our findings, the high incidence of single and multiple antibiotic resistance requires the routine checking of antibiotic resistance in all patients with suspected H. pylori infections. Multiplex ARMS-PCR is a simple and rapid test that can be now used for more efficient treatment of H. pylori infections and reduces the misuse of antibiotics.


Assuntos
Antibacterianos/farmacologia , Claritromicina/farmacologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Quinolonas/farmacologia , Adulto , China/epidemiologia , DNA Girase/genética , DNA Girase/metabolismo , DNA Bacteriano/genética , Farmacorresistência Bacteriana , Feminino , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/genética , Humanos , Masculino , Pessoa de Meia-Idade , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , RNA Ribossômico 23S/genética
20.
J Clin Microbiol ; 59(5)2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33692136

RESUMO

Colombia, South America has one of the world's highest burdens of Helicobacter pylori infection and gastric cancer. While multidrug antibiotic regimens can effectively eradicate H. pylori, treatment efficacy is being jeopardized by the emergence of antibiotic-resistant H. pylori strains. Moreover, the spectrum of and genetic mechanisms for antibiotic resistance in Colombia is underreported. In this study, 28 H. pylori strains isolated from gastric biopsy specimens from a high-gastric-cancer-risk (HGCR) population living in the Andes Mountains in Túquerres, Colombia and 31 strains from a low-gastric-cancer-risk (LGCR) population residing on the Pacific coast in Tumaco, Colombia were subjected to antibiotic susceptibility testing for amoxicillin, clarithromycin, levofloxacin, metronidazole, rifampin, and tetracycline. Resistance-associated genes were amplified by PCR for all isolates, and 29 isolates were whole-genome sequenced (WGS). No strains were resistant to amoxicillin, clarithromycin, or rifampin. One strain was resistant to tetracycline and had an A926G mutation in its 16S rRNA gene. Levofloxacin resistance was observed in 12/59 isolates and was significantly associated with N87I/K and/or D91G/Y mutations in gyrA Most isolates were resistant to metronidazole; this resistance was significantly higher in the LGCR (31/31) group compared to the HGCR (24/28) group. Truncations in rdxA and frxA were present in nearly all metronidazole-resistant strains. There was no association between phylogenetic relationship and resistance profiles based on WGS analysis. Our results indicate H. pylori isolates from Colombians exhibit multidrug antibiotic resistance. Continued surveillance of H. pylori antibiotic resistance in Colombia is warranted in order to establish appropriate eradication treatment regimens for this population.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Claritromicina/farmacologia , Colômbia/epidemiologia , Farmacorresistência Bacteriana/genética , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/genética , Humanos , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Filogenia , RNA Ribossômico 16S/genética , RNA Ribossômico 23S , América do Sul , Neoplasias Gástricas/tratamento farmacológico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...