RESUMO
Helicobacter pylori (H. pylori) is a major cause of peptic ulcer disease (PUD), which needs effective eradication of the organism to heal ulcers and prevent a recurrence. In recent years, increasing resistance of H. pylori to clarithromycin and amoxicillin have decreased peptic ulcer cure rate following treatment with standard triple therapy worldwide. The addition of probiotics with standard triple therapy has shown excellent efficacy in H. pylori eradication and has appeared to be an alternative treatment strategy. This study aimed to assess the efficacy of standard triple therapy plus probiotics for H. pylori eradication and ulcer healing compared to standard triple therapy alone. This double-blind, randomized placebo-controlled clinical trial included 158 with endoscopically proven H. pylori-positive PUD who were randomly allocated equally into two groups; Group A was treated with standard triple therapy plus probiotics, and Group B was treated with standard triple therapy plus placebo for 14 days. The outcome was evaluated at the end of treatment (14th day) (symptoms plus adverse events) and after 60 days of treatment completion (H. pylori eradication and ulcer healing). One hundred forty four (144) study subjects (73 in Group A and 71 in Group B) completed the study. Significantly higher H. pylori eradication rate (82.2%vs. 67.6%, p=0.043) and ulcer healing rate (92.3% vs. 60.0%, p=0.049) were observed in the standard triple therapy plus probiotic group than the standard triple therapy plus placebo group. Early relief of epigastric pain was also seen among patients getting probiotics than the placebo in addition to standard triple therapy (42.3% vs. 15.1%, p<0.001).The addition of probiotics significantly improves the H. pylori eradication rate and ulcer healing rate among the patients getting standard triple therapy. Further large-scale, multi-center studies are needed to recommend routine use of probiotics with standard triple therapy for H. pylori eradication.
Assuntos
Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Úlcera Péptica , Probióticos , Humanos , Probióticos/uso terapêutico , Probióticos/administração & dosagem , Úlcera Péptica/microbiologia , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/terapia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/terapia , Masculino , Feminino , Método Duplo-Cego , Pessoa de Meia-Idade , Adulto , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Amoxicilina/uso terapêutico , Amoxicilina/administração & dosagem , Claritromicina/uso terapêutico , Claritromicina/administração & dosagem , Resultado do TratamentoRESUMO
Introduction: The decreasing Helicobacter pylori eradication rate is primarily attributed to antibiotic resistance, and further exacerbated by uniform drug administration disregarding a host's metabolic capability. Consequently, applying personalized treatment based on antibiotic resistance-associated variants and the host's metabolic phenotype can potentially increase the eradication rate. Method: A custom next-generation sequencing panel for personalized H. pylori eradication treatment (NGS-PHET) was designed which targeted the regions for amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin-resistance in H. pylori and human proton-pump inhibitor (PPI) metabolism. The libraries were constructed following customized methods and sequenced simultaneously. The customized framework criteria, grounded in previously reported antibiotic resistance associated variants and the host's PPI metabolism, was applied to the NGS-PHET results and suggested a personalized treatment for each subject, which was validated through each subject's actual eradication outcome. Results: Both previously reported and novel variants were identified from H. pylori sequencing results. Concurrently, five CYP2C19 homozygous extensive metabolizers and three CYP3A4 intermediate metabolizers were identified. Among the total of 12 subjects, clarithromycin triple therapy was suggested for five subjects, bismuth quadruple therapy was suggested for six subjects, and rifabutin triple therapy was suggested for one subject by following the customized framework criteria. The treatment suggestion for nine of the 12 subjects was consistent with the treatment that each subject achieved eradication with. Discussion: Applying the methodology using the NGS-PHET and customized framework helps to perform eradication treatment quickly and effectively in most patients with antibiotic-resistant H. pylori strains, and is also useful in research to find novel antibiotic-resistance candidates.
Assuntos
Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Sequenciamento de Nucleotídeos em Larga Escala , Medicina de Precisão , Humanos , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Medicina de Precisão/métodos , Inibidores da Bomba de Prótons/uso terapêutico , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Masculino , Farmacorresistência Bacteriana/genética , Pessoa de Meia-Idade , Feminino , Adulto , Quimioterapia Combinada , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Amoxicilina/uso terapêutico , Amoxicilina/farmacologia , Citocromo P-450 CYP2C19/genética , Testes de Sensibilidade Microbiana , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Tetraciclina/farmacologia , Tetraciclina/uso terapêutico , Resultado do TratamentoRESUMO
Mycobacterium marinum infection often affects the extremities, causing single or multiple skin lesions. With the improvement of molecular detection technology and the clinical application of NGS pathogen detection, the diagnosis rate of Mycobacterium marinum skin disease is gradually increasing. This article reported the case of a 54-year-old man who was stung by a marine fish and gradually developed swelling and nodules on his right hand and right upper limb. He was diagnosed with Mycobacterium marinum infection by detection of the tuberculosis resistance gene dissolution curve of the pus and the identification of the bacteria. Oral rifampicin combined with clarithromycin and minocycline was given for anti-infection treatment. During follow-up, the abscesses and nodules gradually shrank and eventually disappeared. By presenting the diagnosis and treatment of this case, the understanding of this disease among clinicians can be improved to avoid misdiagnosis and missed diagnosis.
Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium marinum , Humanos , Pessoa de Meia-Idade , Masculino , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium marinum/isolamento & purificação , Dermatopatias Bacterianas/diagnóstico , Dermatopatias Bacterianas/microbiologia , Dermatopatias Bacterianas/tratamento farmacológico , Claritromicina/uso terapêutico , Rifampina/uso terapêutico , Antibacterianos/uso terapêuticoRESUMO
The treatment of Mycobacterium avium infections is still long, complex, and often poorly tolerated, besides emergence of resistances. New active molecules that are more effective and better tolerated are deeply needed. Mefloquine and its enantiomers ((+) Erythro-mefloquine ((+)-EMQ) and (-)-Erythro-mefloquine ((-)-EMQ)) have shown efficacy in both in vitro and in vivo, in a mouse model of M. avium intraveinous infection. However, no study reports aerosol model of infection or combination with gold standard treatment. That was the aim of our study. In an aerosol model of M. avium infection in BALB/c mice, we used five treatment groups as followed: Clarithromycin-Ethambutol-Rifampicin (CLR-EMB-RIF, standard of care, n = 15), CLR-EMB-MFQ (n = 15), CLR-EMB-(+)-EMQ (n = 15), CLR-EMB-(-)-EMQ (n = 15) and an untreated group (n = 25). To evaluate drug efficacy, we sacrificed each month over 3 months, 5 mice from each group. Lung homogenates were diluted and plated for colony forming unit count (CFU) expressed in Log10. At each time point, we found a significant difference between the untreated group and each of the treatment groups (p<0.005). The (+)-EMQ-CLR-EMB group was the group with the lowest CFU count at each time point but never reached statistical significance. The results of each group 3 months after treatment are: (+)-EMQ-CLR-EMB (4.43 ± 0.26), RIF-CLR-EMB (4.83 ± 0.37), (-)-EMQ-CLR-EMB (4.82 ± 0.18), MFQ-CLR-EMB (4.70 ± 0.21). In conclusion, MFQ and its enantiomers appear to be as effective as rifampicin in combination therapy. Further studies are needed to evaluate the ability of these drugs to prevent selection of clarithromycin resistant strains and potential for lung sterilization.
Assuntos
Modelos Animais de Doenças , Mefloquina , Camundongos Endogâmicos BALB C , Mycobacterium avium , Animais , Mefloquina/farmacologia , Camundongos , Mycobacterium avium/efeitos dos fármacos , Estereoisomerismo , Feminino , Rifampina/farmacologia , Claritromicina/farmacologia , Antituberculosos/farmacologia , Antituberculosos/química , Etambutol/farmacologia , Quimioterapia Combinada , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Pulmão/microbiologia , Pulmão/efeitos dos fármacos , Pulmão/patologiaRESUMO
Helicobacter pylori infection constitutes a silent pandemic of global concern. In the last decades, the alarming increase in multidrug resistance evolved by this pathogen has led to a marked drop in the eradication rates of traditional therapies worldwide. By using a high-throughput screening strategy, in combination with in vitro DNA binding assays and antibacterial activity testing, we identified a battery of novel drug-like HsrA inhibitors with MIC values ranging from 0.031 to 4 mg/L against several antibiotic-resistant strains of H. pylori, and minor effects against both Gram-negative and Gram-positive species of human microbiota. The most potent anti-H. pylori candidate demonstrated a high therapeutic index, an additive effect in combination with metronidazole and clarithromycin as well as a strong antimicrobial action against Campylobacter jejuni, another clinically relevant pathogen of phylum Campylobacterota. Transcriptomic analysis suggests that the in vivo inhibition of HsrA triggers lethal global disturbances in H. pylori physiology including the arrest of protein biosynthesis, malfunction of respiratory chain, detriment in ATP generation, and oxidative stress. The novel drug-like HsrA inhibitors described here constitute valuable candidates to a new family of narrow-spectrum antibiotics that allow overcoming the current resistome, protecting from dysbiosis, and increasing therapeutic options for novel personalized treatments against H. pylori.
Assuntos
Antibacterianos , Proteínas de Bactérias , Helicobacter pylori , Testes de Sensibilidade Microbiana , Helicobacter pylori/efeitos dos fármacos , Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Claritromicina/farmacologia , Metronidazol/farmacologiaRESUMO
The core intent of the existing effort was to explore a triple therapy to eradicate Helicobacter pylori. A hard gelatin capsule filled with metronidazole (MNZ) floating microspheres aided with Plantago ovata seed mucilage (POSM) and Clarithromycin (CMN) floating microspheres aided with Abelmoschus esculentus fruit mucilage (AEFM). These mucilages were adopted as they have gastro-protective actions. These microspheres were designed by a central composite design. The influence of polymers used was checked towards the drug entrapment efficacy and floating time was tallied as a response. The capsule also contains Pantoprazole sodium (PZS) enteric-coated mini-tablets. These mini-tablets were checked for the coating thickness as a response (Design Expert). The microspheres and the mini-tablets were gauged for tests and a positive response was reported. The study summarizes that microspheres of MNZ & CMN and PZS enteric-coated mini-tablets can be used to eradicate H. pylori effectively. POSM and AEFM can aid MNZ and CMN microspheres formulations and have ulcer-curing and gastric-protective abilities.
Assuntos
Abelmoschus , Claritromicina , Infecções por Helicobacter , Helicobacter pylori , Metronidazol , Microesferas , Plantago , Helicobacter pylori/efeitos dos fármacos , Claritromicina/administração & dosagem , Metronidazol/administração & dosagem , Metronidazol/farmacologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Plantago/química , Abelmoschus/química , Antibacterianos/administração & dosagem , Pantoprazol/administração & dosagem , Pantoprazol/farmacologia , Cápsulas , Polímeros/química , Sementes/química , Comprimidos com Revestimento Entérico , Quimioterapia Combinada , Frutas , Gelatina/química , Humanos , Antiulcerosos/administração & dosagem , Antiulcerosos/farmacologiaRESUMO
Taking Liangshui River, the reclaimed water-receiving river in Beijing, as the research area, the types, detection frequencies, and concentrations of 16 antibiotics in water and sediment were analyzed, and their temporal-spatial variation and occurrence characteristics were discussed. The results showed that nine and 13 target antibiotics were detected in the water and sediment of Liangshui River, with the antibiotic concentration ranges of ND-116.68 ng·L-1 and ND-235.42 ng·g-1, respectively. The main antibiotics in water were ofloxacin and clarithromycin, and the main antibiotic in sediment was ofloxacin. The total concentration of antibiotics in water and sediment showed a gradual decrease from the upstream to the downstream in the Liangshui River mainstream, and the concentration of antibiotics in tributaries was higher than that in the mainstream. The inflow of tributaries had an obvious impact on the antibiotic concentration in water for the Liangshui River but had little impact on its sediment. The total concentration of antibiotics in water and sediment during the dry season was generally higher than that during the wet season. The detected antibiotics with the highest concentration were quinolones in water during the wet season and macrolides in the dry season. Quinolones had the highest concentration in sediment in both seasons. The ecological risk assessment results showed that clarithromycin had a low risk in water in the dry season and sediment in both seasons, whereas the other antibiotics had no risk. The combined ecological risk and the most sensitive trophic level ecological risk assessment showed that all sampling sites had low risk or no risk, and the risk of the dry season was generally greater than that of the wet season. The risk values of some sampling points were close to the medium risk threshold during the dry season, which requires further attention.
Assuntos
Antibacterianos , Monitoramento Ambiental , Sedimentos Geológicos , Rios , Poluentes Químicos da Água , Rios/química , Poluentes Químicos da Água/análise , Antibacterianos/análise , Medição de Risco , Pequim , Sedimentos Geológicos/química , Ofloxacino/análise , China , Eliminação de Resíduos Líquidos/métodos , Claritromicina/análiseRESUMO
Mycobacterium chelonae (M. chelonae) is a member of the rapidly growing non-tuberous mycobacteria and can cause disseminated tissue infection, particularly, in the limbs. We reviewed medical records of two kidney transplant patients. We describe their background disease and transplantation details, with the use of immunosuppressive medication. We also discuss the presentation of M. chelonae infection and treatment. Both patients received deceased brain-dead donor kidney transplants for end-stage kidney disease. Both developed cutaneous manifestations of M. chelonae, progressing to disseminated infections. Case 1 was on low-dose prednisolone (2 mg) and tacrolimus, whereas, case 2 received varying doses of prednisolone (5-40 mg) and sirolimus. Antibiotics advised by infectious disease specialists were initiated within a month of skin lesion appearance. Effective treatment involved a combination of antibiotics such as clarithromycin, azithromycin, linezolid and tigecycline. These cases underline the efficacy of clarithromycin and azithromycin as long-term antibiotic treatment, with linezolid and tigecycline for management of acute dissemination.
Assuntos
Antibacterianos , Transplante de Rim , Infecções por Mycobacterium não Tuberculosas , Mycobacterium chelonae , Humanos , Transplante de Rim/efeitos adversos , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Masculino , Antibacterianos/uso terapêutico , Pessoa de Meia-Idade , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Claritromicina/uso terapêutico , Feminino , Adulto , Falência Renal Crônica/cirurgia , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Tigeciclina/uso terapêuticoRESUMO
BACKGROUND: We compared efficacy of vonoprazan-dual or triple therapies and bismuth-quadruple therapy for treatment-naive Helicobacter pylori (HP) infection in Southern China, where primary resistance rates of clarithromycin and levofloxacin are >30%. METHODS: This was an investigator-initiated, three-arm, randomized clinical trial in Southern China. Between March 2022 and August 2023, treatment-naïve HP-infected adults were randomly assigned to receive one of three 14-day regimens (1:1:1 ratio): vonoprazan-dual (VA-dual; vonoprazan 20 mg twice daily and amoxicillin 1 g thrice daily), vonoprazan-triple (VAC-triple; vonoprazan 20 mg/amoxicillin 1 g/clarithromycin 500 mg twice daily), or bismuth-quadruple therapy containing bismuth, esomeprazole, tetracycline, and metronidazole. Primary outcome was noninferiority in HP eradication, evaluated by UBT 4-6 weeks post-treatment by intention-to-treat (ITT) and per-protocol (PP) analysis (based on subjects who completed 14-day treatment and rechecked UBT). Bonferroni-adjusted p-value of <0.017 was used to determine statistical significance. RESULTS: A total of 298 subjects (mean age: 35.7 ± 8.4 years; male: 134 [45.0%]; VC-dual: 100, VAC-triple: 98, bismuth-quadruple: 100) were enrolled, and 292 (98.0%) had UBT rechecked. ITT analysis showed that both VA-dual (eradication rate of 96.0%) and VAC-triple therapies (95.9%) were noninferior to bismuth-quadruple therapy (92.0%) (difference: 4.0%, 95% CI: -2.9% to 11.5%, p < 0.001; and 3.9%, 95% CI: -3.1% to 11.5%, p < 0.001, respectively). PP analysis also revealed noninferiority (96.7% or 96.7% vs. 97.4%, with difference: -2.9% and -2.9%, p = 0.009 and 0.010, respectively). The frequency of adverse events was 39.0%, 56.1%, and 71.0% in VA-dual, VAC-triple, and bismuth-quadruple therapies, respectively. CONCLUSIONS: VA-dual and VA-triple therapies are highly effective and noninferior to bismuth-quadruple therapy in Southern China. Given the lower adverse effects and fewer antibiotic use, VA-dual therapy is the preferred first-line treatment for HP infection. TRIAL REGISTRATION: Chinese Clinical Trial Registry (No. ChiCTR2200056375). Registered on February 4, 2022, https://www.chictr.org.cn/showproj.aspx?proj=14131.
Assuntos
Antibacterianos , Bismuto , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Pirróis , Sulfonamidas , Humanos , Infecções por Helicobacter/tratamento farmacológico , Sulfonamidas/uso terapêutico , Sulfonamidas/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Helicobacter pylori/efeitos dos fármacos , Bismuto/uso terapêutico , Pirróis/uso terapêutico , Pirróis/administração & dosagem , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , China , Resultado do Tratamento , Claritromicina/uso terapêutico , Amoxicilina/uso terapêutico , Amoxicilina/administração & dosagem , Metronidazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Adulto Jovem , Esomeprazol/uso terapêutico , Esomeprazol/administração & dosagemRESUMO
BACKGROUND: Helicobacter pylori (H. pylori)is a Gram-negative, microaerophilic, and spiral shape bacterium that resides inside the human stomach. The human stomach serves as its primary reservoir. Complaints about stomach complication due to H. pylori infections are reported in the majority of populations around the globe. Chronic gastritis and intestinal metaplasia of the gastric mucosa are major complications of a long-term H. pylori infections that can lead to gastric cancer in severe cases. This study aims to characterize H. pylori isolates from gastroenteritis patients and to determine the resistance of H. pylori to various antibiotics. METHODS: In the current study, a total of (n = 80) gastric biopsy samples were randomly collected from gastroenteritis patients in brain-heart infusion broth. These were inoculated on Columbia blood agar supplemented with Helicobacter pylori selective supplement (DENT). After culturing, Microscopy and biochemical tests were performed. The susceptibility profile of H. pylori isolates was evaluated using the Kirby Bauer disk diffusion method. On the basis of the drug resistance profile, a total of (n = 20) isolates including (n = 10) from females and (n = 10) from males were selected for the detection and characterization of resistant genes. After confirmation of H. pylori using 16s rRNA, polymerase chain reaction (PCR) was done for the detection of resistance genes including Metronidazole resistance (rdxA gene), Clarithromycin resistance (23s rRNA gene) and Amoxicillin resistance (Penicillin-binding protein A1 (pbpA1) gene). RESULTS: In a total of (n = 80) samples, H. pylori was isolated from 72.5% (n = 58) samples. Among the positive patients, there were 62% (n = 36) of female positive patients while in males, its ratio was 38% (n = 22). It was more common in the age between 30-50 years 55.17% (n = 32). It has shown the highest resistance towards Metronidazole 90% (n = 52), and the lowest toward Levofloxacin 65% (n = 38). Metronidazole resistance gene (rdxA gene) was detected in (n = 13) isolates including (n = 9) isolates from females and (n = 4) from males. In the case of, the Clarithromycin resistance gene (23s rRNA) (n = 10) was positive for H. pylori including (n = 6) isolates from females and (n = 7) were positive for Amoxicillin (pbpA1 gene) including (n = 2) in female and (n = 5) from male patients. CONCLUSION: This study highlights the increasing incidence of H. pylori infections in both male and female patients. It also revealed the current status of antibiotic resistance and its resistance genes in patients facing gastrointestinal issues. Continuous surveillance of resistant clones will help in formulating strategies that can help in combating of resistant clone. It will also help clinician in proper prescription and management of H. pylori infections.
Assuntos
Amoxicilina , Antibacterianos , Claritromicina , Farmacorresistência Bacteriana , Gastroenterite , Infecções por Helicobacter , Helicobacter pylori , Metronidazol , Humanos , Helicobacter pylori/genética , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Claritromicina/farmacologia , Feminino , Amoxicilina/farmacologia , Masculino , Metronidazol/farmacologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/complicações , Gastroenterite/microbiologia , Gastroenterite/tratamento farmacológico , Farmacorresistência Bacteriana/genética , Adulto , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Proteínas de Bactérias/genéticaRESUMO
BACKGROUND AND AIM: Bismuth and non-bismuth quadruple therapy are the guideline-recommended first-line therapy in children with Helicobacter pylori infection in areas with high antibiotic resistance. However, their efficacy in children is uncertain and there are few well-designed studies. Here, we evaluated the eradication rates of standard triple therapy, bismuth-based quadruple therapy and sequential therapy in children with H. pylori infection. METHODS: A randomised controlled trial was conducted in children infected with H. pylori in West China Second Hospital. They were randomly assigned to 14-day standard triple therapy (omeprazole + amoxicillin + clarithromycin), 14-day bismuth quadruple therapy (bismuth + omeprazole + amoxicillin + clarithromycin) and 10-day sequential therapy (omeprazole + amoxicillin for 5 days followed by omeprazole + clarithromycin + metronidazole for 5 days). The eradication rate was assessed by a 13C-urea breath test 4 to 6 weeks after therapy completion. Symptom improvement and adverse events were compared among the groups. RESULTS: In total, 132 patients were enrolled. The eradication rates of 14-day standard triple therapy, 14-day bismuth quadruple therapy and 10-day sequential therapy were 70.0%, 78.9% and 50.0% in per-protocol analysis and 63.6%, 68.2% and 43.2% in intention-to-treat analysis, respectively. Symptom improvement and adverse drug event rates were similar in the three groups. CONCLUSION: The three therapeutic regimens evaluated in this study are equally not recommendable for H. pylori infection treatment due to unsatisfactory eradication rates. The high prevalence of clarithromycin resistance makes the use of clarithromycin-based quadruple therapy not advisable, even in combination with amoxicillin and bismuth salts.
Assuntos
Amoxicilina , Antibacterianos , Bismuto , Claritromicina , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Metronidazol , Omeprazol , Humanos , Infecções por Helicobacter/tratamento farmacológico , Feminino , Masculino , Criança , Omeprazol/administração & dosagem , Omeprazol/uso terapêutico , Metronidazol/administração & dosagem , Metronidazol/uso terapêutico , Amoxicilina/administração & dosagem , Claritromicina/administração & dosagem , Claritromicina/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Bismuto/administração & dosagem , Bismuto/uso terapêutico , Adolescente , Resultado do Tratamento , Esquema de Medicação , Pré-Escolar , Testes Respiratórios , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/uso terapêuticoRESUMO
Background: Helicobacter pylori (Hp) infection predisposes to malignant and non-malignant diseases warranting eradication. In Belgium, resistance rates for clarithromycin demonstrate regional variations making the use of standard triple therapy (STT) borderline acceptable. According to a recent Belgian survey, STT and bismuth-based quadruple therapy (BQT), are equally frequent prescribed as first line treatment for treatment naïve Hp positive patients. This study aims to evaluate the eradication rates (ER) of BQT versus STT. Methods: Multicentre, non-blinded randomized, prospective study comparing ER in treatment-naïve Hp positive patients. ER were compared by intention to treat (ITT) and per protocol (PP) analysis. Results: Overall 250 patients were included (STT 126, BQT 124). Seventeen patients were lost to follow-up (6,8%). No significant difference in ER between BQT and STT was observed in ITT (73% vs 68%, p= 0,54) neither in PP analysis (81% vs 75%, p= 0,33). Side effects and endoscopic findings were comparable between groups. Post-hoc analysis showed no differences according to gender or site allocation. Conclusion: The numerical advantage of BQT did not translate in a significant improvement of ER when compared with STT. These results question the cost-effectiveness of BQT, while confirming the suboptimal eradication rates on STT. A nationwide monitoring of resistance patterns, maximal investments in treatment adherence as well as a detailed follow-up of the changing treatment landscape are mandatory to continuously optimise Hp ER in Belgium.
Assuntos
Antibacterianos , Bismuto , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Feminino , Masculino , Bélgica , Helicobacter pylori/efeitos dos fármacos , Pessoa de Meia-Idade , Bismuto/uso terapêutico , Estudos Prospectivos , Antibacterianos/uso terapêutico , Adulto , Inibidores da Bomba de Prótons/uso terapêutico , Inibidores da Bomba de Prótons/administração & dosagem , Idoso , Claritromicina/uso terapêutico , Amoxicilina/uso terapêutico , Amoxicilina/administração & dosagem , Metronidazol/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: The optimal duration of regimens for tailored therapy based on genotypic resistance for clarithromycin has yet to be established. AIM: This study was a nationwide, multicenter, randomized trial comparing empirical therapy with tailored therapy based on genotypic resistance for first-line eradication of Helicobacter pylori. We also compared the eradication rates of 7- and 14-day regimens for each group. PATIENTS AND METHODS: Patients with H. pylori infection were first randomized to receive empirical or tailored therapy. Patients in each group were further randomized into 7- or 14-day regimens. Empirical therapy consisted of a triple therapy (TT) regimen (twice-daily doses of pantoprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg) for 7 or 14 days. Tailored therapy consisted of TT of 7 or 14 days in patients without genotypic resistance. Patients with genotypic resistance were treated with bismuth quadruple therapy (BQT) regimens (twice-daily doses of pantoprazole 40 mg, three daily doses of metronidazole 500 mg, and four times daily doses of bismuth 300 mg and tetracycline 500 mg) for 7 or 14 days. A 13C-urea breath test assessed eradication rates. The primary outcome was eradication rates of each group. RESULTS: A total of 593 patients were included in the study. The eradication rates were 65.7% (201/306) in the empirical therapy group and 81.9% (235/287) in the tailored therapy group for intention-to-treat analysis (p < 0.001). In the per-protocol analysis, the eradication rates of the empirical therapy and tailored groups were 70.3% (201/286) and 85.5% (235/274) (p < 0.001), respectively. There was no difference in compliance between the two groups. The rate of adverse events was higher in the tailored group compared to the empirical group (p < 0.001). DISCUSSION: Our study confirmed that tailored therapy based on genotypic resistance was more effective than empirical therapy for H. pylori eradication in Korea. However, no significant difference was found between 7- and 14-day regimens for each group. Future studies are needed to determine the optimal duration of therapy for empirical and tailored therapy regimens.
Assuntos
Antibacterianos , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Masculino , Feminino , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , República da Coreia , Adulto , Idoso , Resultado do Tratamento , Farmacorresistência Bacteriana , Amoxicilina/uso terapêutico , Amoxicilina/administração & dosagem , Claritromicina/uso terapêutico , Metronidazol/uso terapêutico , Pantoprazol/uso terapêutico , Genótipo , Adulto JovemRESUMO
Clarithromycin (CLR) is currently a key antibiotic for Helicobacter pylori infection treatment, however, the data on CLR resistance patterns in Russia are missing. Here, we applied WGS-based approach to H. pylori clinical isolates from Russia to comprehensively investigate sequence variation, identify putative markers of CLR resistance and correlate them with phenotypic susceptibility testing. The phenotypic susceptibility of 44 H. pylori isolates (2014-2022) to CLR was determined by disc diffusion method: 23 isolates were CLR-resistant and 21-CLR-susceptible. All isolates were subjected to WGS and submitted to GenBank. Based on complete sequence analysis, we showed that among all sequence variants, the combination of mutations A2146G/A2147G in the 23S rRNA gene is the most reliable for prediction of phenotypic susceptibility. For the first time, the average number of mutations in 106 virulence-associated genes between resistant and susceptible groups were compared. Moreover, this study presents the first WGS insight into genetic diversity of H. pylori in Russia with a particular focus on the molecular basis of drug resistance: the novel mutations were described as potential markers for the resistance development. Of these, the most prominent was a frameshift deletion (252:CGGGT) in HP0820 coding region, which is a good candidate for further investigation.
Assuntos
Antibacterianos , Claritromicina , Farmacorresistência Bacteriana , Infecções por Helicobacter , Helicobacter pylori , Testes de Sensibilidade Microbiana , Sequenciamento Completo do Genoma , Claritromicina/farmacologia , Helicobacter pylori/genética , Helicobacter pylori/efeitos dos fármacos , Federação Russa/epidemiologia , Humanos , Farmacorresistência Bacteriana/genética , Antibacterianos/farmacologia , Sequenciamento Completo do Genoma/métodos , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Mutação , RNA Ribossômico 23S/genética , Genoma Bacteriano , Masculino , Variação Genética , Feminino , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
Amorphous solid dispersion (ASD) in a polymer matrix is a powerful method for enhancing the solubility and bioavailability of otherwise crystalline, poorly water-soluble drugs. 6-Carboxycellulose acetate butyrate (CCAB) is a relatively new commercial cellulose derivative that was introduced for use in waterborne coating applications. As CCAB is an amphiphilic, carboxyl-containing, high glass transition temperature (Tg) polymer, characteristics essential to excellent ASD polymer performance, we chose to explore its ASD potential. Structurally diverse drugs quercetin, ibuprofen, ritonavir, loratadine, and clarithromycin were dispersed in CCAB matrices. We evaluated the ability of CCAB to create ASDs with these drugs and its ability to provide solubility enhancement and effective drug release. CCAB/drug dispersions prepared by spray drying were amorphous up to 25 wt % drug, with loratadine remaining amorphous up to 50% drug. CCAB formulations with 10% drug proved effective at providing in vitro solubility enhancement for the crystalline flavonoid drug quercetin as well as ritonavir, but not for the more soluble APIs ibuprofen and clarithromycin and the more hydrophobic loratadine. CCAB did provide slow and controlled release of ibuprofen, offering a simple and promising Long-duration ibuprofen formulation. Formulation with clarithromycin showed the ability of the polymer to protect against degradation of the drug at stomach pH. Furthermore, CCAB ASDs with both loratadine and ibuprofen could be improved by the addition of the water-soluble polymer poly(vinylpyrrolidone) (PVP), with which CCAB shows good miscibility. CCAB provided solubility enhancement in some cases, and the slower drug release exhibited by CCAB, especially in the stomach, could be especially beneficial, for example, in formulations containing known stomach irritants like ibuprofen.
Assuntos
Celulose , Ibuprofeno , Loratadina , Polímeros , Solubilidade , Polímeros/química , Celulose/química , Celulose/análogos & derivados , Ibuprofeno/química , Ibuprofeno/farmacocinética , Loratadina/química , Loratadina/análogos & derivados , Loratadina/farmacocinética , Liberação Controlada de Fármacos , Quercetina/química , Claritromicina/química , Ritonavir/química , Química Farmacêutica/métodos , Composição de Medicamentos/métodosRESUMO
Clarithromycin extended-release (CLA-ER) was used as companion drug to rifampicin (RIF) for Mycobacterium ulcerans infection in the intervention arm of a WHO drug trial. RIF enhances CYP3A4 metabolism, thereby reducing CLA serum concentrations, and RIF concentrations might be increased by CLA co-administration. We studied the pharmacokinetics of CLA-ER at a daily dose of 15 mg/kg combined with RIF at a dose of 10 mg/kg in a subset of trial participants, and compared these to previously obtained pharmacokinetic data. Serial dried blood spot samples were obtained over a period of ten hours, and analyzed by LC-MS/MS in 30 study participants-20 in the RIF-CLA study arm, and 10 in the RIF-streptomycin study arm. Median CLA Cmax was 0.4 mg/L-and median AUC 3.9 mg*h/L, following 15 mg/kg CLA-ER. Compared to standard CLA dosed at 7.5 mg/kg previously, CLA-ER resulted in a non-significant 58% decrease in Cmax and a non-significant 30% increase in AUC. CLA co-administration did not alter RIF Cmax or AUC. Treatment was successful in all study participants. No effect of CLA co-administration on RIF pharmacokinetics was observed. Based on our serum concentration studies, the benefits CLA-ER over CLA immediate release are unclear.
Assuntos
Úlcera de Buruli , Claritromicina , Preparações de Ação Retardada , Mycobacterium ulcerans , Rifampina , Humanos , Claritromicina/farmacocinética , Claritromicina/administração & dosagem , Masculino , Feminino , Adulto , Rifampina/farmacocinética , Rifampina/administração & dosagem , Rifampina/uso terapêutico , Pessoa de Meia-Idade , Úlcera de Buruli/tratamento farmacológico , Úlcera de Buruli/microbiologia , Mycobacterium ulcerans/efeitos dos fármacos , Preparações de Ação Retardada/farmacocinética , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Idoso , Adulto Jovem , Área Sob a Curva , Espectrometria de Massas em TandemRESUMO
The minimum bactericidal concentration (MBC) of antibiotics is an important parameter for the potency of a drug in eradicating a bacterium as well as an important measure of the potential of a drug candidate in research and development. We have established a fluorescence-based microscopy method for the determination of MBCs against the non-tuberculous mycobacterium Mycobacterium abscessus (Mycobacteroides abscessus) to simplify and accelerate the performance of MBC determination compared to counting colony forming units on agar. Bacteria are labelled with the trehalose-coupled dye 3HC-2-Tre and analysed in a 96-well plate. The results of the new method are consistent with MBC determination by plating on agar. The method was used to evaluate the bactericidality of the antibiotics rifabutin, moxifloxacin, amikacin, clarithromycin and bedaquiline. Bactericidal effects against M. abscessus were observed, which are consistent with literature data.
Assuntos
Antibacterianos , Testes de Sensibilidade Microbiana , Microscopia de Fluorescência , Mycobacterium abscessus , Mycobacterium abscessus/efeitos dos fármacos , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana/métodos , Microscopia de Fluorescência/métodos , Amicacina/farmacologia , Rifabutina/farmacologia , Diarilquinolinas/farmacologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Claritromicina/farmacologia , Moxifloxacina/farmacologiaRESUMO
We report here on the structure-activity relationships of hybrids combining 3-descladinosyl clarithromycin with quinolones linked by extended diamine connectors. Several hybrids, exemplified by 23Bc, 23Be, 23Bf, 26Be, and 30Bc, not only restored potency against inducibly resistant pathogens but also exhibited significantly enhanced activities against constitutively resistant strains of Staphylococcus pneumoniae and Staphylococcus pyogenes, which express high-level resistance independent of clarithromycin or erythromycin induction. Additionally, the novel hybrids showed susceptibility against Gram-negative Haemophilus influenzae. Notably, hybrid 23Be demonstrated dual modes of action by inhibiting both protein synthesis and DNA replication in vitro and in vivo. Given these promising characteristics, 23Be emerges as a potential candidate for the treatment of community-acquired bacterial pneumonia.
Assuntos
Antibacterianos , Claritromicina , Desenho de Fármacos , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Claritromicina/farmacologia , Claritromicina/química , Claritromicina/síntese química , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Estrutura Molecular , Diaminas/química , Diaminas/farmacologia , Diaminas/síntese química , Haemophilus influenzae/efeitos dos fármacos , Oximas/química , Oximas/farmacologia , Oximas/síntese química , Relação Dose-Resposta a Droga , Humanos , Animais , Streptococcus pyogenes/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacosRESUMO
INTRODUCTION: Increasing the effectiveness of eradication therapy is an important task in gastroenterology. The aim of this study was to evaluate the efficacy and safety of postbiotic containing inactivated (nonviable) Limosilactobacillus (Lactobacillus) reuteri DSM 17648 (Pylopass) as adjuvant treatment of Helicobacter pylori eradication in patients with functional dyspepsia (FD). METHODS: This randomized, double-blind, placebo-controlled, multicenter, parallel study included H. pylori -positive patients with FD. The postbiotic group received Pylopass 200 mg bid for 14 days in combination with eradication therapy (esomeprazole 20 mg bid + amoxicillin 1,000 mg bid + clarithromycin 500 mg bid for 14 days) and another 14 days after the completion of eradication therapy. The study was registered in the ISRCTN registry (ISRCTN20716052). RESULTS: Eradication efficiency was 96.7% for the postbiotic group vs 86.0% for the placebo group ( P = 0.039). Both groups showed significant improvements in quality of life and reduction of most gastrointestinal symptoms with no significant differences between groups. The overall number of digestive adverse effects in the postbiotic group was lower than in the placebo group. Serious adverse effects were not registered. DISCUSSION: The postbiotic containing inactivated L. reuteri DSM 17648 significantly improves the effectiveness of H. pylori eradication therapy in FD and decreases overall number of digestive adverse effects of this therapy.
Assuntos
Amoxicilina , Antibacterianos , Claritromicina , Quimioterapia Combinada , Dispepsia , Infecções por Helicobacter , Helicobacter pylori , Limosilactobacillus reuteri , Probióticos , Qualidade de Vida , Humanos , Método Duplo-Cego , Dispepsia/microbiologia , Dispepsia/diagnóstico , Dispepsia/tratamento farmacológico , Dispepsia/terapia , Masculino , Feminino , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/terapia , Infecções por Helicobacter/microbiologia , Adulto , Helicobacter pylori/isolamento & purificação , Probióticos/administração & dosagem , Probióticos/efeitos adversos , Probióticos/uso terapêutico , Pessoa de Meia-Idade , Amoxicilina/administração & dosagem , Amoxicilina/efeitos adversos , Amoxicilina/uso terapêutico , Claritromicina/administração & dosagem , Claritromicina/uso terapêutico , Claritromicina/efeitos adversos , Resultado do Tratamento , Antibacterianos/efeitos adversos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Esomeprazol/administração & dosagem , Esomeprazol/efeitos adversos , Esomeprazol/uso terapêutico , Adulto JovemRESUMO
Airway epithelial-mesenchymal transition (EMT) is the important pathological feature of airway remodeling in asthma. While macrolides are not commonly used to treat asthma, they have been shown to have protective effects on the airways, in which mechanisms are not yet fully understood. This study aims to investigate the impact of clarithromycin on airway EMT in asthma and its potential mechanism. The results revealed an increase in Kv1.3 expression in the airways of ovalbumin (OVA)-induced asthmatic mice, with symptoms and pathological changes being alleviated after treatment with the Kv1.3 inhibitor 5-(4-phenoxybutoxy)psoralen (PAP-1). Clarithromycin was found to attenuate airway epithelial-mesenchymal transition through the inhibition of Kv1.3 and PI3K/Akt signaling. Further experiments in vitro confirmed that PAP-1 could mitigate EMT by modulating the PI3K/Akt signaling in airway epithelial cells undergoing transformation into mesenchymal cells. These findings confirmed that clarithromycin might have a certain protective effect on asthma-related airway remodeling and represent a promising treatment strategy.