RESUMO
BACKGROUND: Sustained intragastric antibiotic exposure is important for Helicobacter pylori eradication, yet little is known about gastric pharmacology of commonly used H. pylori regimens. For rifabutin, differing intragastric concentrations based on dosing regimen may account for differences in reported eradication rates. AIM: To compare intragastric rifabutin concentrations between low-dose rifabutin (50 mg three time daily; as in RHB-105) and generically dosed rifabutin 150 mg once daily, 150 mg twice daily, and 300 mg once daily using a validated Physiologically-based pharmacokinetic (PBPK) model. METHODS: We obtained plasma pharmacokinetic data from the RHB-105 clinical development programs and used it to develop and validate a whole-body PBPK model using PK-SIM software. We modified the existing rifabutin model to include the impact of omeprazole on gastric pH and emptying time. Modelled intragastric rifabutin exposure was expressed as the time that each regimen maintained its concentration ≥MIC90 . RESULTS: Rifabutin 50 mg three times daily achieved significantly longer times with intragastric concentration above MIC90 (22.3 ± 1.1 h) than 150 mg once daily (8.3 ± 1.7 h), 150 mg twice daily (16.3 ± 2.3 h), or 300 mg once daily (8.5 ± 1.9 h) while providing the lowest mean maximal plasma concentration and mean area under the plasma concentration-time curve of all regimens studied. CONCLUSIONS: PBPK modelling showed rifabutin 50 mg three times daily had higher intragastric exposure times than 150 mg once daily or twice daily, or 300 mg once daily. This low-dose rifabutin regimen provides the highest potential for H. pylori eradication while minimising systemic rifabutin exposure.
Assuntos
Antiulcerosos , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Rifabutina/uso terapêutico , Omeprazol/uso terapêutico , Antibacterianos/uso terapêutico , Quimioterapia CombinadaRESUMO
Nontuberculous mycobacteria (NTM) are the pathogens of concern in people with cystic fibrosis (pwCF) due to their association with deterioration of lung function. Treatment requires the use of a multidrug combination regimen, creating the potential for drug-drug interactions (DDIs) with cystic fibrosis transmembrane conductance regulator (CFTR)-modulating therapies, including elexacaftor, tezacaftor, and ivacaftor (ETI), which are eliminated mainly through cytochrome P450 (CYP) 3A-mediated metabolism. An assessment of the DDI risk for ETI coadministered with NTM treatments, including rifabutin, clofazimine, and clarithromycin, is needed to provide appropriate guidance on dosing. The CYP3A-mediated DDIs between ETI and the NTM therapies rifabutin, clarithromycin, and clofazimine were evaluated using physiologically based pharmacokinetic (PBPK) modeling by incorporating demographic and physiological "system" data with drug physicochemical and in vitro parameters. Models were verified and then applied to predict untested scenarios to guide continuation of ETI during antibiotic treatment, using ivacaftor as the most sensitive CYP3A4 substrate. The predicted area under the concentration-time curve (AUC) ratios of ivacaftor when coadministered with rifabutin, clofazimine, or clarithromycin were 0.31, 2.98, and 9.64, respectively, suggesting moderate and strong interactions. The simulation predicted adjusted dosing regimens of ETI administered concomitantly with NTM treatments, which required delayed resumption of the standard dose of ETI once the NTM treatments were completed. The dosing transitions were determined based on the characteristics of the perpetrator drugs, including the mechanism of CYP3A modulation and their elimination half-lives. This study suggests increased doses of elexacaftor/tezacaftor/ivacaftor 200/100/450 mg in the morning and 100/50/375 mg in the evening when ETI is coadministered with rifabutin and reduced doses of elexacaftor/tezacaftor 200/100 mg every 48 h (q48h) and ivacaftor 150 mg daily or a dose of elexacaftor/tezacaftor/ivacaftor 200/100/150 mg q72h when coadministered with clofazimine or clarithromycin, respectively. Importantly, the PBPK simulations provide evidence in support of the use of treatments for NTM in pwCF receiving concomitant dose-adjusted ETI therapy.
Assuntos
Fibrose Cística , Micobactérias não Tuberculosas , Humanos , Antibacterianos/uso terapêutico , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Claritromicina/uso terapêutico , Clofazimina/uso terapêutico , Benzodioxóis/uso terapêutico , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Pirrolidinas , Fibrose Cística/tratamento farmacológico , Interações Medicamentosas , Rifabutina/uso terapêuticoRESUMO
INTRODUCTION: Spinal Tuberculosis (STB) represents between 1% and 2% of total tuberculosis cases. STB management remains challenging; the first-line approach consists of medical treatment, while surgery is reserved for patients with complications. No data regarding STB treatment with bedaquiline-containing regimens are available in the literature. CASE DESCRIPTION: Herein, we report the case of a 21-year-old man from Côte d'Ivoire with a multidrug resistance STB with subcutaneous abscess. After approval of the hospital off-label drug committee, we started bedaquiline 400 mg daily for two weeks, followed by 200 mg three times per week, for 22 weeks, associated with linezolid 600 mg daily, rifabutin 450 mg daily, and amikacin 750 mg daily (interrupted after eight weeks). During treatment, we performed a weekly EKG. No QT prolongation was shown, but inverted T waves appeared, requiring several cardiological consultations and cardiac MRI, but no cardiac dysfunction was found. After 24 weeks, bedaquiline was replaced with moxifloxacin 400 mg daily. The patient continued treatment for another year. We performed another computer tomography at the end of treatment, confirming the cure. DISCUSSION: A salvage regimen containing bedaquiline proved effective in treating multidrug-resistance tuberculosis spinal infection without causing severe adverse effects. However, further studies are needed to evaluate better bedaquiline bone penetration and the correct duration of treatment with bedaquiline in MDR spinal tuberculosis.
Assuntos
Mycobacterium tuberculosis , Osteomielite , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose da Coluna Vertebral , Abscesso/tratamento farmacológico , Adulto , Amicacina/farmacologia , Amicacina/uso terapêutico , Antituberculosos/efeitos adversos , Diarilquinolinas/farmacologia , Diarilquinolinas/uso terapêutico , Humanos , Linezolida/farmacologia , Masculino , Moxifloxacina/farmacologia , Moxifloxacina/uso terapêutico , Uso Off-Label , Osteomielite/tratamento farmacológico , Rifabutina/farmacologia , Rifabutina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose da Coluna Vertebral/induzido quimicamente , Tuberculose da Coluna Vertebral/diagnóstico por imagem , Tuberculose da Coluna Vertebral/tratamento farmacológico , Adulto JovemRESUMO
BACKGROUND: Rifamycins are the cornerstone of anti-tuberculosis therapy while they are potent inducers of drug metabolizing enzymes. For the first time, we evaluated the effect of rifampicin (RIF) and rifabutin (RBT) on the pharmacokinetics (PK) of dolutegravir (DTG) in patients with HIV and tuberculosis (TB)/ mycobacterium avium complex (MAC) co-infection. METHODS: Both HIV/TB (or MAC) co-infected patients and HIV infected patients without TB/MAC were enrolled. Patients in the RIF group received DTG 50 mg twice daily together with 600mg of RIF, while patients in the RBT group received DTG 50 mg once daily together with 300 mg of RBT. The DTG pharmacokinetic profiles in different groups were assessed. RESULTS: A total of 13 subjects in the RIF group, 12 subjects in the RBT group, and 10 subjects in non-TB/MAC group were enrolled. The geometric mean ratio (GMR) of the trough concentration (Ctr) of DTG in the RIF group to non-TB/MAC group was 1.33 [90% confidence interval (CI):0.97 to 1.81], while the GMR of the maximum concentration (Cmax) of DTG was 1.29 (90% CI: 1.23 to 1.36). The GMR of the Ctr of DTG in the RBT group to non-TB/MAC group was 0.41 (90% CI: 0.30 to 0.57), while the GMR of the Cmax of DTG was 0.55 (90% CI: 0.52 to 0.57). CONCLUSIONS: Due to the relatively low trough concentrations of DTG with RBT, DTG 50mg once daily together with RBT could only serve as an alternative option for HIV/TB (or MAC) co-infected patients.
Assuntos
Coinfecção , Infecções por HIV , Infecção por Mycobacterium avium-intracellulare , Tuberculose , Coinfecção/tratamento farmacológico , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis , Humanos , Complexo Mycobacterium avium , Infecção por Mycobacterium avium-intracellulare/complicações , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Oxazinas , Piperazinas , Piridonas , Rifabutina/uso terapêutico , Rifampina , Tuberculose/complicações , Tuberculose/tratamento farmacológicoRESUMO
INTRODUCTION: Helicobacter pylori causes dyspepsia, peptic ulcer, and gastric malignancies. Treatments for Helicobacter pylori are mostly empirical depending on regional antibiotic resistances and the patient's history and less frequently susceptibility guided. Helicobacter pylori has a low resistance to rifabutin and has been proposed as an alternative for third-line treatment and beyond but recently has also gained attention for use as first- and second-line treatment. AREAS COVERED: In this review, the authors systematically searched medical databases in order to present the current eradication rates for any treatment based on the two antibiotics, rifabutin and amoxicillin with a potent acid inhibitor. They also assessed the safety and tolerance of all the relative regimens. EXPERT OPINION: Treatment with a rifabutin- and amoxicillin-containing regimen is a valuable option when treating difficult to eradicate Helicobacter pylori infections. Its efficacy is overall 71.4%, and it is not influenced by previous antibiotics, gender, smoking habits, and age. Its results were better when used as a first- or second-line treatment. In third-line therapy and beyond, eradication rates are lower. Adverse effects of all rifabutin regimens occurred in 23% of patients and were mostly mild with bone marrow suppression being very low and reversible.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Adulto , Amoxicilina/uso terapêutico , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Humanos , Rifabutina/uso terapêuticoRESUMO
BACKGROUND: Protease inhibitor-based antiretroviral therapy may be used in resource-limited settings in persons with human immunodeficiency virus and tuberculosis (HIV-TB). Data on safety, pharmacokinetics/pharmacodynamics (PK/PD), and HIV-TB outcomes for lopinavir/ritonavir (LPV/r) used with rifampin (RIF) or rifabutin (RBT) are limited. METHODS: We randomized adults with HIV-TB from July 2013 to February 2016 to arm A, LPV/r 400 mg/100 mg twice daily + RBT 150 mg/day; arm B, LPV/r 800 mg/200 mg twice daily + RIF 600 mg/day; or arm C, LPV/r 400 mg/100 mg twice daily + raltegravir (RAL) 400 mg twice daily + RBT 150 mg/day. All received two nucleoside reverse transcriptase inhibitors and other TB drugs. PK visits occurred on day 12 ± 2. Within-arm HIV-TB outcomes were summarized using proportions and 95% CIs; PK were compared using Wilcoxon tests. RESULTS: Among 71 participants, 52% were women; 72% Black; 46% Hispanic; median age, 37 years; median CD4+ count, 130 cells/mm3; median HIV-1 RNA, 4.6 log10 copies/mL; 46% had confirmed TB. LPV concentrations were similar across arms. Pooled LPV AUC12 (157 203 hours × ng/mL) and Ctrough (9876 ng/mL) were similar to historical controls; RBT AUC24 (7374 hours × ng/mL) and Ctrough (208 ng/mL) were higher, although 3 participants in arm C had RBT Cmax <250 ng/mL. Proportions with week 48 HIV-1 RNA <400 copies/mL were 58%, 67%, and 61%, respectively, in arms A, B, and C. CONCLUSIONS: Double-dose LPV/r+RIF and LPV/r+RBT 150mg/day had acceptable safety, PK and TB outcomes; HIV suppression was suboptimal but unrelated to PK. Faster RBT clearance and low Cmax in 3 participants on RBT+RAL requires further study.
Assuntos
Fármacos Anti-HIV , Coinfecção , Infecções por HIV , Inibidores da Protease de HIV , Tuberculose , Adulto , Fármacos Anti-HIV/efeitos adversos , Coinfecção/tratamento farmacológico , Quimioterapia Combinada , Feminino , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Humanos , Lopinavir/uso terapêutico , Masculino , Rifabutina/uso terapêutico , Rifampina/uso terapêutico , Ritonavir/uso terapêutico , Tuberculose/complicações , Tuberculose/tratamento farmacológicoRESUMO
RATIONALE & OBJECTIVES: Maintenance dialysis patients are at an increased risk for active tuberculosis (TB). In 2012, British Columbia, Canada, began systematically screening maintenance dialysis patients for latent TB infection (LTBI) and treating people with evidence of LTBI when appropriate. We examined LTBI treatment outcomes and compared treatment outcomes before and after rollout of the systematic screening program. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: The study comprised 365 people in British Columbia, Canada, initiating at least 90 days of dialysis from January 1, 2001, to May 31, 2017, and starting LTBI therapy: 290 (79.5%) people in the recent cohort and 75 (20.5%) in the historical cohort. People starting LTBI therapy from January 1, 2012, onward were classified as the recent cohort, whereas people starting LTBI therapy before January 1, 2012, were classified as the historical cohort. EXPOSURE: Systematic LTBI screening and therapy. OUTCOMES: Proportion of people who experience grade 3 to 5 adverse events (AEs) or any grade rash and end-of-treatment outcomes. ANALYTICAL APPROACH: Outcomes were reported using descriptive statistics. 2-sample test of proportions using χ2 distribution was used to test for statistical significance between the recent and historical cohorts. RESULTS: 298 (81.6%) people successfully completed LTBI therapy. The proportion of people experiencing a grade 3 to 4 AE or any grade rash was 21.1%. Most AEs were related to gastrointestinal events, general malaise, or pruritus that resulted in regimen changes. 2 (0.5%) people were hospitalized for AEs related to LTBI therapy. No significant difference was found between the recent and historical cohorts in all outcomes of interest. No grade 5 AEs (deaths) were attributed to LTBI therapy. LIMITATIONS: Retrospective data and generalizability outside low-TB-burden settings. CONCLUSIONS: Our findings suggest that a high proportion of people receiving maintenance dialysis can complete LTBI therapy. The rate of grade 3 to 4 AEs was high and associated with frequent medication changes during therapy. LTBI therapy in maintenance dialysis may be safe but requires close monitoring.
Assuntos
Antituberculosos/uso terapêutico , Falência Renal Crônica/terapia , Tuberculose Latente/tratamento farmacológico , Diálise Renal , Idoso , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Estudos de Coortes , Exantema/induzido quimicamente , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Isoniazida/uso terapêutico , Falência Renal Crônica/complicações , Tuberculose Latente/complicações , Tuberculose Latente/diagnóstico , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Prurido/induzido quimicamente , Estudos Retrospectivos , Rifabutina/uso terapêutico , Rifampina/uso terapêutico , Resultado do Tratamento , Vitamina B 6/uso terapêuticoAssuntos
Antiácidos/uso terapêutico , Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Adenocarcinoma/etiologia , Adenocarcinoma/microbiologia , Adenocarcinoma/prevenção & controle , Amoxicilina/uso terapêutico , Bismuto/uso terapêutico , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana , Quimioterapia Combinada , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Helicobacter pylori , Humanos , Metronidazol/uso terapêutico , Testes de Sensibilidade Microbiana , Omeprazol/uso terapêutico , Guias de Prática Clínica como Assunto , Pirróis/uso terapêutico , Rifabutina/uso terapêutico , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/prevenção & controle , Sulfonamidas/uso terapêutico , Tetraciclina/uso terapêutico , Resultado do TratamentoRESUMO
As one of the most prevalent infections globally, Helicobacter pylori (H. pylori) continues to present diagnostic and therapeutic challenges for clinicians worldwide. Diagnostically, the "test-and-treat" strategy is the recommended approach for healthcare practitioners when managing this potentially curable disease. The choice of testing method should be based on several factors including patient age, presenting symptoms, and medication use, as well as test reliability, availability, and cost. With rising antibiotic resistance, particularly of macrolides, care must be taken to ensure that therapy is selected based on regional resistance patterns and prior antibiotic exposure. In the USA, macrolide antibiotic resistance rates in some areas have reached or exceeded a generally accepted threshold, such that clarithromycin triple therapy may no longer be an appropriate first-line empiric treatment. Instead, bismuth quadruple therapy should be considered, while levofloxacin-based or alternative macrolide-containing therapies are also options. Once treated, it is essential to test for eradication as untreated H. pylori is associated with serious complications including peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. This review article aims to consolidate current knowledge of H. pylori infection with a particular emphasis on diagnostic and treatment strategies.
Assuntos
Antibacterianos/uso terapêutico , Antiulcerosos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Amoxicilina/uso terapêutico , Antígenos de Bactérias/análise , Biópsia , Bismuto/uso terapêutico , Testes Respiratórios , Claritromicina/uso terapêutico , Técnicas de Cultura , Doxiciclina/uso terapêutico , Farmacorresistência Bacteriana , Quimioterapia Combinada , Dispepsia/etiologia , Fezes/química , Gastroscopia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Helicobacter pylori , Humanos , Levofloxacino/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/etiologia , Metronidazol/uso terapêutico , Nitrocompostos , Compostos Organometálicos/uso terapêutico , Úlcera Péptica/etiologia , Reação em Cadeia da Polimerase , Rifabutina/uso terapêutico , Salicilatos/uso terapêutico , Terapia de Salvação , Testes Sorológicos , Neoplasias Gástricas/etiologia , Tetraciclina/uso terapêutico , Tiazóis/uso terapêutico , Resultado do Tratamento , Ureia/metabolismoRESUMO
BACKGROUND: Opportunistic infections, while well studied in the AIDS population, continue to have variable and surprising presentations. Here, we present a case of disseminated histoplasmosis with disseminated nontuberculous mycobacterial infection in a 50 year old man with long standing AIDS living in a non-endemic area. CASE PRESENTATION: Patient presented with a constellation of symptoms, and imaging of the chest showed a pulmonary mass with cavitation, multiple nodules, and ground glass opacities. Further investigations revealed granulomatous lung nodules and fungemia consistent with Histoplasma capsulatum, and coinfection with disseminated nontuberculous mycobateria in a nonendemic area. CONCLUSIONS: Immunocompromised patients risk co-inhabitation by multiple infectious organisms. Some of these organisms may preside in the host for years prior to reactivation. Clinicians in non endemic areas should therefore be careful to not overlook specific organisms based on a lack of a recent travel history. Physicians in nonendemic areas should become more familiar with the clinical findings and diagnostic approach of infectious such as Histoplasmosis, to ensure earlier recognition and treatment in immunocompromised individuals.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Síndrome da Imunodeficiência Adquirida/complicações , Bacteriemia/complicações , Fungemia/complicações , Histoplasmose/complicações , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/patologia , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Anfotericina B/uso terapêutico , Antibacterianos/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Antifúngicos/uso terapêutico , Antituberculosos/uso terapêutico , Azitromicina/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , California , Emtricitabina/uso terapêutico , Etambutol/uso terapêutico , Fungemia/diagnóstico , Fungemia/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Histoplasmose/patologia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/patologia , Oxazinas , Piperazinas , Piridonas , Rifabutina/uso terapêutico , Tenofovir/uso terapêutico , Tomografia Computadorizada por Raios XAssuntos
Antibacterianos/uso terapêutico , Doença de Crohn/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções Oportunistas/microbiologia , Prednisona/uso terapêutico , Rifabutina/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Idoso , Animais , Doença de Crohn/imunologia , Peixes/microbiologia , Humanos , Masculino , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/imunologia , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/imunologia , Resultado do Tratamento , Microbiologia da ÁguaRESUMO
BACKGROUND Rifamycins are a group of antibiotics mainly used in the treatment of tuberculosis (TB), however they interact with antiretroviral therapy (ART). Rifabutin allows more regimens options for concomitant imunodeficiency virus (HIV) treatment compared to rifampicin. OBJECTIVE Compare the outcomes of TB-HIV co-infected patients who used rifampicin or rifabutin. METHODS We analysed data from a prospective cohort study at National Institute of Infectious Diseases Evandro Chagas, Rio de Janeiro (RJ), Brazil. Patients who were treated for TB and HIV with rifampicin or rifabutin, from February 2011 to September 2016 were included. FINDINGS There were 130 TB-HIV patients, of whom 102 were treated with rifampicin and 28 with rifabutin. All patients in the rifabutin-treated group and 55% of the rifampicin-treated group patients were ART-experienced. Patients treated with rifampicin had similar abandon and cure rates, interruptions in treatment due to adverse reactions, immune reconstitution inflammatory syndrome and a similar mortality rate as those treated with rifabutin. However, rifampicin-treated patients had higher CD4 counts and more frequently undetectable HIV viral load by the end of treatment (67% versus 18%, p < 0.001) compared to rifabutin-treated patients, even when only ART-experienced patients were evaluated (66,6% versus 36,3%, p = 0.039). CONCLUSIONS Patients who used rifabutin had worst immune and virological control. This group had more ART-experienced patients. New and simpler regimens are needed for patients who do not respond to previous antiretroviral therapies.
Assuntos
Humanos , Rifamicinas/uso terapêutico , Tuberculose/prevenção & controle , Avaliação de Resultados em Cuidados de Saúde , Rifabutina/uso terapêutico , Rifampina , HIVAssuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Rifabutina/efeitos adversos , Uveíte/induzido quimicamente , Criança , Ciprofloxacina/uso terapêutico , Substituição de Medicamentos , Feminino , HIV , Infecções por HIV/patologia , Humanos , Hospedeiro Imunocomprometido , Rifabutina/uso terapêutico , Uveíte/diagnóstico , Suspensão de TratamentoRESUMO
Helicobacter pylori-associated gastritis leads to the development of gastric cancer. Kyoto global consensus report on H. pylori gastritis recommended H. pylori eradication therapy to prevent gastric cancer. To manage H. pylori infection, it is important to choose the appropriate regimen considering regional differences in resistance to clarithromycin and metronidazole. Quinolones and rifabutin-containing regimens are useful as third- and fourth-line rescue therapies.
Assuntos
Erradicação de Doenças/tendências , Gastrite/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/prevenção & controle , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Claritromicina/efeitos adversos , Claritromicina/uso terapêutico , Consenso , Farmacorresistência Bacteriana , Gastrite/complicações , Diretrizes para o Planejamento em Saúde , Infecções por Helicobacter/diagnóstico , Humanos , Incidência , Japão/epidemiologia , Metronidazol/efeitos adversos , Metronidazol/uso terapêutico , Programas Nacionais de Saúde , Quinolonas/uso terapêutico , Rifabutina/uso terapêutico , Neoplasias Gástricas/etiologiaRESUMO
Helicobacter pylori (H. pylori) is a common gastrointestinal bacterial strain closely associated with the incidence of chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. A current research and clinical challenge is the increased rate of antibiotic resistance in H. pylori, which has led to a decreased H. pylori eradication rate. In this article, we review recent H. pylori infection and reinfection rates and H. pylori resistance to antibiotics, and we discuss the pertinent treatments. A PubMed literature search was performed using the following keywords: Helicobacter pylori, infection, reinfection, antibiotic resistance, bismuth, proton pump inhibitors, vonoprazan, susceptibility, quintuple therapy, dual therapy, and probiotic. The prevalence of H. pylori has remained high in some areas despite the decreasing trend of H. pylori prevalence observed over time. Additionally, the H. pylori reinfection rate has varied in different countries due to socioeconomic and hygienic conditions. Helicobacter pylori monoresistance to clarithromycin, metronidazole or levofloxacin was common in most countries. However, the prevalence of amoxicillin and tetracycline resistance has remained low. Because H. pylori infection and reinfection present serious challenges and because H. pylori resistance to clarithromycin, metronidazole or levofloxacin remains high in most countries, the selection of an efficient regimen to eradicate H. pylori is critical. Currently, bismuth-containing quadruple therapies still achieve high eradication rates. Moreover, susceptibility-based therapies are alternatives because they may avoid the use of unnecessary antibiotics. Novel regimens, e.g., vonoprazan-containing triple therapies, quintuple therapies, high-dose dual therapies, and standard triple therapies with probiotics, require further studies concerning their efficiency and safety for treating H. pylori.
Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Quimioterapia Combinada/métodos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Amoxicilina/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/classificação , Bismuto/uso terapêutico , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana/genética , Furazolidona/uso terapêutico , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Humanos , Levofloxacino/uso terapêutico , Metronidazol/uso terapêutico , Mutação , Prevalência , Probióticos/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Pirróis/uso terapêutico , Rifabutina/uso terapêutico , Sulfonamidas/uso terapêutico , Tetraciclina/uso terapêutico , Resistência a TetraciclinaRESUMO
We recently shown a novel neuro-immune competition between vasoactive intestinal peptide (VIP) and PGD2 for CRTH2 receptor, and that genistein augmented VIP and PGD2-induced eosinophil chemotaxis. However, there are neither studies on the CRTH2 gene expression in allergic rhinitis (AR) nor in the effect of tyrosine kinase inhibitors in CRTH2 gene regulation. Our Objectives were to study the gene expression modulation of CRTH2 receptor in AR patients and the effect of tyrosine kinase inhibitors (TKIs) on CRTH2 gene modulation. Nasal provocation tests, ELISA, qRT-PCR, western blot, flow cytometry and chemotaxis assays in modified micro-Boyden chambers, were all used, to achieve our objectives. Herein we show that AR patients increased the amounts of VIP and PGD2 in their nasal secretions in the early phase reaction, however CRTH2 gene expression from leukocytes recovered in their nasal secretions was upregulated only during the late phase reaction. The TKIs; Genistein, Erbstatin and Herbimycin A, induced the gene expression of CRTH2 and increased the protein content of CRTH2 in both human lymphocytes and eosinophils. This was functional as PGD2/VIP-induced eosinophil chemotaxis was augmented by the TKIs and inhibited by pervanadate, the tyrosine phosphatase inhibitor. These results open channels for therapeutic modalities targeting CRTH2 molecules in AR.
Assuntos
Movimento Celular/efeitos dos fármacos , Eosinófilos/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Mucosa Nasal/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Receptores Imunológicos/metabolismo , Receptores de Prostaglandina/metabolismo , Rinite Alérgica/tratamento farmacológico , Adulto , Antígenos de Dermatophagoides/imunologia , Células Cultivadas , Eosinófilos/imunologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Genisteína/uso terapêutico , Humanos , Hidroquinonas/uso terapêutico , Linfócitos/imunologia , Masculino , Neuroimunomodulação , Prostaglandina D2/metabolismo , Receptores Imunológicos/genética , Receptores de Prostaglandina/genética , Rinite Alérgica/imunologia , Rifabutina/análogos & derivados , Rifabutina/uso terapêutico , Peptídeo Intestinal Vasoativo/metabolismoRESUMO
BACKGROUND/AIMS: Optimized regimen has not yet been established for failures of multiple Helicobacter pylori (H. pylori) eradication. Hence, we aimed to evaluate the efficacy of rifabutin-based rescue therapy, at least after three eradication failures. METHODS: Twelve patients, who failed in the treatment for H. pylori eradication at least three times, were consecutively enrolled between 2007 and 2015 at Seoul National University Bundang Hospital. The rifabutin-based rescue regimen was consisted of proton pump inhibitor (PPI), rifabutin (150 mg b.i.d.), and amoxicillin (1 g b.i.d.), given for 7 or 14 days. MIC concentration test by the agar dilution method was performed on six patients prior to rifabutin-based rescue therapy. RESULTS: One patient did not take this regimen, and per-protocol (PP) analysis was performed in 11 patients. The overall eradication rate by intention-to-treat and PP analysis with rifabutin-based rescue therapy was 50.0% (6/12 patients) and 54.5% (6/11 patients), respectively. There was no difference of the eradication rate depending on the underlying disease, smoking, alcohol, number of previous eradication failures, and CYP2C19 genotype. All of the six patients were susceptible to rifabutin, but only three of them succeeded in eradicating with H. pylori. Side effects occurred in two patients (18.2%), and compliance was 90.9%. CONCLUSIONS: Even the eradication rate of rifabutin-based rescue therapy was not very good. Rifabutin-based rescue therapy could be considered as a rescue therapy, perhaps as the fourth or the fifth-line treatment option. No correlation of rifabutin sensitivity with eradication success rate of H. pylori suggests that frequent administration of high dose PPI and amoxicillin might be important.
Assuntos
Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Rifabutina/uso terapêutico , Amoxicilina/uso terapêutico , Citocromo P-450 CYP2C19/genética , Farmacorresistência Bacteriana/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Genótipo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Testes de Sensibilidade Microbiana , Inibidores da Bomba de Prótons/uso terapêutico , Rifabutina/farmacologia , Falha de TratamentoRESUMO
Nontuberculous mycobacterial infections can often occur in individuals with adequate immune function. Such infections typically have cutaneous involvement and are caused by rapidly growing mycobacterium. Other nontuberculous mycobacteria species, like Mycobacterium haemophilum, almost always present as opportunistic infections occurring in severely immunocompromised hosts. Here, we present a complicated and protracted course of diagnosing M. haemophilum lower extremity cutaneous infection in a matched-unrelated donor stem cell transplant recipient.
Assuntos
Antibacterianos/uso terapêutico , Celulite (Flegmão)/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/cirurgia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium haemophilum/isolamento & purificação , Infecções Oportunistas/tratamento farmacológico , Biópsia , Celulite (Flegmão)/complicações , Celulite (Flegmão)/diagnóstico , Celulite (Flegmão)/microbiologia , Ciprofloxacina/uso terapêutico , Claritromicina/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Hospedeiro Imunocomprometido , Terapia de Imunossupressão/efeitos adversos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Extremidade Inferior , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções Oportunistas/complicações , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/microbiologia , Rifabutina/uso terapêutico , Tacrolimo/efeitos adversos , Tacrolimo/uso terapêutico , Doadores não RelacionadosRESUMO
BACKGROUND: There have been a number of studies with conflicting results which have examined the effect of anti-tuberculous therapy in Crohn's disease. A meta-analysis was performed to evaluate the use of anti-tuberculous therapy for the maintenance of remission in Crohn's disease. OBJECTIVES: To evaluate the effects of anti-tuberculous therapy for the maintenance of remission in patients with Crohn's disease. SEARCH METHODS: We searched MEDLINE, EMBASE, the Cochrane LIbrary, and the Cochrane IBD Group Specialized Register from inception to June 22, 2015. SELECTION CRITERIA: Randomized controlled trials (RCTs) of anti-tuberculous therapy compared to placebo or another active therapy in patients with quiescent Crohn's disease were considered for inclusion. DATA COLLECTION AND ANALYSIS: At least two authors independently extracted data and assessed the quality of included studies using the Cochrane risk of bias tool. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes.. The primary outcome was relapse. Secondary outcomes included adverse events, withdrawals due to adverse events and serious adverse events. All data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the primary and secondary outcomes was evaluated using the GRADE criteria. MAIN RESULTS: Four placebo-controlled RCTs including 206 participants were included. Three trials included an 8 to 16 week induction phase with tapering corticosteroids (prednisone, prednisolone or methylprednisolone) as induction therapy. Anti-tuberculous therapy included monotherapy with clofazimine, combination therapy with clofazimine, rifampin, ethambutol, and dapsone or combination therapy with clarithromycin, rifabutin and clofazimine. All of the studies were rated as unclear risk of bias for allocation concealment, three were rated as unclear risk of bias for random sequence generation and two were rated as unclear risk of bias for blinding or participants and personnel. There was a statistically significant difference in relapse rates favoring anti-tuberculous therapy over placebo. Thirty-nine per cent (44/112) of patients in the anti-tuberculous therapy group relapsed at 9 months to 2 years compared to 67% (63/94) of placebo patients (RR 0.58, 95% CI 0.45 to 0.75, I(2) = 47%). A GRADE analysis indicates that the overall quality of the evidence supporting this outcome was very low due to unknown risk of bias and sparse data. Adverse events occurred more frequently in the anti-tuberculous therapy group (37/159) compared to the placebo group (14/163) with a pooled RR of 2.57 (95% CI 1.45 to 4.55; N=322; studies=4, I(2)=64%). A GRADE analysis indicates that the overall quality of the evidence supporting this outcome was very low due to unknown risk of bias, unexplained heterogeneity and sparse data. There was no difference in withdrawals due to adverse events. Nine per cent (14/159) of anti-tuberculous therapy patients withdrew due to adverse events compared to 7% (11/163) of placebo patients (RR 1.29, 95% CI 0.60 to 2.77, I(2) = 0%). Common adverse events included increased skin pigmentation and rashes. No serious adverse events were reported in any of the included studies. AUTHORS' CONCLUSIONS: Anti-tuberculous therapy may provide a benefit over placebo for the prevention of relapse in participants with Crohn's disease in remission. However, this result is very uncertain due to unclear study quality and the small numbers of patients assessed. Further studies are needed to provide better quality evidence for the use of anti-tuberculous therapy for maintaining remission in people with quiescent Crohn's disease.
Assuntos
Antituberculosos/uso terapêutico , Doença de Crohn/prevenção & controle , Quimioterapia de Manutenção/métodos , Prevenção Secundária , Antituberculosos/efeitos adversos , Claritromicina/uso terapêutico , Clofazimina/uso terapêutico , Doença de Crohn/tratamento farmacológico , Etambutol/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Metilprednisolona/uso terapêutico , Prednisona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Indução de Remissão , Rifabutina/uso terapêutico , Rifampina/uso terapêuticoRESUMO
Nitazoxanide (NTZ) has moderate mycobactericidal activity and is also an inducer of autophagy in mammalian cells. High-payload (40-50% w/w) inhalable particles containing NTZ alone or in combination with antituberculosis (TB) agents isoniazid (INH) and rifabutin (RFB) were prepared with high incorporation efficiency of 92%. In vitro drug release was corrected for drug degradation during the course of study and revealed first-order controlled release. Particles were efficiently taken up in vitro by macrophages and maintained intracellular drug concentrations at one order of magnitude higher than NTZ in solution for 6 h. Dose-dependent killing of Mtb and restoration of lung and spleen architecture were observed in experimentally infected mice treated with inhalations containing NTZ. Adjunct NTZ with INH and RFB cleared culturable bacteria from the lung and spleen and markedly healed tissue architecture. NTZ can be used in combination with INH-RFB to kill the pathogen and heal the host.