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1.
Medicine (Baltimore) ; 100(17): e25283, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33907090

RESUMO

ABSTRACT: We report the clinical results and problems of combined administration of rifampicin, ethambutol, and clarithromycin (REC) for the treatment of Mycobacterium avium complex (MAC) infection of the hand (hand MAC).Participants included 7 patients with hand MAC. After resection of the infected lesion, REC was prescribed for 12 months. For these patients, the site of infection, clinical course after initiation of REC, adverse drug effects (ADEs), and incidence of recurrence were evaluated.Sites of infection were the flexor tenosynovium in 5 patients, extensor tenosynovium in 1 patient, and both flexor and extensor tenosynovium in 1 patient. ADEs of REC occurred in 5 patients, and included visual disturbance caused by ethambutol in 2 patients, liver function abnormality caused by rifampicin in 2 patients, and fever with diarrhea caused by rifampicin in 1 patient. For 2 of these 5 patients, desensitization therapy was applied and REC was able to be reinstated. In the remaining 3 patients, the causative drugs were discontinued and levofloxacin, a new quinolone, was administered. Complete healing was achieved in 5 patients, and recurrence was observed in 2 patients. These 2 patients with recurrence included 1 patient in whom REC was completed and 1 patient in whom REC therapy was modified due to ADE.REC provided relatively good clinical results as a treatment for hand MAC. However, recurrences were observed even after the completion of REC and the use of an alternative drug. Optimal duration of REC and appropriate alternative drugs need to be identified in the future.


Assuntos
Antibacterianos/administração & dosagem , Claritromicina/administração & dosagem , Etambutol/administração & dosagem , Complexo Mycobacterium avium , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Rifampina/administração & dosagem , Tenossinovite/tratamento farmacológico , Idoso , Quimioterapia Combinada , Feminino , Mãos/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infecção por Mycobacterium avium-intracellulare/microbiologia , Tenossinovite/microbiologia
2.
Lancet Child Adolesc Health ; 5(5): 350-356, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33770510

RESUMO

BACKGROUND: Shorter regimens for tuberculosis prevention can improve completion rates and protection against developing active tuberculosis disease after tuberculosis exposure. We aimed to assess the safety and feasibility of 1 month of daily isoniazid and rifapentine (1HP) in children and adolescents in a low-resource setting in south Asia with low prevalence of HIV. METHODS: This prospective cohort study was done in eight tuberculosis facilities in Karachi, Pakistan. Eligible participants were aged 2-19 years and were household contacts of patients with drug-susceptible tuberculosis infection. After clinical, radiological, and laboratory evaluation to rule out tuberculosis disease, participants were prescribed 1HP as a preventive regimen. Isoniazid was administered as 100 mg or 300 mg oral tablets and rifapentine was administered as 150 mg oral tablets. Dosing was according to participant bodyweight. The primary endpoints were the cumulative probability of a household contact completing all stages of the preventive care cascade, assessed in all eligible participants, and the proportion of household contacts completing 1HP, assessed among all those who initiated the regimen. Safety was assessed in all household contacts who initiated the 1HP regimen. FINDINGS: Between Dec 21, 2019, and March 20, 2020, 1395 household contacts of 253 patients with tuberculosis were identified, including 678 household contacts who were eligible to participate. 628 (93%) completed evaluation, of whom ten (2%) had active tuberculosis disease. Of the 618 individuals eligible for tuberculosis prevention, 408 (66%) initiated 1HP, 385 (94%) of whom completed the regimen. The median duration of 1HP was 31 days (IQR 30-32) in those who completed the regimen. The cumulative probability of completing all steps of the tuberculosis prevention cascade was 58%. A girl aged 11 years developed tuberculosis disease within 6 months of completing 1HP. A boy aged 14 years developed a burning sensation during 1HP therapy and discontinued the regimen. No other adverse events were observed. INTERPRETATION: 1HP can be safely and feasibly implemented as tuberculosis prevention in children and adolescents in programmatic settings. FUNDING: The Global Fund to Fight AIDS, Tuberculosis and Malaria.


Assuntos
Antituberculosos/administração & dosagem , Duração da Terapia , Isoniazida/administração & dosagem , Rifampina/análogos & derivados , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Tuberculose/prevenção & controle , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Paquistão/epidemiologia , Estudos Prospectivos , Rifampina/administração & dosagem , Adulto Jovem
3.
AAPS PharmSciTech ; 22(3): 116, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33763801

RESUMO

We focused to explore a suitable solvent for rifampicin (RIF) recommended for subcutaneous (sub-Q) delivery [ethylene glycol (EG), propylene glycol (PG), tween 20, polyethylene glycol-400 (PEG400), oleic acid (OA), N-methyl-2-pyrrolidone (NMP), cremophor-EL (CEL), ethyl oleate (EO), methanol, and glycerol] followed by computational validations and in-silico prediction using GastroPlus. The experimental solubility was conducted over temperature ranges T = 298.2-318.2 K) and fixed pressure (p = 0.1 MPa) followed by validation employing computational models (Apelblat, and van't Hoff). Moreover, the HSPiP solubility software provided the Hansen solubility parameters. At T = 318.2K, the estimated maximum solubility (in term of mole fraction) values of the drug were in order of NMP (11.9 × 10-2) ˃ methanol (6.8 × 10-2) ˃ PEG400 (4.8 × 10-2) ˃ tween 20 (3.4 × 10-2). The drug dissolution was endothermic process and entropy driven as evident from "apparent thermodynamic analysis". The activity coefficients confirmed facilitated RIF-NMP interactions for increased solubility among them. Eventually, GastroPlus predicted the impact of critical input parameters on major pharmacokinetics responses after sub-Q delivery as compared to oral delivery. Thus, NMP may be the best solvent for sub-Q delivery of RIF to treat skin tuberculosis (local and systemic) and cutaneous related disease at explored concentration.


Assuntos
Antibióticos Antituberculose/farmacocinética , Simulação por Computador , Sistemas de Liberação de Medicamentos/métodos , Rifampina/farmacocinética , Termodinâmica , Antibióticos Antituberculose/administração & dosagem , Previsões , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/farmacocinética , Reprodutibilidade dos Testes , Rifampina/administração & dosagem , Absorção Cutânea/efeitos dos fármacos , Absorção Cutânea/fisiologia , Solubilidade , Absorção Subcutânea
4.
BMC Infect Dis ; 21(1): 174, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579208

RESUMO

BACKGROUND: Prosthetic joint infections (PJI) are a major cause of morbidity and mortality burden worldwide. While surgical management is well defined, rifampicin (RIF) dose remains controversial. The aim of our study was to determine whether Rifampicin dose impact infection outcomes in PJI due to Staphylococcus spp. METHODS: single-center retrospective study including 411 patients with PJI due to Rifampicin-sensitive Staphylococcus spp. Rifampicine dose was categorized as follow: < 10 mg/kg/day, 10-20 mg/kg/day or > 20 mg/kg/day. The primary endpoint was patient recovery, defined as being free of infection during 12 months after the end of the initial antibiotic course. RESULTS: 321 (78%) received RIF for the full antibiotic course. RIF dose didn't affect patients recovery rate with 67, 76 and 69% in the < 10, 10-20 and > 20 mg/kg/day groups, respectively (p = 0.083). In univariate analysis, recovery rate was significantly associated with gender (p = 0.012) but not to RIF dose, or Staphylococcus phenotype (aureus or coagulase-negative). In multivariate analysis, age (p = 0.01) and treatment duration (p <  0.01) were significantly associated with recovery rate. CONCLUSION: These data suggest that lower doses of RIF are as efficient and safe as the recommended high-dose French regimen in the treatment of PJI.


Assuntos
Antibacterianos/administração & dosagem , Artrite Infecciosa/tratamento farmacológico , Infecções Relacionadas à Prótese/tratamento farmacológico , Rifampina/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Idoso , Antibacterianos/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Rifampina/efeitos adversos , Staphylococcus/efeitos dos fármacos , Resultado do Tratamento
5.
BMC Infect Dis ; 21(1): 90, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33478428

RESUMO

BACKGROUND: Ending the global tuberculosis (TB) epidemic requires a focus on treating individuals with latent TB infection (LTBI) to prevent future cases. Promising trials of shorter regimens have shown them to be effective as preventative TB treatment, however there is a paucity of data on self-administered treatment completion rates. This pilot trial assessed treatment completion, adherence, safety and the feasibility of treating LTBI in the UK using a weekly rifapentine and isoniazid regimen versus daily rifampicin and isoniazid, both self-administered for 12 weeks. METHODS: An open label, randomised, multi-site pilot trial was conducted in London, UK, between March 2015 and January 2017. Adults between 16 and 65 years with LTBI at two TB clinics who were eligible for and agreed to preventative therapy were consented and randomised 1:1 to receive either a weekly combination of rifapentine/isoniazid ('intervention') or a daily combination of rifampicin/isoniazid ('standard'), with both regimens taken for twelve weeks; treatment was self-administered in both arms. The primary outcome, completion of treatment, was self-reported, defined as taking more than 90% of prescribed doses and corroborated by pill counts and urine testing. Adverse events were recorded. RESULTS: Fifty-two patients were successfully enrolled. In the intervention arm 21 of 27 patients completed treatment (77.8, 95% confidence interval [CI] 57.7-91.4), compared with 19 of 25 (76.0%, CI 54.9-90.6) in the standard of care arm. There was a similar adverse effect profile between the two arms. CONCLUSION: In this pilot trial, treatment completion was comparable between the weekly rifapentine/isoniazid and the daily rifampicin/isoniazid regimens. Additionally, the adverse event profile was similar between the two arms. We conclude that it is safe and feasible to undertake a fully powered trial to determine whether self-administered weekly treatment is superior/non-inferior compared to current treatment. TRIAL REGISTRATION: The trial was funded by the NIHR, UK and registered with ISRCTN ( 26/02/2013-No.04379941 ).


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Rifampina/análogos & derivados , Rifampina/uso terapêutico , Adolescente , Adulto , Antituberculosos/administração & dosagem , Antituberculosos/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Isoniazida/administração & dosagem , Isoniazida/efeitos adversos , Isoniazida/uso terapêutico , Londres , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Rifampina/administração & dosagem , Rifampina/efeitos adversos , Autoadministração , Resultado do Tratamento , Adulto Jovem
6.
J Orthop Res ; 39(2): 402-414, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33336805

RESUMO

Infection is a devastating complication following an open fracture. We investigated whether local rifampin-loaded hydrogel can combat infection and improve healing in a murine model of methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. A transverse fracture was made at the tibia midshaft of C57BL/6J mice aged 10-12 weeks and stabilized with an intramedullary pin. A total of 1 × 106 colony-forming units (CFU) of MRSA was inoculated. A collagen-based hydrogel containing low-dose (60 µg) and high-dose (300 µg) rifampin was applied before closure. Postoperative treatment response was assessed through bacterial CFU counts from tissue and hardware, tibial radiographs and microcomputed tomography (µCT), immunohistochemistry, and histological analyses. All untreated MRSA-infected fractures progressed to nonunion by 28 days with profuse MRSA colonization. Infected fractures demonstrated decreased soft callus formation on safranin O stain compared to controls. Areas of dense interleukin-1ß stain were associated with poor callus formation. High-dose rifampin hydrogels reduced the average MRSA load in tissue (p < 0.0001) and implants (p = 0.041). Low-dose rifampin hydrogels reduced tissue bacterial load by 50% (p = 0.021). Among sterile models, 88% achieved union compared to 0% of those infected. Mean radiographic union scale in tibia scores improved from 6 to 8.7 with high-dose rifampin hydrogel (p = 0.024) and to 10 with combination local/systemic rifampin therapy (p < 0.0001). µCT demonstrated reactive bone formation in MRSA infection. Histology demonstrated restored fracture healing with bacterial elimination. Rifampin-loaded hydrogels suppressed osteomyelitis, prevented implant colonization, and improved healing. Systemic rifampin was more effective at eliminating infection and improving fracture healing. Further investigation into rifampin-loaded hydrogels is required to correlate these findings with clinical efficacy.


Assuntos
Antibióticos Antituberculose/administração & dosagem , Fraturas Expostas/complicações , Osteomielite/tratamento farmacológico , Rifampina/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Animais , Carga Bacteriana/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Consolidação da Fratura/efeitos dos fármacos , Hidrogéis , Masculino , Staphylococcus aureus Resistente à Meticilina , Camundongos Endogâmicos C57BL , Osteomielite/etiologia , Infecções Estafilocócicas/etiologia
7.
Carbohydr Polym ; 252: 116978, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33183580

RESUMO

This work proposes the development and characterization of solid lipid nanoparticles (SLNs) loaded with rifampicin (RIF) aiming to enhance mucoadhesion of the SLNs and consequently internalization by the alveolar macrophages (AMs). The lipid nanoparticles (NPs) were characterized and the results showed that the NPs obtained present a spherical or a starry shape with diameter around 250-500 nm, a monodisperse population, with zeta potential between -31 mV for uncoated SLNs and +33 mV for coated SLNs. The drug EE was approximately 90 % and the loading capacity (LC) 4.5 %. The SLNs coated with chitosan by the association method (aC-SLNs) show an effective mucoadhesive profile, verified by the turdimetry and surface loading method, corroborated with the cellular assays. The presence of chitosan in the aC-SLNs promotes higher mucoadhesive properties to the NPs and permeability in A549, suggesting that the safe aC-SLNs-RIF can be used as a promising drug delivery system for improving tuberculosis treatment.


Assuntos
Antibióticos Antituberculose/administração & dosagem , Quitosana/química , Portadores de Fármacos/química , Lipídeos/química , Macrófagos Alveolares/efeitos dos fármacos , Nanopartículas/química , Rifampina/administração & dosagem , Células A549 , Liberação Controlada de Fármacos , Humanos , Tamanho da Partícula , Tuberculose/tratamento farmacológico
8.
Cir. plást. ibero-latinoam ; 46(4): 483-488, oct.-dic. 2020. ilus
Artigo em Espanhol | IBECS | ID: ibc-198736

RESUMO

Presentamos un caso en el que empleamos con éxito plasma rico en plaquetas heterólogo (PRPh) para la reparación de una quemadura de difícil evolución en un paciente pediátrico. Mostramos la seguridad y eficacia del uso del PRPh proveniente de la madre en un caso de quemadura AB-A por agua caliente. Se trata de una paciente de 3 años de edad que fue intervenida quirúrgicamente en otro centro, sin resultados positivos y profundizándose, por lo que se vio complicada su recuperación. El objetivo fue regenerar el tejido afectado e inducir de manera asistida la formación de tejido epitelial utilizando PRPh de la madre de la paciente. Aplicamos técnica de curación cerrada en 2 sesiones ambulatorias mediante la aplicación de PRPh sin necesidad de procedimientos adicionales. No se presentaron complicaciones, signos de rechazo ni infecciones y la recuperación se obtuvo en 14 días


The safety and efficacy of the use of heterologous rich platelet plasma (hRPP) from the mother is shown in a case of AB-A burn by hot water. This is a 3-year-old patient who was surgically operated in another center, without positive results and deepening, so recovery was complicated. The objective was to regenerate the affected tissue and to induce in an assisted way the formation of epithelial tissue using hRPP from the patient's mother. We apply the closed healing technique in 2 outpatient sessions by applying hRPP without the need for additional procedures. There were no complications, signs of rejection or infections, and their recovery was obtained in 14 days


Assuntos
Humanos , Feminino , Pré-Escolar , Queimaduras/terapia , Plasma Rico em Plaquetas , Resultado do Tratamento , Regeneração , Segurança do Paciente , Rifampina/administração & dosagem , Curativos Oclusivos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Cicatrização , Administração Tópica
9.
PLoS Negl Trop Dis ; 14(12): e0008888, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33373362

RESUMO

Brucella spp. are facultative intracellular pathogens that can persistently colonize host cells and cause the zoonosis- brucellosis. The WHO recommended a treatment for brucellosis that involves a combination of doxycycline, rifampicin, or streptomycin. The aim of this study was to screen rifampicin-resistance related genes by transcriptomic analysis and gene recombination method at low rifampicin concentrations and to predict the major rifampicin- resistance pathways in Brucella spp. The results showed that the MIC value of rifampicin for B. melitensis bv.3 Ether was 0.5 µg / mL. Meanwhile, B. melitensis had an adaptive response to the resistance of low rifampicin in the early stages of growth, while the SNPs changed in the rpoB gene in the late stages of growth when incubated at 37°C with shaking. The transcriptome results of rifampicin induction showed that the functions of significant differentially expressed genes were focused on metabolic process, catalytic activity and membrane and membrane part. The VirB operon, ß-resistance genes, ABC transporters, quorum-sensing genes, DNA repair- and replication -related genes were associated with rifampicin resistance when no variations of the in rpoB were detected. Among the VirB operons, VirB7-11 may play a central role in rifampicin resistance. This study provided new insights for screening rifampicin resistance-related genes and also provided basic data for the prevention and control of rifampicin-resistant Brucella isolates.


Assuntos
Antibióticos Antituberculose/farmacologia , Brucella melitensis/efeitos dos fármacos , Rifampina/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Membrana Celular , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Farmacorresistência Bacteriana , Regulação Bacteriana da Expressão Gênica , Genoma Bacteriano , Testes de Sensibilidade Microbiana , Rifampina/administração & dosagem
10.
Int J Nanomedicine ; 15: 7491-7507, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116484

RESUMO

Background: Tuberculosis (TB) is a leading cause of death amongst infectious diseases. The poor response to antitubercular agents necessitates the long-term use of high drug doses, resulting in low patient compliance, which is the main reason for chemotherapy failure and contributes to the development of multidrug-resistant TB. Patient non-compliance has been a major obstacle in the successful management of TB. The aim of this work was to develop and characterise rifapentine (RPT)-loaded PLGA-based nanoparticles (NPs) for reducing dosing frequency. Methods: RPT-loaded PLGA and PLGA-PEG NPs were prepared using premix membrane homogenisation combined with solvent evaporation method. The resulting NPs were characterised in terms of physicochemical characteristics, toxicity, cellular uptake and antitubercular activity. NPs were further evaluated for pharmacokinetic and biodistribution studies in mice. Results: The resulting NPs showed suitable and safe physicochemical characteristics and could be taken up by macrophages. RPT-loaded NPs were more effective against Mycobacterium tuberculosis than free RPT. In vivo studies revealed that NPs could improve pharmacokinetic parameters, particularly for RPT/PLGA-PEG NPs. Moreover, both formulations had no toxicity to the organs of mice and could reduce hepatotoxicity. Conclusion: The application of PLGA-based NPs as sustained-release delivery vehicles for RPT could prolong drug release, modify pharmacokinetics, increase antitubercular activity and diminish toxicity, thereby allowing low dosage and frequency.


Assuntos
Antituberculosos/administração & dosagem , Mycobacterium tuberculosis/efeitos dos fármacos , Nanopartículas/administração & dosagem , Rifampina/análogos & derivados , Administração Oral , Animais , Antituberculosos/farmacocinética , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Hemólise/efeitos dos fármacos , Humanos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Nanopartículas/química , Tamanho da Partícula , Poliésteres/química , Polietilenoglicóis/química , Prostaglandinas A/química , Rifampina/administração & dosagem , Rifampina/farmacocinética , Distribuição Tecidual
11.
Medicine (Baltimore) ; 99(44): e22258, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126298

RESUMO

We aimed to investigate the effect of interval between food intake and drug administration at fasting condition on the plasma concentrations of first-line anti- tuberculosis (TB) drugs in Chinese population. Newly diagnosed TB patients administered the anti-TB drugs under fasting conditions orally, and then had prepared breakfast at 30 minutes and 120 min after dosing, respectively. Blood sampling was also performed 120  minutes after dosing for the detection of Cmax purpose. Overall, twenty-five participants were included in our analysis. The Cmaxs of 30  minutes interval and 120  minutes interval were 21.8 ±â€Š2.0 and 19.2 ±â€Š2.0 µg/mL for rifampin, 1.6 ±â€Š0.2 and 2.1 ±â€Š0.2 µg/mL for isoniazid (INH), 1.5 ±â€Š0.1and 1.5 ±â€Š0.2 µg/mL for ethambutol (EMB), and 49.2 ±â€Š3.7 and 41.5 ±â€Š3.9 µg/mL for pyrazinamide, respectively. Statistical analysis revealed that there was no statistical difference between 2 groups. Additionally, 88.0% and 72.0% of the 25 participants at 2-hour interval group had peak concentrations less than the lower limit of the reference range for INH and EMB, respectively. The Cmaxs of INH were 0.9 ±â€Š0.4 µg/ml for rapid acetylator, which was significantly lower than those of intermediate (1.4 ±â€Š1.0 µg/mL), and slow acetylator (2.5 ±â€Š1.0 µg/mL), respectively (P < .01). In conclusion, our data demonstrate that early food intake at 30 minutes after drug administration had no significant influence on the plasma concentrations. In addition, a high proportion of patients receiving first-line anti-TB regimen fail to achieve the expected plasma drug ranges of INH and EMB (P > .05).


Assuntos
Antituberculosos/sangue , Ingestão de Alimentos , Jejum/sangue , Fatores de Tempo , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/tratamento farmacológico , Administração Oral , Adulto , Antituberculosos/administração & dosagem , China , Esquema de Medicação , Etambutol/administração & dosagem , Etambutol/sangue , Feminino , Humanos , Isoniazida/administração & dosagem , Isoniazida/sangue , Masculino , Pirazinamida/administração & dosagem , Pirazinamida/sangue , Rifampina/administração & dosagem , Rifampina/sangue , Resultado do Tratamento
12.
Arch. bronconeumol. (Ed. impr.) ; 56(8): 493-498, ago. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-198189

RESUMO

BACKGROUND: Tuberculosis (TB) represents a diagnostic and therapeutic challenge for solid organ transplant recipients, particularly after lung transplant (LT). Our aim was to determine the impact of TB in LT patients in Spain, considering prevalence, clinical presentation, prevention and therapeutic management. In addition, differences in outcome between rifampicin (RIF) versus non-RIF containing regimens were analyzed. METHODS: Multicenter, observational retrospective study, including all cases of TB diagnosed in recipients after LT, in five pulmonary transplant units in Spain, between January 1990 and December 2017. RESULTS: Among 2962 LT recipients, 45 cases of TB were diagnosed, resulting in a prevalence of 1.52%. Most of them (88.89%) were diagnosed during the first year posttransplantation, 86.67% with pulmonary presentation. Screening for latent TB infection (LTBI) was done in 36 of the 45 patients and LTBI was detected pretransplant in 12 (33.33%). Less than half of the patients with disease (42.22%) received rifampicin (RIF). Lower probability of TB worsening was found in RIF-containing regimens (p = 0.049), as well as longer survival (p = 0.001). RIF use was not associated with an increased risk in rejection (p = 0.99), but doses of calcineurin inhibitors (CNI) had to be raised an average of 215%. CONCLUSIONS: Risk of TB after LT was lower in our series than previously reported. TB should be searched during the first year posttransplant in patients with TB risk factors. Pulmonary presentation was predominant. More sensitive algorithms for detecting LTBI before LT are crucial. It is reasonable to use RIF-containing regimens over non-RIF regimens based on the tendency toward better outcome in our series. RIF regimen requires close monitoring of CNI trough level for 2-3 weeks, until stability is achieved


ANTECEDENTES: La tuberculosis (TB) representa un reto diagnóstico y terapéutico para los receptores de trasplantes de órgano sólido, en particular tras un trasplante de pulmón (TP). Nuestro objetivo fue determinar el impacto de la TB en los pacientes con TP en España, tomando en consideración su prevalencia, presentación clínica, prevención y manejo terapéutico. Además, se analizaron las diferencias en los resultados finales entre los tratamientos que incluían rifampicina (RIF) frente a aquellos que no la incluían. MÉTODOS: Estudio multicéntrico, observacional y retrospectivo que incluía todos los casos de TB diagnosticados en pacientes receptores de TP, en 5 unidades de trasplante pulmonar en España, entre enero de 1990 y diciembre de 2017. RESULTADOS: Entre los 2.962 pacientes receptores de TP, se diagnosticaron 45 casos de TB, siendo esta una prevalencia del 1,52%. La mayoría (el 88,89%) se diagnosticaron durante el primer año postrasplante; el 86,67% de ellos fue con presentación pulmonar. Se realizó cribado en busca de infección tuberculosa latente (ITBL) en 36 de los 45 pacientes y se detectó ITBL pretrasplante en 12 de ellos (33,33%). Menos de la mitad de los pacientes con la enfermedad (42,22%) recibieron tratamiento con RIF. Se halló una menor probabilidad de empeoramiento de la TB en los tratamientos que incluían RIF (p = 0,049), así como mayor supervivencia (p = 0,001). El uso de RIF no se asoció a un aumento en el riesgo de rechazo (p = 0,99), pero fue necesario aumentar en una media del 215% las dosis de inhibidores de calcineurina (ICN). CONCLUSIONES: El riesgo de TB tras un TP fue menor en nuestra serie que lo referido previamente. Debería investigarse la TB durante el primer año postrasplante en aquellos pacientes con factores de riesgo para TB. La presentación pulmonar fue la predominante. Es crucial elaborar algoritmos con mayor sensibilidad para detectar ITBL antes del TP. Es razonable utilizar tratamientos que incluyan RIF frente a aquellos que no la incluyen basándonos en la tendencia a un resultado final más favorable en nuestra serie de casos. Los tratamientos con RIF requieren un seguimiento minucioso de los niveles de ICN durante 2-3 semanas hasta que se alcance una situación estable


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Transplante de Pulmão/efeitos adversos , Tuberculose Pulmonar/prevenção & controle , Tuberculose Pulmonar/tratamento farmacológico , Rifampina/administração & dosagem , Antibióticos Antituberculose/administração & dosagem , Resultado do Tratamento , Estudos Retrospectivos
13.
Saudi Med J ; 41(7): 753-756, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32601645

RESUMO

Elizabethkingia meningoseptica (E. meningoseptica ) are Gram-negative bacteria commonly associated with nosocomial infections in neonates. This is a case study of E. meningoseptica, presented as meningitis and sepsis in a term baby. The female infant was born by vaginal delivery at 37 weeks gestational age. The case was peculiar because the baby was neither premature nor immuno-compromised, which are known risk factors for E. meningoseptica infection. The onset began on the second day of the neonate's life. On day 3, peripheral blood culture and cerebrospinal fluid findings isolated a gram-negative bacteria identified as E. meningoseptica. The first-line antibiotics therapy was changed to ciprofloxacin, vancomycin, and rifampicin, based on the laboratory determination of antimicrobial sensitivity. The patient's clinical condition improved, although post hemorrhagic ventricular dilatation was revealed by imaging studies. Clinicians should possess proper awareness of the antibiotic sensitivity of E. meningoseptica, as it is important in preventing high rates of morbidity and mortality.


Assuntos
Antibacterianos/administração & dosagem , Ciprofloxacino/administração & dosagem , Infecções por Flavobacteriaceae , Flavobacteriaceae , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/microbiologia , Rifampina/administração & dosagem , Sepse/tratamento farmacológico , Sepse/microbiologia , Vancomicina/administração & dosagem , Antibacterianos/farmacologia , Ciprofloxacino/farmacologia , Farmacorresistência Bacteriana , Quimioterapia Combinada , Feminino , Flavobacteriaceae/efeitos dos fármacos , Flavobacteriaceae/isolamento & purificação , Humanos , Recém-Nascido , Rifampina/farmacologia , Arábia Saudita , Resultado do Tratamento , Vancomicina/farmacologia
14.
J Card Surg ; 35(10): 2672-2678, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32678965

RESUMO

BACKGROUND: Short duration, antimicrobial prophylaxis that includes antistaphylococcal activity is recommended at the time of left ventricular assist device (LVAD) implantation to reduce infection-related complications. There continues to be wide variability in surgical infection prophylaxis (SIP) regimens among implantation centers. The aim of this study is to characterize current SIP regimens at different LVAD centers. METHODS: A survey study was conducted from 26 September 2017 to 25 October 2017. Surveys were distributed electronically to LVAD coordinators and infectious diseases specialists at 75 US medical centers identified as having an LVAD program. Data collection included information about antimicrobial selection, duration, Staphylococcus aureus screening, and decolonization procedures. RESULTS: We received 29 survey responses. The majority of surveys were completed by infectious diseases physicians (72.4% [21 out of 29]). Most responding centers reported LVAD programs established for greater than 10 years (20 out of 29 [69%]). Cardiac transplantation was performed in 28 out of 29 (96%) centers. Of centers reporting a defined SIP regimen for non-penicillin allergic patients (96% [28 out of 29]), 17.9% (5 out of 28) reported a four-drug regimen, 35.7% (10 out of 28) reported a three-drug regimen, and 46.4% (13 out of 28) reported a two-drug regimen, while no centers reported a single-drug regimen. Empiric fluconazole was common (50% [14 out of 28]) and 96.4% (27 out of 28) of regimens included vancomycin. Duration of antimicrobial prophylaxis (24 hours to 5 days), S. aureus screening, decolonization procedures, and alterations due to drug allergies varied across participating centers. CONCLUSIONS: Our survey results indicate wide variation in SIP regimens among participating LVAD centers. These results highlight the need for studies evaluating the implications of SIP regimens, and whether clinical factors that prolong antimicrobial duration impact postoperative infection rates.


Assuntos
Antibacterianos/administração & dosagem , Antibioticoprofilaxia , Coração Auxiliar/efeitos adversos , Implantação de Prótese/efeitos adversos , Infecções Relacionadas à Prótese/prevenção & controle , Infecção da Ferida Cirúrgica/prevenção & controle , Inquéritos e Questionários , Aztreonam/administração & dosagem , Cefalosporinas/administração & dosagem , Estudos Transversais , Quimioterapia Combinada , Fluconazol/administração & dosagem , Humanos , Levofloxacino/administração & dosagem , Infecções Relacionadas à Prótese/etiologia , Rifampina/administração & dosagem , Infecção da Ferida Cirúrgica/etiologia , Vancomicina/administração & dosagem
16.
J Med Vasc ; 45(4): 177-183, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32571557

RESUMO

OBJECTIVE: To evaluate the short and long-term results of in situ prosthetic graft treatment using rifampicin-soaked silver polyester graft in patients with aortic infection. MATERIAL AND METHOD: All the patients surgically managed in our center for an aortic infection were retrospectively analyzed. The primary endpoint was the intra-hospital mortality, secondary outcomes were limb salvage, persistent or recurrent infection, prosthetic graft patency, and long-term survival. RESULTS: From January 2004 to December 2015, 18 consecutive patients (12 men and 6 women) were operated on for aortic infection. Six mycotic aneurysms and 12 prosthetic infections, including 8 para-entero-prosthetic fistulas, were treated. In 5 cases, surgery was performed in emergency. During the early postoperative period, we performed one major amputation and two aortic infections were persistent. Intra-hospital mortality was 27.7%. The median follow-up among the 13 surviving patients was 26 months. During follow-up, none of the 13 patients presented reinfection or bypass thrombosis. CONCLUSION: This series shows that in situ revascularization with rifampicin-soaked silver polyester graft for aortic infection have results in agreement with the literature in terms of intra-hospital mortality with a low reinfection rate.


Assuntos
Aneurisma Infectado/cirurgia , Antibacterianos/administração & dosagem , Aneurisma Aórtico/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Poliésteres , Infecções Relacionadas à Prótese/cirurgia , Rifampina/administração & dosagem , Prata , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma Infectado/diagnóstico por imagem , Aneurisma Infectado/microbiologia , Aneurisma Infectado/mortalidade , Antibacterianos/efeitos adversos , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/microbiologia , Aneurisma Aórtico/mortalidade , Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Feminino , França , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Poliésteres/efeitos adversos , Desenho de Prótese , Infecções Relacionadas à Prótese/diagnóstico por imagem , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/mortalidade , Estudos Retrospectivos , Rifampina/efeitos adversos , Fatores de Risco , Prata/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
17.
PLoS One ; 15(5): e0232482, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32357366

RESUMO

The study was designed to assess whether plant extracts / phytochemical (D-Pinitol) synergistically combine with antituberculosis drugs and act on Mycobacterium smegmatis (M. smegmatis) as well as assess their mode of action on Mycobacterium tuberculosis (M.tb) Filamenting temperature sensitive mutant Z (FtsZ) protein. Resazurin microtitre plate assay (Checker board) was performed to analyze the activity of plant extracts against M. smegmatis. Synergistic behaviour of plant extracts / D-Pinitol with Isoniazid (INH) and Rifampicin (RIF) were determined by time-kill and checker board assays. Elongation of M. smegmatis cells due to this treatment was determined by light microscopy. The effect of Hexane methanol extract (HXM) plant extracts on cell viability was determined using PI/SYTO9 dual dye reporter Live/Dead assay. Action of HXM plant extracts / D-Pinitol on inhibition of FtsZ protein was done using Guanosine triphosphatase (GTPase) light scattering assay and quantitative Polymerase Chain Reaction (qPCR). The Hexane-methanolic plant extract of Acacia nilotica, Aegle marmelos and Glycyrrhiza glabra showed antimycobacterial activity at 1.56 ± 0.03, 1.32 ± 0.02 and 1.25 ± 0.03 mg/mL respectively and that of INH and RIF were 4.00 ± 0.06 µg/mL and 2.00 ± 0.04 µg/mL respectively. These plant extracts and major phytochemical exudate D-Pinitol was found to act synergistically with antimycobacterial drugs INH and RIF with an FIC index ~ 0.20. Time-Kill kinetics studies indicate that, these plant extracts were bacteriostatic in nature. D-Pinitol in conjunction with INH and RIF exhibited a 2 Log reduction in the growth of viable cells compared to untreated. Attempt to elucidate their mode of action through phenotypic analysis indicated that these plant extracts and D-Pinitol was found to interfere in cell division there by leading to an abnormal elongated cellular morphology. HXM extracts and D-Pinitol synergistically combined with the first line tuberculosis drugs, INH and RIF, to act on M. smegmatis. The increase in the length of M. smegmatis cells on treatment with D-Pinitol and HXM extract of the plants indicated that they hinder the cell division mechanism thereby leading to a filamentous phenotype, and finally leading to cell death. In addition, the integrity of the bacterial cell membrane is also altered causing cell death. Further gene expression analysis showed that these plant extracts and D-Pinitol hampers with function of FtsZ protein which was confirmed through in vitro inhibition of FtsZ-GTPase enzymatic activity.


Assuntos
Proteínas de Bactérias/genética , Proteínas do Citoesqueleto/genética , Mycobacterium smegmatis/efeitos dos fármacos , Mycobacterium smegmatis/genética , Plantas Medicinais , Antituberculosos/administração & dosagem , Proteínas de Bactérias/antagonistas & inibidores , Divisão Celular/efeitos dos fármacos , Proteínas do Citoesqueleto/antagonistas & inibidores , Sinergismo Farmacológico , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Genes Bacterianos/efeitos dos fármacos , Humanos , Técnicas In Vitro , Inositol/administração & dosagem , Inositol/análogos & derivados , Isoniazida/administração & dosagem , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium smegmatis/citologia , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Extratos Vegetais/administração & dosagem , Rifampina/administração & dosagem , Temperatura
18.
Am J Med Sci ; 359(6): 372-377, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32317167

RESUMO

Tuberculosis is a global burden with an unacceptably high mortality rate, especially in low- and middle-income countries. We reported the case of 34-year-old Somali female with no significant risk factors who initially presented with headache and blurred vision. The patient subsequently developed altered mental status and significant vision changes. Initial lumbar puncture showed lymphocytic pleocytosis with negative gram stain, acid-fast bacilli stain, and culture. Initial polymerase chain reaction for tuberculosis was negative. The patient worsened despite receiving broad-spectrum antibiotics. The patient had a prolonged hospital course and eventually required lumbar drain placement for hydrocephalus. Repeated polymerase chain reactions for Mycobacterium tuberculosis from the lumbar drain samples was positive, and the diagnosis of tuberculous meningitis was confirmed. The patient improved after lumbar drain placement and treatment with isoniazid, rifampin, pyrazinamide, ethambutol and steroid tapering. This case illustrated the challenge of diagnosing tuberculous meningitis.


Assuntos
Tuberculose Meníngea/diagnóstico por imagem , Tuberculose Meníngea/tratamento farmacológico , Adulto , Antituberculosos/administração & dosagem , Asma/complicações , Etambutol/administração & dosagem , Feminino , Cefaleia/complicações , Hospitalização , Humanos , Hidrocefalia/complicações , Hidrocefalia/cirurgia , Isoniazida/administração & dosagem , Leucocitose , Imagem por Ressonância Magnética , Reação em Cadeia da Polimerase , Pirazinamida/administração & dosagem , Rifampina/administração & dosagem , Somália , Punção Espinal , Tuberculose Meníngea/complicações , Estados Unidos , Transtornos da Visão/complicações
19.
Lancet HIV ; 7(6): e401-e409, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32240629

RESUMO

BACKGROUND: Short-course preventive therapy with 12 doses of once-weekly rifapentine (900 mg) plus isoniazid (900 mg) could greatly improve tuberculosis control, especially in areas with high co-endemicity with HIV. However, a small previous trial of such therapy with dolutegravir in healthy, HIV-negative adults was halted early after two of the four patients developed serious adverse events. Because of the potential use of this therapy, and variable safety outcomes of tuberculosis drugs seen in patients with and without HIV, we aimed to characterise safety, pharmacokinetics, and virological suppression in adults who are HIV positive. METHODS: DOLPHIN was a phase 1/2, single-arm trial done at The Aurum Institute (Tembisa Clinical Research Site, Tembisa, South Africa), with pharmacokinetic visits done at VxPharma (Pretoria, South Africa). Adults (≥18 years) with HIV infection and undetectable viral load (<40 copies per mL) after at least 8 weeks of efavirenz-based or dolutegravir-based regimens were recruited in three consecutive groups, subject to approval by the independent safety monitoring committee. Participants received 50 mg of daily dolutegravir in place of efavirenz for 8 weeks, then began once-weekly rifapentine (900 mg)-isoniazid (900 mg) for 12 weeks. Groups 1A (n=12) and 1B (n=18) had intensive dolutegravir pharmacokinetic sampling at week 8 (before rifapentine-isoniazid), at week 11 (after the third dose of rifapentine)-isoniazid and at week 16 after the eighth dose. Group 2 (n=30) were treated with the same schedule and had sparse dolutegravir pharmacokinetic sampling at weeks 8, 11, and 16. Participants were followed 4 weeks after completion of prophylactic tuberculosis treatment. HIV viral loads were measured at baseline and at weeks 11 and 24. Primary endpoints were adverse events (grade 3 or higher) and dolutegravir population pharmacokinetics, assessed in participants who began rifapentine-isoniazid. This trial was registered at ClinicalTrials.gov, NCT03435146. FINDINGS: Between Jan 24, 2018, and Nov 25, 2018, 61 participants were enrolled into three groups; one participant withdrew (from group 1A). 43 (70%) of 60 participants were women and all participants were black African. Median age was 40 years (IQR 35-48), CD4 cell count was 683 cells per µL (447-935), and body-mass index was 28·9 kg/m2 (24·0-32·9). Three grade 3 adverse events occurred; two elevated creatinine and one hypertension. Rifapentine-isoniazid increased dolutegravir clearance by 36% (relative standard error 13%) resulting in a 26% decrease in dolutegravir area under the curve. Overall geometric mean ratio of trough concentrations with versus without rifapentine-isoniazid was 0·53 (90% CI 0·49-0·56) though this ratio varied by day after rifapentine-isoniazid dose. All but one trough value was above the 90% maximal inhibitory concentration for dolutegravir and HIV viral loads were less than 40 copies per mL in all patients. INTERPRETATION: Our results suggest 12 doses of once-weekly rifapentine-isoniazid can be given for tuberculosis prophylaxis to patients with HIV taking dolutegravir-based antiretroviral therapy, without dose adjustments. Further exploration of the pharmacokinetics, safety, and efficacy in children and pharmacodynamics in individuals naive to antiretroviral therapy is needed. FUNDING: UNITAID.


Assuntos
Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Isoniazida/administração & dosagem , Rifampina/análogos & derivados , Tuberculose/prevenção & controle , Adulto , Esquema de Medicação , Feminino , Infecções por HIV/virologia , HIV-1/genética , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Isoniazida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oxazinas , Piperazinas , Piridonas , Rifampina/administração & dosagem , Rifampina/efeitos adversos , África do Sul , Resultado do Tratamento , Carga Viral
20.
Fontilles, Rev. leprol ; 32(4): 263-271, ene.-abr. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-193432

RESUMO

OBJETIVO: La profilaxis post-exposición de la lepra con dosis única de rifampicina (SDR-PEP) ha demostrado ser efectiva y aplicable y está recomendada por la OMS desde 2018. Esta caja de herramientas SDR-PEP se desarrolló a través de la experiencia de la profilaxis lepra post-eliminación (LPEP). Se ha diseñado para facilitar y estandarizar la implementación del seguimiento de contactos y la administración SDR-PEP en regiones y países que iniciaron la intervención. RESULTADOS: Se desarrollaron cuatro instrumentos, incorporando la evidencia existente actual para SDR-PEP y los métodos y enseñanzas del proyecto LPEP en ocho países. (1) El conjunto de diapositivas Powerpoint política/apoyo que ayudarán a los programadores sobre la evidencia, practicabilidad y recursos necesarios para SDR-PEP, (2) La colección de diapositivas PowerPoint sobre formación e implementación en el campo para formar al personal implicado en el seguimiento de contactos y PEP con SDR, (3) manual genérico de campo SDR-PEP que puede ser usado para formar un protocolo específico de campo para el seguimiento de contactos y SDR-PEP como referencia para el personal directamente implicado. Finalmente, (4) el manual director SDR-PEP, que resume los distintos componentes de la caja de herramientas y contiene las instrucciones para su uso. CONCLUSIÓN: En respuesta al interés manifestado por varios países de implementar el seguimiento de contactos de lepra con PEP con SDR, con las recomendaciones OMS sobre SDR-PEP, esta caja de herramientas basada en la evidencia concreta pero flexible, ha sido diseñada para servir a los directores de programas nacionales de lepra con un medio práctico para trasladar los planteamientos a la práctica. Está disponible gratuitamente en la página de Infolep y actualizada constantemente: https://www.leprosy-information.org/keytopic/leprosy-post-exposure-prophylaxis-lpep-programme


OBJECTIVE: Leprosy post-exposure prophylaxis with single-dose rifampicin (SDRPEP) has proven effective and feasible, and is recommended by WHO since 2018. This SDR-PEP toolkit was developed through the experience of the leprosy post-exposure prophylaxis (LPEP) programme. It has been designed to facilitate and standardise the implementation of contact tracing and SDR-PEP administration in regions and countries that start the intervention. RESULTS: Four tools were developed, incorporating the current evidence for SDRPEP and the methods and learnings from the LPEP project in eight countries. (1) the SDR-PEP policy/advocacy PowerPoint slide deck which will help to inform policy makers about the evidence, practicalities and resources needed for SDR-PEP, (2) the SDR-PEP field implementation training PowerPoint slide deck to be used to train front line staff to implement contact tracing and PEP with SDR, (3) the SDR-PEP generic field guide which can be used as a basis to create a location specific field protocol for contact tracing and SDR-PEP serving as a reference for frontline field staff. Finally, (4) the SDR-PEP toolkit guide, summarising the different components of the toolkit and providing instructions on its optimal use. CONCLUSION: In response to interest expressed by countries to implement contact tracing and leprosy PEP with SDR in the light of the WHO recommendation of SDRPEP, this evidence-based, concrete yet flexible toolkit has been designed to serve national leprosy programme managers and support them with the practical means to translate policy into practice. The toolkit is freely accessible on the Infolep homepages and updated as required: https://www.leprosy-information.org/keytopic/leprosy-postexposure-prophylaxis-lpep-programme


Assuntos
Humanos , Profilaxia Pós-Exposição/métodos , Hanseníase/prevenção & controle , Rifampina/administração & dosagem , Hansenostáticos/administração & dosagem , Dose Única
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