RESUMEN
BACKGROUND: Tuberculosis (TB) lymphadenitis is the most common form of extra-pulmonary TB, and the treatment duration is six months. This non-inferiority based randomized clinical trial in South India evaluated the efficacy and safety of a four-month ofloxacin containing regimen in tuberculosis lymphadenitis (TBL) patients. METHODS: New, adult, HIV-negative, microbiologically and or histopathologically confirmed superficial lymph node TB patients were randomized to either four-month oflaxacin containing test regimen [ofloxacin (O), isoniazid (H), rifampicin (R), pyrazinamide (Z) -2RHZO daily/ 2RHO thrice-weekly] or a six-month thrice-weekly control regimen (2HRZ, ethambutol/4RH). The treatment was directly observed. Clinical progress was monitored monthly during and up to 12 months post-treatment, and thereafter every three months up to 24 months. The primary outcome was determined by response at the end of treatment and TB recurrence during the 24 months post-treatment. RESULTS: Of the 302 patients randomized, 298 (98.7%) were eligible for modified intention-to-treat (ITT) analysis and 294 (97%) for per-protocol (PP) analysis. The TB recurrence-free favourable response in the PP analysis was 94.0% (95% CI: 90.1-97.8) and 94.5% (95% CI: 90.8-98.2) in the test and control regimen respectively, while in the ITT analysis, it was 92.7% and 93.2%. The TB recurrence-free favourable response in the test regimen was non-inferior to the control regimen 0.5% (95% CI: -4.8-5.9) in the PP analysis based on the 6% non-inferiority margin. Treatment was modified for drug toxicity in two patients in the test regimen, while one patient had a paradoxical reaction. CONCLUSION: The 4-month ofloxacin containing regimen was found to be non-inferior and as safe as the 6-month thrice-weekly control regimen.
Asunto(s)
Antituberculosos , Ofloxacino , Tuberculosis Ganglionar , Humanos , Ofloxacino/administración & dosificación , Ofloxacino/efectos adversos , Ofloxacino/uso terapéutico , Adulto , Masculino , Femenino , Tuberculosis Ganglionar/tratamiento farmacológico , Antituberculosos/uso terapéutico , Antituberculosos/efectos adversos , Antituberculosos/administración & dosificación , Resultado del Tratamiento , Persona de Mediana Edad , India , Rifampin/uso terapéutico , Rifampin/administración & dosificación , Rifampin/efectos adversos , Adulto Joven , Isoniazida/uso terapéutico , Isoniazida/administración & dosificación , Isoniazida/efectos adversos , Quimioterapia Combinada , Pirazinamida/uso terapéutico , Pirazinamida/administración & dosificación , Pirazinamida/efectos adversos , Etambutol/uso terapéutico , Etambutol/administración & dosificación , Etambutol/efectos adversos , Esquema de Medicación , AdolescenteRESUMEN
Objective: To evaluate the efficacy and safety of first-line anti-tuberculosis (TB) drugs combined with linezolid in treatment of children with tuberculous meningitis (TBM). Methods: A retrospective cohort study design was performed. Eight-nine Children diagnosed as TBM during January 1st 2016 and December 31st 2023 in Department of Infectious Disease, Children's Hospital of Chongqing Medical University were enrolled in the study. According to different treatment regimens, children were divided into a group of first-line anti-tuberculous drugs (isoniazid, rifampicin, pyrazinamide, ethambutol (HRZE)) and a group of HRZE and linezolid combination (HRZEL). The efficacy and safety of the 2 regimens were compared and the relationship between linezolid drug concentration and adverse reactions were analyzed. Comparisons between groups were performed using χ2 test and Mann-Whitney U test. Results: The 89 children with TBM included 53 males and 36 females with an onset age of 4.6 (1.4, 9.6) years. There were 27 cases in the HZREL group and 62 cases in the HRZE group. Before treatment, positive rate of interferon-gamma release assays (IGRA) in HRZEL group was lower than that in HRZE group (64% (16/25) vs.92% (55/60), χ2=9.82, P<0.05), but protein level of cerebrospinal fluid (CSF) was higher than that in HRZE group (1.2 (1.0, 2.0) vs.0.8 (0.4,1.4) g/L, Z=0.32, P<0.05). By the end of the intensive phase, there were no significant differences of rates of CSF improvement and etiology negativity between HRZEL group and HRZE group (both P>0.05).The 44 TBM children with high CSF protein (>1 g/L) included 25 males and 19 females with an onset age of 6.7 (3.0, 11.8) years. There were 21 cases in the HZREL group and 23 cases in the HRZE group accordingly. Before treatment, there were no significant differences of positive rate of IGRA test and CSF protein level between the 2 groups (62% (13/21) vs. 87% (20/23), 1.7 (1.1, 2.2) vs. 1.5 (1.2, 1.9) g/L, χ2=3.67, Z=0.23, both P>0.05). There were no significant differences in CSF indicators, etiology negativity or imaging remission between the two groups by the end of intensive phase (all P>0.05). Higher frequencies of granulocytopenia, gastrointestinal symptoms as well as withdrawal or change of drugs were found in HRZEL group when compared to those in HRZE group (44% (12/27) vs. 19% (12/62), 7% (2/27) vs. 0, 33% (9/27) vs. 3% (2/62), χ2=6.01, 4.70, 15.74, all P<0.05). Conclusions: The efficacy of HRZEL regimen is similar to conventional HRZE regimen in children with TBM, but with higher adverse effect. Prudentially evaluating the pros and cons of linezolid in the usage of drug-susceptible TB and carefully monitoring of linezolid associated adverse effects is suggested.
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Antituberculosos , Quimioterapia Combinada , Linezolid , Tuberculosis Meníngea , Humanos , Tuberculosis Meníngea/tratamiento farmacológico , Estudios Retrospectivos , Masculino , Femenino , Linezolid/uso terapéutico , Linezolid/administración & dosificación , Antituberculosos/uso terapéutico , Antituberculosos/administración & dosificación , Antituberculosos/efectos adversos , Niño , Preescolar , Resultado del Tratamiento , Lactante , Rifampin/uso terapéutico , Rifampin/administración & dosificación , Etambutol/uso terapéutico , Etambutol/administración & dosificación , Pirazinamida/uso terapéutico , Pirazinamida/administración & dosificación , Isoniazida/uso terapéutico , Isoniazida/administración & dosificación , Isoniazida/efectos adversosRESUMEN
Mycobacterium avium complex pulmonary disease (MAC-PD) requires long-term treatment. We analyzed the outcomes of 992 MAC-PD patients according to disease severity and compared the outcomes of intermittent and daily therapy for mild disease. Patients were divided into groups according to severity using the body mass index, age, cavity, erythrocyte sedimentation rate, and sex (BACES) system, and culture conversion rates were evaluated. We also evaluated the effects of intermittent treatment on the culture conversion rates in mild disease group. Using the BACES, 992 patients were divided into mild (n = 331), moderate (n = 503), and severe (n = 158) disease groups, and culture conversion at the end of treatment was achieved in 85% (282/331), 80% (403/503), and 61% (97/158), respectively. Differences in culture conversion among the severity groups were significant (p < 0.001). In patients with mild disease, culture conversion rates were similar between intermittent (84%, 166/198) and daily (87%, 116/133) treatment (p = 0.396), and intermittent antibiotic therapy did not negatively impact culture conversion (adjusted hazard ratio 1.08; confidence interval 0.83-1.41; p = 0.578). MAC-PD patients with mild disease had higher culture conversion rates. Daily and intermittent therapy yielded similar culture conversion rates for mild disease. Treatment strategies with lower pill burden may be applicable in mild MAC-PD.
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Enfermedades Pulmonares/tratamiento farmacológico , Pulmón/efectos de los fármacos , Mycobacterium avium/efectos de los fármacos , Tuberculosis Aviar/tratamiento farmacológico , Anciano , Animales , Antituberculosos/administración & dosificación , Índice de Masa Corporal , Etambutol/administración & dosificación , Femenino , Humanos , Pulmón/microbiología , Pulmón/patología , Enfermedades Pulmonares/microbiología , Enfermedades Pulmonares/patología , Masculino , Mycobacterium avium/patogenicidad , Índice de Severidad de la Enfermedad , Esputo/efectos de los fármacos , Esputo/microbiología , Resultado del Tratamiento , Tuberculosis Aviar/microbiología , Tuberculosis Aviar/patologíaRESUMEN
Effective treatment reduces a tuberculosis patient's ability to infect others even before they test negative in sputum or culture. Currently, the basis of reduced infectiousness of the Mycobacterium tuberculosis (Mtb) with effective treatment is unclear. We evaluated changes in aerosolized bacteria expelled by patients through a transcriptomic approach before and after treatment initiation (up to 14 days) by RNA sequencing. A distinct change in the overall transcriptional profile was seen post-treatment initiation compared to pretreatment, only when patients received effective treatment. This also led to the downregulation of genes associated with cellular activities, cell wall assembly, virulence factors indicating loss of pathogenicity, and a diminished ability to infect and survive in new host cells. Based on this, we identified genes whose expression levels changed with effective treatment. The observations of the study open up avenues for further evaluating the changes in bacterial gene expression during the early phase of treatment as biomarkers for monitoring response to tuberculosis treatment regimens and provide means of identifying better correlates of Mtb transmission.
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Antituberculosos/administración & dosificación , Mycobacterium tuberculosis/genética , Tuberculosis Pulmonar/tratamiento farmacológico , Adulto , Antituberculosos/uso terapéutico , Etambutol/administración & dosificación , Etambutol/uso terapéutico , Femenino , Humanos , Isoniazida/administración & dosificación , Isoniazida/uso terapéutico , Masculino , Mycobacterium tuberculosis/efectos de los fármacos , Pirazinamida/administración & dosificación , Pirazinamida/uso terapéutico , Rifampin/administración & dosificación , Rifampin/uso terapéutico , Transcriptoma/efectos de los fármacos , Resultado del Tratamiento , Tuberculosis Pulmonar/microbiología , Adulto JovenRESUMEN
Ethambutol is an integral part of Antitubercular therapy (ATT) and is often associated with optic neuropathy, However, neuroimaging of ethambutol induced optic neuropathy has been sparsely reported in the literature. We describe the case of a 45-year male patient, diagnosed as Tuberculous spondylodiscitis and was on ATT. Four months after ATT initiation, he presented with visual blurring in both the eyes with bitemporal hemianopia and central scotomas. Visual evoked potential (VEP) revealed prolonged latencies in N75 and P100 waveforms bilaterally. Magnetic Resonance Imaging (MRI) showed optic chiasma and bilateral optic tract hyperintensities on 3D Fluid Attenuated Inversion Recovery (FLAIR) and 3D Double Inversion Recovery (DIR) sequences. Ethambutol was discontinued immediately. On follow-up after 8 weeks, visual acuity reversed back to normal in both eyes.
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Etambutol , Hemianopsia , Enfermedades del Nervio Óptico , Tuberculosis Osteoarticular/tratamiento farmacológico , Trastornos de la Visión , Antituberculosos/administración & dosificación , Antituberculosos/efectos adversos , Etambutol/administración & dosificación , Etambutol/efectos adversos , Potenciales Evocados Visuales , Hemianopsia/diagnóstico , Hemianopsia/etiología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Enfermedades del Nervio Óptico/inducido químicamente , Enfermedades del Nervio Óptico/diagnóstico por imagen , Enfermedades del Nervio Óptico/fisiopatología , Recuperación de la Función , Tuberculosis Osteoarticular/diagnóstico , Trastornos de la Visión/diagnóstico , Trastornos de la Visión/etiología , Privación de TratamientoRESUMEN
BACKGROUND: Treatment failure of Mycobacterium avium complex (MAC) pulmonary disease occurs in about 30% of people with cystic fibrosis (CF) and may be a result of abnormal drug concentrations. METHODS: Prospective, cross-over, single-dose PK study of 20 pancreatic insufficient individuals with CF and 10 healthy controls (HC). CF subjects received simultaneous doses of oral azithromycin, ethambutol, and rifampin in the fasting state and with food and pancreatic enzymes, separated by two weeks. HC received fasting doses only. A non-compartmental model was used to estimate PK parameters of drugs and metabolites. RESULTS: Azithromycin maximum concentration (Cmax ) was higher and rifampin Cmax was lower in fasting CF subjects compared to HC, while other PK measures, including those for ethambutol, were similar. Addition of food and enzymes did not improve the Cmax of the antimycobacterial drugs. Nineteen of 20 CF subjects had one or more abnormal Cmax z-scores in either the fasting or fed state (or both), when compared to HC. CONCLUSION: PK profiles of azithromycin and ethambutol were similar between CF and HC, except azithromycin Cmax was slightly higher in people with CF after a single dose. Rifampin PK parameters were altered in persons with CF. Addition of food and enzymes in CF subjects did not improve PK parameters. Standard dosing guidelines should be used as a starting point for people with CF initiating MAC therapy and therapeutic drug monitoring should be routinely performed to prevent the possibility of treatment failure due to abnormal drug concentrations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02372383 Prior abstract publication: 1. Martiniano S, Wagner B, Brennan L, Wempe M, Anderson P, Nick J, Sagel S. Pharmacokinetics of oral MAC antibiotics in cystic fibrosis. Am J Resp Crit Care Med A4842-A4842, 2017. 2. Martiniano SL, Wagner BD, Brennan L, Wempe MF, Anderson PL, Nick JA, Sagel SD. Pharmacokinetics of oral MAC antibiotics in cystic fibrosis. J Cyst Fibros 16: S52-53, 2017.
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Azitromicina/farmacocinética , Fibrosis Quística/tratamiento farmacológico , Etambutol/farmacocinética , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Rifampin/farmacocinética , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Antibióticos Antituberculosos/farmacocinética , Antituberculosos/administración & dosificación , Antituberculosos/farmacocinética , Azitromicina/administración & dosificación , Estudios Cruzados , Fibrosis Quística/microbiología , Etambutol/administración & dosificación , Humanos , Complejo Mycobacterium avium , Estudios Prospectivos , Rifampin/administración & dosificaciónRESUMEN
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 12âmonths. 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.
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Antibacterianos/administración & dosificación , Claritromicina/administración & dosificación , Etambutol/administración & dosificación , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Rifampin/administración & dosificación , Tenosinovitis/tratamiento farmacológico , Anciano , Quimioterapia Combinada , Femenino , Mano/microbiología , Humanos , Masculino , Persona de Mediana Edad , Infección por Mycobacterium avium-intracellulare/microbiología , Tenosinovitis/microbiologíaRESUMEN
Alcohol dehydrogenases (ADHs) are most known for their roles in oxidation and elimination of ethanol. Although less known, ADHs also play a critical role in the metabolism of a number of drugs and metabolites that contain alcohol functional groups, such as abacavir (HIV/AIDS), hydroxyzine (antihistamine), and ethambutol (antituberculosis). ADHs consist of 7 gene family numbers and several genetic polymorphic forms. ADHs are cytosolic enzymes that are most abundantly found in the liver, although also present in other tissues including gastrointestinal tract and adipose. Marked species differences exist for ADHs including genes, proteins, enzymatic activity, and tissue distribution. The active site of ADHs is relatively small and cylindrical in shape. This results in somewhat narrow substrate specificity. Secondary alcohols are generally poor substrates for ADHs. In vitro-in vivo correlations for ADHs have not been established, partly due to insufficient clinical data. Fomepizole (4-methylpyrazole) is a nonspecific ADH inhibitor currently being used as an antidote for the treatment of methanol and ethylene glycol poisoning. Fomepizole also has the potential to treat intoxication of other substances of abuse by inhibiting ADHs to prevent formation of toxic metabolites. ADHs are inducible through farnesoid X receptor (FXR) and other transcription factors. Drug-drug interactions have been observed in the clinic for ADHs between ethanol and therapeutic drugs, and between fomepizole and ADH substrates. Future research in this area will provide additional insights about this class of complex, yet fascinating enzymes.
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Alcohol Deshidrogenasa/metabolismo , Fármacos Anti-VIH/farmacocinética , Antituberculosos/farmacocinética , Etanol/metabolismo , Antagonistas de los Receptores Histamínicos H1/farmacocinética , Alcohol Deshidrogenasa/antagonistas & inhibidores , Alcohol Deshidrogenasa/genética , Animales , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/química , Antituberculosos/administración & dosificación , Antituberculosos/química , Didesoxinucleósidos/administración & dosificación , Didesoxinucleósidos/química , Didesoxinucleósidos/farmacocinética , Interacciones Farmacológicas , Etambutol/administración & dosificación , Etambutol/química , Etambutol/farmacocinética , Etanol/química , Fomepizol/farmacología , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/química , Humanos , Hidroxizina/administración & dosificación , Hidroxizina/química , Hidroxizina/farmacocinética , Isoenzimas/antagonistas & inhibidores , Isoenzimas/genética , Isoenzimas/metabolismo , Oxidación-Reducción/efectos de los fármacos , Receptores Citoplasmáticos y Nucleares/metabolismo , Especificidad de la Especie , Especificidad por SustratoRESUMEN
OBJECTIVES: Adequate anti-tuberculosis (TB) treatment is an important factor that can affect the patient's outcome. Higher mortality is found in patients who do not receive optimal treatment that includes isoniazid and rifampicin. The objective of this study is to evaluate the association of use of alternative TB treatment regimens (without rifampicin and isoniazid) and mortality among patients requiring intensive care. METHODS: Retrospective cohort study, from January 2010 to December 2018. Patients aged > 18 years with a TB diagnosis, admitted to the ICU of a general, tertiary care, university-affiliated hospital (Hospital de Clínicas de Porto Alegre - HCPA) were included. Data on TB treatment used and outcomes of treatment were collected. RESULTS: 462 patients met the inclusion criteria and were included in the analysis; 284 used the usual treatment regimen (rifampicin, isoniazid, pyrazinamide and ethambutol - all orally), and 178 used alternative treatment regimens (IV levofloxacin plus oral ethambutol plus IM streptomycin or IV amikacin, without rifampicin and isoniazid). The mortality was higher among users of alternative treatment regimens (63.5%) than among usual treatment regimen users (51.4%) (P = 0.011). In a multivariate analysis, age, albumin and death were independently associated with alternative treatment regimens use. CONCLUSIONS: TB programmes in which IV rifampicin is not widely available should consider including it, especially for critically ill TB patients, for whom there may be improved survival.
OBJECTIFS: Un traitement antituberculeux (TB) adéquat est un facteur important pouvant influencer les résultats du patient. Une mortalité plus élevée est observée chez les patients qui ne reçoivent pas un traitement optimal comprenant de l'isoniazide et de la rifampicine. L'objectif de cette étude est d'évaluer l'association entre l'utilisation d'autres schémas thérapeutiques anti-TB (sans rifampicine ni isoniazide) et la mortalité chez les patients nécessitant des soins intensifs. MÉTHODES: Etude de cohorte rétrospective, de janvier 2010 à décembre 2018. Les patients âgés de >18 ans avec un diagnostic de TB, admis à l'unité de soins intensifs d'un hôpital général, avec des soins tertiaires, affilié à l'Université (Hôpital de Clínicas de Porto Alegre-HCPA) ont été inclus. Des données sur le traitement anti-TB utilisé et les résultats du traitement ont été collectés. RÉSULTATS: 462 patients répondaient aux critères d'inclusion et ont été inclus dans l'analyse; 284 ont utilisé le schéma thérapeutique habituel (rifampicine, isoniazide, pyrazinamide et éthambutol - tous par voie orale) et 178 ont utilisé des schémas thérapeutiques alternatifs (lévofloxacine IV plus éthambutol oral plus streptomycine IM ou amikacine IV, sans rifampicine ni isoniazide). La mortalité était plus élevée chez les utilisateurs de schémas thérapeutiques alternatifs (63,5%) que chez les utilisateurs de schémas thérapeutiques habituels (51,4%) (P = 0,011). Dans l'analyse multivariée, l'âge, l'albumine et le décès ont été indépendamment associés à l'utilisation de schémas thérapeutiques alternatifs. CONCLUSIONS: Les programmes de lutte contre la TB dans lesquels la rifampicine IV n'est pas largement disponible devraient envisager de l'inclure, en particulier pour les patients atteints de TB et sévèrement malades, pour lesquels la survie peut être améliorée.
Asunto(s)
Antibióticos Antituberculosos/administración & dosificación , Unidades de Cuidados Intensivos , Tuberculosis/tratamiento farmacológico , Tuberculosis/mortalidad , APACHE , Adulto , Amicacina/administración & dosificación , Brasil/epidemiología , Vías de Administración de Medicamentos , Esquema de Medicación , Quimioterapia Combinada/métodos , Etambutol/administración & dosificación , Femenino , Humanos , Isoniazida/administración & dosificación , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pirazinamida/administración & dosificación , Estudios Retrospectivos , Rifampin/administración & dosificación , Estreptomicina/administración & dosificaciónRESUMEN
Mycobacteriosis caused by Mycobacterium avium subsp. avium was observed in a parental loft of 70 meat-breed pigeons. It was decided to undertake treatment as the birds represented a substantial value to the owner. A multiagent therapy using azithromycin, marbofloxacin, and ethambutol was administered. After 4 mo of therapy, the desired results were not obtained. At the end of treatment, the birds were in poor general condition, with white blood cells above 20 g/L, and after clutching, 2-yr-old and older birds were euthanatized. Overall, postmortem lesions were found in 17 out of 49 necropsied individuals. Slide agglutination tests with a M. avium subsp. avium lysate were conducted in all examined pigeons. In 28 pigeons, blood count was conducted once a month during therapy, while in 24 pigeons, a tuberculin sensitivity test was conducted before the planned euthanatization. The tuberculin sensitivity test did not prove useful in the diagnosis of ill individuals. Slide agglutination yielded positive results in only four birds, all of which also had postmortem lesions. Blood count in a large number of cases allowed distinguishing between ill and healthy individuals, which was used for subsequent selection. The comparison of cultured strains with the (CCG)4-based PCR method showed the variation of M. avium isolates up to a maximum of 30%. The described case proves that the treatment of mycobacteriosis in pigeon flocks is not effective, mainly due to the high resistance to M. avium subsp. avium. In addition, therapy may contribute to an even greater increase in mycobacterial resistance to antibiotics, which may pose a potential risk to public health.
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Antibacterianos/administración & dosificación , Columbidae , Mycobacterium/fisiología , Enfermedades de las Aves de Corral/tratamiento farmacológico , Tuberculosis Aviar/tratamiento farmacológico , Animales , Azitromicina/administración & dosificación , Cruzamiento , Quimioterapia Combinada , Etambutol/administración & dosificación , Femenino , Fluoroquinolonas/administración & dosificación , Masculino , Carne , Enfermedades de las Aves de Corral/microbiología , Resultado del Tratamiento , Tuberculosis Aviar/microbiologíaRESUMEN
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 30âminutes and 120âmin after dosing, respectively. Blood sampling was also performed 120â minutes after dosing for the detection of Cmax purpose. Overall, twenty-five participants were included in our analysis. The Cmaxs of 30â minutes interval and 120â minutes interval were 21.8â±â2.0 and 19.2â±â2.0âµg/mL for rifampin, 1.6â±â0.2 and 2.1â±â0.2âµg/mL for isoniazid (INH), 1.5â±â0.1and 1.5â±â0.2âµg/mL for ethambutol (EMB), and 49.2â±â3.7 and 41.5â±â3.9âµg/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 0.9â±â0.4âµg/ml for rapid acetylator, which was significantly lower than those of intermediate (1.4â±â1.0âµg/mL), and slow acetylator (2.5â±â1.0âµg/mL), respectively (Pâ<â.01). In conclusion, our data demonstrate that early food intake at 30âminutes 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 (Pâ>â.05).
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Antituberculosos/sangre , Ingestión de Alimentos , Ayuno/sangre , Factores de Tiempo , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/tratamiento farmacológico , Administración Oral , Adulto , Antituberculosos/administración & dosificación , China , Esquema de Medicación , Etambutol/administración & dosificación , Etambutol/sangre , Femenino , Humanos , Isoniazida/administración & dosificación , Isoniazida/sangre , Masculino , Pirazinamida/administración & dosificación , Pirazinamida/sangre , Rifampin/administración & dosificación , Rifampin/sangre , Resultado del TratamientoRESUMEN
OBJECTIVES: Drug-resistance represents a major threat in the fight against tuberculosis. Globally, isoniazid-monoresistant tuberculosis (Hr-TB) is twice as common as multidrug/rifampicin-resistant (MDR/RR)-TB. Recently updated WHO guidelines now recommend treatment of Hr-TB with rifampicin, ethambutol, pyrazinamide and levofloxacin for at least six months. Our primary objective was to define the frequency, treatment and outcomes for Hr-TB in Queensland, Australia. We also sought to determine the frequency of fluoroquinolone use and whether its inclusion improved outcomes. METHODS: Retrospective case series of tuberculosis notifications in Queensland between 2000 and 2017 with at least low-level isoniazid resistance and preserved susceptibility to other first-line oral agents. RESULTS: Hr-TB was identified in 7.2% of all notifications. Where outcomes were assessable (163/198), 76.1% were treated with first-line agents only and 11.0% received at least six months of a fluoroquinolone-containing regimen (consistent with recent WHO guidelines). Favourable outcomes were achieved in 95.7%, comparable to fully susceptible disease (94.9%). Inclusion of a fluoroquinolone did not significantly improve outcomes compared with a regimen containing first-line agents only, although these cases were more likely to have high-level resistance. Previous treatment made an unfavourable outcome more likely. CONCLUSIONS: Hr-TB is prevalent in Queensland. Treatment outcomes in our cohort were comparable to fully susceptible disease. The current WHO-recommended regimen did not confer advantage over an appropriately constructed regimen containing first-line agents only. Our findings suggest that, in a well-resourced setting with good programmatic management, the addition of a fluoroquinolone may not substantially improve outcomes - potentially allowing these agents to be reserved for more extensively resistant disease.
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Antituberculosos/administración & dosificación , Fluoroquinolonas/administración & dosificación , Isoniazida , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Australia , Niño , Preescolar , Quimioterapia Combinada , Etambutol/administración & dosificación , Combinación Etinil Estradiol-Norgestrel/administración & dosificación , Femenino , Humanos , Levofloxacino/administración & dosificación , Masculino , Persona de Mediana Edad , Pirazinamida/administración & dosificación , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenAsunto(s)
Antiinflamatorios/efectos adversos , Colitis Ulcerosa/tratamiento farmacológico , Huésped Inmunocomprometido , Infliximab/efectos adversos , Infecciones por Mycobacterium no Tuberculosas/inmunología , Claritromicina/administración & dosificación , Esquema de Medicación , Quimioterapia Combinada , Etambutol/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Rifampin/administración & dosificaciónAsunto(s)
Antituberculosos/uso terapéutico , Cerebro/diagnóstico por imagen , Etambutol/uso terapéutico , Mycobacterium tuberculosis/aislamiento & purificación , Pirazinamida/uso terapéutico , Rifampin/uso terapéutico , Tuberculoma/tratamiento farmacológico , Tuberculosis Meníngea/tratamiento farmacológico , Adulto , Antibacterianos/uso terapéutico , Antituberculosos/administración & dosificación , Etambutol/administración & dosificación , Cefalea/tratamiento farmacológico , Cefalea/etiología , Humanos , Isoniazida/administración & dosificación , Isoniazida/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Moxifloxacino/uso terapéutico , Reacción en Cadena de la Polimerasa , Pirazinamida/administración & dosificación , Rifampin/administración & dosificación , Resultado del Tratamiento , Tuberculoma/diagnóstico por imagen , Tuberculosis Meníngea/diagnósticoRESUMEN
BACKGROUND: To address the multifaceted challenges associated with tuberculosis (TB) in-person directly observed therapy (DOT), the World Health Organization recently recommended that countries maximize the use of digital adherence technologies. Sub-Saharan Africa needs to investigate the effectiveness of such technologies in local contexts and proactively contribute to global decisions around patient-centered TB care. This study aims to evaluate the effectiveness of pillbox-enabled self-administered therapy (SAT) compared to standard DOT on adherence to TB medication and treatment outcomes in Ethiopia. It also aims to assess the usability, acceptability, and cost-effectiveness of the intervention from the patient and provider perspectives. METHODS: This is a multicenter, randomized, controlled, open-label, superiority, effectiveness-implementation hybrid, mixed-methods, two-arm trial. The study is designed to enroll 144 outpatients with new or previously treated, bacteriologically confirmed, drug-sensitive pulmonary TB who are eligible to start the standard 6-month first-line anti-TB regimen. Participants in the intervention arm (n = 72) will receive 15 days of HRZE-isoniazid, rifampicin, pyrazinamide, and ethambutol-fixed-dose combination therapy in the evriMED500 medication event reminder monitor device for self-administration. When returned, providers will count any remaining tablets in the device, download the pill-taking data, and refill based on preset criteria. Participants can consult the provider in cases of illness or adverse events outside of scheduled visits. Providers will handle participants in the control arm (n = 72) according to the standard in-person DOT. Both arms will be followed up throughout the 2-month intensive phase. The primary outcomes will be medication adherence and sputum conversion. Adherence to medication will be calculated as the proportion of patients who missed doses in the intervention (pill count) versus DOT (direct observation) arms, confirmed further by IsoScreen urine isoniazid test and a self-report of adherence on eight-item Morisky Medication Adherence Scale. Sputum conversion is defined as the proportion of patients with smear conversion following the intensive phase in intervention versus DOT arms, confirmed further by pre-post intensive phase BACTEC MGIT TB liquid culture. Pre-post treatment MGIT drug susceptibility testing will determine whether resistance to anti-TB drugs could have impacted culture conversion. Secondary outcomes will include other clinical outcomes (treatment not completed, death, or loss to follow-up), cost-effectiveness-individual and societal costs with quality-adjusted life years-and acceptability and usability of the intervention by patients and providers. DISCUSSION: This study will be the first in Ethiopia, and of the first three in sub-Saharan Africa, to determine whether electronic pillbox-enabled SAT improves adherence to TB medication and treatment outcomes, all without affecting the inherent dignity and economic wellbeing of patients with TB. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04216420. Registered on 2 January 2020.
Asunto(s)
Antituberculosos/administración & dosificación , Terapia por Observación Directa , Etambutol/administración & dosificación , Isoniazida/administración & dosificación , Mycobacterium tuberculosis/aislamiento & purificación , Pirazinamida/administración & dosificación , Rifampin/administración & dosificación , Tuberculosis Pulmonar/tratamiento farmacológico , Adolescente , Adulto , Anciano , Análisis Costo-Beneficio , Equipos y Suministros Eléctricos , Estudios de Equivalencia como Asunto , Etiopía/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Aceptación de la Atención de Salud , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Autoadministración , Esputo/microbiología , Resultado del Tratamiento , Tuberculosis Pulmonar/epidemiología , Adulto JovenRESUMEN
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.
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Tuberculosis Meníngea/diagnóstico por imagen , Tuberculosis Meníngea/tratamiento farmacológico , Adulto , Antituberculosos/administración & dosificación , Asma/complicaciones , Etambutol/administración & dosificación , Femenino , Cefalea/complicaciones , Hospitalización , Humanos , Hidrocefalia/complicaciones , Hidrocefalia/cirugía , Isoniazida/administración & dosificación , Leucocitosis , Imagen por Resonancia Magnética , Reacción en Cadena de la Polimerasa , Pirazinamida/administración & dosificación , Rifampin/administración & dosificación , Somalia , Punción Espinal , Tuberculosis Meníngea/complicaciones , Estados Unidos , Trastornos de la Visión/complicacionesAsunto(s)
Antituberculosos/administración & dosificación , Imidazoles/administración & dosificación , Mycobacterium tuberculosis/efectos de los fármacos , Piperidinas/administración & dosificación , Piridinas/administración & dosificación , Tuberculosis Pulmonar/tratamiento farmacológico , Administración Oral , Antituberculosos/efectos adversos , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Etambutol/administración & dosificación , Humanos , Imidazoles/efectos adversos , Isoniazida/administración & dosificación , Piperidinas/efectos adversos , Pirazinamida/administración & dosificación , Piridinas/efectos adversos , Rifampin/administración & dosificaciónRESUMEN
We report a case of liver transplant patient who presented with lung masses, found to be Mycobacterium spindle cell pseudotumors. The masses demonstrated hypermetabolic activities on positron emission tomography. Core biopsy revealed sheets of spindle histiocytic cells with abundant acid-fast bacilli identified as Mycobacterium avium-intracellulare complex. This finding is a rare presentation of Mycobacterium infection, mainly nontuberculous Mycobaterium. It is characterized by a benign, spindle cell mass-forming reaction. Most of the reported cases had acquired immune deficiency syndrome or organ transplant. Histopathology illustrating the proliferation of spindle cell shaped histiocytes containing numerous acid-fast bacilli is the gold standard for diagnosis. The standard treatment has not been well established; previously reported cases followed the standard treatment for Mycobacterium based on organ involvement. Our case is the first case to our knowledge that reports pulmonary Mycobacterium spindle cell pseudotumors in a liver transplant recipient.
Asunto(s)
Trasplante de Hígado , Complejo Mycobacterium avium/aislamiento & purificación , Infección por Mycobacterium avium-intracellulare/patología , Granuloma de Células Plasmáticas del Pulmón/microbiología , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Antituberculosos/administración & dosificación , Antituberculosos/uso terapéutico , Azitromicina/administración & dosificación , Azitromicina/uso terapéutico , Etambutol/administración & dosificación , Etambutol/uso terapéutico , Femenino , Humanos , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Infección por Mycobacterium avium-intracellulare/microbiología , Granuloma de Células Plasmáticas del Pulmón/diagnóstico , Granuloma de Células Plasmáticas del Pulmón/tratamiento farmacológicoRESUMEN
BACKGROUND: The number of patients with nontuberculous mycobacteriosis (NTM) has increased exponentially in recent years. In Japan, approximately 88.8% of patients with NTM suffer from Mycobacterium avium-intracellulare complex (MAC) lung disease. Incidence of MAC lung disease is increasing in particularly among the middle-aged and elderly women owing to a rapid increase in nontuberculous mycobacterial infections. General treatment for MAC lung disease is chemotherapy. The type of chemotherapy recommended by specialists to prevent the development of a drug-resistant strain of the bacteria consists of a combination of clarithromycin (CAM), rifampicin, and ethambutol (EB). CAM monotherapy is contraindicated by specialists owing to its high potential to induce drug-resistant bacterial strains in patients with MAC lung disease. In addition, administering EB at doses not less than 1000 mg d-1 is not recommended to avoid adverse drug reactions. However, it is unclear how much such treatment cases exist in real world clinical settings. This is because no long-term investigation has been carried out. MATERIALS AND METHODS: This study investigated treatment with these drugs from 2005 to 2017, by studying 1135 patients with MAC lung disease based on health insurance claims database. RESULTS: Results showed that approximately 9.2% (101 cases) were prescribed long-term CAM monotherapy for 3 months or longer and approximately 3.6% (18 cases) were prescribed high doses of EB. CONCLUSION: CAM monotherapy over a long period of time is potentially detrimental to some patients. Better awareness of the types of treatments and their potential negative effects will be beneficial to clinical practitioners.
Asunto(s)
Claritromicina/administración & dosificación , Bases de Datos Factuales , Etambutol/administración & dosificación , Revisión de Utilización de Seguros , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Encuestas y Cuestionarios , Adolescente , Adulto , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Antituberculosos/administración & dosificación , Niño , Preescolar , Claritromicina/efectos adversos , Estudios de Cohortes , Bases de Datos Factuales/estadística & datos numéricos , Esquema de Medicación , Farmacorresistencia Bacteriana/efectos de los fármacos , Farmacorresistencia Bacteriana/fisiología , Quimioterapia Combinada , Femenino , Humanos , Lactante , Recién Nacido , Revisión de Utilización de Seguros/estadística & datos numéricos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Complejo Mycobacterium avium/efectos de los fármacos , Complejo Mycobacterium avium/fisiología , Infección por Mycobacterium avium-intracellulare/epidemiología , Estudios Retrospectivos , Adulto JovenRESUMEN
Ethambutol hydrochloride (ETB), high dose anti-tubercular drug exhibits poor micromeritics and compressibility. The current study aimed to enhance flow, compressibility and packing characteristics, thereby improving processability of ETB by spherical agglomeration. Quasi emulsion solvent diffusion method was used for agglomeration process in which saturated aqueous ETB solution was prepared and the crystallization was carried out subsequently at different ratios of acetone and ethyl acetate which act as anti-solvent. Further the process was optimised statistically using 32 factorial design keeping 'speed of stirring' and 'ratio acetone and ethyl acetate' as independent variables and particle size as dependent variable. Optimised batch of ethambutol hydrochloride spherical agglomerates (ETB-SA) was characterised for sieve analysis, solid state characteristics and Kawakita analysis. The uniformity of ETB-SA was observed with SEM while XRPD studies revealed reduction in crystallinity for ETB-SA. DSC and FTIR indicated no polymeric or chemical alteration during crystallization process. The flow properties of ETB-SA were found superior and its Kawakita parameters indicated improved packability and flowability compared to ETB. ETB has high solubility in water therefore was no significant difference was observed in in vitro dissolution of ETB and ETB-SA. Thus spherical agglomeration, a revered particle engineering technique, continues to be a salient approach for enhancing processability of high-dose drugs like ETB.