RESUMEN
INTRODUCTION: Intestinal obstruction is a common complication in patients with advanced malignancies, often attributed to the disease itself or as a side effect of opioid analgesics used for pain management. However, the occurrence of intestinal obstruction following antituberculosis therapy is rare. CASE PRESENTATION: We report a unique case of a 58-year-old Asian male diagnosed with stage IV pancreatic carcinoma and pulmonary tuberculosis. The patient was initiated on a regimen of ethambutol hydrochloride, pyrazinamide, rifampicin, and isoniazid tablets (II) for tuberculosis, alongside morphine for the management of severe cancer-related pain. Subsequently, he developed symptoms indicative of intestinal obstruction. Despite discontinuation of morphine, the patient's symptoms persisted until he autonomously ceased all medications, leading to a rapid improvement in his condition. This unexpected resolution highlighted the antituberculosis drugs as the probable cause of his intestinal obstruction. CONCLUSIONS: This case underscores the importance of considering antituberculosis drugs as a potential cause of intestinal obstruction, especially in patients who do not respond to conventional management strategies for drug-induced gastrointestinal side effects. It also emphasizes the need for heightened vigilance and monitoring when prescribing these medications to patients with advanced malignancies, to promptly identify and address rare but significant side effects.
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Antituberculosos , Obstrucción Intestinal , Neoplasias Pancreáticas , Tuberculosis Pulmonar , Humanos , Masculino , Persona de Mediana Edad , Antituberculosos/efectos adversos , Antituberculosos/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/complicaciones , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/complicaciones , Obstrucción Intestinal/inducido químicamente , Obstrucción Intestinal/etiología , Etambutol/efectos adversos , Etambutol/uso terapéutico , Pirazinamida/efectos adversos , Pirazinamida/uso terapéutico , Isoniazida/efectos adversos , Isoniazida/uso terapéutico , Rifampin/efectos adversos , Rifampin/uso terapéutico , Dolor en Cáncer/tratamiento farmacológicoRESUMEN
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.
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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
PURPOSE: We aimed to investigate the visual recovery time in patients with ethambutol-induced toxic optic neuropathy (EON) and identify the factors associated with the visual recovery time. METHODS: In this retrospective cohort study, we reviewed the medical records of 35 eyes from 35 patients with EON. Visual recovery was defined as a gain of three or more lines from the nadir. RESULTS: Patients were observed following discontinuation of ethambutol (EMB), with the mean follow-up period of 21.0 ± 16.0 months. The visual acuity at nadir was logarithm of the minimum angle of resolution 1.4 ± 0.4, and the final visual acuity was logarithm of the minimum angle of resolution 0.6 ± 0.5. Twenty-seven eyes (77.1%) showed significant visual recovery. In Kaplan-Meier survival, the mean estimated time for visual recovery was 15.2 ± 3.0 months, and 50% of the patients experienced visual recovery at 8.3 ± 2.2 months following EMB discontinuation. Multivariate Cox regression analysis identified several significant risk factors for delayed visual recovery, including duration of EMB medication ≤6 months, period from symptom onset to EMB discontinuation >14 days, and baseline peripapillary retinal nerve fiber layer thickness >98 µm. CONCLUSIONS: Our study indicated a mean time of visual recovery of 15 months for EON cases. Therefore, patients diagnosed with EON should be followed up for more than 1 to 2 years to evaluate their visual recovery. Delayed EMB discontinuation, short duration of EMB use, and initial peripapillary retinal nerve fiber layer thickening were associated with delayed visual recovery. Therefore, patients taking EMB should be followed up regularly for early detection of EON and immediate discontinuation of EMB to prevent severe damage to the optic nerve.
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Etambutol , Enfermedades del Nervio Óptico , Humanos , Etambutol/efectos adversos , Antituberculosos/efectos adversos , Neuropatía Óptica Tóxica , Estudios Retrospectivos , Enfermedades del Nervio Óptico/inducido químicamente , Enfermedades del Nervio Óptico/diagnóstico , Tomografía de Coherencia ÓpticaRESUMEN
OBJECTIVES: The research aimed to study the following questions: (1) five well-known gout-related medications were selected to test the validity of the prescription symmetry sequence analysis in Taiwan; (2) four exploratory medications were selected to test their relation to gout flares. METHODS: We utilized the 2003-2017 dataset of the Taiwan National Health Insurance Program containing all claims data with 2 million beneficiaries as a data source. In order to explore the temporal association, we designed a scenario of medication-induced gout flares. Nine medications were selected as the index agent, including aspirin (low-dose), thiazide diuretics, loop diuretics, ethambutol, pyrazinamide, metformin, pioglitazone, fenofibrate, and losartan. The gout flare was defined as subjects with use of the marker agent for treatment of gout flares. The observation-window period between initiation of the index agent and initiation of the marker agent was 1 year. Subjects who used an index agent and a marker agent on the same day were excluded. The prescription symmetry sequence analysis was carried out to compare the observed number of persons who took an index agent prior to starting a marker agent with the observed number of persons who took a marker agent before starting an index agent. The adjusted sequence ratio (adjusted SR) with 95% confidence interval was applied to estimate the relation between an index agent and the marker agent. RESULTS: Among five medications including aspirin (low-dose), thiazide diuretics, loop diuretics, ethambutol, and pyrazinamide, the adjusted sequence ratio ranged from 1.15 to 3.35 and all reached statistical significance. Fenofibrate use and losartan use were associated with a lower probability of gout flares, with reaching statistical significance (adjusted SR = 0.60 for fenofibrate and adjusted SR = 0.92 for losartan). Metformin use was associated with a greater probability of gout flares, with reaching statistical significance (adjusted SR = 1.14). Pioglitazone use did not reach statistical significance. CONCLUSION: Based on the confirmatory analysis including five well-known gout-related medications, this study supports that the prescription symmetry sequence analysis can be used to detect an adverse drug event associated with one potential offending agent. The exposure to fenofibrate or losartan might be a protective factor against gout flares. Metformin use could be associated with a greater probability of gout flares, but this finding should be validated by other studies. KEY POINTS: ⢠What is already known about this subject? 1. The prescription symmetry sequence analysis is a useful method for detecting an adverse drug reaction associated with one potential offending drug. 2. Numerous medications are found to induce gout flares. ⢠What does this study add? 1. The prescription symmetry sequence analysis supports the evidence that aspirin (low-dose), thiazide diuretics, loop diuretics, ethambutol and pyrazinamide are associated with a greater probability of gout flares. 2. The exposure to fenofibrate or losartan might be a protective factor against gout flares. 3. Metformin use could be associated with a greater probability of gout flares. ⢠How might this impact on clinical practice or future developments? 1. Clinicians should always consider the possibility of medication-induced gout flares. If gout flares develop, discontinuation of risky medications is the first step. Then prescribing cascades can be eliminated.
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Fenofibrato , Gota , Metformina , Humanos , Gota/diagnóstico , Inhibidores de los Simportadores del Cloruro de Sodio/efectos adversos , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/efectos adversos , Pirazinamida/efectos adversos , Losartán/efectos adversos , Pioglitazona/efectos adversos , Fenofibrato/efectos adversos , Etambutol/efectos adversos , Brote de los Síntomas , Prescripciones , Aspirina/uso terapéutico , Metformina/efectos adversosRESUMEN
AIM: To screen patients on ethambutol and evaluate its role on visual functions and toxic optic neuropathy. SETTING AND DESIGN: Retrospective, observational single tertiary centre cohort of 80 patients. METHODS AND MATERIAL: A total of 69 from the initial 80 patients with visual complaints were categorised into two groups A and B; ongoing anti-tubercular therapy with ethambutol and having stopped ethambutol for greater than six months respectively. All patients underwent vision (V) testing on ETDRS chart and anterior and posterior segment evaluation. Additionally, patients in group A recorded color vision (CV) on Ishihara chart and visual evoked potential (VEP). STATISTICAL ANALYSIS USED: P value was calculated using Chi square test (SPSS ver. 20). RESULTS: Out of 69 patients in our study, 58 (84.05%) patients recorded reduced visual acuity. The mean visual acuity was 0.58 logMAR units. 33 out of our 58 (57%) patients with reduced visual acuity showed normal optic discs while 25 out of 58 (43%) showed altered optic discs. In group B, 14 out of 32 patients with vision of less than 20/20 also had optic disc pallor (p = 0.02). 12 out of 15 patients in group A recorded an altered color vision and also had a vision of less than 20/20 (p = 0.023). 15 patients who recorded altered VEP also had vision of less than 20/20 (p = 0.037). CONCLUSION: Visual acuity, color vision and vep are sensitive and sustainable tools which can be implemented in regular screening. Ethambutol toxicity is a real problem and a collaborative approach is necessary to establish screening protocols and prevent ethambutol induced toxic optic neuropathy.
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Etambutol , Enfermedades del Nervio Óptico , Humanos , Antituberculosos/efectos adversos , Etambutol/efectos adversos , Potenciales Evocados Visuales , Enfermedades del Nervio Óptico/inducido químicamente , Enfermedades del Nervio Óptico/diagnóstico , Estudios Retrospectivos , Neuropatía Óptica Tóxica/tratamiento farmacológico , Trastornos de la Visión/inducido químicamenteRESUMEN
BACKGROUND: Standard treatment for tuberculosis (TB) in children and adults includes an initial two-month course of ethambutol, a drug that in rare cases can cause optic neuropathy and irreversible vision loss. There is a lack of clear guidance on what vision assessments are needed before and during treatment with ethambutol, with the Royal College of Ophthalmologists, National Institute for Health and Care Excellence, British National Formulary and British Thoracic Society offering different guidance. We aimed to assess how vision is routinely tested in patients treated with ethambutol in TB services across England. METHODS: An online survey developed by Public Health England was sent to all TB services in England in 2018 to assess current practice and inform the development of best practice recommendations for visual assessment of patients treated with ethambutol for TB. RESULTS: Sixty-six TB professionals from across England responded, a response rate of 54%. The results showed variations in practice, including when to omit ethambutol from treatment, the timing and frequency of visual assessment, the type of visual assessment, referral processes and management of visual changes. CONCLUSION: This national survey highlights the need for clear guidelines on the testing of vision for patients taking ethambutol at recommended doses, before and during treatment. We suggest a pragmatic approach to visual assessment to reduce variation in practice, proposing a stepwise pathway for patients on standard TB treatment for local adaptation.
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Enfermedades del Nervio Óptico , Tuberculosis , Adulto , Niño , Humanos , Etambutol/efectos adversos , Antituberculosos/efectos adversos , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Nervio ÓpticoRESUMEN
OBJECTIVES: To assess the efficacy and safety of rifampicin-based triple therapy (rifampicin, isoniazid, and ethambutol) for treating NPM. METHODS: This single-center, single-arm, prospective clinical trial was conducted at the Second Hospital of Shandong University (Jinan, China). Patients with pathologically diagnosed granulomatous lobular mastitis and periductal mastitis received triple drugs, i.e., rifampicin (450 mg/day), isoniazid (300 mg/day), and ethambutol (15 mg/kg/day), until complete response or the investigator decided to discontinue treatment. The primary endpoint was the complete response rate (CRR) assessed by the investigator. The secondary endpoints included the overall remission rate (ORR), recurrence rate (RR), and safety. RESULTS: A total of 218 patients were enrolled in the study between January 1, 2013 and October 31, 2020. With a median follow-up time of 48 months, the CRR and the ORR were 78.44% and 94.04%, respectively. While 13 patients (5.96%) demonstrated no response and 19 relapsed (8.72%). Adverse events (AEs) were not common. The most common AEs during treatment were liver dysfunction (1.83%), gastrointestinal reactions (1.83%), fatigue (1.83%), erythema (1.38%), and menstrual disorders (0.92%). CONCLUSION: Rifampicin, isoniazid, and ethambutol demonstrated promising response rates with acceptable safety profiles in patients with NPM. Further confirmatory trial is warranted in the future. TRIAL REGISTRATION: The study was approved by the Ethics Committee of the Second Hospital of Shandong University and retrospectively registered at the China Clinical Trial Registration Center (registration number: ChiCTR2100049591).
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Mastitis , Rifampin , Femenino , Humanos , Etambutol/efectos adversos , Isoniazida/efectos adversos , Estudios Prospectivos , Rifampin/efectos adversosAsunto(s)
Enfermedades del Nervio Óptico , Tuberculosis , Humanos , Etambutol/efectos adversos , Enfermedades del Nervio Óptico/inducido químicamente , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/epidemiología , Nervio Óptico , India/epidemiología , Antituberculosos/efectos adversosRESUMEN
Ethambutol is an antibiotic widely used for treatment of Mycobacterium species. Although it is safe to use in patients, the ocular toxic impact, including optic neuropathy and retinopathy, can be observed in patients using ethambutol. After discontinuation of the drug, the ocular toxic effects can be reversible in some patients, but some are not. Ethambutol-induced optic neuropathy has been recognized for more than six decades and the prevalence of optic neuropathy from a standard dose of ethambutol has been reported as 0.7-1.29%. Several factors associated with ethambutol-induced optic neuropathy include dosage/duration of drug, the medical conditions of patients such as renal and hepatic dysfunction and preexisting mitochondrial mutations. Currently, there is no specific treatment and prevention of ethambutol-induced optic neuropathy. In addition, the potential underlying mechanisms of ethambutol-induced optic neuropathy is still unclear. Therefore, this review aimed to summarize and discuss evidence from clinical, in vitro, and in vivo studies in order to explore the potential pathophysiology of ethambutol-induced optic neuropathy. Any contradictory findings are also included and discussed. The insights gained from the review will facilitate the discovery of novel approaches for prevention and treatment of optic neuropathy-induced by ethambutol.
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Etambutol , Enfermedades del Nervio Óptico , Humanos , Etambutol/efectos adversos , Antituberculosos/toxicidad , Enfermedades del Nervio Óptico/inducido químicamente , OjoRESUMEN
Physiological changes during pregnancy may alter the pharmacokinetics (PK) of antituberculosis drugs. The International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1026s was a multicenter, phase IV, observational, prospective PK and safety study of antiretroviral and antituberculosis drugs administered as part of clinical care in pregnant persons living with and without HIV. We assessed the effects of pregnancy on rifampin, isoniazid, ethambutol, and pyrazinamide PK in pregnant and postpartum (PP) persons without HIV treated for drug-susceptible tuberculosis disease. Daily antituberculosis treatment was prescribed following World Health Organization-recommended weight-band dosing guidelines. Steady-state 12-hour PK profiles of rifampin, isoniazid, ethambutol, and pyrazinamide were performed during second trimester (2T), third trimester (3T), and 2-8 of weeks PP. PK parameters were characterized using noncompartmental analysis, and comparisons were made using geometric mean ratios (GMRs) with 90% confidence intervals (CI). Twenty-seven participants were included: 11 African, 9 Asian, 3 Hispanic, and 4 mixed descent. PK data were available for 17, 21, and 14 participants in 2T, 3T, and PP, respectively. Rifampin and pyrazinamide AUC0-24 and C max in pregnancy were comparable to PP with the GMR between 0.80 and 1.25. Compared to PP, isoniazid AUC0-24 was 25% lower and C max was 23% lower in 3T. Ethambutol AUC0-24 was 39% lower in 3T but limited by a low PP sample size. In summary, isoniazid and ethambutol concentrations were lower during pregnancy compared to PP concentrations, while rifampin and pyrazinamide concentrations were similar. However, the median AUC0-24 for rifampin, isoniazid, and pyrazinamide met the therapeutic targets. The clinical impact of lower isoniazid and ethambutol exposure during pregnancy needs to be determined.
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Antituberculosos , Tuberculosis , Adolescente , Femenino , Humanos , Embarazo , Antituberculosos/efectos adversos , Antituberculosos/farmacocinética , Etambutol/efectos adversos , Etambutol/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Isoniazida/efectos adversos , Isoniazida/farmacocinética , Periodo Posparto , Estudios Prospectivos , Pirazinamida/efectos adversos , Pirazinamida/farmacocinética , Rifampin/efectos adversos , Rifampin/farmacocinética , Tuberculosis/tratamiento farmacológico , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase IV como Asunto , Estudios Observacionales como AsuntoRESUMEN
Rifampicin is an important agent for tuberculosis treatment; however, it is often discontinued because of adverse reactions. The treatment regimen then can be administered as that for rifampicin-resistant tuberculosis, which can be toxic. We retrospectively reviewed 114 patients with drug-susceptible pulmonary tuberculosis who discontinued rifampicin due to adverse reactions during an 18 year period at a tertiary referral center, of which 92 (80.7%) exhibited favorable response. Hepatotoxicity was the leading cause of intolerance. Patients with a favorable response were younger and less likely to have comorbidities. The majority of patients were administered four medications during the intensive phase and three to four during the consolidative phase. For those with a favorable response, the median duration of treatment was 10.2 months and the most common intensive regimen was a combination of isoniazid, ethambutol, pyrazinamide, and fluoroquinolone (25%). The most common consolidation regimen was a combination of isoniazid, ethambutol, and fluoroquinolone (22.8%). Among the patients with a favorable response, two (2.2%) experienced recurrence after a follow-up of 3.4 (interquartile range 1.8-6.8) years. For patients with drug-susceptible pulmonary tuberculosis who do not tolerate rifampicin owing to its toxicity, a shorter regimen may be a useful alternative.
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Rifampin , Tuberculosis Pulmonar , Humanos , Rifampin/efectos adversos , Etambutol/efectos adversos , Isoniazida/efectos adversos , Estudios Retrospectivos , Tuberculosis Pulmonar/tratamiento farmacológico , FluoroquinolonasRESUMEN
INTRODUCTION: Toxic optic neuropathy is a severe optic nerve injury that can compromise the prognosis for vision, justifying early clinical and ancillary diagnosis. CASE DESCRIPTION: We report the case of an 11-year-old child being treated for tuberculous meningitis with a combination of ethambutol and three other anti-bacillary drugs, referred for a rapidly progressive bilateral decline in visual acuity. On ophthalmologic examination, the visual acuity was counting fingers within 1ft in both eyes, and bilateral optic disc pallor was noted, without other associated abnormalities. Neurological imaging was unremarkable, with red-green dyschromatopsia and a bilateral cecocentral scotoma. Faced with this clinical and paraclinical picture, we arrived at the diagnosis of ethambutol toxic optic neuropathy, with a multidisciplinary decision leading to a change in the antibacillary treatment protocol. No clinical improvement was noted after 3 months of follow-up. DISCUSSION: Optic nerve toxicity is rare in children and is classically described as dose- and time-dependent. CONCLUSION: Ethambutol ocular toxicity is extremely rare in children, and the required action when detected is to discontinue the drug. Reversibility is not always assured, which requires early detection of toxic optic neuropathy by close clinical and ancillary monitoring and, above all, sensitization of the treating physicians (pediatricians, pulmonologists and neurologists).
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Enfermedades del Nervio Óptico , Tuberculosis Meníngea , Humanos , Niño , Etambutol/efectos adversos , Antituberculosos/efectos adversos , Neuropatía Óptica Tóxica , Tuberculosis Meníngea/complicaciones , Tuberculosis Meníngea/diagnóstico , Tuberculosis Meníngea/tratamiento farmacológico , Enfermedades del Nervio Óptico/inducido químicamente , Enfermedades del Nervio Óptico/diagnósticoRESUMEN
A hyperuricemic rat model induced by adenine and ethambutol was established to investigate the anti-hyperuricemia activity and its mechanism of the flavonoid extract from saffron floral bio-residues. Sixty-seven SD rats were randomly divided into control group, model group, positive control group, and flavonoid extract groups(with 3 doses), respectively, and each group contained 11 or 12 rats. The hyperuricemic model was established by continuous oral administration of adenine(100 mg·kg~(-1)) and ethambutol(250 mg·kg~(-1)) for 7 days. At the same time, the positive control group was given allopurinol(20 mg·kg~(-1) per day) and the flavonoid extract groups were given the flavonoid extract at doses of 340, 170 and 85 mg·kg~(-1) per day, respectively. On day 8, rat serum, liver, kidney, and intestinal tissues were collected, and the levels of uric acid in serum and tissue, the xanthine oxidase activities and antioxi-dant activities in serum and liver were evaluated, and the kidney histopathology was explored. In addition, an untargeted serum metabolomics study was performed. According to the results, the flavonoid extract effectively reduced the uric acid levels in serum, kidney and ileum and inhibited the xanthine oxidase activities and elevated the antioxidant activities of serum and liver in hyperuricemic rat. At the same time, it reduced the levels of inflammation factors in kidney and protected renal function. Moreover, 68 differential metabolites of hyperuricemic rats were screened and most of which were lipids and amino acids. The flavonoid extract significantly retrieved the levels of differential metabolites in hyperuricemic rats, such as SM(d18:1/20:0), PC[18:0/18:2(92,12Z)], palmitic acid and citrulline, possibly through the following three pathways, i.e., arginine biosynthesis, glycine, serine and threonine metabolism, and histidine metabolism. To sum up, the flavonoid extract of saffron floral bio-residues lowered the uric acid level, increased the antioxidant activity, and alleviated inflammatory symptoms of hyperuricemic rats, which may be related to its inhibition of xanthine oxidase activity and regulation of serum lipids and amino acids metabolism.
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Crocus , Hiperuricemia , Ratas , Animales , Flavonoides/farmacología , Ácido Úrico , Xantina Oxidasa , Etambutol/efectos adversos , Ratas Sprague-Dawley , Hiperuricemia/tratamiento farmacológico , Riñón , Antioxidantes/farmacología , Extractos Vegetales/efectos adversos , Aminoácidos , Adenina/efectos adversos , LípidosRESUMEN
BACKGROUND: Tuberculosis is usually treated with a 6-month rifampin-based regimen. Whether a strategy involving shorter initial treatment may lead to similar outcomes is unclear. METHODS: In this adaptive, open-label, noninferiority trial, we randomly assigned participants with rifampin-susceptible pulmonary tuberculosis to undergo either standard treatment (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks) or a strategy involving initial treatment with an 8-week regimen, extended treatment for persistent clinical disease, monitoring after treatment, and retreatment for relapse. There were four strategy groups with different initial regimens; noninferiority was assessed in the two strategy groups with complete enrollment, which had initial regimens of high-dose rifampin-linezolid and bedaquiline-linezolid (each with isoniazid, pyrazinamide, and ethambutol). The primary outcome was a composite of death, ongoing treatment, or active disease at week 96. The noninferiority margin was 12 percentage points. RESULTS: Of the 674 participants in the intention-to-treat population, 4 (0.6%) withdrew consent or were lost to follow-up. A primary-outcome event occurred in 7 of the 181 participants (3.9%) in the standard-treatment group, as compared with 21 of the 184 participants (11.4%) in the strategy group with an initial rifampin-linezolid regimen (adjusted difference, 7.4 percentage points; 97.5% confidence interval [CI], 1.7 to 13.2; noninferiority not met) and 11 of the 189 participants (5.8%) in the strategy group with an initial bedaquiline-linezolid regimen (adjusted difference, 0.8 percentage points; 97.5% CI, -3.4 to 5.1; noninferiority met). The mean total duration of treatment was 180 days in the standard-treatment group, 106 days in the rifampin-linezolid strategy group, and 85 days in the bedaquiline-linezolid strategy group. The incidences of grade 3 or 4 adverse events and serious adverse events were similar in the three groups. CONCLUSIONS: A strategy involving initial treatment with an 8-week bedaquiline-linezolid regimen was noninferior to standard treatment for tuberculosis with respect to clinical outcomes. The strategy was associated with a shorter total duration of treatment and with no evident safety concerns. (Funded by the Singapore National Medical Research Council and others; TRUNCATE-TB ClinicalTrials.gov number, NCT03474198.).
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Antituberculosos , Diarilquinolinas , Linezolid , Rifampin , Tuberculosis Pulmonar , Humanos , Antituberculosos/efectos adversos , Antituberculosos/uso terapéutico , Esquema de Medicación , Quimioterapia Combinada , Etambutol/efectos adversos , Etambutol/uso terapéutico , Isoniazida/efectos adversos , Isoniazida/uso terapéutico , Linezolid/efectos adversos , Linezolid/uso terapéutico , Pirazinamida/efectos adversos , Pirazinamida/uso terapéutico , Rifampin/efectos adversos , Rifampin/uso terapéutico , Resultado del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/complicaciones , Diarilquinolinas/efectos adversos , Diarilquinolinas/uso terapéuticoRESUMEN
PURPOSE: A case report of a 40-year-old patient with tuberculosis treated with ethambutol is described. Within six months of starting treatment, there was a painless sudden decline in visual function. Despite the known complications of ethambutol treatment, it was discontinued after another three months. METHODS: In the case report, we highlight the damage to the dominantly peripheral visual pathways. Using electrophysiological examinations, we showed a significant alteration in the optic nerves. Optical Coherence Tomography (OCT) showed progressive loss of vessel density and nerve fibre layer of retinal ganglion cells. Perimetric examination showed both a central decrease in sensitivity and mainly scotomas in the temporal parts of the visual fields. Although there was improvement in visual fields over time, OCT findings indicated progression of ethambutol-induced optic neuropathy (EON). Magnetic Resonance Imaging confirmed the alteration in the peripheral part of the visual pathway (intraorbital, intracranial parts of optic nerves, chiasma, and optic tracts). CONCLUSION: Even though EON is not an unknown complication, new cases still occur and, unfortunately, with an irreversible course. Therefore, it is important to draw attention constantly to this complication and to consider it not only in ophthalmologists' surgeries.
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Enfermedades del Nervio Óptico , Tuberculosis , Humanos , Adulto , Etambutol/efectos adversos , Antituberculosos/efectos adversos , Enfermedades del Nervio Óptico/inducido químicamente , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/patología , Nervio Óptico/diagnóstico por imagen , Nervio Óptico/patología , Tomografía de Coherencia Óptica/métodosRESUMEN
OBJECTIVE: The study was conducted to evaluate the ocular toxicity of ethambutol given in both intensive and continuation phases of treatment in children with drug-sensitive tuberculosis. METHODS: A prospective study of 94 eyes from 47 patients receiving an ethambutol-containing regimen was conducted between 1 December, 2018 and 31 August, 2020. Visual acuity, visual field, visual evoked response (VER), contrast sensitivity, colour perception, and retinal nerve fiber layer (RNFL) thickness [using optical coherence tomography (OCT)] were tested for each patient before, during, and after the treatment. RESULTS: On follow-up, visual acuity, color vision, contrast sensitivity, fundus, and visual fields were not affected in any of the patients. There was no statistically significant increase in the mean latency of the P(100) wave at any point in time. On OCT, no significant loss of mean RNFL thickness was detected. CONCLUSIONS: Ethambutol is safe to use up to a dose of 20 mg/kg/day throughout the entire course of anti-tubercular therapy in children with drug-sensitive tuberculosis.
Asunto(s)
Etambutol , Tuberculosis , Niño , Humanos , Etambutol/efectos adversos , Neuropatía Óptica Tóxica , Estudios Prospectivos , Antituberculosos/efectos adversos , Tuberculosis/tratamiento farmacológico , RetinaRESUMEN
RATIONALE: Drug induced liver injury (DILI) is a common side effect causing treatment discontinuation during tuberculosis (TB) treatment, and pyrazinamide (PZA) usually leads to a delayed and prolonged abnormal liver function of the 4 standard anti-tuberculosis regimens. However, a prolonged hepatitis lasting more than 4 months is rarely reported. PATIENT CONCERNS: A 78-year-old man presented with general weakness and poor appetite on his seventh week of anti-TB treatment for tuberculosis lymphadenitis. DIAGNOSIS: Drug induced liver injury, PZA-related. NAT2 slow acetylator phenotype was accidentally found during workup of DILI. INTERVENTION: A liver biopsy was performed and PZA-related DILI was suspected. All anti-TB medications were therefore discontinued. OUTCOME: After withholding all anti-TB medications for 4 months, the elevations of aminotransferases and hyperbilirubinemia completely resolved. Anti-TB therapy was switched to ethambutol and levofloxacin for 15 months without adverse events. Long-term ultrasound follow-up was performed and cervical lymphadenopathy completely resolved. CONCLUSION: Our patient presents with PZA related prolonged DILI resolved after drug discontinuation for 4 months. NAT2 slow acetylator phenotype may be related to this condition through unknown mechanisms.