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Introducción: La tuberculosis es una de las 10 principales causas de muerte a nivel mundial. En 2020, causó 1,5 millones muertes. Se estima que llegó a 10,0 millones de nuevos casos durante el mismo año. Reporte de caso: varón de 93 años, antecedente de TBC pulmonar hace 15 años y contacto TBC actual. Presenta disnea y dolor pleurítico por 4 meses. Toracocentesis concluye exudado, biopsia pleural compatible con pleuritis granulomatosa no caseificante. Recibe esquema antituberculoso, desarrollando RAFA hepática. Se realiza reto farmacológico para diseñar un nuevo esquema de tratamiento. Paciente logra recuperarse. Se concluye que el manejo de tuberculosis debe individualizarse según paciente.
Introduction: Tuberculosis is one of the 10 leading causes of death worldwide. In 2020, it caused 1.5 million deaths. It is estimated that it reached 10.0 million new cases during the same year. Case of report: 93-year-old male, history of pulmonary TB 15 years ago and current TB contact. He presented dyspnea and pleuritic pain for 4 months. Thoracocentesis concludes exudate, pleural biopsy compatible with non-caseating granulomatous pleurisy. Receive antituberculosis regimen, developing hepatic RAFA. Pharmacological challenge is performed to design a new treatment scheme. Patient manages to recover. It is concluded that the management of tuberculosis should be individualized.
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Background: First line Anti-TB therapy with rifampicin, isoniazid, pyrazinamide, and ethambutol / streptomycin is very effective. However, major adverse reactions to antituberculous drugs can cause significant morbidity and mortality. One of the main reasons for non?adherence to anti?TB therapy (ATT) is ADRs, even under DOTS. Present study was carried out in tertiary care hospital. The objective of the study was to evaluate types and frequency of ADRs in intensive and continuation phase of category I and II Anti-TB medication.Methods: A prospective observational study conducted in Department of TB- Chest and Medicine, Govt. Medical College, Aurangabad, Maharashtra, India. All the TB patients reporting at DOTS Center of institute were enrolled and monitored for ADRs. The causality and severity of the reactions were determined using Naranjo algorithm and Hartwig questionnaire.Results: Total, n = 241 tuberculosis patients on DOTS therapy were enrolled for the study. Out of 241 patients, 17 were dropouts so 224 patients assessed for ADRs. 127 (56.69%) developed adverse drug reactions. The higher numbers of ADRs were observed in age group 31-40 yrs followed by 21-30 yrs, ADRs were more common in men. Pulmonary TB (73.66%) cases were more common than extra pulmonary TB. Majority of adverse drug reactions were Gastrointestinal (GI) problems (30.92%), followed by Liver dysfunction and Hepatotoxicity (20.39%) and skin problems (17.10%). The causality of ADRs, in majority cases were found to be Probable (56.57%). Around 19 patients require treatment interruption and most of the patients were managed with supportive medication without removing anti tubercular drug from regimen.Conclusions: ADRs are major limiting factor for completion of drug therapy under RNTCP and occurrence of drug resistance which requires attention of all health care professionals.
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Background: Tuberculosis is second leading cause of death in the world. The causative organism is Mycobacterium tuberculosis. The objective was to study the adverse reactions of the patients attending the DOTS center and to assess their causality and severity of reported ADRs.Methods: Present study was a prospective observational study carried at the DOTS center of Dr. Bhim Rao Ambedkar Memorial Hospital, Raipur, Chhattisgarh, India between August 2011 to July 2012 (One year). The patients were monitored for adverse drug reactions. The assessment of ADRs were based upon the WHO assessment scale, Naranjo scale, European A.B.O scale.Results: Total number of patients attending DOTS center was 816. The number of males (428) exceeded that of females (388). Majority of patients in this study belonged to 21-30 years (26.96%) next 31-40 years (25.24%) and 41-50 years (16.5%) of age group. Prevalence of ADRs were more in males (57%) than in females 32 (43%). Majority of ADRs reported were moderate 33 (35.22%) followed by 29 (46,77%) were mild, no severe ADRs reported. According to severity of ADRs seen were gastritis 28 (45%) followed by 10 (16% ) rashes , 10 (16,12%) of arthralgia, 3 (4.83%) of hepatitis, 6 (9.7%) of peripheral neuropathy, 2 (3%) onsets of ADRs after starting anti-tubercular drug were 12 (19.35%) in 0-1 week followed by 19 (30%) ADRs showed onset in 1-2 week and 2-3 week, 8 (13%) in 3-4 week 3 (5%) in 4-5 week and 1 (2%) in 5-6 week.Conclusions: The casual link between the ADRs and the suspected anti-tubercular drug by Naranjo scale definitely relationship was established between the anti-tubercular drug and ADRs in 7 (11.25%) patient while 22 (35.45%) probable and 33 (53.22%) ADRs were categorized as possible.
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Background: The emergence of drug resistant mycobacteria has become a significant public health problem world over creating an obstacle to effective TB control. ADRs are common in patients of MDR-TB on DOTs-Plus drug regimen. Present study was carried out in tertiary care hospital. Identification of types and frequency of adverse drug reactions in Intensive and continuation phase of MDR-TB Patients.Methods: It was a prospective observational study conducted in Department of TB- Chest and Medicine, Govt. Medical College, Aurangabad, Maharashtra, India. All the MDR-TB patients admitted at the directly observed treatment, short course plus (DOTS plus) Center at Medical College Hospital were enrolled and were monitored for ADRs. The causality and severity of the reactions were determined using Naranjo algorithm and Hartwig questionnaire, respectively.Results: A total of 121 tuberculosis patients of MDR-TB on DOTS therapy were enrolled for the study. Out of 121 patients, 13 were dropouts, 6 died, 7 defaulted so 108 patients assessed for ADRs, 48 patients developed 61 (56.48%) adverse drug reactions. The higher numbers of ADRs were observed in age group 31-40yrs followed by 21-30yrs which were more common in men. Majority of adverse drug reactions were Gastrointestinal (GI) problems 32 (52.45%), followed by Ototoxicity 7 (11.48%) and Psychiatric Manifestations 6 (9.84%) and skin problems 3 (4.92%). On evaluation of the causality of ADRs, majority were found to be Possible (59.02%). The severity assessment showed that most of the patients ADRs were of moderate level (50.82%).Some patients required treatment withdrawal and replacement with other drug and most of the patients were managed with supportive medication without removing anti-tubercular drug from their treatment regimen.Conclusions: ADRs are major factor limiting completion of drug therapy under RNTCP and occurrence of drug resistance which requires attention of all health care professionals.
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Objective To compare the efficacy and safety among individualized regimens ( IR ) containing clofazimine ( Cfz ) , linezolid ( Lzd ) or meropenem-clavulanic acid ( MC ) in treatment of multidrug/extensively resistant tuberculosis (MDR/XDR-TB) by using network meta-analysis.Methods Randomized controlled trials ( RCTs) and observational studies of Cfz-IR, Lzd-IR and MC-IR regimens in the treatment of MDR/XDR-TB published from January 2000 to August 2017 at home and abroad were retrieved.The literature was screened according to inclusion and exclusion criteria.The quality of the literature was evaluated and valid data were extracted.The efficacy and safety of Cfz-IR, Lzd-IR and MC-IR in the treatment of MDR/XDR-TB were directly and indirectly compared by network meta-analysis.Relative risk ( RR) or relative comparative effect ( Mean) or adverse reaction rate and 95％confidence interval ( CI) were used as indicators of systematic evaluation , and Berg' s funnel plot was used for the existing publication bias.Results A total of 20 papers and 21 studies were included.There were 2490 cases in the study group and 2303 cases in the control group included.According to the direct comparison of the network meta-analysis, the efficacy for treatment of MDR/XDR-TB of Lzd-IR ( RR=1.18, 95％ CI 1.02-1.36, Z=2.28, P <0.05) and MC-IR(RR=1.23,95％CI 1.01-1.50,Z=2.10,P<0.05)was better than that of IR in control group.The rates of adverse reactions of Lzd-IR, Cfz-IR and MC-IR were 29％(95％CI 0.24-0.35), 21％(95％CI 0.13-0.28) and 7％ (95％ CI 0.03-0.10), respectively.The top-down efficacy outcomes of the 4 individualized chemotherapy regimens were MC-IR (66.4％), Lzd-IR(22.6％), Cfz-IR (10.0％) and IR without Cfz, Lzd or MC (1.0％).The fitting model showed that MC-IR (Z=3.04, P<0.05) and Lzd-IR (Z=2.31, P<0.05) significantly shortened the "off"time compared with IR without Cfz, Lzd or MC.Conclusion The network meta-analysis shows that the efficacy and safety of regimen MC-IR are significantly higher than those of Lzd-IR and Cfz-IR in treatment of MDR/XDR-TB.
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Objective To estimate to what extent the mixture of ursolic acid and oleanolic acid, in addition to the antitubercular standard regime, affects the hepatotoxicity profile. Methods Liver injury was induced in male BALB/c mice by administering, per os and daily for 11 weeks, a combination of anti-Tubercular (anti-TB) agents Rifampicin (10 mg/kg), Isoniazid (10 mg/kg), and Pyrazinamide (30 mg/kg). The ursolic acid and oleanolic acid mixture at doses of 100 or 200 μg/mouse/day was subcutaneously injected throughout the entire study period (11 weeks). Biochemical and hematological analysis was supplemented by liver histological examination. Results Animals treated with the mixture of triterpenic acids exhibited significantly decreased aspartate transaminase and alanine aminotransferase levels and amelioration of the histopathological alterations produced by the anti-TB drugs. Conclusions The triterpene mixture was able to prevent the steatosis induced by the anti-TB drugs.
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Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs isoniazid, rifampin and pyrazinamide, which are basic for treatment of drug-sensible and drug-resistant tuberculosis. In the search for pharmacological alternatives to prevent liver damage, antitubercular drugs have been the subject of numerous studies and published reviews, a great majority of them carried out by Asian countries. At the same time, hepatoprotectors from plant source are now emerging as a possible alternative to counteract the toxic effects of these therapeutic agents. The present review aims to highlight the most recent studies on the subject, based information published in scientific databases such as Scopus and PubMed.
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Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs isoniazid, rifampin and pyrazinamide, which are basic for treatment of drug-sensible and drug-resistant tuberculosis. In the search for pharmacological alternatives to prevent liver damage, antitubercular drugs have been the subject of numerous studies and published reviews, a great majority of them carried out by Asian countries. At the same time, hepatoprotectors from plant source are now emerging as a possible alternative to counteract the toxic effects of these therapeutic agents. The present review aims to highlight the most recent studies on the subject, based information published in scientific databases such as Scopus and PubMed.
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OBJECTIVE@#To estimate to what extent the mixture of ursolic acid and oleanolic acid, in addition to the antitubercular standard regime, affects the hepatotoxicity profile.@*METHODS@#Liver injury was induced in male BALB/c mice by administering, per os and daily for 11 weeks, a combination of anti-Tubercular (anti-TB) agents Rifampicin (10 mg/kg), Isoniazid (10 mg/kg), and Pyrazinamide (30 mg/kg). The ursolic acid and oleanolic acid mixture at doses of 100 or 200 μg/mouse/day was subcutaneously injected throughout the entire study period (11 weeks). Biochemical and hematological analysis was supplemented by liver histological examination.@*RESULTS@#Animals treated with the mixture of triterpenic acids exhibited significantly decreased aspartate transaminase and alanine aminotransferase levels and amelioration of the histopathological alterations produced by the anti-TB drugs.@*CONCLUSIONS@#The triterpene mixture was able to prevent the steatosis induced by the anti-TB drugs.
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AIM@#Hepatotoxicity is a significantly increasing health problem worldwide, and the extent of the problem has stimulated interest in the search for hepatotherapeutic agents from plants. This study investigated the hepatoprotective and in vivo antioxidant activities of the hydroethanolic extract of Mucuna pruriens leaves in antitubercular and alcohol-induced hepatotoxicity assays in rats.@*METHOD@#In each of the models used, seven groups were allotted. The different groups received normal saline (10 mL·kg(-1), p.o.); hepatotoxicant (isoniazid-rifampicin, INH-RIF, 100 mg·kg(-1), i.p. or 20% ethanol 5 g·kg(-1), p.o.) and normal saline (10 mL·kg(-1), p.o.); hepatotoxicant and extract at doses of 100, 200, and 400 mg·kg(-1) p.o.; hepatotoxicant and silymarin 50 mg·kg(-1) p.o.; and extract at 400 mg·kg(-1) p.o. On the 21(st) day of treatment, blood was collected for assessment of serum biochemical parameters and harvested liver samples were assessed for antioxidants.@*RESULTS@#The hepatotoxicants significantly (P < 0.05-0.001) increased the levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), bilirubin, and malondialdehyde (MDA); and reduced the levels of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and reduced glutathione GSH compared to control. M. pruriens significantly reversed (P < 0.05-0.001) the elevation in the level of ALT, AST, ALP, and bilirubin caused by the hepatotoxicants. The extract (200 and 400 mg·kg(-1)) significantly reversed (P < 0.05) the diminution in the level of in vivo antioxidants and increased the level of MDA produced by INH-RIF. M. pruriens (100-400 mg·kg(-1)) elicited significant reduction (P < 0.001) in the level of MDA compared to the alcohol group. Silymarin also reversed the deleterious effects of the hepatotoxicants.@*CONCLUSION@#The hydroethanolic extract of Mucuna pruriens leaves possesses hepatoprotective activity with enhancement of in vivo antioxidants as a possible mechanism of action.
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Animals , Female , Humans , Male , Alanine Transaminase , Metabolism , Antioxidants , Antitubercular Agents , Toxicity , Aspartate Aminotransferases , Metabolism , Catalase , Metabolism , Chemical and Drug Induced Liver Injury , Ethanol , Toxicity , Glutathione Peroxidase , Metabolism , Liver , Liver Diseases, Alcoholic , Malondialdehyde , Metabolism , Mucuna , Chemistry , Plant Extracts , Plant Leaves , Chemistry , Protective Agents , Rats, Wistar , Superoxide Dismutase , MetabolismABSTRACT
Background: Anti TB drug induced hepatotoxicity has higher incidence in Indian population [11.5%] than western population [4.5%]. Antitubercular drug induced hepatotoxicity is mediated through oxidative and free radical damage to hepatocytes. Lagenaria siceraria [Bottle Gourd] is reported to have antioxidant and hepatoprotective activity. Hence in the present study we tested hepatoprotective and antioxidant activity of fruit extract of L. Siceraria in anti tubercular drug induced hepatotoxicity. Methods: We administered antitubercular drugs alone and in combination with fruit extract of Lagenaria siceraria (EELS 100mg/kg and EELS 200mg/kg) in healthy albino rats by oral route for 15 days. On 16th day blood collection for biochemical analysis is done by cardiac puncture. Biochemical markers used are serum transaminases (SGPT/SGOT), serum alkaline phosphatase [ALP], total bilirubin, total protein, superoxide dismutase [SOD] and malondialdehyde [MDA]. Liver is dissected for histopathological examinations. Results: Groups that received EELS [100 mg/kg & 200 mg/kg], in combination with anti tubercular drugs, showed significant reduction [p value <0.001] in biochemical parameters for hepatotoxicity [SGOT, SGPT, ALP, Total bilirubin, Total protein] in comparison with group that received anti tubercular drugs alone. Combined treatment of EELS [100 mg/kg & 200 mg/kg] & Anti tubercular drugs showed significant reduction in oxidative stress [SOD & MDA, p<0.001] as compared to anti tubercular drug alone. Histopathological examination of liver showed grade I & grade 0 changes in combination group while grade IV changes in group receiving anti tubercular drugs alone. Conclusion: Ethanolic extract of Lagenaria siceraria fruit possesses significant hepatoprotective and antioxidant activity in antitubercular drugs induced hepatotoxicity.
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Background: Drug-induced hepatotoxicity is a potentially serious adverse effect of antituberculosis treatment (ATT) regimens containing isoniazid, rifampicin and pyrazinamide. Many in vitro and in vivo studies revealed that honey possess antioxidant property and hepotoprotective property but there is no systematic work available to test the effect of honey on antitubercular drugs induced hepatotoxicity in rats. Hence present study was carried out to explore the prophylactic and therapeutic effect of honey with its antioxidant activity against hepatotoxicity induced by antitubercular drugs (Isoniazid, Rifampicin and Pyrazinamide) in albino rats. Methods: Hepatotoxicity in rats treated with antitubercular drugs (Isoniazid, Rifampicin and Pyrazinamide) was studied by assessing parameters such as Serum alanine aminotransferase (ALT), Serum aspartate aminotransferase (AST), Serum total protein, Serum Malondialdehyde (MDA) and Serum Superoxide dismutase activity (SOD). The effect of Honey as co-administration and administration after establishment of hepatotoxicity on above parameter was investigated. These biochemical observations were supplemented by Histopathological examination of liver. Results: Honey significantly reversed changes in serum levels of AST, ALT, MDA, SOD, total protein and also histopathological changes produced by Antitubercular drugs. It was found that honey significantly prevented as well as reversed Antitubercular drugs induced hepatotoxicity and antioxidant activity. Conclusions: The results of present study show that honey has significant prophylactic and therapeutic value against antitubercular drugs induced hepatotoxicity.
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Tuberculosis infection remains an important cause of mortality. The clinical and radiological manifestations can be non-specific and resemble many other conditions, including malignancies. This could lead to diagnostic delay. We report the case of a 48-year-old woman with tuberculosis presenting with a right upper lobe mass manifesting as metastatic lung cancer. She also had liver cirrhosis secondary to chronic hepatitis B infection. She developed hepatitis two weeks into her tuberculosis treatment. Our case highlights the importance of considering tuberculosis in patients suspected to have underlying malignancy and to be aware of the potential adverse effects of treatment.
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Lung Neoplasms , Neoplasms , Antitubercular AgentsABSTRACT
Tuberculosis (TB) is a major public-health problem in India, having the highest number of incident and multidrug-resistant (MDR) TB cases. The study was carried out to appraise the prevalence of first-line anti- TB drug resistance in Mycobacterium tuberculosis (MTB) and its patterns among different types of TB patients from different settings in a province of North India. Of 3,704 clinical specimens, 345 (9.3%) were culturepositive, and drug-susceptibility testing was carried out for 301 MTB strains. A high level of primary and acquired drug resistance of MTB was observed in the region studied, with weighted mean of 10.5% and 28.08%, 12.81% and 29.72%, 17.12% and 29.94%, 11.97% and 27.84%, and 10.74% and 23.54% for rifampicin, isoniazid, streptomycin, ethambutol-resistant and MDR cases respectively. Drug resistance was significantly higher in pulmonary (p=0.014) and acquired drug-resistant TB cases (p<0.001). Any drug resistance (p=0.002) and MDR TB were significantly (p=0.009) associated with HIV-seropositive cases. An urgent plan is needed to continuously monitor the transmission trends of drug-resistant strains, especially MDR-TB strains, in the region.
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Pellagra is a niacin deficiency disorder characterized clinically by diarrhea, dermatitis, and dementia. However, few drugs also cause pellagroid dermatitis. Recently, we encountered two cases of pellagroid dermatitis; both were on second line of antituberculosis drugs. Case 1 was of multidrug-resistant pulmonary tuberculosis. Patient was on ethionamide since one year before developing pellagroid dermatitis. Case 2 was of central nervous system tuberculoma and was on second line of antitubercular drugs. This patient was on ethionamide and isoniazid (INH) since six months before developing pellagroid dermatitis. This patient had previously taken first line of antituberculous therapy, inclusive of INH, for 1 year without any dermatitis. The skin lesions in both patients were symmetric hyperpigmented thickened plaques with prominent skin markings resembling lichen simplex chronicus. Nicotinamide 300 mg in three divided doses healed the lesions completely within 4 weeks and 3 weeks in first and second patient, respectively.
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Exfoliative dermatitis to all four first line drugs singly or rarely in combination has been reported. Here we report a rare case of pulmonary tuberculosis with exfoliative dermatitis to all four oral first line antitubercular drugs. (Rifampicin, Isoniazid, Ethambutol, Pyrazinamide). To the best of our knowledge, this is the first such case.