INTRODUCTIONEthambutol is used in the treatment of tuberculosis, which is still prevalent in Southeast Asia, and can be associated with permanent visual loss. We report 3 cases which presented with bitemporal hemianopia.

CLINICAL PICTUREThree patients with ethambutol-associated toxic optic neuropathy are described. All 3 patients had loss of central visual acuity, colour vision (Ishihara) and visual field. The visual field loss had a bitemporal flavour, suggesting involvement of the optic chiasm.

TREATMENTDespite stopping ethambutol on diagnosis, visual function continued to deteriorate for a few months. Subsequent improvement was mild in 2 cases. In the third case, visual acuity and colour vision normalised but the optic discs were pale.

OUTCOMEAll 3 patients had some permanent loss of visual function.

CONCLUSIONSEthambutol usage is associated with permanent visual loss and should be avoided if possible or used with caution and proper ophthalmological follow-up. The author postulates that in cases of ethambutol associated chiasmopathy, ethambutol may initially affect the optic nerves and subsequently progress to involve the optic chiasm.

Aged ; Antitubercular Agents ; adverse effects ; Ethambutol ; adverse effects ; Female ; Hemianopsia ; chemically induced ; Humans ; Male ; Middle Aged ; Optic Nerve Diseases ; chemically induced ; Tuberculosis ; drug therapy

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.
Rats ; Animals ; Flavonoids/pharmacology* ; Uric Acid ; Crocus ; Xanthine Oxidase ; Ethambutol/adverse effects* ; Rats, Sprague-Dawley ; Hyperuricemia/drug therapy* ; Kidney ; Antioxidants/pharmacology* ; Plant Extracts/adverse effects* ; Amino Acids ; Adenine/adverse effects* ; Lipids

BACKGROUND: Anti-tuberculosis drugs used in combination cause adverse drug reactions, but the prevalence of the reactions and risk factors have not been determined. This study aims to identify the prevalence and risk factors of adverse drug reactions (ADR) to the use of first line anti-tuberculosis drugs. METHODS: A total of 435 newly diagnosed patients with tuberculosis (44.1 years+/-19.0 years) were eligible for this study. All patients received daily oral isoniazid (300 or 400 mg), rifampicin (450 or 600 mg) and ethambutol (800 mg) for 6 months, and pyrazinamide (20 mg/kg) for 2 months. Blood tests were performed regularly (before treatment, 2 weeks after treatment, and bimonthly there after). Patients were interviewed 2 months and 6 months after treatment. A serious ADR was defined as any ADR that resulted in the discontinuation of one or more of the drugs. RESULTS: An ADR was noted in 52.6% of all patients. Gastrointestinal (19.3%), cutaneous (17.7%), hepatic (13.8%), renal (12.6%), and neurological (10.3%) ADRs were frequent and hematological (4.4%), musculoskeletal (3.0%) ADRs were less frequent. A skin ADR was associated with an elevated baseline of liver enzymes (odds ratio, 3.48; 95% CI, 1.2 to 9.9), whereas a hepatic ADR was associated with a history of chronic liver disease (odds ratio, 4.82; 95% CI, 1.7 to 13.2). The prevalence of any serious ADR was 9.7%. Occurrence of any serious ADR was associated with a history of chronic liver disease (odds ratio, 4.29; 95% CI, 1.4 to 13.6). CONCLUSIONS: Anti-tuberculosis drugs given in combination frequently caused a ADR and the findings suggest that a patient receiving anti-tuberculosis treatment should be closely monitored.
Drug-Related Side Effects and Adverse Reactions* ; Ethambutol ; Hematologic Tests ; Hepatitis ; Humans ; Isoniazid ; Liver ; Liver Diseases ; Prevalence* ; Pyrazinamide ; Rifampin ; Risk Factors ; Skin ; Tuberculosis

PURPOSE: Although there have been reported cases of drug reactions with eosinophilia and systemic symptoms (DRESS) syndrome caused by antituberculosis drugs, there has been no research to examine its prevalence. This study assessed the prevalence and clinical characteristics of DRESS syndrome caused by antituberculosis drugs. METHODS: The electronic medical records of a cohort consisting of adult patients diagnosed with tuberculosis between July 2006 and June 2010 were reviewed and retrospectively inspected. We searched the surveillance system for adverse drug reactions and the electronic medical records to identify patients who reported severe cutaneous adverse reactions to antituberculosis drugs. These patients were then re-assessed using a European Registry of Severe Cutaneous Adverse Reactions to Drugs and Collection of Biological Samples (RegiSCAR) scoring system. Clinical characteristics, including the symptoms and latency of DRESS syndrome, the therapeutic dosage and period of steroids, and the final duration of tuberculosis therapy, were examined. RESULTS: Of the 1,253 adult patients with tuberculosis receiving antituberculosis drugs, 15 were identified as potential cases of DRESS syndrome (prevalence of 1.2%). Ethambutol was the most frequently used drug (53.5%), followed by rifampicin (26.7%), pyrazinamide (20.0%), streptomycin (13.3%), and isoniazid (6.7%). The median latency after day 1 of antituberculosis medication was 42 days. The median daily dose of steroids, expressed in prednisone-equivalent units, was 33-mg/day, and the median dosing period was 14 days. The duration of tuberculosis treatment was 76 days longer than the standard treatment period of 180 days. There was a significant difference in the peak eosinophil counts of DRESS syndrome patients according to RegiSCAR scores. Moreover, there was a significant quantitative correlation between the RegiSCAR score and peak eosinophil count. A negative correlation was also found between the RegiSCAR score and latency. CONCLUSIONS: This study confirmed the prevalence of DRESS syndrome in a cohort of adult patients with tuberculosis.
Adult ; Cohort Studies* ; Drug Hypersensitivity Syndrome ; Drug-Related Side Effects and Adverse Reactions ; Electronic Health Records ; Eosinophilia* ; Eosinophils ; Ethambutol ; Humans ; Isoniazid ; Prevalence* ; Pyrazinamide ; Retrospective Studies* ; Rifampin ; Steroids ; Streptomycin ; Tuberculosis

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome reflects a serious hypersensitivity reaction to drugs, characterized by skin rash, fever, lymph node enlargement, and internal organ involvement. So far, numerous drugs such as sulfonamides, phenobarbital, sulfasalazine, carbamazepine, and phenytoin have been reported to cause the DRESS syndrome. We report a case in a 29-yr-old female patient who had been on celecoxib and anti-tuberculosis drugs for one month to treat knee joint pain and pulmonary tuberculosis. Our patient's clinical manifestations included fever, lymphadenopathy, rash, hypereosinophilia, and visceral involvement (hepatitis and pneumonitis). During the corticosteroid administration for DRESS syndrome, swallowing difficulty with profound muscle weakness had developed. Our patient was diagnosed as DRESS syndrome with eosinophilic polymyositis by a histopathologic study. After complete resolution of all symptoms, patch tests were positive for both celecoxib and ethambutol. Although further investigations might be needed to confirm the causality, celecoxib and ethambutol can be added to the list of drugs as having the possibility of DRESS syndrome.
Adult ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Antitubercular Agents/adverse effects ; Arthritis/complications/*drug therapy ; Drug Eruptions/*etiology/pathology ; Eosinophilia/*chemically induced/pathology ; Ethambutol/*adverse effects ; Female ; Humans ; Myositis/chemically induced/pathology ; Pyrazoles/*adverse effects ; Sulfonamides/*adverse effects ; Syndrome ; Tuberculosis, Pulmonary/complications/*drug therapy

INTRODUCTIONThe aim of this study was to analyse the thickness of the retinal nerve fibre layer (RNFL) of pulmonary tuberculosis patients on ethambutol and isoniazid.

MATERIALS AND METHODSThis was a prospective cohort study where patients with newly diagnosed pulmonary tuberculosis requiring chemotherapy, including ethambutol and isoniazid, were imaged using scanning laser polarimetry. Their mean baseline RNFL thickness and various scanning laser polarimetry parameters of both eyes were measured 2 weeks after the commencement of chemotherapy. The measurements were repeated at 3 months and 6 months after treatment. The various parameters of the baseline and the follow-up measurements were compared using paired sample t-test with Bonferroni correction.

RESULTSTwenty-four patients (16 males and 8 females; mean age, 51.0 +/- 17.6 years) were recruited. There was no statistically significant difference between the baseline and the follow-up measurements in RNFL thickness and all other scanning laser polarimetry parameters.

CONCLUSIONIn this cohort of subjects, there was no subclinical change in RNFL thickness detected by scanning laser polarimetry in pulmonary tuberculosis patients on chemotherapy, including ethambutol and isoniazid, after 6 months of treatment.

Adult ; Aged ; Aged, 80 and over ; Antitubercular Agents ; adverse effects ; therapeutic use ; Diagnostic Techniques, Ophthalmological ; Ethambutol ; adverse effects ; therapeutic use ; Female ; Humans ; Isoniazid ; adverse effects ; therapeutic use ; Lasers ; Male ; Middle Aged ; Prospective Studies ; Retinal Diseases ; chemically induced ; diagnosis ; Tuberculosis, Pulmonary ; drug therapy

We analyzed 57 patients with tuberculous nonfunctioning kidneys, which were diagnosed pathologically or bacteriologically at Seoul National University, from October 1981 to December 1989. The patients were divided into 3 groups according to the treatment ; Group 1 : 12 patients, only chemotherapy for more than 12 months ; Group 2 :32, nephrectomy and chemotherapy for more than 6 months ; Group 3 . 13, nephrectomy and chemotherapy only for 3 months. As a standard antituberculous regimen, isoniazid, rifampin, and ethambutol were used, and pyrazinamide was added in 15 patients. The follow-up tests were urinalysis, urine AFB smear and culture, and intravenous pyelography. The duration of the follow-up was 6 to 1O8 months, with a mean of 23.3 months. There was no evidence of recurrence in any patient among the 3 groups. Two postoperative complications (hematoma and fistula formation) occurred in 45 nephrectomized patients. Pathologic examination of the resected kidneys revealed findings compatible with tuberculosis in all patients of Groups 2 and 3. Coexisting cortical adenomas were found incidentally in 2 patients. Final diagnoses of the other 2 patients were hydronephrosis and chronic pyelonephritis without any evidence of tuberculosis, although these 2 patients were excluded in this study. Severe drug toxicity occurred in 7 patients that belonged to Groups 1 and 2. In conclusion, early nephrectomy for accurate diagnosis and removal of infective foci was the justifiable initial procedure, and this should be followed by postoperative antituberculous chemotherapy for the shortest acceptable period in tuberculous nonfunctioning kidneys. In highly selective cases where the lesion is completely localized in one kidney, we can consider early nephrectomy and a 3-month course of chemotherapy as one treatment modality.
Adenoma ; Diagnosis ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; Ethambutol ; Fistula ; Follow-Up Studies ; Humans ; Hydronephrosis ; Isoniazid ; Kidney* ; Nephrectomy ; Postoperative Complications ; Pyelonephritis ; Pyrazinamide ; Recurrence ; Rifampin ; Seoul ; Tuberculosis ; Urinalysis ; Urography

The correlation between serum anti-tuberculosis (TB) drug levels and the drug-induced hepatotoxicity (DIH) remains unclear. The purpose of this study was to investigate whether anti-TB DIH is associated with basal serum drug levels. Serum peak levels of isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) were analyzed in blood samples 2 hr after the administration of anti-TB medication. Anti-TB DIH and mild liver function test abnormality were diagnosed on the basis of laboratory and clinical criteria. Serum anti-TB drug levels and other clinical factors were compared between the hepatotoxicity and non-hepatotoxicity groups. A total of 195 TB patients were included in the study, and the data were analyzed retrospectively. Seventeen (8.7%) of the 195 patients showed hepatotoxicity, and the mean aspartate aminotransferase/alanine aminotransferase levels in the hepatotoxicity group were 249/249 IU/L, respectively. Among the 17 patients with hepatotoxicity, 12 showed anti-TB DIH. Ten patients showed PZA-related hepatotoxicity and 2 showed INH- or RMP-related hepatotoxicity. However, intergroup differences in the serum levels of the 4 anti-TB drugs were not statistically significant. Basal serum drug concentration was not associated with the risk anti-TB DIH in patients being treated with the currently recommended doses of first-line anti-TB treatment drugs.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alanine Transaminase/blood ; Antitubercular Agents/adverse effects/*blood/therapeutic use ; Aspartate Aminotransferases/blood ; Drug-Induced Liver Injury/*blood ; Ethambutol/adverse effects/blood/therapeutic use ; Female ; Humans ; Isoniazid/adverse effects/blood/therapeutic use ; Liver/*pathology ; Liver Function Tests ; Male ; Middle Aged ; Pyrazinamide/adverse effects/blood/therapeutic use ; Retrospective Studies ; Rifampin/adverse effects/blood/therapeutic use ; Tuberculosis, Pulmonary/drug therapy ; Young Adult

The correlation between serum anti-tuberculosis (TB) drug levels and the drug-induced hepatotoxicity (DIH) remains unclear. The purpose of this study was to investigate whether anti-TB DIH is associated with basal serum drug levels. Serum peak levels of isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) were analyzed in blood samples 2 hr after the administration of anti-TB medication. Anti-TB DIH and mild liver function test abnormality were diagnosed on the basis of laboratory and clinical criteria. Serum anti-TB drug levels and other clinical factors were compared between the hepatotoxicity and non-hepatotoxicity groups. A total of 195 TB patients were included in the study, and the data were analyzed retrospectively. Seventeen (8.7%) of the 195 patients showed hepatotoxicity, and the mean aspartate aminotransferase/alanine aminotransferase levels in the hepatotoxicity group were 249/249 IU/L, respectively. Among the 17 patients with hepatotoxicity, 12 showed anti-TB DIH. Ten patients showed PZA-related hepatotoxicity and 2 showed INH- or RMP-related hepatotoxicity. However, intergroup differences in the serum levels of the 4 anti-TB drugs were not statistically significant. Basal serum drug concentration was not associated with the risk anti-TB DIH in patients being treated with the currently recommended doses of first-line anti-TB treatment drugs.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alanine Transaminase/blood ; Antitubercular Agents/adverse effects/*blood/therapeutic use ; Aspartate Aminotransferases/blood ; Drug-Induced Liver Injury/*blood ; Ethambutol/adverse effects/blood/therapeutic use ; Female ; Humans ; Isoniazid/adverse effects/blood/therapeutic use ; Liver/*pathology ; Liver Function Tests ; Male ; Middle Aged ; Pyrazinamide/adverse effects/blood/therapeutic use ; Retrospective Studies ; Rifampin/adverse effects/blood/therapeutic use ; Tuberculosis, Pulmonary/drug therapy ; Young Adult

Pseudomembranous colitis (PMC) is known to be associated with the long-term administration of antibiotics, which alter normal gastrointestinal flora and allow overgrowth of Clostridium difficile. However, antituberculosis agents are rarely reported as a cause of this disease. Besides, most cases of antituberculosis agent-induced PMC have been observed in patients with pulmonary tuberculosis but not with tuberculous meningitis. This report presents a case of PMC associated with antituberculosis therapy in a patient with tuberculous meningitis. A 29-year-old female patient was admitted due to headaches and diplopia that had lasted for 2 weeks. She had not recently received antimicrobial therapy. She was diagnosed with tuberculous meningitis by cerebrospinal fluid findings and neurologic examination, including brain imaging study. She was treated with standard antituberculosis agents (HERZ regimen: isoniazid, ethambutol, rifampicin, and pyrazinamide). After 11 days of HERZ, she developed a fever, sudden widespread skin eruption, and elevation of liver enzymes. Considering adverse drug reactions, antituberculosis agents were stopped. One week later, her symptoms were relieved. Thus, antituberculosis agents were reintroduced one at a time after liver function returned to normal. However, she presented with frequent mucoid, jelly-like diarrhea, and lower abdominal pain. Sigmoidscopy revealed multiple yellowish plaques with edematous mucosa, which were compatible with PMC. She was treated with oral vancomycin considering drug interactions. Symptoms were relieved and did not recur when all antituberculosis agents except pyrazinamide were started again. Therefore, when a patient complains of abdominal pain or diarrhea after initiation of antituberculosis therapy, the physician should consider the possibility of antituberculosis agent-associated PMC.
Abdominal Pain ; Adult ; Anti-Bacterial Agents ; Cerebrospinal Fluid ; Clostridium difficile ; Diarrhea ; Diplopia ; Drug Interactions ; Drug-Related Side Effects and Adverse Reactions ; Enterocolitis, Pseudomembranous* ; Ethambutol ; Female ; Fever ; Headache ; Humans ; Isoniazid ; Liver ; Mucous Membrane ; Neuroimaging ; Neurologic Examination ; Pyrazinamide ; Rifampin ; Skin ; Tuberculosis, Meningeal* ; Tuberculosis, Pulmonary ; Vancomycin