We assessed the incidence of adverse drug reactions (ADRs) with anti-TB medications and evaluated the risk factors for developing ADRs in previously treated tuberculosis patients in China. All patients received the first-line anti-TB regimen (2HREZS/6HRE) as recommended by the national guidelines. Clinical and laboratory evaluations were performed once a month. Out of the 354 participants, 262 (74.0%) experienced ADRs such as hyperuricemia (65.0%, 230/354), hepatotoxicity (6.2%, 22/354) and hearing disturbances (4.8%, 17/354). ADRs were significantly associated with diabetes mellitus [OR (95% CI): 15.5 (2.07-115.87)]; however, weight more than 50 kg [OR (95% CI): 0.41 (0.22-0.85)] was a protective factor for occurrence of ADRs. Hyperuricemia is the most common adverse event but, most patients with hyperuricemia showed increased tolerance for high uric acid levels. Low body weight and diabetes mellitus increased the risk of the occurrence of ADRs during anti-TB treatment.
Adolescent ; Adult ; Antitubercular Agents ; adverse effects ; therapeutic use ; Diabetes Mellitus ; Female ; Humans ; Male ; Middle Aged ; Prevalence ; Retrospective Studies ; Risk Factors ; Tuberculosis, Pulmonary ; drug therapy ; epidemiology ; Young Adult

BACKGROUNDDrug is an important cause of liver injury and accounts for up to 40% of instances of fulminant hepatic failure. Drug-induced liver injury (DILI) is increasing while the diagnosis becomes more difficult. Though many drugs may cause DILI, Chinese herbal medicines have recently emerged as a major cause due to their extensive use in China. We aimed to provide drug safety information to patients and health carers by analyzing the clinical and pathological characteristics of the DILI and the associated drug types.

METHODSA retrospective analysis was conducted in 287 patients diagnosed with DILI enrolled in our hospital from January 2011 to December 2015. The categories of causative drugs, clinical and pathological characteristics were reviewed.

RESULTSWestern medicines ranked as the top cause of DILI, accounting for 163 out of the 287 DILI patients (56.79%) in our study. Among the Western medicine, antituberculosis drugs were the highest cause (18.47%, 53 patients) of DILI.   Antibiotics (18 patients, 6.27%) and antithyroid (18 patients, 6.27%) drugs also ranked among the major causes of DILI. Chinese herbal medicines are another major cause of DILI, accounting for 36.59% of cases (105 patients). Most of the causative Chinese herbal medicines were those used to treat osteopathy, arthropathy, dermatosis, gastropathy, leukotrichia, alopecia, and gynecologic diseases. Hepatocellular hepatitis was prevalent in DILI, regardless of Chinese herbal medicine or Western medicine-induced DILI.

CONCLUSIONSRisks and the rational use of medicines should be made clear to reduce the occurrence of DILI. For patients with liver injury of unknown origin, liver tissue pathological examination is recommended for further diagnosis.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents ; adverse effects ; Antithyroid Agents ; adverse effects ; Antitubercular Agents ; adverse effects ; Chemical and Drug Induced Liver Injury ; diagnosis ; etiology ; Child ; China ; Drugs, Chinese Herbal ; adverse effects ; Female ; Humans ; Liver ; drug effects ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

The emergence of drug-resistant tuberculosis (TB) is a growing problem worldwide. The lack of safe and effective drugs, together with the frequent development of adverse drug reactions can result in worse outcomes. Therefore, new TB drugs able to bolster the current TB treatment regimen are urgently required. Novel drugs that are effective and safe against Mycobacterium tuberculosis are required to reduce the number of drugs and the duration of treatment in both drug-susceptible TB and multi-drug-resistant (MDR)-TB. This review covers promising novel TB drugs and regimens that are currently under development. Bedaquiline and delamanid are the most promising novel drugs for the treatment of MDR-TB, each having a high efficacy and tolerability. However, the best regimen for achieving better outcomes and reducing adverse drug reactions remains yet to be determined, with safety concerns regarding cardiac events due to QT prolongation still to be addressed. Pretomanid is a novel drug that potentially shortens the duration of treatment in both drug-susceptible and drug-resistant TB. Many regimens consisting of injection free drugs with shorter treatment duration compared to the conventional treatment are now undergoing clinical trials. Therefore a simple and short treatment with higher efficacy, and lesser adverse drug reactions and drug-drug interaction is expected for patients with MDR-TB.
Antitubercular Agents ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Mycobacterium tuberculosis ; Tuberculosis ; Tuberculosis, Multidrug-Resistant

BACKGROUND/AIMS: To determine the incidence and clinical characteristics of tuberculosis (TB) medication-associated Clostridium difficile infection. METHODS: This multicenter study included patients from eight tertiary hospitals enrolled from 2008 to 2013. A retrospective analysis was conducted to identify the clinical features of C. difficile infection in patients who received TB medication. RESULTS: C. difficile infection developed in 54 of the 19,080 patients prescribed TB medication, representing a total incidence of infection of 2.83 cases per 1,000 adults. Fifty-one of the 54 patients (94.4%) were treated with rifampin. The patients were usually treated with oral metronidazole, which produced improvement in 47 of the 54 patients (87%). Twenty-three patients clinically improved with continuous rifampin therapy for C. difficile infection. There were no significant differences in improvement between patients treated continuously (n=21) and patients in whom treatment was discontinued (n=26). CONCLUSIONS: The incidence of C. difficile infection after TB medication was not low considering the relatively low TB medication dosage compared to other antibiotics. It may not be always necessary to discontinue TB medication. Instead, decisions concerning discontinuation of TB medication should be based on TB status.
Adult ; Aged ; Aged, 80 and over ; Anti-Infective Agents/therapeutic use ; Antibiotics, Antitubercular/*adverse effects ; *Clostridium difficile ; Enterocolitis, Pseudomembranous/chemically induced/drug therapy/*epidemiology ; Female ; Humans ; Incidence ; Male ; Metronidazole/therapeutic use ; Middle Aged ; Retrospective Studies ; Rifampin/*adverse effects ; Treatment Outcome ; Tuberculosis/*drug therapy

A worsening scenario of drug-resistant tuberculosis has increased the need for new treatment strategies to tackle this worldwide emergency. There is a pressing need to simplify and shorten the current 6-month treatment regimen for drug-susceptible tuberculosis. Rifamycins and fluoroquinolones, as well as several new drugs, are potential candidates under evaluation. At the same time, treatment outcomes of patients with drug-resistant tuberculosis should be improved through optimizing the use of fluoroquinolones, repurposed agents and newly developed drugs. In this context, the safety and tolerance of new therapeutic approaches must be addressed.
Animals ; Antitubercular Agents/adverse effects/*therapeutic use ; *Drug Discovery ; *Drug Repositioning ; Drug Resistance, Bacterial ; Drug Therapy, Combination ; Extensively Drug-Resistant Tuberculosis/drug therapy/microbiology ; Humans ; Lung/*drug effects/microbiology ; Mycobacterium tuberculosis/*drug effects/pathogenicity ; Treatment Outcome ; Tuberculosis, Multidrug-Resistant/diagnosis/*drug therapy/microbiology ; Tuberculosis, Pulmonary/diagnosis/*drug therapy/microbiology

BACKGROUND/AIMS: We investigated the time of onset of antituberculous drug-induced hepatotoxicity (ADIH) and related characteristics. METHODS: Adult patients (n = 1,031) treated with first-line antituberculous drugs between February 2009 and January 2013 were enrolled. RESULTS: Of the 1,031 patients, 108 patients (10.5%) developed ADIH a mean of 39.6 +/- 43.7 days after treatment initiation. Twenty-eight patients (25.9%) developed ADIH within 7 days, 73 (67.6%) within 30 days, and the rest after 30 days. The < or = 30-day group was characterized by higher peak alanine aminotransferase (ALT) level and a high proportion of patients with maintenance of first-line antituberculous drugs compared to the > 30-day group. In subgroup analysis, the < or = 7-day group was characterized by higher baseline aspartate aminotransferase and ALT, high proportion of patients with maintenance of first-line antituberculous drugs, and high proportion of patients with extrapulmonary tuberculosis compared to patients with ADIH that developed beyond 7 days. In multivariate analysis, serum ALT > 40 IU/L (odds ratio [OR], 2.995; 95% confidence interval [CI], 1.580 to 5.680; p = 0.001) and presence of anti-hepatitis C virus (OR, 4.204; 95% CI, 1.822 to 9.700, p = 0.001) were independent risk factors for development of ADIH. CONCLUSIONS: Approximately 70% of the cases of ADIH occurred in the first month of antituberculous treatment, and were associated with continuation of the first-line drug regimen.
Adult ; Aged ; Alanine Transaminase/blood ; Antitubercular Agents/*adverse effects ; Aspartate Aminotransferases/blood ; Biomarkers/blood ; Chemical and Drug Induced Liver Injury/blood/*diagnosis/etiology ; Chi-Square Distribution ; Clinical Enzyme Tests ; Coinfection ; Drug Monitoring/*methods ; Drug Therapy, Combination ; Early Diagnosis ; Female ; Hepatitis/complications/diagnosis ; Humans ; *Liver Function Tests ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Predictive Value of Tests ; Retrospective Studies ; Risk Factors ; Time Factors

Tuberculosis (TB) remains a major global health problem, and the incidence of TB cases has not significantly decreased over the past decade in Korea. The standard short course regimen is highly effective against TB, but requires multiple TB-specific drugs and a long treatment duration. Recent studies using late-generation fluoroquinolones and/or high-dose rifapentine-containing regimens to shorten the duration of TB treatment showed negative results. Extending the treatment duration may be considered in patients with cavitation on the initial chest radiograph and positivity in sputum culture at 2 months of treatment for preventing TB relapse. Current evidence does not support the use of fixed-dose combinations compared to separate drugs for the purpose of improving treatment outcomes. All patients receiving TB treatment should be monitored regularly for response to therapy, facilitation of treatment completion, and management of adverse drug reactions. Mild adverse effects can be managed with symptomatic therapy and changing the timing of the drug administration, but severe adverse effects require a discontinuation of the offending drugs.
Antitubercular Agents ; Drug-Related Side Effects and Adverse Reactions ; Fluoroquinolones ; Humans ; Incidence ; Korea ; Radiography, Thoracic ; Recurrence ; Sputum ; Tuberculosis ; Tuberculosis, Pulmonary*

Adult ; Antitubercular Agents ; adverse effects ; Humans ; Isoniazid ; adverse effects ; Male ; Pulmonary Fibrosis ; chemically induced ; diagnosis

PURPOSE: Adverse cutaneous reactions to antituberculous drugs (ATD), such as maculopapular eruption (MPE), are the most common causes of discontinuation of scheduled treatment of tuberculosis. We previously reported that tumor necrosis factor (TNF)-alpha genetic polymorphism -308G/A is significantly associated with ATD-induced hepatitis. This study aimed to investigate associations between TNF-alpha -308G/A and ATD-induced MPE. METHODS: Patients with ATD-induced MPE and controls without any adverse reactions to ATD were recruited from the database of the Adverse Drug Reaction Pharmacogenomic Research Group database of Korea. We compared the genotype frequency of TNF-alpha-308G/A between patients with ATD-induced MPE and ATD-tolerant controls. RESULTS: A total of 69 patients with ATD-induced MPE and 229 control subjects were enrolled for this study. There were no significant differences in genotype frequency between the patients and the controls, suggesting lack of associations between TNF-alpha-308G/A and ATD-induced MPE. CONCLUSION: The TNF-alpha genetic polymorphism -308G/A may not be related to the development of ATD-induced MPE, in contrast to ATD-induced hepatitis. These findings suggest that associations between TNF-alpha-308G/A and ATD-induced adverse reactions can be phenotype-specific.
Antitubercular Agents ; Drug Eruptions ; Drug-Related Side Effects and Adverse Reactions ; Genotype ; Hepatitis ; Humans ; Korea ; Polymorphism, Genetic* ; Tuberculosis ; Tumor Necrosis Factor-alpha*

No abstract available.
Adult ; Antineoplastic Agents/*adverse effects ; Antitubercular Agents/therapeutic use ; Biopsy ; Female ; Gastrointestinal Stromal Tumors/*drug therapy/pathology/surgery ; Humans ; Imatinib Mesylate/*adverse effects ; Lung Diseases, Interstitial/*chemically induced/diagnosis ; Mycobacterium tuberculosis/*isolation & purification ; Protein Kinase Inhibitors/*adverse effects ; Rectal Neoplasms/*drug therapy/pathology/surgery ; Tomography, X-Ray Computed ; Tuberculosis, Pulmonary/diagnosis/drug therapy/*microbiology