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

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

There are several reports to demonstrate that rifampicin, a major anti-tuberculosis agent, is associated with some adverse renal effects, with a few cases of rifampicin-induced minimal change disease (MCD). In the present case, a 68-year-old female presented with nausea, vomiting, foamy urine, general weakness and edema. She had been taking rifampicin for 4 weeks due to pleural tuberculosis. The patient had no proteinuria before the anti-tuberculosis agents were started, but urine tests upon admission showed heavy proteinuria with a 24-h urinary protein of 9.2 g/day, and serum creatinine, albumin, and total cholesterol levels were 1.36 mg/dL, 2.40 g/dL, and 283 mg/dL, respectively. MCD was diagnosed, and the patient achieved complete remission after cessation of rifampicin without undergoing steroid therapy.
Aged ; Antibiotics, Antitubercular/*adverse effects/therapeutic use ; Edema/etiology ; Female ; Humans ; Kidney Function Tests ; Kidney Glomerulus/pathology ; Nausea/etiology ; Nephrosis, Lipoid/*chemically induced/pathology ; Proteinuria ; Remission Induction ; Rifampin/*adverse effects/therapeutic use ; Treatment Outcome ; Tuberculosis, Pleural/*drug therapy

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

PURPOSE: The aim of this study was to elucidate the effects of immunocompromising comorbidities on treatment response and adverse reactions in older tuberculosis (TB) patients. MATERIALS AND METHODS: The medical records of 182 patients older than 65 years with proven TB by positive culture of Mycobacterium tuberculosis and with available drug susceptibility tests were reviewed retrospectively. These patients were subsequently assigned to either the comorbidity group (n=78) or non-comorbidity group (n=104) depending on whether they had immunocompromising comorbidities. RESULTS: The mean durations of treatment were 9.9+/-3.3 months in the comorbidity group and 9.3+/-3.2 months in the non-comorbidity group (p=0.21). M. tuberculosis culture results converted to negative in most patients with available follow-up cultures at two months after treatment. The successful treatment rates were 94.9% and 98.9% in the comorbidity and non-comorbidity groups, respectively (p=0.30). The most common side effects of anti-TB treatment were skin rash/pruritus (13% in the comorbidity group vs. 11% in the non-comorbidity group, p=0.79), gastro-intestinal problems (14% vs. 9%, p=0.25) and hepatotoxicity (14% vs. 7%, p=0.09). CONCLUSION: The present study shows that the successful treatment rate for TB is high and that immunocompromising comorbidities have no effect on the response to treatment and adverse effects in older TB patients.
Age Factors ; Aged ; Aged, 80 and over ; Antitubercular Agents/adverse effects/*therapeutic use ; Comorbidity ; Female ; Humans ; *Immunocompromised Host ; Isoniazid/adverse effects/*therapeutic use ; Male ; Retrospective Studies ; Rifampin/adverse effects/*therapeutic use ; Risk Factors ; Treatment Outcome ; Tuberculosis/*drug therapy/epidemiology/immunology

Pseudomembranous colitis (PMC) is known to be associated with the administration of antibiotics which alter normal gastrointestinal flora and allow overgrowth of Clostridium difficile. Most cases of rifampicin-induced PMC are seen in patients with pulmonary tuberculosis, but not with gastrointestinal tuberculosis. We report a case of PMC associated with rifampicin therapy in a patient with gastrointestinal tuberculosis. A 65-year-old female patient with rectal cancer and gastrointestinal tuberculosis was admitted due to abdominal pain and diarrhea. She was treated with anti-tuberculosis agents containing rifampicin. On colonoscopic examination, mucoid exudates and yellowish plaque lesions were observed. Anti-tuberculosis agents were stopped, and the patient was treated with metronidazole. Symptoms were relieved and did not recur when all the anti-tuberculosis agents except rifampicin were started again. When a patient complains of abdominal pain or diarrhea while taking rifampicin, the physician should consider the possibility of rifampicin-associated PMC.
Aged ; Antibiotics, Antitubercular/*adverse effects/therapeutic use ; Enterocolitis, Pseudomembranous/*diagnosis/etiology/pathology ; Female ; Humans ; Rectal Neoplasms/*complications/diagnosis ; Rifampin/*adverse effects/therapeutic use ; Sigmoidoscopy ; Tuberculosis, Gastrointestinal/complications/diagnosis/*drug therapy

OBJECTIVETo study the effect of rifampin (RFP) on the metabonomic profile of rat urine and its relationship with traditional toxicity evaluation of blood biochemical indicators and histopathology.

METHODSThirty-six male Wistar rats were randomly divided into control group, 50 mg/kg RFP group, and 100 mg/kg RFP group, with 12 rats in each group. Rats in each group were given intragastric infusion with a daily dose of 0, 50 mg/kg RFP, and 100 mg/kg RFP for 3, 7, and 14 days, respectively. Then 4 rats in each group were killed on the next day of administration to collect blood samples and liver sample for the determination of blood biochemical indicators and for the pathological analysis of the liver. The urine specimens over 24 hours of each rat were collected before and after each treatment until the rat was killed. 1H nuclear magnetic resonance (1H NMR) spectra of these urine specimens were acquired and subjected to data preprocess and principal component analyses (PCA).

RESULTSThe level of serum total bilirubin of the rat administrated with 100 mg/(kg x d) RFP for 7 days was significantly higher than that of control group (P < 0.05). Mild hepatotoxicity to the rat, treated with RFP of higher dosage (100 mg/kg) and longer duration (14 days), was revealed by the traditional histopathological method. The metabonomic spectra of rat urine in different groups differed from each other; a trajectory bias in determination of rat urine by 1H NMR occurred depending on the administration duration. As demonstrated by 1H NMR spectra of urine in rats treated with RFP, the concentration of urinary citrate and 2-oxoglutarate decreased, along with the remarkable increase of the concentrations of urinary taurine and glucose (compared with those of the control group).

CONCLUSIONSBeing consistent with the results of traditional toxicity evaluation measurements, metabonomic method is more sensitive. The 1H-NMR metabonomic profile of the rat urine is closely related with the duration of RFP. The hepatic toxicity induced by RFP is related to the reduction of energy metabolism in tricarboxylic acid cycle and the perturbation of glucose and lipid metabolism.

Animals ; Antibiotics, Antitubercular ; administration & dosage ; toxicity ; Blood Chemical Analysis ; Drug-Related Side Effects and Adverse Reactions ; Infusions, Parenteral ; Liver ; drug effects ; pathology ; Male ; Metabolomics ; Models, Animal ; Random Allocation ; Rats ; Rats, Wistar ; Rifampin ; administration & dosage ; toxicity ; Urine ; chemistry

Neuroleptic malignant syndrome (NMS), a potentially fatal adverse reaction to neuroleptics, is known to occur more often in the initial stage of antipsychotic treatment. We describe a patient with chronic schizophrenia who, in a few days after the addition of antituberculotic drugs to his antipsychotic regimen, developed probable NMS without pyrexia. We reasoned that rifampin, a strong hepatic enzyme inducer, decreased the plasma chlorpromazine concentration of the patient, with the result of cholinergic hyperactivity and finally, the symptoms of NMS. Therefore, physicians should be aware of drug interactions and the likelihood of NMS, and consider antipsychotic dose adjustment when prescribing drugs that may influence pharmacokinetic properties of antipsychotics in a patient with schizophrenia receiving long-term antipsychotic treatment.
Adult ; Antitubercular Agents/*adverse effects ; Chlorpromazine/*adverse effects ; Creatine Kinase/blood ; Drug Interactions ; Enzyme Induction/drug effects ; Humans ; Male ; Neuroleptic Malignant Syndrome/*etiology ; Rifampin/*adverse effects ; Schizophrenia/*drug therapy