ethionamide and Tuberculosis--Meningeal

Topics: Adolescent; Adult; Aged; Aminosalicylic Acids; Child, Preschool; Clinical Trials as Topic; Cycloserine; Diabetes Mellitus; Ethambutol; Ethionamide; Female; Humans; Isoniazid; Liver Cirrhosis; Male; Mycoplasma Infections; Pregnancy; Streptomycin; Tuberculosis; Tuberculosis, Meningeal; Tuberculosis, Pulmonary

Multiple drug hypersensitivity (MDH) is an allergy to two or more chemically unrelated drugs. We present a case of MDH caused by antituberculosis agents during the treatment of tuberculous meningitis (TBM). A 64-year-old man without a history of drug allergy developed fever and severe headache. Examination of cerebrospinal fluid showed lymphocytosis, a low glucose level, and a high ADA activity, suggestive of TBM. The patient was treated with isoniazid, rifampicin, pyrazinamide, and ethambutol, and his symptoms resolved quickly. However, 20 days after the initiation of therapy, he developed remittent fever without mucocutaneous lesions. A drug-induced lymphocyte stimulation test was positive for isoniazid, rifampicin, and pyrazinamide, which was consistent with a diagnosis of MDH. All the antituberculosis drugs were replaced with levofloxacin and ethionamide, both of which have excellent cerebrospinal fluid penetration, and the fever subsided. The patient made a full recovery from TBM. Because standard antituberculosis regimens include three or four antituberculosis drugs, it is difficult to determine the culprit drug when hypersensitivity occurs. Moreover, there can be multiple causative drugs as illustrated by the present case. During a time-consuming desensitization therapy, TBM could flare up, leading to permanent neurological damage. Thus, treatment with suitable alternative drugs should be started immediately.

Topics: Antitubercular Agents; Drug Hypersensitivity; Drug Therapy, Combination; Ethambutol; Ethionamide; Humans; Immunologic Tests; Isoniazid; Levofloxacin; Lymphocyte Activation; Male; Middle Aged; Pyrazinamide; Rifampin; Treatment Outcome; Tuberculosis, Meningeal

Animal studies point to increased virulence of certain mycobacterial strains, notably those of the Beijing genotype. There are limited data on mycobacterial genotypic diversity in children with tuberculous meningitis (TBM). We investigated mycobacterial genotypic diversity in children with TBM and analyzed the relationship among genotype, clinical presentation and outcome.. Data were extracted from an ongoing prospective study on children with confirmed TBM from 1992 through 2003 at a referral hospital in the Western Cape Province, South Africa. Mycobacterial isolates were genotyped by standardized restriction fragment length polymorphism methodology. Clinical data at diagnosis, inflammatory progression during the first month of antituberculosis therapy and neurologic outcomes after 6 months of therapy were analyzed according to the principal genetic group of the strain and the presence of the Beijing strain, respectively.. Fifty-nine children were included (median age at diagnosis, 23 months); 37 presented with stage II and 22 with stage III presented with TBM. At completion of antituberculosis therapy, 6 children were neurologically normal, 22 were moderately neurologically impaired, 23 were severely neurologically impaired and 6 children died; detailed outcomes were not available in 2 children. All 3 principal genetic groups were represented (group 1, 27.1%; group 2, 59.3%; group 3, 13.6%); the most prevalent strains were of the Beijing genotype (family 29; 25.4%), followed by family 28 (10.2%) and family 11 (8.5%). Predictors of poor neurologic outcome included advanced disease at diagnosis and male gender. There was no association between the principal genetic group of the strain or the presence of the Beijing genotype, and clinical presentation or outcome.. We found no association between Mycobacterium tuberculosis genotypes and clinical presentation or outcome.

Topics: Adolescent; Antibiotics, Antitubercular; Antitubercular Agents; Child; Child, Preschool; Ethionamide; Female; Genotype; Humans; Infant; Isoniazid; Male; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Pyrazinamide; Retrospective Studies; Rifampin; Treatment Outcome; Tuberculosis, Meningeal

The purpose of the present study was to determine the long-term outcome of 76 children (40 females and 36 males) diagnosed and treated with modern antituberculosis drugs. The median age of the children on admission was 29.5 months and on follow-up 9 years. Antituberculosis therapy consisted of daily isoniazid (20 mg/kg), rifampicin (20 mg/kg), ethionamide (20 mg/kg), and pyrazinamide (40 mg/kg) for 6 months. Twenty-three children received daily prednisone (2-4 mg/kg) for the first month of treatment. Raised intracranial pressure was actively monitored and treated. Patients with non-communicating hydrocephalus received ventriculo-peritoneal shunts shortly after admission while communicating hydrocephalus was treated with oral acetazolamide (100 mg/kg/day) and furosemide (1 mg/kg/day) in 3-4 divided doses. Communicating hydrocephalus that did not respond to this regimen within the first month of treatment also underwent ventriculo-peritoneal shunting. Only 20% of children were functionally completely normal at follow-up. Main areas of functional deficit were cognitive impairment (80%), poor scholastic progress (43%), and emotional disturbance (40%). Twenty-five per cent of children had evidence of motor impairment, but all could walk and only 5 of 76 children (6% of total) were unable to run. One child was blind but no child had sensori-neural deafness. It was concluded that these disabilities in children from mainly deprived socioeconomic backgrounds have serious implications for their future social, academic, and career prospects. A high index of suspicion of TBM in high tuberculosis incidence communities will help prevent the morbidity documented in this study.

Topics: Acetazolamide; Anti-Inflammatory Agents; Antitubercular Agents; Brain; Child; Cognition Disorders; Diuretics; Drug Therapy, Combination; Ethionamide; Female; Follow-Up Studies; Furosemide; Humans; Hydrocephalus; Isoniazid; Male; Mycobacterium tuberculosis; Prednisolone; Pyrazinamide; Quality of Life; Rifampin; Tuberculosis, Meningeal; Ventriculoperitoneal Shunt; Wechsler Scales

We report a case of an HIV-infected child with a second episode of tuberculosis 22 months after completing antituberculosis treatment. DNA fingerprinting of organisms from both episodes showed an identical strain of Mycobacterium tuberculosis. We believe this to be the first case of confirmed relapsed tuberculosis in an HIV-infected child, and suggest that a longer course of antituberculosis treatment be given to such children. ¿ 2000 The British Infection Society.

Topics: AIDS-Related Opportunistic Infections; Amoxicillin-Potassium Clavulanate Combination; Antibiotics, Antitubercular; Antitubercular Agents; Child, Preschool; DNA, Bacterial; Drug Therapy, Combination; Ethionamide; HIV; HIV Infections; Humans; Isoniazid; Male; Mycobacterium tuberculosis; Polymorphism, Restriction Fragment Length; Pyrazinamide; Radiography, Thoracic; Rifampin; Secondary Prevention; South Africa; Tomography, X-Ray Computed; Tuberculin Test; Tuberculosis; Tuberculosis, Meningeal

Topics: Antitubercular Agents; Central Nervous System Infections; Dexamethasone; Drug Therapy, Combination; Ethionamide; Glucocorticoids; Humans; Immunocompetence; Infant; Isoniazid; Male; Prednisolone; Pyrazinamide; Rifampin; Streptomycin; Treatment Failure; Tuberculoma; Tuberculosis, Meningeal; Tuberculosis, Miliary; Tuberculosis, Multidrug-Resistant

Short course chemotherapy for tuberculous meningitis (TBM) is advocated by several groups, but relatively few children have been so treated and followed up.. A prospective, observational study of isoniazid (INH), rifampicin (RMP) and ethionamide (ETH) in a dosage of 20 mg/kg, and pyrazinamide (PZA) 40 mg/kg, all given once daily in hospital for 6 months. Surviving children were followed up for a year after discharge.. Ninety five children, 39 (41%) at stage III, 52 (55%) at stage II and 4 (4%) at stage I TBM were studied. Ten (26%) at stage III and 3 (6%) at stage II died before completion of therapy. Five surviving children (6%) moved on discharge and were untraceable; seven children (9%) were lost during follow up and three were inadvertently restarted on antituberculosis therapy. Two children with severe stage III disease died after discharge. One child experienced a probable disease recrudescence 1 month after discharge. Eighteen children (20%) developed a mildly elevated serum bilirubin concentration during the first month of treatment. In five of these children INH, RMP, ETH and PZA were stopped and streptomycin (SM) and ethambutol substituted. In all cases the original treatment was restarted without incident. One child developed overt jaundice after 5 months of treatment due to hepatitis A infection.. Our experience suggests that young children with TBM can be safely treated for 6 months with high doses of antituberculosis agents without overt hepatotoxicity and with a low risk of relapse.

Topics: Antibiotics, Antitubercular; Antitubercular Agents; Child; Child, Preschool; Drug Therapy, Combination; Ethionamide; Humans; Infant; Isoniazid; Prospective Studies; Pyrazinamide; Rifampin; Treatment Outcome; Tuberculosis, Meningeal

Topics: Antineoplastic Combined Chemotherapy Protocols; Antitubercular Agents; Child, Preschool; Drug Contamination; Ethionamide; Female; Humans; Iatrogenic Disease; Immunocompromised Host; Isoniazid; Male; Meningitis, Bacterial; Mycobacterium bovis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrazinamide; Rifampin; Streptomycin; Tuberculosis, Meningeal

A direct in-line pre-column extraction technique in which guanidinium and ammonium sulfate are used, followed by column switching, was employed to analyze serum, plasma and cerebrospinal fluid samples of patients treated for tuberculous meningitis. Resolution of a wide range of polar to non-polar xenobiotics was obtained on a C8 silica column by using a linear gradient from a binary system consisting of solvent A (0.05 M KH2PO4) and solvent B (acetonitrile-isopropanol, 4:1, v/v). Apart from the antituberculosis drugs (isoniazid, pyrazinamide, ethionamide and rifampicin) the patients received up to sixteen different medicines for prevention of complications and the treatment of symptoms. Qualitative resolution of all the drugs was obtained by the chromatographic system. Quantitation of pyrazinamide and ethionamide was achieved with high precision and low inter-sample variation.

Topics: Antitubercular Agents; Chromatography, High Pressure Liquid; Drug Monitoring; Ethionamide; Humans; Isoniazid; Pyrazinamide; Spectrophotometry, Ultraviolet; Tuberculosis, Meningeal; Xenobiotics

Cerebrospinal fluid ethionamide concentrations were determined in 18 children (median age 26.5 months) with tuberculous meningitis complicated by raised intracranial pressure. Lumbar spinal fluid specimens were obtained before and after weekly hour-long monitoring of intracranial pressure. Thirty-five paired and four single specimens were evaluated. A dosage schedule of 15 mg/kg was used on 26 occasions, and a spinal fluid ethionamide concentration of 2.5 micrograms/ml, the in vitro minimal inhibitory concentration for Mycobacterium tuberculosis, was exceeded on only seven occasions (27%). A dosage of 20 mg/kg was administered on 13 occasions, and in only two instances (15%) was a concentration of 2.5 micrograms/ml not achieved. Ethionamide in a single daily dosage of 20 mg/kg should be considered for the initial treatment of tuberculous meningitis when the presence of isoniazid-resistant M. tuberculosis cannot be excluded.

Topics: Child, Preschool; Drug Administration Schedule; Ethionamide; Humans; Infant; Intracranial Pressure; Monitoring, Physiologic; Tuberculosis, Meningeal

The possible development of hepatotoxic effects as a result of high dosages of isoniazid, rifampin, pyrazinamide, and ethionamide was assessed in 56 young children (median age, 22 months) treated for severe tuberculous meningitis (TBM). Only one of the 56 children became jaundiced, probably as result of hepatitis A infection. Of 33 children observed for at least eight weeks, only five (15%) had normal serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase levels throughout, but in only three patients were AST or ALT values greater than 200 U/L, and enzyme levels tended to normalize toward the end of the period. In this group of 33 children, those at stage III TBM had higher enzyme levels than did those at stage II. The remaining 23 children were observed for a mean period of only four weeks, and 18 (75%) had at least one abnormal liver function test result.

Topics: Alanine Transaminase; Antitubercular Agents; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Child, Preschool; Drug Combinations; Ethionamide; gamma-Glutamyltransferase; Humans; Infant; Isoniazid; Liver Diseases; Pyrazinamide; Rifampin; Tuberculosis, Meningeal

Topics: Aminosalicylic Acid; Antitubercular Agents; Drug Evaluation; Drug Therapy, Combination; Ethambutol; Ethionamide; Humans; Isoniazid; Pyrazinamide; Rifampin; Streptomycin; Tuberculosis, Meningeal

Topics: Ethionamide; Humans; Streptomycin; Tuberculosis, Meningeal

Topics: Adult; Aminosalicylic Acids; Antitubercular Agents; Ethionamide; Female; Humans; Injections, Intravenous; Isoniazid; Kanamycin; Male; Middle Aged; Streptomycin; Tuberculoma; Tuberculosis, Lymph Node; Tuberculosis, Meningeal; Tuberculosis, Pulmonary; Viomycin

Topics: Actinomycosis; Ampicillin; Anticonvulsants; Antifungal Agents; Antimalarials; Arbovirus Infections; Bacteria; Brain Edema; Cephalosporins; Chloramphenicol; Encephalitis; Encephalitis Viruses; Encephalomyelitis; Erythromycin; Ethionamide; Herpesviridae Infections; Humans; Kanamycin; Meningitis, Viral; Meningococcal Infections; Meningoencephalitis; Methicillin; Mycoses; Myelitis; Oxacillin; Penicillins; Polymyxins; Protozoan Infections; Rickettsia Infections; Streptomycin; Sulfonamides; Tetracycline; Tuberculosis, Meningeal

Topics: Acid-Base Equilibrium; Albumins; Carbon Dioxide; Chlorides; Cortisone; Diagnosis, Differential; Electroencephalography; Encephalitis; Ethionamide; Glucose; Humans; Hydrogen-Ion Concentration; Isoniazid; Lactates; Meningitis; Meningitis, Viral; Methods; Neurologic Manifestations; Oxygen; Sodium; Spinal Cord Diseases; Streptomycin; Tuberculosis, Meningeal

Topics: Aminosalicylic Acids; Child; Drug Resistance, Microbial; Ethionamide; Humans; Isoniazid; Male; Mycobacterium tuberculosis; Streptomycin; Tuberculosis, Meningeal; Tuberculosis, Pulmonary

Topics: Adult; Drug Tolerance; Ethionamide; Humans; Male; Middle Aged; Radiography; Sputum; Tuberculosis, Meningeal; Tuberculosis, Pulmonary

Topics: Adrenal Cortex Hormones; Amphotericin B; Anti-Bacterial Agents; Antitubercular Agents; Ethionamide; Humans; Isoniazid; Meningitis; Meningitis, Viral; Mycoses; Prognosis; Sarcoidosis; Streptodornase and Streptokinase; Streptomycin; Syphilis; Tuberculosis, Meningeal

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Antitubercular Agents; Child; Cycloserine; Ethionamide; Isoniazid; Kanamycin; Mycobacterium Infections; Prednisone; Pyrazinamide; Streptomycin; Tuberculosis; Tuberculosis, Cardiovascular; Tuberculosis, Meningeal; Tuberculosis, Miliary; Tuberculosis, Osteoarticular; Tuberculosis, Pleural; Tuberculosis, Pulmonary; Tuberculosis, Urogenital; Viomycin

Topics: Child; Ethionamide; Isoniazid; Lymph Nodes; Toxicology; Tuberculosis; Tuberculosis, Lymph Node; Tuberculosis, Meningeal; Tuberculosis, Pulmonary

Topics: Adolescent; Aminosalicylic Acid; Aminosalicylic Acids; Cycloserine; Drug Resistance; Drug Resistance, Microbial; Drug Synergism; Drug Therapy; Ethionamide; Humans; Isoniazid; Kanamycin; Mycobacterium tuberculosis; Pyrazinamide; Streptomycin; Tuberculosis; Tuberculosis, Meningeal

Topics: Child; Ethionamide; Humans; Tuberculosis; Tuberculosis, Meningeal

Topics: Ethionamide; Humans; Isoniazid; Tuberculosis; Tuberculosis, Meningeal; Veins

Topics: Administration, Intravenous; Ethionamide; Humans; Isoniazid; Tuberculosis; Tuberculosis, Meningeal

Topics: Antitubercular Agents; Ethionamide; Humans; Tuberculosis; Tuberculosis, Meningeal