Paradoxical reaction to antituberculosis treatment is rare in paediatric population. We report a 9-year-old girl with high fever and productive cough for the last three weeks. Tuberculine test and Quantiferon were positive, erythrocyte sedimentation rate was 64 mm/h, culture and polymerase chain reaction for M. tuberculosis negative, and chest X ray showed a widened right mediastinum. Tuberculosis was diagnosed, therefore treatment with standard doses of rifampicin, isoniazid, pyrazinamide and ethambutol was started. Twenty-one days later she presented high fever with no other symptoms, worsening of radiological findings and normal blood tests, serologies and brain magnetic resonance imaging. The patient presented a paradoxical reaction and was given prednisone 1 mg/kg/day, fever disappeared in 24 hours. It is important to consider a paradoxical reaction when other causes of clinical and/or radiological worsening have been ruled out, to avoid unnecessary tests and treatment modifications.
The visual acuity of the patient with ethambutol optic neuropathy will recover within 3 to 4 months after discontinuing the drug. We studied the extent of the recovery of other visual functions. Thirty-six axial type ethambutol optic neuropathy patients, who visited our neuro-ophthalmology clinic from January, 1990, to December, 1993, were included in this study. Fifteen patients (29 eyes) regained their visual acuity to better than 1.0. The average follow-up period following the recovery is 21.7 months. Pattern reversal VEP, Farnsworth-Munsell 100-Hue color vision test, critical flicker frequency (CFF), visual field perimetry, contrast sensitivity and edge-light pupil cycle time were assessed for every affected eye. Latency (P100) of visually evoked potential was delayed in 34.5% (10/29) of eyes. In color vision, 48.3% (14/29) of eyes had deutan or tritan defect. An abnormality of red CFF with value lower than 31 Hz was revealed 51.7% (15/29) eyes. In the visual field, 58.6% (17/29) of eyes had paracentral scotoma, arcuate scotoma, or enlargement of physiologic blind spot. Contrast sensitivity was depressed in 62.1% (18/29) of eyes, mainly at middle and low spatial frequency. Pupil cycle time was prolonged in 72.4% (21/29) of eyes. Aside from visual acuity, other visual functions of the recovered ethambutol optic neuropathy patients were incomplete. The extent of recovery of the visual function is as follows: visual acuity-VEPs-color sense-CFF-visual field-contrast sensitivity-pupil cycle time.
We conducted a randomized, partially blinded dose-ranging study to determine tolerability, safety, and antimicrobial activity of daily rifapentine for pulmonary tuberculosis treatment.
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The World Health Organization encourages the use of fixed dose combinations (FDCs) of rifampicin (RMP) and isoniazid together with pyrazinamide or pyrazinamide plus ethambutol for the treatment of tuberculosis. The main advantages of such FDCs are the simplification of procurement and prescribing practices and the protection they afford against the potential selection of RMP-resistant strains of Mycobacterium tuberculosis. There is convincing evidence, however, that the rifampicin absorption from FDCs manufactured under suboptimal conditions may be significantly impaired, and this appears to be especially problematic with combined formulations of rifampicin, isoniazid and pyrazinamide. In view of the marked dose-dependence of rifampicin's bacterial sterilizing action, it is therefore essential that tuberculosis control programmes only use rifampicin-containing FDCs with proven rifampicin bioavailability. The comprehensive literature on the pharmacology of rifampicin is reviewed, together with the methods employed for determining it and its most important metabolite, desacetyl-rifampicin, in either serum or urine. By contrast, published information concerning the absorption of rifampicin from currently marketed combined formulations and on laboratory methods for precisely assessing their bioavailability is very sparse. There is therefore a crucial need to establish the quality of currently marketed rifampicin-containing FDCs in studies using adequate numbers of volunteers, precise analytical techniques and sophisticated statistical techniques.
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Mycobacterium xenopi is a nontuberculous mycobacterium (NTM) that rarely causes pulmonary disease in Asia. Here we describe the first case of M. xenopi pulmonary disease in Korea. A 66-year-old man was admitted to our hospital with a 2-month history of productive cough and hemoptysis. His past medical history included pulmonary tuberculosis 44 years earlier, leading to a right upper lobectomy. Chest X-ray upon admission revealed cavitary consolidation involving the entire right lung. Numerous acid-fast bacilli were seen in his initial sputum, and M. xenopi was subsequently identified in more than five sputum cultures, using molecular methods. Despite treatment with clarithromycin, rifampicin, ethambutol, and streptomycin, the infiltrative shadow revealed on chest X-ray increased in size. The patient's condition worsened, and a right completion pneumonectomy was performed. The patient consequently died of respiratory failure on postoperative day 47, secondary to the development of a late bronchopleural fistula. This case serves as a reminder to clinicians that the incidence of NTM infection is increasing in Korea and that unusual NTM are capable of causing disease in non-immunocompromised patients.
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Significant advances in the treatment of tuberculosis have occurred with the introduction of short-course therapy using isoniazid and rifampin throughout therapy. The addition of pyrazinamide to the initial phase of therapy permits shortening of the total duration of treatment to 6 months for most patients. This regimen is well tolerated, results in rapid disappearance of bacilli from the sputum, and has a low rate of relapse. Ethambutol should be added to this regimen for any patient with an increased chance of having isoniazid resistant disease. Periodic culturing of the sputum from patients with pulmonary tuberculosis is essential for monitoring response to therapy. Patient noncompliance with therapy is the most common cause of treatment failure, and any patient suspected of being noncompliant should receive directly observed therapy. For this purpose, most treatment regimens may be adapted to twice weekly administration.
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With the exception of pyrazinamide, all of the tested drugs interfered with the in vitro growth of C. posadasii. The 2 day MIC ranges of the tested drugs were as follows: rifampicin 1,060-4,250 mg/L; isoniazid < or =250 mg/L; ethambutol < or =620 mg/L. Pronounced in vitro synergism was demonstrated for combined antituberculosis drugs. The combination of rifampicin plus pyrazinamide was the only one that did not inhibit fungal growth.
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Ethambutol (EMB) concentrations that kill Mycobacterium tuberculosis in vitro accumulated in squirrel monkey tissues and cells known to be sites of tubercular infections. After oral administration of a clinically relevant 25 mg/kg dose, the whole-body distribution and intracellular localization of EMB were studied by radioautography. Tissue concentrations of drug were assayed by radiochemical and microbiological methods. The EMB was distributed rapidly and widely to most body tissues including lung and localized within pulmonary alveolar and axillary lymph node macrophages. The EMB in lung at 2 and 5 h after drug administration was markedly higher than the corresponding plasma concentrations and exceeded concentrations that are bactericidal in vitro for tubercle bacilli. These observations may help explain the early bactericidal activity of EMB in humans. Similarities in plasma and tissue concentrations of the drug in both species suggest the usefulness of the squirrel monkey as a model for the use of EMB in humans.
Extensively drug-resistant tuberculosis (XDR-TB) has emerged as one of the biggest threats to public health and TB control programs worldwide. XDR-TB is caused by Mycobacterium tuberculosis (MTB) strains resistant to rifampin and isoniazid, as well as to a fluoroquinolone and to at least one injectable aminoglycoside. Drug resistance in MTB has primarily been associated with single nucleotide polymorphisms (SNPs) in particular genes. However, it has also been shown that efflux pumps may play a role in resistance of MTB. Upregulation of drug efflux pumps can decrease the intracellular concentration of drugs and reduce their efficacy.