Objective: This study determined the incidence of and risk factors for color-vision abnormalities among Filipino patients undergoing directly observed treatment short-course (DOTS) for tuberculosis. Methods: A prospective single-cohort study involving newly diagnosed patients with category-1 tuberculosis, recruited from DOTS health centers in Manila, was conducted. All patients were given a fixed-dose combination of rifampicin, isoniazid, ethambutol, and pyrazinamide for 60 days, after which treatment was continued with rifampicin and isoniazid for 4 more months. The participants underwent complete eye evaluation including color-vision testing and were followed up every month up to the conclusion of treatment. Results: Out of 93 patients initially enrolled, 64 completed the prescribed follow-up and constituted the study group. Baseline color vision was normal. After 1 month of therapy, color vision tested with the Ishihara plates remained normal in all patients, but one failed the Farnsworth Panel D 15 and was classified as tritan while 30 (47.88%) failed the Lanthony Desaturated test. The type of abnormality was unclassified in 20 (66.67 %)patients and tritan in 10 (33.3%). Visual acuity remained unchanged from baseline. Repeat testing after ethambutol and pyrazinamide were stopped showed that color vision was normal using the Ishihara plates and the Farnsworth test, while 5 failed the Lanthony test. Of these, 3 were unclassified and 2 were tritan. In the 3rd to 6th months follow-up, no color-vision abnormalities were noted in the 3 tests. The only risk factor identified was age (p = 0.01) with older patients having a higher risk. Conclusion The incidence of color-vision abnormalities among patients undergoing DOTS was 47.88% using the Lanthony Desaturated test after an average of 39.66 days on quadruple anti-TB therapy. Age was the only significant risk factor observed. The color-vision abnormalities returned to normal within an average of 37.85 days after discontinuing ethambutol and pyrazinamide.
Ethambutol ; Tuberculosis ; Color Vision

Objectives: To determine the retinal nerve fiber layer thickness (RNFL) in eyes with ethambutol-induced toxic optic neuropathy (ETON) at the time of diagnosis and to describe the visual outcomes at 1, 3, and 6 months after discontinuation of ethambutol Methods: This was a retrospective chart review of 8 patients (15 eyes) diagnosed with ETON that had RNFL thickness measurements using Cirrus® spectral-domain optical coherence tomography (OCT) at the time of diagnosis. Visual function was measured on initial visit and at 1, 3, and 6-month follow-up. Snellen visual acuity was converted to logMAR. Color vision was measured using Ishihara 14-plate test chart. Results: The mean duration from commencement of ethambutol intake to onset of visual symptoms was 16 weeks (range: 8-24). While, the mean duration from onset of visual symptoms to discontinuation of ethambutol was 4 weeks (range: 2-14). The mean global RNFL thickness at time of diagnosis was 101.2 ± 17.0 microns. Mean RNFL in the temporal, superior, nasal, and inferior sectors were as follows: 79.2 ± 15.4, 119.7 ± 27.9, 71.7 ± 9.2, and 136.7 ± 25.8 microns. Global and sectoral RNFL thicknesses were either normal or thick when compared to age-matched normal database. No eye displayed global or sectoral RNFL thinning. Mean baseline visual acuity and color vision were logMAR 1.2 and 5 plates, respectively. At 1, 3, and 6 months after discontinuation of ethambutol, mean visual acuity and color vision were 0.96 and 6, 0.63 and 11, and 0.44 and 13, respectively. Conclusion Patients with early ETON have normal or thick RNFL at time of diagnosis. They display good visual recovery 6 months following discontinuation of ethambutol.
Ethambutol ; Toxic Optic Neuropathy ; Tomography, Optical Coherence

Objective: To determine if vitamin supplementation can prevent the development of color vision abnormalities in patients taking ethambutol as part of DOTS for tuberculosis (TB). Methods: A randomized, placebo-controlled, single-blind clinical trial was conducted among newly diagnosed category-1 TB patients enrolled in DOTS health centers in the third district of Manila from June 2011 to August 2012. Before starting therapy, the participants underwent a complete eye evaluation including baseline color vision tests using the Ishihara Color Vision Plates (Ishihara), Farnsworth Panel D-15 (FD 15), and Lanthony Desaturated D-15. Only subjects who passed the three color vision tests were included in the study. They were divided into 2 groups: Group A received vitamin supplementation and Group B received a placebo. Follow-up color vision testing was done monthly for 3 months. Results: There were 105 patients included in the study, 77 males and 28 females, age ranging from 16 to 68 years with a mean of 37 years. Forty three (43) patients received vitamin supplementation (group A) and 62 received placebo (group B). After one month of DOTS, 5 of 43 patients (11. 6%) in group A and 10 of 62 patients (16.1%) in group B developed color vision abnormalities, detected only with the Lanthony Desaturated test. The absolute risk reduction (ARR) of color vision abnormalities by vitamin supplementation was 4.5%, with the number needed to treat (NNT) of 23. After the second month of therapy, ARR was 7.4% and NNT was 14. ARR was highest in the third month at 8.3%, with a corresponding decreased NNT of 12. Among patients who developed color vision abnormalities, reversal of the abnormalities was observed in 80% of 5 subjects in group A, and 40% of 10 patients in group B. By the third month of treatment, all in group A already had normal color vision, while 40% in group B still showed abnormal color vision. Conclusion This study showed that vitamin supplementation was effective in reducing the risk of, and in reversing cases of, color vision abnormalities among patients undergoing DOTS therapy for tuberculosis.
Tuberculosis ; Ethambutol ; Color Vision ; Optic Neuritis

BACKGROUND: Multidrug resistant tuberculosis (MDRTB) strains rely on the prompt availability of drug susceptibility test results. We evaluated the reliability and turnaround time of MGIT 960 system, automated version of the MGIT, for antimicrobial susceptibility test of Mycobacteria tuberculosis. METHODS: Ninety six isolates have been tested for susceptibility to isoniazid (INH), rifampin (RIF), ethambutol (EMB) and streptomycin (SM). Results were compared with those obtained by traditional solid media (absolute concentration method, indirect method). RESULTS: There was no statistically significant difference between the susceptibility testing results of the two methods except for EMB. Discrepant results were obtained for 8 isolates (8.3%) with INH, for 3 isolates (3.1%) with RIF, for 13 isolates (13.5%) with EMB, for 10 isolates (10.4%) with SM. Using the indirect method as the gold standard, the sensitivity of INH, RIF, EMB and SM susceptibility testing by the MGIT system were 94.1%, 98.8%, 86.7% and 90.0%, respectively. The specificity were 85.7%, for INH and RIF and 83.3%, for EMB and SM. Turnaround times were significant shorter in MGIT (average 12 days) than in solid media (average 57 days) (P < 0.05) CONCLUSIONS: These data demonstrate that the MGIT system is accurate and rapid for INH, RIF and SM susceptibility test of M. tuberculosis, but EMB susceptibility testing requires further evaluation.
Ethambutol ; Isoniazid ; Mycobacterium tuberculosis* ; Mycobacterium* ; Rifampin ; Sensitivity and Specificity ; Streptomycin ; Tuberculosis

Author presented nine patients of eye toxicity from Ethambutol. They used daily the drug, 15~30mg per kilogram body weight during the period of one month to six months. With the relationship of drug induced toxic amblyopia and optic neuritis, seven patients out of nine showed severe visual disturbance. Five of them have the peripheral constriction. Three cases showed relative ring scotoma and one case showed relative central scotoma.
Amblyopia ; Body Weight ; Constriction ; Ethambutol* ; Humans* ; Optic Neuritis ; Scotoma

A 73-year-old female patient, who had been treated with antituberculous drugs for 4 months, was referred to our department because of generalized macules and papules present for 15 days. Clinical examination revealed polygonal, flat papules of erythematous to violaceous hue on the entire skin. Histopathologic findings were similar to those of lichen planus. In a provocation test with ethambutol, the skin lesions were aggravated and the new lesions developed. We considered this case to be a lichenoid drug eruption due to ethambutol. The skin lesions gradually cleared after ethambutol was eliminated from the patient's tuberculosis therapy.
Aged ; Drug Eruptions* ; Ethambutol* ; Female ; Humans ; Lichen Planus ; Skin ; Tuberculosis

BACKGROUND: Ethambutol (EMB) is one of important first-line drug in the treatment of tuberculosis. Molecular techniques to detect embB gene mutations have been considered as an method to define the EMB resistance. We investigated the mutation rate within embB gene among EMB resistant strains using reverse hybridization techniques. METHODS: We made 11 probes that had wild or mutated sequences containing codons 306, 406, or 497 within embB gene respectively. These probes were reverse-hybridized with PCR products amplified from embB gene which were isolated from 149 ethambutol resistant strains and 50 pan-susceptible strains. RESULTS: Out of 149 ethambutol resistant strains, one hundred (67.1%) had mutation at least one base at codon 306, 406, or 497 in embB gene. Mutation at codon 306, 406, 497 were demonstrated in 75 (50.3%), 16 (10.7%), and 13 strains (8.7%) respectively. There were four strains that showed multi-mutation at codon 306 and codon 406 simultaneously. A high proportion (8.1%) had single mutation at codon 406. There was no mutation observed in embB gene among 50 pan-susceptible strains. CONCLUSION: Reverse hybridization will be useful technique for detection of gene mutation correlated to ethambutol resistance.
Codon ; Ethambutol ; Genotype ; Mutation Rate ; Mycobacterium tuberculosis* ; Mycobacterium* ; Polymerase Chain Reaction ; Tuberculosis

Tuberculous (TB) pleuritis is the second most common form of extrapulmonary tuberculosis. Because the yield of pleural fluid mycobacterial culture is as low as 20% and the pleural biopsy is rather invasive, the measurement of adenosine deaminase (ADA) has been a cornerstone of the diagnosis of TB pleuritis. If the ADA level of pleural fluid is higher than 70 IU/L, the diagnosis of TB pleuritis can be made safely. The treatment is based on a standard short course anti-TB treatment starting with isoniazid, rifampicin, ethambutol, and pyrazinamide. Although systemic steroids and drainage of pleural fluid have been tried to reduce the residual pleural thickening, the results are contradicting.
Adenosine Deaminase ; Biopsy ; Drainage ; Ethambutol ; Isoniazid ; Pleural Effusion ; Pleurisy ; Pyrazinamide ; Rifampin ; Steroids ; Tuberculosis

BACKGROUND: Resistance of Mycobacterium tuberculosis to anti-tuberculosis (TB) drugs is almost exclusively due to spontaneous chromosomal mutations in target genes. Rapid detection of drug resistance to both first- and second-line anti-TB drugs has become a key component of TB control programs. Technologies that allow rapid, cost-effective, and high-throughput detection of specific nucleic acid sequences are needed. This study was to develop a high-throughput assay based on allele-specific primer extension (ASPE) and MagPlex-TAG microspheres to detect anti-TB drug resistance mutations. METHODS: DNA samples from 357 M. tuberculosis clinical isolates and H37Rv were amplified by multiplex PCR using four primer sets, followed by multiplex ASPE using 23 TAG-ASPE primers. The products were sorted on the TAG-ASPE array and detected by using the Luminex xMAP system. Genotypes were also determined by sequencing. RESULTS: Genetic drug susceptibility typing by the TAG-ASPE method was 100% concordant with those obtained by sequencing. Compared with phenotypic drug susceptibility testing (DST) as a reference method, the sensitivity and specificity of the TAG-ASPE method were 83% (95% confidence interval [CI], 79-88%) and 97% (95% CI, 90-100%) for isoniazid. For rifampin testing, the sensitivity and specificity were 90% (95% CI, 86-93%) and 100% (95% CI, 99-100%). Also, the sensitivity and specificity were 58% (95% CI, 51-65%) and 86% (95% CI, 79-93%) for ethambutol. CONCLUSIONS: This study demonstrated the TAG-ASPE method is suitable for highly reproducible, cost-effective, and high-throughput clinical genotyping applications.
DNA ; Drug Resistance* ; Ethambutol ; Genotype ; Isoniazid ; Microspheres ; Multiplex Polymerase Chain Reaction ; Mycobacterium tuberculosis ; Rifampin ; Tuberculosis ; Viperidae

Mycobacterium kansasii is a slow-growing, nontuberculous mycobacterium (NTM) that primarily affects lung tissue. Cutaneous infection with M. kansasii has not been reported previously in heart transplant recipients in Korea. We report a case of cutaneous infection caused by M. kansasii in a heart transplant recipient. The patient was treated successfully for 18 months with ciprofloxacin, clarithromycin, ethambutol, and rifampin.
Ciprofloxacin ; Clarithromycin ; Ethambutol ; Heart ; Heart Transplantation ; Humans ; Korea ; Lung ; Mycobacterium ; Mycobacterium kansasii ; Nontuberculous Mycobacteria ; Rifampin ; Transplants