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Rationale: Mycobacterium avium complex pulmonary disease (MAC-PD) is associated with substantial morbidity, and standard daily multidrug therapy is difficult to tolerate., Objectives: To characterize response to a three-times-weekly (TIW) regimen of clarithromycin, ethambutol, and rifampin., Methods: A 1-yr prospective noncomparative trial of TIW treatment was conducted during 2000-2003 in 17 U.S. cities. Participants were 91 HIV-negative adults, diagnosed with moderate to severe MAC-PD, who originally participated in a trial of an inhaled IFN-gamma treatment. Improvement in sputum culture, high-resolution computed tomography (HRCT), and symptoms were assessed., Results: Treatment response rates (and median response times) were 44% (2 mo or longer) for culture, 60% (5.5-11.5 mo) for HRCT, and 53% (8.5 mo) for symptoms. Having noncavitary, compared with cavitary, disease increased culture response by 4.0 times (95% confidence interval [CI], 1.7-9.2) and HRCT response by 4.9 times (95% CI, 1.9-13.0). Culture response was 1.5 times (95% CI, 1.1-2.2) higher for older subjects and 2.2 times (95% CI, 1.0-4.7) higher for previously untreated subjects. Being smear-negative increased culture response by 2.3 times (95% CI, 1.1-5.2) but decreased HRCT response by 4.4 times (95% CI, 1.7-11.5). Increasing ethambutol use by 5 mo increased culture response by 1.5 times (95% CI, 1.0-2.1) but decreased symptom response. Not having chronic obstructive pulmonary disease, bronchiectasis, or poor lung function increased symptom response by 1.9 to 3.9 times., Conclusions: TIW therapy was less effective for MAC-PD patients with cavitary disease and a history of chronic obstructive pulmonary disease, bronchiectasis, or previous treatment for MAC-PD. Further research is needed to study the long-term outcomes of TIW treatment.

Introduction: The aim of this study was to analyse the thickness of the retinal nerve fibre layer (RNFL) of pulmonary tuberculosis patients on ethambutol and isoniazid., Materials and Methods: This was a prospective cohort study where patients with newly diagnosed pulmonary tuberculosis requiring chemotherapy, including ethambutol and isoniazid, were imaged using scanning laser polarimetry. Their mean baseline RNFL thickness and various scanning laser polarimetry parameters of both eyes were measured 2 weeks after the commencement of chemotherapy. The measurements were repeated at 3 months and 6 months after treatment. The various parameters of the baseline and the follow-up measurements were compared using paired sample t-test with Bonferroni correction., Results: Twenty-four patients (16 males and 8 females; mean age, 51.0 +/- 17.6 years) were recruited. There was no statistically significant difference between the baseline and the follow-up measurements in RNFL thickness and all other scanning laser polarimetry parameters., Conclusion: In this cohort of subjects, there was no subclinical change in RNFL thickness detected by scanning laser polarimetry in pulmonary tuberculosis patients on chemotherapy, including ethambutol and isoniazid, after 6 months of treatment.

Background: Leber's hereditary optic neuropathy (LHON) predominantly affects young men between 10 and 30 years of age. However, two cases of LHON during ethambutol administration have been reported in older men and one case in an older woman. We now report a second case of an older woman in whom administration of ethambutol triggered the development of LHON., Case: A 70-year-old woman received ethambutol, rifampicin, isoniazid, and pyrazinamide for the treatment of tuberculosis., Observations: Three months after the beginning of this treatment, a marked decrease in visual acuity occurred in both eyes and ethambutol was discontinued. Her corrected visual acuity was 0.03 in both eyes. There was no hyperemia, swelling of the optic disc, or capillary dilatation in either eye. Centrocecal scotomas were found bilaterally. After 1 month, her visual acuity had further decreased to 0.01, and the scotomas had enlarged. At this time, genetic analysis revealed a point mutation in mitochondrial DNA 11778., Conclusions: Ethambutol can be a risk factor for LHON because the number of reported ethambutol-related LHON cases has increased to four, including the present one. Ethambutol administration to patients with a family history of LHON should be avoided.

Introduction: Ethambutol is used in the treatment of tuberculosis, which is still prevalent in Southeast Asia, and can be associated with permanent visual loss. We report 3 cases which presented with bitemporal hemianopia., Clinical Picture: Three patients with ethambutol-associated toxic optic neuropathy are described. All 3 patients had loss of central visual acuity, colour vision (Ishihara) and visual field. The visual field loss had a bitemporal flavour, suggesting involvement of the optic chiasm., Treatment: Despite stopping ethambutol on diagnosis, visual function continued to deteriorate for a few months. Subsequent improvement was mild in 2 cases. In the third case, visual acuity and colour vision normalised but the optic discs were pale., Outcome: All 3 patients had some permanent loss of visual function., Conclusions: Ethambutol usage is associated with permanent visual loss and should be avoided if possible or used with caution and proper ophthalmological follow-up. The author postulates that in cases of ethambutol associated chiasmopathy, ethambutol may initially affect the optic nerves and subsequently progress to involve the optic chiasm.

Tuberculosis (TB) is an infectious disease affecting humans of all ages in all parts of the world. The dentist plays an important role in the identification and control of this condition by early recognition of oral lesions that may precede the detection of the pulmonary form. Occurrence of increased incidence of mycobacterial infections as a part of the spectrum of AIDS only emphasizes the importance of early diagnosis. A case of a tuberculous ulcer on the tongue along with oral ulcerations, which occurred as a consequence of oral antituberculosis therapy (ATT), is presented. Such complications have rarely been reported in the literature and the management of these is described herein. The tuberculous ulcer healed uneventfully in five weeks after institution of ATT and the other ATT-induced ulcers healed after a week of topical anesthetic application. The clinical presentations, differential diagnoses to be considered, and management of such oral manifestations is discussed. The occupational risk posed by TB to the dentist and appropriate precautions to be observed have been highlighted.

Objective: To review the literature on ocular toxicity of ethambutol--its background, clinical presentation, toxicity characteristics, management, monitoring, and preventive measures., Data Sources: Literature search of Medline from 1962 to May 2005., Study Selection: All related literature in English using the search formula: (ethambutol OR myambutol) AND (eye* OR ophthal* OR ocular) AND (adverse OR toxic)., Data Extraction: All information was collected and analysed by authors., Data Synthesis: Ethambutol hydrochloride is a commonly used first-line anti-tuberculous agent. Although rare, ocular toxicity in the form of optic neuritis (most commonly retrobulbar neuritis) has been well documented since its first use in the 1960s. Classically described as dose- and duration-related and reversible on therapy discontinuation, reversibility of optic neuritis remains controversial. International guidelines on prevention and early detection of ethambutol-induced ocular toxicity have been published. Nonetheless, opinion of the clinical effectiveness of regular vision tests to enable early detection of toxicity is divided., Conclusions: The course of ethambutol-induced ocular toxicity is unpredictable. Measures to ensure a high level of awareness in medical staff and patients of this potential adverse effect appear to be the best current preventive method. Classified by the World Health Organization as a place with an intermediate tuberculosis burden and good health infrastructure, Hong Kong is in a good position to examine the unanswered questions about ethambutol-induced ocular toxicity.

A 51-year-old male patient developed irreversible blindness following pulmonary tuberculosis treatment. The patient's medical history was reviewed, and thorough ophthalmologic examination undertaken (visual acuity, intraocular pressure, Kugel-Perimeter visual field checkup) on initial examination and throughout the next 2 years during the third month treatment with isoniazide, rifampicin, pirazinamide and ethambutol. Ocular symptoms occurred at 3 weeks of the initial symptoms, the patient was examined by an ophthalmologist, and treatment with ethambutol was discontinued; visual impairment progressed to bilateral optic nerve atrophy; almost no signs of improvement were found during the next 2 years of observation, in spite of treatment. Ethambutol is known to be an antituberculotic associated with ocular toxicity. Even in recommended dosage, ethambutol can lead to unpredictable and permanent damage to the optic nerve. The exact mechanism for optic neuritis has not yet been explained.

Pyrazinamide (PZA) combined with either ethambutol (EMB) or a fluoroquinolone for 6-12 months is one of the treatments recommended for latent tuberculosis infection (LTBI) in contacts exposed to multidrug-resistant tuberculosis (MDR-TB). The aim of the present study was to describe the side effects related to combined PZA and EMB treatment given for LTBI, in contacts previously exposed to MDR-TB. In total, 12 consecutive contacts, all of African origin and aged 38+/-5 yrs, were treated with daily PZA (23+/-4 mg.kg(-1)) and EMB (17+/-4 mg.kg(-1)) at Geneva University Hospital outpatient clinic (Switzerland), as a result of contact-tracing procedures for two patients with contagious MDR-TB. Clinical status and liver function tests (aspartate aminotransferase (ALAT) and alanine aminotransferase (ASAT)) were monitored monthly. In seven cases (58%) treatment was discontinued after a median of 119 days, due to hepatic toxicity in six cases (ALAT or ASAT elevation more than four times the upper normal limit), and gastrointestinal symptoms in one case. In conclusion, combined pyrazinamide and ethambutol for latent tuberculosis infection may be associated with a high risk of hepatic toxicity, and warrants close monitoring. There is clearly a need for alternative preventive treatments for contacts exposed to multidrug-resistant tuberculosis.

In the treatment of tuberculosis the patients normally receive a two month daily treatment with Isoniazid, Rifampicin, Pyrazinamid and Ethambutol, followed by a daily treatment with Isoniazid and Rifampicin for four month. The atypical mycobacterial infections can be addressed as a local infection and are amendable to surgical therapy, eventually followed by a daily treatment with antibiotics for four to twelve weeks. In Germany it is obligatory to inform the local public health department about typical mycobacterial infections. Hygiene procedures following German law are discussed in this review.

Aim: To determine the anatomical site and extent of electrophysiological dysfunction in patients with ethambutol associated visual loss., Methods: A comparative case series. Four patients with ethambutol associated visual loss underwent multifocal electroretinography (mERG). Two patients had advanced visual loss while two had early signs of toxicity. The N1-P1, N1, P1 amplitudes, N1, and P1 latencies were compared to 10 age and sex matched controls., Results: mERG abnormalities were detected in the ethambutol treated patients. The N1 amplitude was significantly lower in the ethambutol treated patients than in the control group., Conclusion: Ethambutol is possibly toxic to the retina, and not only the optic nerve. The multifocal ERG may be of value to diagnose and monitor patients taking ethambutol.

Ethambutol (EMB) is an important component of multidrug treatment regimens for Mycobacterium avium complex lung disease. Ocular toxicity is the most important potential EMB toxicity, especially in the elderly population with M. avium complex lung disease. Two hundred twenty-nine patients with M. avium complex lung disease, 55% women and 53% with nodular/bronchiectatic disease, received a mean of 16.1 +/- 10.8 months of multidrug therapy that included EMB. Fifty patients (22%) were known to have preexisting ocular disease. While on EMB, 97 (42%) patients consulted an opthalmologist and 24 (10%) stopped EMB at least temporarily. Eight of 139 patients (6%) on daily therapy were diagnosed with EMB ocular toxicity, whereas 0 of 90 patients on intermittent therapy had EMB ocular toxicity (p = 0.05). All patients with EMB ocular toxicity developed symptoms between outpatient clinic appointments; none were diagnosed with routine visual acuity and color vision testing. All patients with EMB ocular disease returned to baseline ocular status after discontinuation of EMB. Intermittent EBM administration was associated with less ocular toxicity than daily EMB administration in this patient population.

Treatments used for several neurological conditions may adversely affect the eye. Vigabatrin-related retinal toxicity leads to a visual field defect. Optic neuropathy may result from ethambutol and isoniazid, and from radiation therapy. Posterior subcapsular cataract is associated with systemic corticosteroids. Transient refractive error changes may follow treatment with acetazolamide or topiramate, and corneal deposits and keratitis with amandatine. Intraocular pressure can be elevated in susceptible individuals by anticholinergic drugs, including oxybutynin, tolterodine, benzhexol, propantheline, atropine and amitriptyline, and also by systemic corticosteroids and by topiramate. Nystagmus, diplopia and extraocular muscle palsies can occur with antiepileptic drugs, particularly phenytoin and carbamazepine. Ocular neuromyotonia can follow parasellar radiation. Congenital ocular malformations can result from in utero exposure to maternally prescribed sodium valproate, phenytoin and carbamazepine. Neurologists must be aware of potential ocular toxicity of these drugs, and appropriately monitor for potential adverse events.

Optic neuritis has been described among the toxic effects of Ethambutol. This side effect is dose related. The mean duration of Ethambutol induced optic neuritis (EON) is three months. We report a case of EON after few days of exposure to Ethambutol and the symptoms resolved after discontinuation of Ethambutol. This most likely represents an idiosyncratic reaction which is different as compared to dose related optic neuritis.

Purpose: To map and identify the pattern, in vivo, of axonal degeneration in ethambutol-induced optic neuropathy using optical coherence tomography (OCT). Ethambutol is an antimycobacterial agent often used to treat tuberculosis. A serious complication of ethambutol is an optic neuropathy that impairs visual acuity, contrast sensitivity, and color vision. However, early on, when the toxic optic neuropathy is mild and partly reversible, the funduscopic findings are often subtle and easy to miss., Methods: Three subjects with a history of ethambutol (EMB)-induced optic neuropathy of short-, intermediate-, and long-term visual deficits were administered a full neuro-ophthalmologic examination including visual acuity, color vision, contrast sensitivity, and fundus examination. In addition, OCT (OCT 3000, Humphrey-Zeiss, Dublin, CA) was performed on both eyes of each subject using the retinal nerve fiber layer (RNFL) analysis protocol. OCT interpolates data from 100 points around the optic nerve to effectively map out the RNFL., Results: The results were compared to the calculated average RNFL of normal eyes accumulated from four prior studies using OCT, n=661. In all subjects with history of EMB-induced optic neuropathy, there was a mean loss of 72% nerve fiber layer thickness in the temporal quadrant (patient A, with eventual recovery of visual acuity and fields, 58% loss; patient B, with intermediate visual deficits, 68% loss; patient C, with chronic visual deficits, 90% loss), with an average mean optic nerve thickness of 26+/-16 microm. There was a combined mean loss of 46% of fibers from the superior, inferior, and nasal quadrants in the (six) eyes of all three subjects (mean average thickness of 55+/-29 microm). In both sets (four) of eyes of the subjects with persistent visual deficits (patients B and C), there was an average loss of 79% of nerve fiber thickness in the temporal quadrant., Conclusions: The OCT results in these patients with EMB-induced optic neuropathy show considerable loss especially of the temporal fibers. This is consistent with prior histopathological studies that show predominant loss of parvo-cellular axons (or small-caliber axons) within the papillo-macular bundle in toxic or hereditary optic neuropathies. OCT can be a valuable tool in the quantitative analysis of optic neuropathies. Additionally, in terms of management of EMB-induced optic neuropathy, it is important to properly manage ethambutol dosing in patients with renal impairment and to achieve proper transition to a maintenance dose once an appropriate loading dose has been reached.

Study Objectives: To determine whether inactive hepatitis B surface antigen (HBsAg) carriers are at a higher risk of drug-induced hepatotoxicity than control subjects during antituberculosis treatment with standard short-course regimens of isoniazid, rifampin, ethambutol, and/or pyrazinamide., Design: Retrospective case-control study., Setting: Tertiary university medical center., Patients: One hundred ten inactive HBsAg carriers with newly diagnosed active tuberculosis who had been treated with isoniazid, rifampin, ethambutol, and/or pyrazinamide were included in the study population. Inactive HBsAg carriers were defined as follows: (1) positive for HbsAg; (2) negative for hepatitis B e antigen (HBeAg), positive for antibody to HBeAg; (3) < 10(5) copies per mL of serum hepatitis B virus DNA; and (4) normal pretreatment aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels. Ninety-seven HBsAg-negative patients who received standard antituberculosis medication were selected as control subjects., Results: The baseline characteristics of the 110 inactive HBsAg carriers were similar to those of the 97 noncarriers. A total of 85% of persons in both groups had received an initial treatment regimen that included pyrazinamide. Thirty-eight inactive HBsAg carriers (35%) and 19 control subjects (20%) exhibited elevated liver enzyme levels during antituberculosis treatment (p = 0.016). Drug-induced hepatotoxicity, which was defined as a liver transaminase level of >/= 120 IU/L, occurred more frequently in HBsAg carriers (9 of 110 carriers; 8%) than in control subjects (4 of 97 control subjects; 4%), although this was not a statistically significant discrepancy (p = 0.230). More importantly, HBsAg carriers (n = 9; 8%) who received antituberculosis therapy evidenced a higher proportion of moderate-to-severe drug-induced hepatotoxicity when compared with the control subjects (n = 2; 2%; p = 0.05). Isoniazid and rifampin were reintroduced as therapy after AST/ALT levels returned to baseline values in 10 patients (6 HBsAg carriers and 4 control subjects) among the 13 patients exhibiting drug-induced hepatotoxicity, and these retrials proved to be successful in 7 patients (5 HBsAg carriers and 2 control subjects)., Conclusions: Tuberculosis treatment in HBsAg-positive and HBeAg-negative inactive carriers could be pursued in the usual manner, using standard short-course regimens of isoniazid, rifampin, ethambutol, and/or pyrazinamide, with the condition that monthly liver function tests are performed.

Introduction: Visual loss is a rare complication of tuberculosis; it can be related to anti-tuberculous drugs or to the infection itself. For the treatment of visual loss, differential diagnosis is important between infection and adverse effect of anti-tuberculous drugs., Case: A 48-year-old male patient with a history of tuberculosis and visual loss during anti-tuberculous drug therapy was admitted to our hospital. Anti-tuberculous drugs had been stopped on the 2nd day of therapy due to development of optic neuritis secondary to ethambutol administration at another hospital. He had miliary tuberculosis, renal failure requiring dialysis and visual disturbances. Anti-tuberculous drugs, including ethambutol, were initiated at our clinic because the period between the ethambutol therapy and visual loss was too short and the dose of ethambutol was not very high. Computed brain tomography was normal. Fundoscopic examination revealed only hypertensive retinopathy. Our diagnosis was tuberculosis-related visual loss, which could be due to neuroretinitis, intraocular tuberculosis or chiasmal tuberculoma. In addition, ethambutol rarely causes visual loss during the early period or when given at lower doses. In our case no complications developed from the treatment and the patient's visual loss and renal function improved. At his last visit, 12 months later, his vision had improved and his serum creatinine was lower, at 2.2 mg/dL., Conclusion: With anti-tuberculous treatment, renal functions and visual disturbances were improved in a patient with miliary tuberculosis. During the anti-tuberculous therapy, visual loss can be related to ethambutol toxicity or the tuberculosis infection itself. Differential diagnosis is very important and anti-tuberculous drugs must be continued if the diagnosis is tuberculosis.

A total of 8.37% of the 1195 patients treated at NDTB Centre with DOTS under RNTCP between January 2002 to June 2003 presented with adverse drug reactions. Patients showing any sort of adverse reactions were studied in detail by personal interviews and a semi-structured questionnaire. The profile of patients presenting with adverse reactions showed that majority of the patients (53%) had gastrointestinal reactions, the commonest presenting complaint being nausea and vomiting. General aches and pains were complained by about 35% and giddiness was the presenting complaint in 27% irrespective of the use of streptomycin, although giddiness was observed more often in Category II patients (59%). Skin rash and itching was complained by about 17% of patients and 11% complained of arthralgia, while only 1% had hepatotoxicity during treatment. Majority of the adverse reactions (67%) were observed within the first four weeks of treatment and only 0.25% of patients treated with DOTS had interruption of treatment for short periods.

We describe the case of a 36-years-old male patient, originating from India, who presented with enlarged cervical lymph nodes and elevated liver chemistry tests. Histologically necrosing granulomas were observed in the lymph nodes, and PCR revealed DNA from mycobacterium tuberculosis. However, in the liver biopsy granulomatous hepatitis without central necrosis was seen. With a positive PCR for mycobacteria from liver tissue and no evidence for other hepatic diseases we started drug treatment with standard quadruple regimen consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide. Five days after onset of therapy, liver chemistry tests rose 10-fold, forcing us to interrupt treatment. Gradual step-wise re-exposition with the same medication after return of liver chemistry tests to baseline was well tolerated without any further side effects. Liver involvement of tuberculosis can have many facets and may be treated by gradual dosing of standard drugs.

Objective: To evaluate the efficacy of split-drug regimens for treatment of patients with sputum smear-positive pulmonary tuberculosis in south India., Design: Randomized controlled clinical trial where eligible patients were randomly allocated to: (i) 2RE(3)HZ(3)(alt)/4RH(2) (split I): rifampicin plus ethambutol given on one day and isoniazid plus pyrazinamide the next day for first 2 months followed by rifampicin plus isoniazid twice weekly for 4 months, or (ii) 3RE(3)HZ(3)(alt)/3RH(2) (split II): similar to regimen 1, except duration was 3 months in each phase, or (iii) 2REHZ(3)/4RH(2) (control): rifampicin, isoniazid, ethambutol and pyrazinamide, given thrice weekly for 2 months followed by isoniazid and rifampicin twice weekly for 4 months. All patients were followed up clinically and bacteriologically every month up to 2 years and every 6 months for up to 5 years., Results: A favourable response (cultures negative for Mycobacterium tuberculosis during the last 2 months of treatment) was observed in 91% of 407 patients in split I, 94% of 415 in split II and 89% of 418 in the control regimen. Ninety-one per cent of 370 patients in split I, 93% of 389 in split II and 90% of 370 in control regimens had quiescent disease at the end of 60 months. Gastrointestinal symptoms were more frequent under the control regimen (P = 0.01)., Conclusion: Split-drug regimens were as effective as the control regimen in terms of favourable response at the end of treatment and quiescent disease at 5 years, and caused fewer gastrointestinal side-effects.

Neutropenia is a rare complication of anti-tuberculous therapy and is usually due to a single agent, most frequently isoniazid. The current case describes a previously healthy immunocompetent patient with tuberculosis of the lymph nodes who developed neutropenia due to a number of first line antibiotics (rifampicin, isoniazid and ethambutol) and streptomycin when introduced in combination and individually thus resulting in repeated treatment disruption. The introduction of twice-weekly subcutaneous granulocyte-colony stimulating factor to correct iatrogenic neutropenia facilitated the continuation and eventual completion of therapy without adverse effect. This is the first description of the use of granulocyte-colony stimulating factor to correct iatrogenic neutropenia due to anti-tuberculous antibiotics and the second description of the occurrence of iatrogenic neutropenia to more than anti-tuberculous antibiotic in an individual.

Ethambutol, a synthetic bacteriostatic agent, is a first line agent against Mycobacterium tuberculosis. Although optic neuritis is the most serious adverse effect of ethambutol, most cases in the literature are reversible. Renal failure prolongs the half-life of ethambutol and increases the risk of ethambutol-induced optic neuritis. We present two patients with end stage renal disease (ESRD), who were on maintenance dialysis and suffering ethambutol-induced optic neuritis. The first woman had been suffering ESRD on hemodialysis for 2 years. After tuberculosis was diagnosed, she was prescribed three-combined anti-tuberculosis medications, including ethambutol 800 mg/day. Bilateral blurred vision suddenly occurred 4 months after the start of treatment, and she became totally blind despite discontinuing ethambutol. The second woman had been on hemodialysis for 5 months. Tuberculosis was diagnosed by lung biopsy. After 3 weeks of three-combined anti-tuberculosis medications including ethambutol (1,200 mg/day), reduced visual acuity and color vision defects occurred. One year after the discontinuation of ethambutol, visual acuity remained little improved. Physicians should be aware of ethambutol-induced optic neuritis and ethambutol should be used cautiously in patients with renal failure.

Unlabelled: To study the incidence of clinical and subclinical optic nerve toxicity with ethambutol therapy in patients with tuberculosis and to evaluate the reversibility of its side effects after cessation of therapy. This prospective randomized controlled study included 60 newly diagnosed adult cases of tuberculosis, who were randomly assigned into two groups. The study group included 30 patients (60eyes) who received ethambutol as a part of their anti-tubercular treatment and the control group included 30 patients (60eyes) who did not receive ethambutol. The patients were examined on monthly basis. The visual parameters studied were best corrected visual acuity, pupillary reactions, optic disc changes, color vision, contrast sensitivity, pupil cycle time, visual field charting and visual evoked potential. Ethambutol was stopped in those patients in whom toxicity was detected and they were followed more frequently. Only one patient (3.3%) showed decrease in visual acuity, three patients (10%) developed visual field defects, two patients (6.7%) showed deterioration of contrast sensitivity, the pupil cycle time was prolonged in one eye and two patients (6.7%) showed abnormal visual evoked potential. During the therapy, all patients in the study group had normal pupillary reactions, fundus picture and color vision., Conclusions: Ethambutol induced ocular toxicity was seen in three patients (10%) in our study. The maximum visual recovery occurred in first six to eight weeks after stopping ethambutol. The visual recovery was complete in only one patient, but it was partial in two patients i.e. visual fields, contrast sensitivity and visual evoked potential remained abnormal.

A male patient with tuberculous lymphadenopathy was treated with a four-fold therapy of ethambutol, isoniacide, rifampicin and pyracinamide. After 10 weeks the patient suffered from photophobia. Although ethambutol was discontinued vision decreased and visual field defects occurred as well as signs of myelopathy. Isoniacide was then discontinued and in the subsequent phase the vision was slowly restored over a period of 36 months. The combined toxicity of ethambutol and isoniacide seems to have been the main cause of the severe and protracted optic neuropathy.

Ethambutol is an antimicrobial agent used frequently to treat tuberculosis. The most commonly recognized toxic effect of ethambutol is optic neuropathy, which generally is considered uncommon and reversible in medical literature. We describe a 43-year-old man who developed signs and symptoms of bilateral optic neuropathy during treatment with ethambutol. This case and a review of the literature show the severe and unpredictable nature of ethambutol toxicity and its potential for irreversible vision loss despite careful ophthalmologic monitoring.

Aim: To evaluate the response rate to antimycobacterial drug therapy in patients with cystic fibrosis (CF) suffering from infection by non-tuberculous mycobacteria (NTM)., Methods: Ten patients, aged 10-34 y, out of 180 CF patients, were diagnosed with NTM disease. They had been regularly checked and examined for pulmonary symptoms, and had had chest X-rays and sputum cultures (including for mycobacteria) performed. One additional 36-y-old female received her CF diagnosis soon after the NTM diagnosis., Results: Mycobacterium avium-intracellulare complex (MAC) was found in 10 out of 11 patients and M. kansasii in 1 patient. Treatment with antimycobacterial drugs resulted in clinical improvement (weight gain or stabilization of weight and/or improved or stabilized lung function in 8 out of 11 patients) and mycobacterial culture turned negative in 10 out of 1., Conclusion: Promising results may be associated with early intervention with antimycobacterial therapy in CF patients.

Purpose: To demonstrate the association between ethambutol and optic neuropathy., Method: Thirteen patients who developed optic neuropathy after being treated with ethambutol for tuberculosis of the lung or lymph node at Siriraj Hospital between 1997 and 2001 were retrospectively reviewed. The clinical characteristics and initial and final visual acuity were analyzed to determine visual outcome., Results: All patients had optic neuropathy between 1 to 6 months (mean = 2.9 months) after starting ethambutol therapy at a dosage ranging from 13 to 20 mg/kg/day (mean = 17 mg/kg/day). Seven (54%) of the 13 patients experienced visual recovery after stopping the drug. Of 6 patients with irreversible visual impairment, 4 patients had diabetes mellitus, glaucoma and a history of heavy smoking., Conclusion: Early recognition of optic neuropathy should be considered in patients with ethambutol therapy. A low dose and prompt discontinuation of the drug is recommended particularly in individuals with diabetes mellitus, glaucoma or who are heavy smokers.

Major adverse reactions to antituberculosis drugs can cause significant morbidity, and compromise treatment regimens for tuberculosis (TB). Among patients treated for active TB we estimated the incidence, and risk factors, of major side effects from first-line anti-TB drugs. Side effects, resulting in modification or discontinuation of therapy, or hospitalization, were attributed on the basis of resolution after withdrawal, and/or recurrence with rechallenge. Among 430 patients treated between 1990 and 1999, the incidence of all major adverse effects was 1.48 per 100 person-months of exposure (95% confidence interval [95% CI], 1.31 to 1.61) for pyrazinamide, compared with 0.49 (95% CI, 0.42 to 0.55) for isoniazid, 0.43 (95% CI, 0.37 to 0.49) for rifampin, and 0.07 (95% CI, 0.04 to 0.10) for ethambutol. Occurrence of any major side effect was associated with female sex (adjusted hazard ratio, 2.5; 95% CI, 1.3 to 4.7), age over 60 years (adjusted hazard ratio, 2.9; 95% CI, 1.3 to 6.3), birthplace in Asia (adjusted hazard ratio, 2.5; 95% CI, 1.3 to 5.0), and human immunodeficiency virus-positive status (adjusted hazard ratio, 3.8; 95% CI, 1.05 to 13.4). Pyrazinamide-associated adverse events were associated with age over 60 years (adjusted hazard ratio, 2.6; 95% CI, 1.01 to 6.6) and birthplace in Asia (adjusted hazard ratio, 3.4; 95% CI, 1.4 to 8.3), whereas rifampin-associated adverse events were associated with age over 60 years (adjusted hazard ratio, 3.9; 95% CI, 1.02 to 14.9) and human immunodeficiency virus-positive status (adjusted hazard ratio, 8.0; 95% CI, 1.5 to 43). The incidence of pyrazinamide-induced hepatotoxicity and rash during treatment for active TB was substantially higher than with the other first-line anti-TB drugs, and higher than previously recognized.

To investigate the secular change in the incidence rate of drug-induced hepatitis (DIH) due to anti-tuberculosis chemotherapy including isoniazid (INH) and rifampicin (RFP), but not including pyrazinamide (PZA), we retrospectively studied the incidence rates of DIH in patients treated with chemotherapy including INH and RFP in four periods 1980-83, 87-88, 91-92, and 1998-2000. The criteria for selection of the patients were as follows. 1. The serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured before, and one month (20-40 days) and 2 months (45-75 days) after starting anti-tuberculosis chemotherapy. When the serum AST and ALT were measured twice or more during period 20-40 days or 45-75 days after starting anti-tuberculosis chemotherapy, the data obtained nearest to 30 or 60 days after were chosen as those of one or two months after starting chemotherapy, respectively. 2. The serum AST and ALT were within normal range before starting anti-tuberculosis chemotherapy. The normal range of serum AST and ALT were < or = 40 K-A and < or = 35 K-A (in 1980-83) or < or = 31 IU/l and 34 IU/l (in 1987-2000), respectively. 3. Chronic active hepatitis and cirrhosis patients were excluded. 4. All alive after completion of anti-tuberculosis chemotherapy. The numbers of the subjects who fulfilled the above criteria were 113, 135, 128 and 154 in 1980-83, 1987-88, 1991-92 and 1998-2000, respectively. DIH was defined serologically by serum AST > or = 40 K-A and/or ALT > or = 35 K-A (in 1980-83), or AST > or = 40 IU/l and/or ALT > or = 40 IU/l (1987-2000). The DIH incidence rate of the subjects classified by the year of treatment and age were examined, and the contributions of the risk factors for DIH, such as age, sex, alcoholics, previous liver disease history, HBs ag positivity, anti-HCV ab positivity, and hypoalbuminenia were studied, and none except the age over 80 y.o. was found to be a risk factor to DIH, in our subjects. In patients with the age over 80 y.o., daily doses of antituberculosis drugs RFP, INH and ethambutol (EB) were significantly higher in patients with DIH than those without DIH, but body weight and serum albumin level were not significantly different between these two groups. There was no risk factor to DIH in our patients less than 80 y.o. and this could be explained by the above-mentioned criteria of study patients selection. To exclude the age dependence of the incidence rate of DIH in our subjects, the incidence rates of DIH were calculated in patients less than 80 y.o. by the period of treatment, and they were 10/111 (9.0%), 23/131 (17.6%), 26/123 (21.1%) and 32/117 (27.4%) in 1980-83, 87-88, 91-92, and 1998-2000, respectively. The secular increase of the incidence rate of DIH was statistically significant (p = 0.01). It is quite clear that this secular increase was not at all attributable to the above-mentioned risk factors. It is suspected that human liver has become more easily affected with INH and RFP in recent years. It is suggested that the new chemical compounds present in our increasingly complicated human milieu give heavier burdens on human liver, weaken the liver function, and enhance the capacity of INH and RFP to cause DIH.

The multicomponent drug Mairin-P that contains isoniazid, 60 mg, rifampicin, 120 mg, pyrazinamide, 300 mg, and ethambutol hydrochloride, 225 mg, has been pharmacokinetically and clinically studied. There was no significant difference in the pharmacokinetic parameters of rifampicin as a component of Mairin-P and in combination with antitubercuous agents as free dosage forms. Treatment of first detected patients with pulmonary tuberculosis who isolate drug-sensitive Mycobacterium tuberculosis with Mairin-P is as effective as conventional treatment regimens with antituberculous drugs. Adverse reactions, including non-correctable one, due to the use of Mairin-P occur less frequently than to that of antituberculous drugs.

A clinical study was carried out between January 1996 and December 1997 in Iwo Nigeria to determine among others the types and frequency of occurrence of side-effects of anti-tuberculous drugs in the 8-month regimen recommended by the Nigerian National Tuberculosis Control Programme Committee (NTCP) for newly diagnosed (ND) Pulmonary Tuberculosis (PTB) cases. This was compared with a 6-month regimen used within the same population of ND PTB subjects at Iwo Nigeria. 65 (13%) of the 500 patients in group one on the 8-month regimen had various side-effects while 7 (14%) of the 50 patients in group two on the 6-month regimen manifested various side-effects. The side-effects rate and frequencies were similar and in both, they were mild and did not materially lead to major change of the anti-tuberculous medications. The regimen used in this study in group one (NTCP recommended) and group two recorded low incidence of side-effects. It confirmed that Directly Observed Treatment Short-course (DOTS) when applied with the recommended regimen by the Nigerian NTCP is effective and is characterised by low and minor side-effects.

Purpose: To study color vision in Congolese patients with tuberculosis receiving ethambutol therapy., Methods: A prospective, descriptive study of color vision test in patients with systemic tuberculosis receiving ethambutol was performed between April 1995 and January 1998 at the Department of Ophthalmology, University of Kinshasa. Color vision tests were assessed with pseudoisochromatic plates (the Ishihara Pseudo-isochromatic Plates), the AO-HRR (American Optical Handy Rand Rittler), the Bölle and Kastel anomaloscope, Farnsworth-Munsell test (the D-15 and the FM-100)., Results: There were 42 patients with a mean age of 33 years (range, 14 to 75 years). The color vision of all the patients was found to be normal as measured by the Ishihara pseudoisochromatic plates. One (2%) patient showed color vision defect (anarchic axis] with the OA-HRR test. Three (7%) of 42 patients displayed blue-yellow color axis or anarchic axis color vision test on the D-15 test. Fifteen (36%) of 42 patients had high total error scores at the Farnsworth-Munsell 100 test. The color axis was as follows: anarchic axis (13.1%), red-green-color and blue-yellow-color combined axis (13.1%), blue-yellow color axis (7.5%). Results of the Bölle and Kastel anomaloscope were normal in all patients., Conclusion: Our results confirm the importance of color vision examinations in the detection of the complications of ethambutol treatment.

A 32 year-old woman developed generalised lichenoid eruptions on her body followed by diffuse loss of scalp hair of the anagen effluvium type. She was receiving several anti-tubercular drugs, including rifampicin, isonicotinic acid hydrazide (INH), pyrazinamide, and ethambutol, for abdominal tuberculosis. INH, which is a leading cause of drug eruptions in the above group of drugs was withdrawn. However, the other antitubercular drugs were continued along with 40 mg of prednisolone in a single daily morning dose. The latter was discontinued slowly over a period of 10 weeks. There was complete recovery of hair loss and the regrowth started after 12 weeks of alopecia. Such anagen effluvium with lichenoid eruption following INH therapy has not been observed previously. The complete recovery from anagen effluvium is difficult to explain, but it could have been because of the early initiation of corticosteroid.

Hyponatremia is seen in 40% to 60% of hospitalized acquired immune deficiency syndrome (AIDS) patients. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) and volume contraction are the most common causes. The serum uric acid level can be used to distinguish between these two causes of hyponatremia. Hypouricemia is the rule in SIADH, whereas hyperuricemia commonly accompanies volume contraction. This report presents an AIDS patient with SIADH and normouricemia secondary to pyrazinamide and ethambutol.

Some anti-tuberculosis chemotherapeutic agents have been established as causing hyperuricaemia. Hyperuricaemia in turn causes renal damage. This study therefore aims at establishing the effect of anti-tuberculosis drugs-induced hyperuricaemia on renal function of the patients. Fifty patients with newly diagnosed pulmonary tuberculosis with mean age of 36.8 years (SD 13.69) consisting of 14 females and 17 males were longitudinally studied each for 6 months to determine the effect of drug-induced hyperuricaemia on their renal function. The Biochemical indices determined included serum urate level, serum creatinine level, and creatinine clearance of newly diagnosed patient with tuberculosis, before and during treatment with anti-tuberculosis therapy. Serum urate level revealed that 16 (51.6%) and 15 (48.4%) of the patients were hyperuricaemic at the end of the first and second months of anti-tuberculosis therapy. There was no significant difference in the mean serum creatinine level of the control group 96 micromol/L when compared with both the pre-treat value 89 micromol/L (P > 0.25) as well as the value at the end of the sixth month of treatment 91 micromol/L (P > 0.40). However, there was a statistically significant difference in the mean creatinine clearance of the control group 102 ml/min/1.73 m2 when compared with the patient's mean pre-treatment value (89 ml/min/1.73 m2) P < 0.05. Also the mean creatinine clearance increased to (103 ml/min/1.73 m2) by the end of the 6th month of treatment, a value that is statistically significant when compared with the pretreatment value of (89 ml/min/1.73 m2) P < 0.05. We submit as follows: that pulmonary tuberculosis as a disease with significant impairment of renal function; despite the associated drug-induced hyperuricaemia recorded during the treatment, renal function steadily improved with the treatment of pulmonary tuberculosis to the extent that comparable values with control was obtained at the end of treatment. We conclude therefore that drug-induced hyperuricaemia associated with treatment of pulmonary tuberculosis has no detectable negative effect on renal function of the patient.

Background and Purpose: In animal studies, ethambutol (EMB) has been shown to be toxic to cone pedicles and to cause their degeneration in the retinas of fish. The purpose of this study was to determine whether EMB is toxic to retinas in humans., Methods: Twenty-seven patients with EMB-induced optic neuropathy and 20 normal control subjects were included in this study. The following details were recorded: age, sex, and systemic condition of the patients, daily dosage of EMB, duration of EMB treatment, visual function at the time of electrophysiologic investigation, time from the onset of blurred vision to the discontinuation of EMB treatment (symptom duration), and time from termination of EMB treatment until electrophysiologic investigation., Results: The electroretinograms were normal in 25 patients. Twelve patients had normal electro-oculogram (EOG) findings in both eyes and the remaining 15 patients had abnormal EOG findings in at least one eye. Ten eyes showed supranormal EOG (light/dark (L/D)) ratios of more than 2.33, and 13 eyes had decreased L/D ratios (< 1.65). The symptom duration was shorter in the supranormal EOG group., Conclusions: The results suggest that a supranormal EOG may be indicative of an early toxic state during EMB therapy and that EMB may cause dysfunction of the retinal pigment epithelium.

Clinically, ethambutol (EMB)-induced psychosis is rare. In our review of the literature, most cases of antituberculosis agent-associated psychoses were caused by isoniazid (INH). We report the case of a 51-year-old man with suspected tuberculosis (TB) pleurisy. An anti-TB trial with INH, rifampicin and EMB was given initially. Dizziness, disorientation, and auditory and visual hallucinations developed after seven days of therapy. Laboratory examinations, including routine biochemistry tests, serum titer of antinuclear antibodies, cerebrospinal fluid analysis and computerized tomography of the head showed no abnormal findings. Following discontinuation of anti-TB agents, the psychiatric symptoms subsided. When the patient was challenged with EMB, the same psychiatric symptoms recurred, but resolved again after discontinuation of EMB. It is important to be aware that EMB can induce psychosis when anti-TB medications are prescribed.