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[Bactericidal activities of rifampicin, ethambutol, enviomycin and streptomycin on Mycobacterium avium-Mycobacterium intracellulare complex strains].

Bacteriostatic and bactericidal activities of rifampicin, ethambutol, enviomycin and streptomycin on Mycobacterium avium-Mycobacterium intracellulare complex (MAI complex) strains were determined. The susceptibility testings were made in Ogawa egg medium, and minimal inhibitory concentrations (MICs) were determined as the lowest concentration of drugs, in which the growth of 20 to 100 colony-forming units was completely inhibited. The MICs correspond to the MICs that can inhibit the growth of 95 to 99% of bacterial population. Bactericidal activity was determined in a modified Dubos liquid medium (1.3 g of Dubos TB Broth Base were dissolved in 180 ml of distilled water and this solution was supplemented by 20 ml of bovine serum). A one ml-sample of bacterial suspensions (10 mg wet weight per ml) was added to 9 ml of the Dubos liquid medium, and the medium was incubated at 37 degrees C for 0, 1, 3 and 7 days under shaking condition (56 strokes per minute; 8 cm amplitude). The bactericidal activity was measured as the number of colony-forming units contained in a 0.02 ml-sample of the medium. The bactericidal activities of rifampicin and ethambutol were weak or absent even in strains 13008 and 13016, which were very susceptible to all four drugs. However, the bactericidal activities of streptomycin and enviomycin could be observed in these strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Antitubercular Agents↗

Isoniazid and ethambutol as a cause of optic neuropathy.

A well-recognized complication of ethambutol use is optic neuropathy, but the potential ocular toxicity of isoniazid is often overlooked. A patient developed optic neuropathy while being treated with isoniazid and ethambutol. The optic neuropathy subsided only when both drugs were discontinued, suggesting an additive toxic effect.

Aged↗

[Risk factors for the occurrence of eye damage following ethambutol treatment].

The present paper deals with two cases of severe irreversible visual disturbances (bilateral opticus atrophy) after combined antituberculous chemotherapy including ethambutol following unilateral nephrectomy because of tuberculosis of the kidneys and with farther complications as damages of the blood vessels and diabetes mellitus. Damages of the kidneys are especially predisposing to side effects by ethambutol and inclusion into an ophthalmological dispensary at short intervals is necessary.

Aged↗

Indirect atomic absorption analysis of ethambutol.

In the presence of cupric ions and sodium hydroxide, ethambutol forms a chelate compound which can be extracted with ethyl-methyl ketone. The amount of ethambutol-copper complex was determined by measuring the copper by Atomic Absorption Spectroscopy (AAS) in the ethylmethyl ketone extract. When this method was applied to pharmaceutical samples satisfactory results were obtained. The method is accurate for routine analyses and very simple to be carried out.

Chemical Phenomena↗

[Antituberculous activity of cyclic analogs of ethambutol].

The activity of new cyclopentanoic and cyclohexanoic analogues of ethambutol on various strains of mycobacteria was determined. Three compounds were effective mainly on tuberculous strains; only one was like ethambutol, being effective on both tuberculous and saprophytic strains.

Ethambutol↗

Pseudomembranous colitis in a patient on rifampicin and ethambutol.

A fifty-seven year old male with renal tuberculosis developed pseudomembranous colitis on rifampicin and ethambutol. Diarrhoea occurred within a week, and six weeks after commencing these antituberculous agents he developed typical sigmoidoscopic and biopsy findings. Withdrawal of the drugs led to rapid recovery. Repeated challenge testing indicated that the symptoms were worse when rifampicin was given, but a test dose of ethambutol also produced temporary aggravation of the diarrhoea.

Biopsy↗

Colorimetric determination of ethambutol hydrochloride.

A precise colorimetric procedure is proposed for estimation of ethambutol hydrochloride, based on reaction of the drug with 2,4-dinitro-1-fluorobenzene under stipulated conditions. The yellow chromophore is quantitated spectrophotometrically at 376 +/- 1 nm. The relationship between absorbance and drug concentration was linear within a range of 5-40 micrograms/mL. The method is suitable for the analytical control of ethambutol HCl and its formulations.

Colorimetry↗

Electron microscopic analysis of Mycobacterium avium complex isolates exposed to ciprofloxacin, rifabutin, ethambutol and clarithromycin.

SETTING: Mycobacterium avium complex (MAC) isolates grown in the presence of clarithromycin, ciprofloxacin, ethambutol or rifabutin were examined by electron microscopy for drug-induced ultrastructural changes. OBJECTIVE: To further the understanding of the activity of clarithromycin, ciprofloxacin, ethambutol and rifabutin against MAC. DESIGN: Four MAC isolates, 1 control and 3 patient, were cultured for 24 or 72 hours in liquid medium containing one of two concentrations of an antimicrobial agent prior to examination by electron microscopy. RESULTS: One or more of the following ultrastructural changes was observed after exposure to the antimicrobial agent: disorganized nucleoid and cytoplasm, condensation of nucleoid, vacuolization, enlargement of the periplasmic space with or without vesicles, intracytoplasmic lipid-like inclusions, and cell lysis. Changes were seen after as little as 24 hours of exposure to the antimicrobial agent and were more evident with the higher of the two concentrations of the drug. Changes were present regardless of the minimum inhibitory concentration (MIC) of the antimicrobial agent against the isolates tested, but were more pronounced if the MIC was less than the concentration of drug tested. CONCLUSION: Consistent ultrastructural changes were observed following exposure to a given antimicrobial agent. No drug-specific changes were identified.

Antitubercular Agents↗

[Visual impairment due to optic neuropathy in 2 patients on amiodarone therapy, i.e. ethambutol and isoniazide].

Two patients, a 69-year-old man and a 49-year-old woman, developed a bilateral decrease in visual acuity, the male patient within two months of starting to use amiodarone (Cordarone) and the female patient within ten months of starting to use ethambutol (Myambutol) and isoniazid. Optic neuropathy occurred in both patients and this was probably caused by the medications. After the medication had been withdrawn, the male patient's vision remained poor (1/300); 6 months later the female patient's vision had improved to 0.8 and 1.0. Before prescribing oculotoxic medications, physicians should know about the patient's visual acuity and any ocular diseases the patient may have. The patient must also be advised to contact their doctor immediately if visual complaints occur. Before and during treatment with ethambutol, ophthalmological examinations should be carried out regularly. In the event of complaints, iatrogenic optic neuropathy must be distinguished from an ischaemic optic neuropathy. The latter is usually associated with an acute unilateral decrease in visual acuity. Withdrawal of the medication is indicated for neuropathy. However, although the vision may improve it will not be completely restored.

Aged↗

[Initial resistance to streptomycin, isoniazid, thiacetazone, rifampicin and ethambutol in bacilliferous tuberculosis in Maniema, Zaire].

Initial resistance to streptomycin, isoniazid, thiacetazone, rifampicin and ethambutol was tested in 102 patients with bacilliferous tuberculosis in Kalima, a rural area in eastern Zaïre. The initial resistance for at least one of these tuberculostatics was 43%. The highest resistance recorded was for streptomycin (31%). No resistance to rifampicin or ethambutol was found. The practical interest of these findings is discussed.

Antitubercular Agents↗

[R,S]-Ethambutol dihydrochloride: variable-temperature studies of a dimorphic system with very similar packing.

The two polymorphs (Forms I and II) of [R,S]-ethambutol dihydrochloride transform enantiotropically and reversibly in a single-crystal-to-single-crystal phase transformation mode. These structurally very similar forms have been characterized and their thermodynamic relationship has been investigated by variable-temperature solid-state carbon-13 nuclear magnetic resonance, variable-temperature powder X-ray diffraction, differential scanning calorimetry, and optical microscopy. The nuclear magnetic resonance results are compared with those for the two polymorphs of the [S,S] diastereomer with known structures.

Crystallization↗

Disposition kinetics of ethambutol in man.

Six normal adult volunteers were administered 15 mg/kg of ethambutol (EMB) by a constant-rate 1-hr infusion. Plasma and urine samples were collected up to 24 and 72 hr, respectively. Peak plasma levels following the 1-hr infusion ranged from 11.6 to 15.4 microgram/ml. Subsequent postinfusion EMB levels exhibited multiphasic decay. In the 12-hr period following infusion, EMB levels showed biexponential decay. However, 24-hr plasma levels in all subjects were observed to be higher than those predicted using a two-compartment body model. The alpha phase in these subjects had a mean half-life of 8.6 min while the half-life of the beta phase ranged from 2.5 to 3.6 hr (mean 3.1). The half-life of the gamma phase estimated from plasma data points between 12 and 24 hr averaged 1.2 +/- 3.6 hr. A terminal gamma t1/2 of 15.4 +/- 1.7 hr was calculated from 12-72 hr urine data. The mean value for the steady-state volume of distribution using a noncompartmental method was 3.89 liters/kg. Plasma EMB clearance ranged from 7.47 to 8.87 ml/min/kg (mean 8.57). The fraction of the dose eliminated unchanged varied from 0.75 to 0.84 (mean 0.79). Renal clearance ranged from 5.93 to 8.45 ml/min/kg (mean 6.81), indicating active tubular secretion.

Absorption↗

Clinical ERG findings in ethambutol intoxication.

The human electroretinogram (ERG), evoked by white flashes of extremely short duration (10 microseconds), shows a typical dependence on flash intensity. Increasing stimulus intensity increases the amplitude of the a-wave until saturation is reached. The amplitude of the b-wave reaches a maximum value with flashes of middle intensity, then decreases at higher stimulus strengths. The values of a-wave amplitude saturation, defined as 100%, may serve as a basis for standardizing the various amplitude-intensity relationships of the a- and b-wave. The b-wave function, calculated in this way, shows different maximum values depending on whether it was determined after light adaptation or in dark adaptation and low interindividual variability. However, the difference between bmax in dark and light adaptation is markedly decreased in the case of ethambutol intoxication. ERG changes are only detected in severe cases (total central scotoma) and are below the discrimination level in cases with moderate symptoms (relative central scotoma, visual acuity greater than 0.4-0.5).

Adult↗

A controlled trial of daily and intermittent rifampicin plus ethambutol in the retreatment of patients with pulmonary tuberculosis: results up to 30 months.

In a controlled clinical trial in Hong Kong, 575 Chinese adults with smear-positive isoniazid-resistant pulmonary tuberculosis, who had previously been treated with first-line chemotherapy, were allocated at random to regimens of rifampicin plus ethambutol daily (ER7), twice-weekly (ER2), once-weekly (ER1), or daily for 2 months and then once-weekly (ER7ER1), or to a standard retreatment regimen of daily ethionamide plus pyrazinamide plus cycloserine (EtZC). The ER7 patients were allocated to 12 or 18 months of chemotherapy, and the remainder to 18 months. As assessed at 18 months, a favourable response was achieved in 87 per cent of 91 ER7 patients, 79 per cent of 84 ER2, 81 per cent of 53 ER1, 87 per cent of 62 ER7ER1, and in 88 per cent of 68 EtZC patients (93 per cent of 59 EtZC patients if those with ethionamide-resistant strains pretreatment are excluded). As assessed at 18 and 30 months the ER7 regime was as effective as the control EtZC regimen, and 18 months of chemotherapy on the ER7 regimen conferred no benefit over 12 months. No patient on either regimen relapsed after 18 months. Adverse reactions were uncommon on the daily rifampicin regimen but relatively common on the intermittent and control regimens. The commonest reaction to the intermittent regimens was the 'flu' syndrome, which was associated with the presence of circulating rifampicin-dependent antibodies (P less than 0-001).

Antibody Formation↗

Rifabutin in combination with clofazimine, isoniazid and ethambutol in the treatment of AIDS patients with infections due to opportunist mycobacteria. Groupe d'Etude et de Traitement des Infections à Mycobacteries Résistantes.

96 AIDS patients with fever and either acid-fast bacilli on microscopic examination of bacteriological samples or mycobacteria isolated by culture were treated with a daily 4-drug combination of 7-10 mg/kg rifabutin, 5 mg/kg isoniazid, 20 mg/kg ethambutol and 100 mg clofazimine. 46 patients were excluded from efficacy assessment: 13 died before or within the first days of treatment, 5 had negative initial cultures, 14 had initial cultures positive for M. tuberculosis, 4 for M. kansasii, 1 for M. flavescens, 1 for M. gordonae, 7 were lost to follow-up and 1 received no rifabutin. In the 50 remaining patients, 31 had disseminated disease due to M. avium intracellulare complex (MAIC) and 19 had apparently localised disease, due to MAIC in 15 cases and to M. xenopi in 4 cases. Side-effects led to withdrawal of isoniazid in 1 case (hepatic enzymes increased) and rifabutin in another (thrombocytopenia). After 1 month of treatment, fever decreased from 38.4 +/- 0.6 degrees C to 37.7 +/- 0.5 degrees C (p less than 0.01) and patients stopped losing weight. After 3 months treatment, only 37 patients were alive and still under treatment. Cultures became negative in 16 of 23 patients with available bacteriological data (9 of 14 patients with disseminated disease and 7 of 9 patients with localised disease), relapse occurred before death in 4 patients. 34 patients died before treatment was completed. Death was considered to be related to mycobacterial infection in 5 cases. We conclude that the 4-drug combination is safe and, in some cases, it appears to be effective.

Acquired Immunodeficiency Syndrome↗

Efficacy of triple drug regimen of amikacin, ethambutol and rifabutin in AIDS patients with symptomatic Mycobacterium avium complex infection.

Treatment with ethambutol 15 mg/kg, rifabutin 6 mg/kg and amikacin 15 mg/kg (IV for 2-4 weeks) in 31 HIV infected patients with severe immunodeficiency and infection caused by Mycobacterium avium complex (MAC) was evaluated in a retrospective study. The patients had one or more of the following clinical features: fever 31, weight loss 13, cough 10, pleurisy I, pericarditis 2, diarrhoea 12, peritonitis I. MAC was cultured from blood in 29, bone marrow in six, sputum in nine, faeces in 15, bowel biopsy in six and liver biopsy in four patients. Twenty-two of the 31 patients showed treatment response after a median time of 14 days, and five had a relapse successfully treated with another course of amikacin. Median survival time was 8 months.

AIDS-Related Opportunistic Infections↗