SEARCH · Search PubMed

Results for “ETHAMBUTOL”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources

PubMed1996

Activities of bay Y 3118, levofloxacin, and ofloxacin alone or in combination with ethambutol against Mycobacterium avium complex in vitro, in human macrophages, and in beige mice.

Levofloxacin, ofloxacin, and Bay Y 3118 are new fluoroquinolones with variable in vitro bacteriostatic and bactericidal activities against the Mycobacterium avium complex (MAC). The potential therapeutic activities of these agents both alone and combined with ethambutol were evaluated in a human macrophage test system and in the beige mouse animal test system with MAC strain 101. Bay Y 3118 at a human-equivalent dose of 30 mg/kg/day for 4 weeks caused a significant reduction in mortality compared with that in untreated controls (P = 0.02). Bay Y 3118 also caused significant reductions in the number of MAC organisms in the blood, liver tissue, and spleen tissue compared with those in untreated controls. Levofloxacin at a human-equivalent dose of 200 mg/kg/day was associated with a significant reduction in mortality (10 versus 39%); however, treatment with either levofloxacin or ofloxacin (200 mg/kg/day) did not result in significant reductions in the numbers of MAC organisms in blood, liver, and spleen compared with those in untreated controls. When Bay Y 3118 was combined with ethambutol, there was no enhancement in therapeutic activity except in the spleen in terms of CFU per gram (reductions of 89% compared with the untreated control, 63% compared with Bay Y 3118 alone, and 72.5% compared with ethambutol alone). Levofloxacin in combination with ethambutol was more active than either drug alone in the reduction of organisms in blood, liver, and spleen. Bay Y 3118 was the most active fluoroquinolone for monotherapy of MAC infection in beige mice, and the combination of ethambutol plus either levofloxacin or ofloxacin was at least additive. In summary, this study demonstrates that quinolones, although active, are inhibitory against MAC in vivo and that there is little correlation between the activity of quinolones in vitro and the activity in mice.

Animals↗

PubMed2006

Determinants of rifampin, isoniazid, pyrazinamide, and ethambutol pharmacokinetics in a cohort of tuberculosis patients.

Evaluation of sources of pharmacokinetic variation can facilitate optimization of tuberculosis treatment regimens by identification of avoidable sources of variation and of risk factors for low or high drug concentrations in patients. Our objective was to describe the pharmacokinetics of rifampin, isoniazid, pyrazinamide, and ethambutol in a cohort of tuberculosis patients established on first-line treatment regimens and to evaluate the determinants of pharmacokinetic variation. Plasma concentration-time profiles were determined for each of the drugs in 142 patients with drug-sensitive pulmonary tuberculosis after 2 months of daily treatment in hospital. Pharmacokinetic measures were described by noncompartmental analysis. Multiple linear regression was used to evaluate the patient and the treatment factors associated with variation of the area under the concentration-time curve from 0 to 8 h. Several factors independently associated with variations in antituberculosis drug concentrations were identified: human immunodeficiency virus infection was associated with 39% and 27% reductions for rifampin and ethambutol, respectively; formulation factors were determinants of rifampin and isoniazid bioavailability; female patients had increased rifampin and isoniazid concentrations but reduced ethambutol concentrations; older patients had higher levels of isoniazid and ethambutol; patients with a history of previous antituberculosis treatment had lower ethambutol concentrations; and the dose per kilogram of body weight was associated with the concentrations of all four agents. Further studies are required to assess the implications of variations in antituberculosis drug concentrations for efficacy and safety before decisions are made to change the dosing strategy in patients at risk.

Adult↗

PubMed1994

Mycobacterium kansasii pulmonary infection: a prospective study of the results of nine months of treatment with rifampicin and ethambutol. Research Committee, British Thoracic Society.

BACKGROUND: Pulmonary disease caused by Mycobacterium kansasii is reported in approximately 50 new patients in Britain annually. Rifampicin and ethambutol are effective in vitro but the optimal duration of treatment, and whether isoniazid should also be given, are uncertain. The British Thoracic Society has conducted a prospective, multicentre study of the treatment of this condition with rifampicin and ethambutol given for nine months. METHODS: One hundred and seventy three patients with two or more positive cultures and radiological evidence of disease were recruited via the Mycobacterium Reference Unit (PHLS) in Cardiff from 113 physicians in England, Scotland, and Wales. Rifampicin and ethambutol were given for nine months, other antituberculosis drugs being discontinued once the culture was identified as M kansasii. Patients were reviewed, sputum cultured, and chest radiographs performed before, during, and at regular intervals for 51 months after chemotherapy. RESULTS: The mean (SD) age was 55.5 (11.7) years, 73% were men, and 50% had other lung problems. Cavitation was seen in 88%, bilateral shadowing in 48%, and three or more lung zones were affected in 46%. All cultures were sensitive to rifampicin and ethambutol but resistant to isoniazid and pyrazinamide. One patient who took chemotherapy irregularly still had positive cultures at seven and eight months. Fifteen patients developed positive cultures after the end of chemotherapy; factors which might account for the relapse were identified in eight. Reinfection rather than relapse was suspected in three of the 15. Radiographic improvement stabilised within three years in 80%. CONCLUSIONS: M kansasii pulmonary infection responds well to nine months of treatment with rifampicin and ethambutol but patients who contract this disease have a high mortality rate from other causes. Isoniazid does not appear to be a necessary part of the regimen.

Adolescent↗

PubMed1999

A retrospective study of the addition of ciprofloxacin to clarithromycin and ethambutol in the treatment of disseminated Mycobacterium avium complex infection.

Disseminated Mycobacterium avium complex (DMAC) infection is associated with increased morbidity and mortality in HIV-infected individuals. The combination antibiotic regimens containing clarithromycin can decrease symptoms and improve survival in patients with DMAC, however, optimal therapy remains to be defined. Quinolones have been widely used in the treatment of DMAC but their utility has not been established. A retrospective cohort study of DMAC infection was established in a metropolitan hospital providing comprehensive care to over 3000 HIV-infected individuals. Medical records of patients with DMAC diagnosed at the Parkland Memorial Hospital from 1991 to 1994 were reviewed for therapeutic regimens for DMAC, concomitant therapy for HIV and Pneumocystis carinii prophylaxis and date of death. Subjects were included if they were treated with clarithromycin and ethambutol. Cases were defined as those patients who received more than 30 days of ciprofloxacin as therapy for DMAC in addition to the other drugs that they received. The primary endpoint was the time to death from the data of DMAC diagnosis. Covariates effecting survival were analysed through the Cox proportional hazards model. Eighty-nine subjects with DMAC who were treated with clarithromycin and ethambutol were identified. Fifty-eight received ciprofloxacin in addition to clarithromycin and ethambutol. The time to death was significantly better in those subjects who were treated with ciprofloxacin than those who were not (489 days vs 281 days, P=0.01). The sole significant predictor of improved survival on Cox proportional hazards model was ciprofloxacin therapy. Subjects treated with combination of clarithromycin, ethambutol and ciprofloxacin had improved survival over those treated with clarithromycin and ethambutol alone.

Anti-Bacterial Agents↗

PubMed1989

Studies on the mechanisms of the synergistic effects of ethambutol and other antibacterial drugs on Mycobacterium avium complex.

Synergistic effects of combinations of anti-mycobacterial drugs on Mycobacterium avium complex (MAC) in vitro was studied by radiometric respirometry. Pronounced synergy was seen for several drug combinations where ethambutol was found to be the key drug in the synergistic potentiation. Microcalorimetric studies show that a very rapid physico-chemical interaction occurs between the cell-surface of MAC and ethambutol. When MAC cells were pretreated with ethambutol and then subjected to streptomycin the thermal response significantly differed from that seen with MAC cells which had not been pretreated. The typical thermal effects of the interaction of ethambutol with live and UV-killed MAC cells was not seen with heat-killed MAC cells. It is proposed that specific cell-surface protein(s) act as receptors in the initial interaction with ethambutol.

Anti-Bacterial Agents↗

PubMed1989

[Differentiation between Mycobacterium malmoense and Mycobacterium nonchromogenicum by ethambutol susceptibility].

Mycobacterium malmoense strains are resistant to 1 microgram/ml ethambutol in Ogawa egg medium, whereas Mycobacterium nonchromogenicum strains are susceptible to this concentration. Therefore, these two Group III nonphotochromogens are differentiated clearly from each other by the susceptibility test for ethambutol 1 microgram/ml. Ninety-five % of Mycobacterium avium complex strains are resistant to this concentration, while M. nonchromogenicum strains are susceptible. Therefore, the test serves for differentiating M. nonchromogenicum from M. avium complex. Previously, Tsukamura (Kekkaku 45: 237, 1970) reported that pathogenic and nonpathogenic mycobacteria of Group II and Group III are differentiated by the susceptibility test to ethambutol, 5 micrograms/ml. However, the use of Ogawa egg medium containing 1 microgram/ml ethambutol is superior to that of 5 micrograms/ml ethambutol for differentiating pathogenic and nonpathogenic ones of the Group III.

Ethambutol↗

PubMed1997

Should ethambutol be recommended for routine treatment of tuberculosis in children? A review of the literature.

SETTING: Review of the literature referenced from Medline and other sources on the use of ethambutol in children. OBJECTIVE: The most well-known side effect of ethambutol is its ocular toxicity. Its use among children is thus generally discouraged. The present article summarizes the studies published on this subject. RESULTS: No authors have reported major ocular side effects among children treated with ethambutol. CONCLUSION: For children aged 5 years or more, ethambutol can be recommended at a dosage of 15 mg/kg/day for routine treatment, without taking more precautions than for adults; this should be included in official recommendations. For younger children, ethambutol can also be used without undue fear of side-effects.

Adolescent↗

PubMed1965

EFFECT OF ETHAMBUTOL ON NUCLEIC ACID METABOLISM IN MYCOBACTERIUM SMEGMATIS AND ITS REVERSAL BY POLYAMINES AND DIVALENT CATIONS.

Forbes, M. (Lederle Laboratories Division, Pearl River, N.Y.), N. A. Kuck, and E. A. Peets. Effect of ethambutol on nucleic acid metabolism in Mycobacterium smegmatis and its reversal by polyamines and divalent cations. J. Bacteriol. 89:1299-1305. 1965.-Mycobacterium smegmatis, harvested from cultures inhibited by ethambutol and then suspended in drug-free medium, exhibited a prolonged lag before growth resumed. Polyamines and magnesium ions shortened this lag. Polyamines and magnesium added to the culture increased the minimal inhibitory concentration of the drug and reversed the inhibitory effect of the drug, even when added after the drug had already inhibited growth. When ethambutol was added to a culture in its exponential phase of growth, synthesis of protein and deoxyribonucleic acid (DNA), as measured by incorporation of S(35) and P(32), continued for 3 hr at a rate slightly less than in the control cells and then essentially ceased. Synthesis of ribonucleic acid (RNA) was depressed, but it proceeded even after protein synthesis had ceased. Even though the synthesis of RNA continued, the net RNA decreased, and inhibited cells became deficient in RNA. Polyamines and divalent cations, which reverse the inhibitory effect of the drug, have been reported to be involved in nucleic acid turnover. These considerations suggested that ethambutol may exert its inhibitory effect by interfering with a function of cellular polyamines and divalent cations in RNA metabolism.

Amines↗

PubMed1977

Sensitive assay procedure for ethambutol hydrochloride via charge transfer complex formation.

The charge transfer complex formation between ethambutol and iodine was investigated and utilized as the basis for a sensitive spectrophotometric procedure for ethambutol and its dosage forms. The solutions exhibited blue-shifted iodine bands at 293 and 360 nm. A Job's plot of corrected absorbance against the mole ratio of ethambutol to iodine indicated a 1:2 drug-iodine ratio. At 293 nm, the absorbance was linear (r=0.9998) over the 0.25-15-microgram/ml concentration range, but the concentration range for best accuracy is 1.6-5.8 microgram/ml. The method can be applied successfully to the analysis of commercially available ethambutol tablets.

Chemical Phenomena↗

PubMed2005

A liquid chromatography/tandem mass spectrometry method for the simultaneous quantification of isoniazid and ethambutol in human plasma.

Isoniazid and ethambutol are commonly used in various combination treatments for tuberculosis, and for this reason a rapid and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated for simultaneous quantification of these two drugs in human plasma. After a simple protein precipitation using methanol, the analytes and the internal standard metformin were chromatographed on a C18 column and detected by MS/MS. An atmospheric pressure chemical ionization interface was chosen to reduce ion suppression from sample matrix components and provide high sensitivity. The LC retention times for isoniazid and ethambutol were 2.46 and 2.27 min, respectively. The method was linear in the concentration range of 10.0-5000 ng/mL for each analyte using 100 microL plasma. The intra- and inter-day precisions, expressed as the relative standard deviation (RSD), were less than 5.7 and 6.4%, determined from QC samples for isoniazid and ethambutol, and the accuracies were within +/-2.1% and +/-4.5% in terms of relative error, respectively. The method was successfully employed in a pharmacokinetic study after oral administration of a multicomponent formulation containing 150 mg isoniazid, 500 mg ethambutol, 150 mg rifampicin and 250 mg pyrazinamide.

Administration, Oral↗

PubMed1989

Recovery after severe ethambutol intoxication--psychophysical and electrophysiological correlations.

Six patients with severe ocular side effects caused by therapeutical doses of the tuberculostatic drug ethambutol were investigated during the course of recovery with psychophysical and electrophysiological methods. Three patients developed an optic atrophy with permanently reduced vision as a likely consequence of additional risk factors such as diabetes, alcohol abuse, and reduced kidney function. The severity of the neuritis of the optic nerve was not related to the total intake of ethambutol. The likelihood of a permanent ocular damage increased sharply if the visual acuity had dropped below a value of 1/10. permanently prolonged latency of the P-100 component was found in visual evoked potentials even in cases with good recovery from ethambutol-induced damage. The recovery of color vision could be monitored very well with the Farnsworth-Munsell 100-Hue Test which revealed a diffuse impairment of color discrimination with a slight prevalence of the red-green axis. In addition to the known disturbances of the red-green antagonistic neurons, it could be demonstrated by measuring transient tritanopia and spectral sensitivity functions that ethambutol also affects the blue-yellow antagonism at the retinal level.

Aged↗

PubMed1979

Ethambutol in pregnancy--foetal exposure.

We report a case of miliary tuberculosis in a pregnant Jamaican woman in whom foetal exposure to ethambutol has been assessed. The mother received 15 mg/kg ethambutol as part of her antituberculosis therapy. Immediately after delivery, amniotic fluid, maternal, placental, and cord blood specimens were obtained and analysed for ethambutol concentrations. The levels were within the therapeutic range in all 4 samples. The concentrations indicate that the placenta is not a significant physiological barrier to the transfer of ethambutol to the foetus.

Adult↗

PubMed1984

Ethambutol-induced hyperuricaemia.

A prospective study involving 134 cases of pulmonary tuberculosis was conducted to determine the incidence and severity of ethambutol-induced hyperuricaemia. The cases were randomly allocated to two groups: one group (71 cases) received ethambutol (20 mg/kg bodyweight/day) streptomycin and isoniazid (SHE), the other group (60 cases) received streptomycin, isoniazid and thioacetazone (SHT). All the cases were hospitalized. A significant rise in serum uric acid levels was found in 66% of SHE patients during the first 60-90 days of treatment, but there was no such change in the SHT patients. In one patient who received ethambutol generalized arthralgia developed and in another acute gouty arthritis was observed. In both cases, symptoms abated when ethambutol was withdrawn and reappeared when it was resumed.

Adolescent↗

PubMed1989

Activity of rifabutin alone and in combination with clofazimine, kanamycin and ethambutol against Mycobacterium intracellulare infections in mice.

Treatment of mice for 12 weeks with clofazimine or kanamycin decreased the number of organisms from lungs, liver and spleen of mice infected with Mycobacterium intracellulare N-260, compared with findings seen with rifabutin or ethambutol. Treatment with various drug combinations (rifabutin-ethambutol, rifabutin-clofazimine, rifabutin-kanamycin, rifabutin-ethambutol-clofazimine, rifabutin-ethambutol-kanamycin, and rifabutin-clofazimine-kanamycin), particularly in the presence of clofazimine, enhanced elimination of the organisms from these organs.

Animals↗

PubMed1980

Determination of ethambutol in plasma using selected ion monitoring.

The determination of ethambutol in plasma is described. Using ethambutol-d4 as an internal standard, ethambutol and the internal standard were extracted with chloroform under alkaline conditions, and converted into their trifluoroacetyl derivatives with trifluoroacetic anhydride in benzene-pyridine (4:1). Selected ion monitoring was carried out by monitoring the peaks at m/z 294 and 296 corresponding to the fragment ion [M/2]+ of the derivatives. Ethambutol was determined by use of the peak height ratio of the peak at m/z 294 against that at m/z 296. The method was utilized for studying the bioavailability and pharmacokinetics of the drug.

Animals↗

PubMed2001

In vitro, ex-vivo and in vivo activities of ethambutol and sparfloxacin alone and in combination against mycobacteria.

The MIC of ethambutol and sparfloxacin for Mycobacterium smegmatis and M. avium was determined using a broth dilution method. The MICs of sparfloxacin and ethambutol were lower for M. smegmatis than M. avium. The combination of ethambutol and sparfloxacin was additive against M. smegmatis but synergistic for M. avium. The effect of these drugs alone and in combination used at C(max) levels was screened against M. avium and M. tuberculosis H(37)Rv growing intracellularly in murine macrophage cell lines. In vivo studies using this combination given at 100 mg/kg of body weight once weekly showed greater activity than the drugs used singly. These results suggest that combination of ethambutol and sparfloxacin has significant activity intracellularly and in animal models against M. avium and M. tuberculosis.

Animals↗

PubMedDate not supplied

Abnormal multifocal electroretinogram (mfERG) in ethambutol toxicity.

OBJECTIVE: To report the abnormal multifocal electroretinogram (mfERG) findings in two cases of presumed ethambutol toxicity. DESIGN: Retrospective observational case series. PARTICIPANTS: Two patients with ethambutol toxicity and visual loss. TESTING: Multifocal electroretinography. MAIN OUTCOME MEASURE: Waveform measurements on multifocal electroretinography. RESULTS: Two patients with bilateral visual loss due to ethambutol toxicity underwent mfERG testing that disclosed both diffuse and central field loss compatible with retinal dysfunction as a contributing mechanism to the visual field loss. CONCLUSION: Ethambutol toxicity affects not only the optic nerve but probably other retinal elements based upon abnormal mfERG findings.

Aged, 80 and over↗

PubMed1982

A gas chromatographic/mass spectrometric study of the trimethylsilylation of ethambutol and a tablets assay method based on the trimethylsilyl derivative.

The trimethylsilylation of ethambutol base and ethambutol hydrochloride was studied by means of GC/MS. The derivatisation is shown to proceed in two distinct steps, and the second derivative is identified, by both chemical ionisation and electron impact Ms, and the di-trimethylsilyl ethambutol. Most of the major mass fragments observed are assigned. A tablets assay method, based on the direct trimethylsilylation of ethambutol hydrochloride in tablets, is also described. It is simple, rapid, and unaffected by the presence of the common excipients in the tablets.

Biological Availability↗