Search PubMed⌕ Search

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.

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

At least 307 records · Page 17Linked to original sources
PubMed1999

The effect of hemodialysis on isoniazid, rifampin, pyrazinamide, and ethambutol.

This study examines hemodialysis clearances of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Seven chronic hemodialysis patients were studied. Six were given single oral doses (INH 300 mg, RIF 600 mg, PZA 1000 mg, and EMB 25 mg/kg) 2 h before hemodialysis (Cobe Centrysystem 3 hemodialysis machine; Fresenius F80B dialyzer; median blood flow rate 400 ml/min; dialysate flow rate 600 ml/min; median hemodialysis time 3.5 h). The seventh subject, being treated for tuberculosis (TB), was studied with his usual regimen. Arterial and venous serum samples were collected at the beginning and end of hemodialysis, and hourly during hemodialysis. Dialysate was collected for the duration of hemodialysis. All samples were assayed for drug concentrations using high-performance liquid chromatography (HPLC) (INH, RIF) and gas chromatography/mass spectrometry (GC/MS) (PZA, EMB) methods. Median recoveries of drug in dialysate were 9% (INH), 4% (RIF), 45% (PZA), and 2% (EMB) of the doses administered. Median hemodialysis clearances calculated by dividing the amount recovered in dialysate by the serum area under the curve during hemodialysis were 124 (INH), 40 (RIF), 270 (PZA), and 46 (EMB) ml/min. INH, RIF, and EMB were not significantly removed by hemodialysis. PZA is significantly dialyzed and should be dosed after hemodialysis.

Adult↗
PubMed1987

Activity of rifabutin alone or in combination with clofazimine or ethambutol or both against acute and chronic experimental Mycobacterium intracellulare infections.

Rifabutin (ansamycin LM 427) when given alone in doses of 5, 10, or 20 mg/kg showed limited in vivo activity against acute or chronic Mycobacterium intracellulare infections studied in beige C57B1/6, or S/W mice. Prophylactic studies in S/W mice in which chemotherapy was given for 3 wk prior to challenge showed slight improvement. Combination chemotherapy consisting of rifabutin (10 mg/kg) and clofazimine (20 mg/kg) achieved complete sterilization of M. intracellulare infections in spleen and lung when initiated immediately after challenge. Inclusion of ethambutol did not offer additional benefit. If chemotherapy is initiated 3 wk after challenge (established infections), the activity of this double drug combination is less effective.

Animals↗
PubMed1988

Combinations of rifampin or rifabutine plus ethambutol against Mycobacterium avium complex. Bactericidal synergistic, and bacteriostatic additive or synergistic effects.

Ethambutol, when combined with rifampin or rifabutine (ansamycin, LM427), produced an additive inhibitory effect against most of the tested M avium complex strains (12 of 16 with rifampin, 13 of 16 with rifabutine). The inhibitory effect was synergistic for the remaining 4 of 16 and 3 of 16 strains. This relationship reduced the minimal inhibitory concentrations for each drug in combination. In addition, the minimal bactericidal concentrations of all 3 drugs were reduced because of synergistic bactericidal activity in 6 of 6 strains tested.

Drug Interactions↗
PubMed1988

Minimal inhibitory concentrations of isoniazid, rifampin, ethambutol, and streptomycin against Mycobacterium tuberculosis strains isolated before treatment of patients in Taiwan.

Minimal inhibitory concentrations (MICs) of isoniazid (INH), rifampin (RMP), ethambutol (EMB), and streptomycin (SM) for susceptible "wild" M. tuberculosis strains isolated from Taiwanese patients were within the limits previously reported for strains isolated in the United States. The highest agar-determined MICs (in 7H10 and 7H11 agar) corresponded well with the critical concentrations established for these media. The highest MICs found radiometrically in 7H12 broth were significantly lower than the critical concentrations proposed for this medium. On the basis of an evaluation of the highest broth-determined MICs found in this and in the previous study (1), we suggest that the following MICs, when determined radiometrically, should be used as breakpoints to classify the strain as "susceptible": for INH, 0.1 microgram/ml or less; for RMP, 0.5 microgram/ml or less; for EMB, 4.0 micrograms/ml or less; for SM, 2.0 micrograms/ml or less.

Antitubercular Agents↗
PubMed1981

Distribution of ethambutol in primate tissues and cells.

Ethambutol (EMB) concentrations that kill Mycobacterium tuberculosis in vitro accumulated in squirrel monkey tissues and cells known to be sites of tubercular infections. After oral administration of a clinically relevant 25 mg/kg dose, the whole-body distribution and intracellular localization of EMB were studied by radioautography. Tissue concentrations of drug were assayed by radiochemical and microbiological methods. The EMB was distributed rapidly and widely to most body tissues including lung and localized within pulmonary alveolar and axillary lymph node macrophages. The EMB in lung at 2 and 5 h after drug administration was markedly higher than the corresponding plasma concentrations and exceeded concentrations that are bactericidal in vitro for tubercle bacilli. These observations may help explain the early bactericidal activity of EMB in humans. Similarities in plasma and tissue concentrations of the drug in both species suggest the usefulness of the squirrel monkey as a model for the use of EMB in humans.

Administration, Oral↗
PubMed1982

Synergistic effect of rifampin, streptomycin, ethionamide, and ethambutol on Mycobacterium intracellulare.

A method of quantitative estimation to determine the interaction of antituberculosis drugs is suggested. The design of experiments, performed on 7H11 agar plates, is adjusted to the following statistical treatment by combined use of probit analysis and isobologram methods. By plotting the values reflecting the inhibition of 75% of the bacterial population (ED75) with their confidence limits on the isobologram, it was found that the clearest results proving synergism between the drugs could be obtained. Six 2-drug combinations and 6 3-drug combinations were tested against strains of Mycobacterium intracellulare (serovar 8), and a synergistic effect was demonstrated in most of them. These were various combinations of rifampin, streptomycin, ethambutol, and ethionamide. The application of probit analysis to the data derived from testing single drugs can provide a quantitative estimation of the actual drug resistance of the M. intracellulare strains.

Drug Synergism↗
PubMed1985

The effect of ethambutol on tubercle bacilli within cultured human macrophages.

Ethambutol (EMB) generally is believed to be clinically mycobacteriostatic. This concept was reexamined in an in vitro model of human tuberculosis that has direct relevance to in vivo effects in human subjects. Cultured human monocyte-derived macrophages infected with virulent Erdman tubercle bacilli were treated with EMB, and the resulting antimycobacterial consequences were measured by counts of acid-fast bacilli and bacterial colony-forming units. When added immediately after infection of the macrophages, EMB inhibited and killed tubercle bacilli within the cells at the same concentrations as it did in bacteriologic culture medium. When added 2 days after infection, it first appeared to increase the viable bacillary count above control culture levels, then killed intramacrophage bacilli at lower concentrations than in bacteriologic culture medium. We speculate that this occurs because macrophages enhance EMB effectiveness by killing tubercle bacilli, which have defective cell walls due to the effects of the drug. The concentrations of EMB that proved mycobactericidal in human macrophages are readily achieved clinically. The purported lesser antituberculosis effectiveness of EMB when compared to other bactericidal agents may be due to its less direct and efficient mode of killing tubercle bacilli, and the necessity therefore, for stricter maintenance of effective drug concentrations in vivo.

Adult↗
PubMed1986

Ethambutol kinetics in patients with impaired renal function.

The pharmacokinetics of ethambutol (EMB) were investigated in 13 hospitalized patients with varying degrees of compromised renal function. Each patient was administered 15 mg/kg EMB by a constant-rate, 1-h infusion. Plasma and urine samples were collected for as long as 24 and 96 h, respectively, for analysis of EMB by electron capture gas-liquid chromatography. Plasma EMB concentrations appeared to decline multi-exponentially, with a terminal phase half-life of 7.4 to 11.8 h. Total body clearance of EMB ranged from 2.0 to 9.6 ml/min/kg and the steady-state volume of distribution from 0.80 to 3.60 L/kg. The fraction of EMB dose excreted unchanged in the urine varied from 0.03 to 0.26, and renal clearance varied from 0.07 to 0.57 ml/min/kg. The results of this study clearly indicate that renal failure decreases total body clearance and renal clearance and prolongs elimination half-life of EMB when compared with that in normal volunteers. The terminal phase elimination rate constant correlated significantly with creatinine clearance and the reciprocal of serum creatinine (y = 0.037 X +0.060, r = 0.795, p less than 0.05; y = 0.042 X +0.061, r = 0.783, p less than 0.05, respectively). Either creatinine clearance or serum creatinine of an individual patient would thus serve as a useful predictor for his or her capacity to eliminate EMB. Dosage adjustment is mandatory for EMB in patients with compromised renal function in order to achieve optimal therapy and to avoid undesirable side effects.

Adult↗
PubMed2005

Ethambutol ocular toxicity in treatment regimens for Mycobacterium avium complex lung disease.

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.

Aged↗
PubMed1980

Peripheral neuropathy associated with ethambutol.

A woman developed peripheral neuropathy and optic neuritis while receiving ethambutol in the retreatment of drug-resistant pulmonary tuberculosis. There was prompt improvement in peripheral neuropathy and the ocular symptoms following the withdrawal of the drug. The clinical events in this case suggest that occasionally symptoms of peripheral neuropathy may precede the development of optic neuritis by several months, and thus serve as a warning for the subsequent development of the more serious visual toxicity.

Ethambutol↗
PubMed1989

Superiority of enviomycin or streptomycin over ethambutol in initial treatment of lung disease caused by Mycobacterium avium complex.

The rate of sputum conversion (continuously negative cultures for six months or more) was compared among four regimens given to 83 patients with moderately advanced, cavitary lung disease caused by Mycobacterium avium complex untreated previously. The regimens of rifampin + isoniazid + enviomycin and rifampin + isoniazid + streptomycin appeared to be superior to the regimen of rifampin + isoniazid + ethambutol. No statistically significant difference was observed between the regimens rifampin + isoniazid + enviomycin and rifampin + isoniazid + streptomycin.

Clinical Protocols↗
PubMed1984

[Effects of sodium iodate, iodoacetic acid and ethambutol on electroretinogram and visual evoked potential in rats].

The effects of sodium iodate (SI), iodoacetic acid (IAA) and ethambutol (EB) on the electroretinogram (ERG) and the visual evoked potential (VEP) were examined in unrestrained rats. A single intravenous dose of SI at 25 mg/kg caused depression of amplitudes of the ERG a-wave and oscillatory potentials 24 hrs after dosing. Following these changes, the amplitude of the ERG b-wave decreased. The depression of the VEP was observed in parallel with the depression in amplitude of the ERG. A single intravenous dose of IAA, even at a dose of 60 mg/kg which induced death of the rats, did not cause any significant abnormality in the ERG and VEP. Repeated subcutaneous dose of EB at 500 mg/kg/day depressed the amplitude of the P1-N1 wave and prolonged the peak latency of the P1 and N1 waves of the VEP without affecting the ERG after administration for 5 to 6 weeks. These abnormalities of the VEP appeared almost in parallel with ataxic gait. Neither gross behavioral changes suggesting visual disturbances nor abnormal ocular fundus was revealed in any rat receiving SI or EB even when marked depression of the ERG and/or VEP was observed. These results indicate that SI damages retinal function and EB does the conduction pathways from the retina to the visual cortex. In addition, the simultaneous recordings of both the ERG and VEP in unrestrained rats were found to be useful for evaluating the visual toxicity, and to furnish useful information on the site of toxic action of drugs.

Animals↗
PubMed2002

Mutations in the embB locus among Korean clinical isolates of Mycobacterium tuberculosis resistant to ethambutol.

Resistance of Mycobacterium tuberculosis to ethambutol (EMB) has been assigned to an operon, embCAB, which has been proposed to be a structural gene for mycobacterial arabinosyl transferases. Recently, genetic events resulting in structural mutations at embB have been proposed as major contributors to the EMB-resistance of isolates whose minimum inhibitory concentration (MIC) level is higher than 20 microgram/ml. On the contrary, isolates with a MIC level lower than 20 microgram/ml do not seem to contain any sequence alterations. In this study, in an effort to understand the role of embB mutations at a low-level of EMB resistance, we investigated the sequence polymorphisms of clinical isolates whose MIC levels are lower than 10 microgram/ml. Accordingly, the sequence alterations of a 312-bp region of the embB gene containing the 306th codon, which has been assigned as a hot-spot for EMB-resistance related mutations, were determined for 21 EMB-resistant and 5 EMB-susceptible clinical isolates. In brief, among 21 EMB- resistant isolates examined, 12 (57.1%) contained mutations in embB (10 at the 306th codon and 2 at other sites), and the remaining isolates 9 contained no mutations in any region of embB. The observed mutations included M306V, M306I, and M306L substitutions that have been reported previously. However, 3 were novel types, which included M306T, A313G and Y319C, D328Y [corrected] double substitutions. On the other hand, all of the EMB-susceptible isolates were found to be free of mutations. In conclusion, our findings suggest that sequence polymorphism of embB may play a pivotal role in the EMB- resistance of M. tuberculosis.

Antitubercular Agents↗
PubMed1998

A case of pulmonary reaction with skin eruption showing a positive peripheral lymphocyte stimulation test result for ethambutol.

We report a case of an elderly male whose pulmonary reaction with skin eruption occurred in the initial phase of chemotherapy composed of isoniazid, rifampicin, and ethambutol (EB). A peripheral lymphocyte stimulation test (LST) showed a positive reaction only to EB. The blood serum analysis of the patient when this reaction occurred revealed an elevated titer of antinuclear antibody. Computed tomography (CT) scan films of the chest when the pulmonary reaction occurred showed multifocal subpleural consolidations. There has been only one reported case of EB-induced pulmonary reaction and its clinical course was very similar to ours. However, LST results and computed tomography (CT) scan findings of the chest were not documented in that case.

Aged↗
PubMed1999

Ethambutol-induced psychosis: a case report.

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.

Antitubercular Agents↗
PubMed2000

Ethambutol retinal toxicity: an electrophysiologic study.

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.

Adult↗
PubMed1976

The value of ethambutol in the treatment of tuberculous meningitis.

This is a prospective treatment study of 86 patients with tuberculous meningitis admitted to the Abbassia Fever Hospital Cairo, Egypt. The causative organism was cultured from the cerebro spinal fluidin 47 patients, was identified by Zeihl Nelson stain in five and in the remaining 34 patients the diagnosis was based on the clinical course and changes in the CSF chemistry and cell count. The data indicate that ethambutol can be used as a companion drug to INH and streptomycin in the treatment of the disease and that the mortality is directly dependent on the state of consciousness upon initiation of therapy.

Adolescent↗
PubMed1992

[Activity of ethambutol, isoniazid and rifampicin on Corynebacterium urealyticum and Corynebacterium jeikeium].

Because corynebacteria and mycobacteria have walls of similar composition, it was of interest to test the effects on resistant corynebacteria of two agents with anti-wall effects, i.e., ethambutol (EMB) and isoniazid (INH). Rifampicin was also studied to extend previous data and clarify conflicting results in the literature. INH was not active in levels achieved in vivo with standard dosages. The minimal inhibitory concentration (MIC) of EMB was under serum levels for only three of 78 strains. All minimal bactericidal concentration (MBCs) were greater than serum levels. With RIF, 59% of strains were susceptible and 19.2% exhibited intermediate susceptibility as defined by the French Committee on Antimicrobial Susceptibility Testing. CMI and CMB distributions were heterogeneous, suggesting a possible acquired heterogeneous resistance to RIF.

Corynebacterium↗