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 1,171 records · Page 65Linked to original sources
PubMed1988

Comparison of a daily and three intermittent retreatment regimens for pulmonary tuberculosis administered under programme conditions.

One daily and 3 thrice weekly retreatment regimens given for 12 months under programme conditions were compared. The daily regimen was rifampicin and ethambutol (RE7). The three intermittent regimens also contained rifampicin and ethambutol: one of them, rifampicin and ethambutol throughout (RE3); the next one supplemented with pyrazinamide for the first 3 months (REZ3); the last one supplemented with prothionamide for the first 3 months (REPt3). The pyrazinamide containing regimen was subdivided into ordinary and high dose groups. The subjects for retreatment were those who have had, at least, more than 6 months of initial triple chemotherapy of isoniazid, PAS and streptomycin at the health centres, and failed to convert to bacteriologically negative status. Among 419 patients who were available for sensitivity tests before commencing retreatment, 393 (94.3%) were resistant to isoniazid. Six hundred and seventy-four patients (674) were allocated randomly to the regimens: 64 patients were excluded due to various pretreatment reasons and 109 did not complete 12 months of chemotherapy. There remain 501 patients who completed their retreatment. As assessed at 12 months, a bacteriologically favourable response was achieved in 68% of 135 RE7 patients, 62% of 129 RE3 patients, 74% of 132 REZ3 patients, and in 79% of 108 REPt3 patients. Adverse reactions were uncommon: 4% in RE7, 5% in RE3 and 9% in REZ3, but 32% in REPt3. Relapse rates during 2 years after termination of chemotherapy were 15% in RE7, 14% in RE3 and REZ3, and 26% in REPt3, as calculated by life table analysis.

Adolescent↗
PubMed1995

Treatment of pulmonary disease caused by Mycobacterium kansasii: results of 18 vs 12 months' chemotherapy.

SETTING: Chest Clinic, Sant Pau Hospital, Barcelona, Spain. OBJECTIVE: To assess the therapeutic response of pulmonary disease due to Mycobacterium kansasii to 12 and 18 months of chemotherapy. DESIGN: 28 patients with criteria of pulmonary disease caused by M. kansasii not associated with HIV-infection were identified in our department in the period 1985-91 (24 male, 4 female, mean age 56 +/- 12 years). 14 patients were treated with rifampicin-isoniazid-ethambutol daily for 12 months (ethambutol only for the first 6 months), and 14 with the same regimen for 18 months. The follow-up after treatment was 12-30 months. RESULTS: All patients showed improvement of radiographic manifestation of disease and sputum conversion (mean time: 4.5 +/- 2 months). The adverse drug effects were minimal. No failures were detected, and only one patient (3.5%), in the group of 12-month chemotherapy, relapsed after finishing the treatment. CONCLUSIONS: Our findings suggest that pulmonary disease due to M. kansasii has an effective response to 12-month chemotherapy regimen and that it is not necessary to prolong the administration of ethambutol for more than 6 months.

Adult↗
PubMed2006

Rapid phenotypic assay of antimycobacterial susceptibility pattern by direct mycobacteria growth indicator tube and phage amplified biological assay compared to BACTEC 460 TB.

The performance of antimycobacterial susceptibility testing for the first line drugs (isoniazid, streptomycine, rifampicin and ethambutol) with mycobacteria growth indicator tube (MGIT) and by bacteriophage amplified biological assay by FAST-plaque TB-MDR were compared to automated radiometric BACTEC 460 TB system. This study was carried on 84 sputum samples of positive Zhiel-Neelsen (ZN) smears. Sputum samples were subjected to culture and antimycobacterial susceptibility testing by BACTEC 460 TB. Samples were also tested by direct susceptibility tests for isoniazid (INH), ethambutol, rifampicin (RIF) and streptomycine by MGIT. Sensitive and resistant isolates for RIF were further studied by FAST-plaque TB-MDR for RIF resistance. The commonest resistance pattern by BACTEC 460 TB was for INH (32%) followed by RIF (24%) either alone or in combination with other drugs. Multiple drugs resistance was 20%. The agreement between BACTEC 460 TB and direct MGIT for resistant strains was 100% for INH and ethambutol, 91.7% for rifampicin, 80% for streptomycine and was 90% for MDR. FAST-plaque TB-MDR detected correctly all RIF resistant strains and 97.2% of the sensitive strains. For majority of strains direct susceptibility tests were available within 6.34-6.404 days (95% confidence interval) with direct mycobacteria growth tube, while results for FAST-plaque TB-MDR appear within 10.5-11.5 days from the time that the sputum was received in the laboratory (95% confidence interval). From this study, we could conclude that direct MGIT AST is the quickest method for screening antimycobacterial susceptibility pattern for the drugs commonly used (INH, RIF, etambutol, streptomycin) as results were available within 6.34-6.404 days. Also FAST-plaque TB-MDR method is accurate for detection of rifampicin resistance after primary culture which can be used as a surrogate marker for presence of MDR strains and the results were available within 10.5-11.5 days.

Adult↗
PubMed1977

Trial of two intermittent short-course regimens (78 doses) in the initial treatment of pulmonary tuberculosis.

A controlled trial was done in Roumania to compare 2 regimens in patients with culture-positive pulmonary tuberculosis. Both regimens were of twice-weekly doses under supervision for 9 months, a total of 78 doses. Patients were followed up for 15 months after the end of treatment. The regimens were as follows: IR, isoniazid and rifampicin for 3 months followed by isoniazid and either streptomycin or ethambutol for 6 months; ISE, isoniazid, streptomycin and ethambutol for 3 months followed by isoniazid and either streptomycin or ethambutol for 6 months. Of 128 IR cases and 104 ISE cases with sensitive cultures initially all were culture-negative at 6 months. At the end of 9 months there were 1.8% of 112 in the IR group which had had 2 positive cultures in the 6-9 month period and 3.4% of 88 in the ISE group. After 15 months from the end of treatment 5.6% of 89 in the IR group had had a bacteriological relapse and 8.9% of 79 in the ISE group. Cultures from all relapsed cases were still sensitive to the drugs used. All relapses occurred during the first 12 months. In only 5.6% of 232 patients did adverse reactions necessitate change of treatment. The efficacy, cost, tolerance and suitability of the regimens for a national programme are discussed.

Antitubercular Agents↗
PubMedDate not supplied

Two 8-month regimens of chemotherapy for treatment of newly diagnosed pulmonary tuberculosis: international multicentre randomised trial.

BACKGROUND: A WHO-recommended 8-month regimen based on ethambutol and isoniazid was evaluated in a randomised clinical trial against a 6-month standard regimen. METHODS: 1355 patients with newly diagnosed smear-positive pulmonary tuberculosis were randomly assigned one of three regimens: daily ethambutol, isoniazid, rifampicin, and pyrazinamide for 2 months, followed by ethambutol and isoniazid for 6 months (2EHRZ/6HE); the same drugs but given three times weekly in the initial intensive phase (2[EHRZ]3/6HE); or the same initial intensive phase as the first regimen, followed by 4 months of daily rifampicin and isoniazid (2EHRZ/4HR). Follow-up was to 30 months after the start of chemotherapy. Sputum was regularly examined by microscopy and culture. Unfavourable outcome was defined as failure during treatment or relapse afterwards. Analyses were by intention to treat. FINDINGS: At 2 months, a significantly higher proportion of patients assigned the daily intensive phase than of those assigned the three-times-weekly regimen were culture negative (700/828 [85%] vs 333/433 [77%], p=0.001). 12 months after the end of chemotherapy, the proportions of unfavourable outcomes were 36 of 346 (10%) with 2EHRZ/6HE, 48 of 351 (14%) with 2(EHRZ)3/6HE, and 17 of 347 (5%) with 2EHRZ/4HR. Both 8-month regimens were significantly inferior to the control 6-month standard regimen (difference between control and 2EHRZ/6HE 5.5% [95% CI 1.6 to 9.4]; between control and 2(EHRZ)3/6HE 8.8% [4.5 to 13.0]). Adverse effects leading to interruption of treatment for 7 days or longer occurred in 28 patients (12 2EHRZ/6HE, five 2[EHRZ]3/6HE, 11 2EHRZ/4HR). INTERPRETATION: The results of this study must be taken into account in recommendations on management of new cases of smear-positive tuberculosis.

Adolescent↗
PubMed1996

[Resistance of Mycobacterium tuberculosis in the province of Castellón].

We conduced a cross-sectional study to determine the prevalence of resistant mycobacteria in our setting. All patients in whom M. tuberculosis had been isolated in cultures of clinical samples (119) between January 1992 and December 1993 took part in the study. Canetti's method of percentages was used for the study of sensitivity to the following drugs: isocyanide, rifampicin, streptomycin, ethambutol and para-aminosalicylic acid. Overall resistance of M. tuberculosis was 9.24%. Specifically, we found resistance to isocyanide in 5.9%, to streptomycin in 4.20%, to rifampicin in 5.04% and to ethambutol in 1.68%. Resistance was primary in 7% and secondary in 21.05%; 2% showed primary resistance to isocyanide, 1% to isocyanide and rifampicin, 2% to streptomycin, 1% to ethambutol and 1% to streptomycin and rifampicin. These resistance indices are in keeping with those published for other areas of Spain.

Adolescent↗
PubMed1997

Pyrolysis mass spectrometry: a predictor of clinical response to treatment in pulmonary opportunist mycobacterial infection: preliminary work with M. malmoense.

Pyrolysis mass spectrometry (Py-MS) yields data reflecting overall cell composition. The changes in composition induced by treatment with rifampicin and ethambutol, alone and in combination, were investigated for a collection of seven strains of Mycobacterium malmoense from pulmonary infections. Two strains, both from patients that had responded to therapy with this combination, showed large changes in composition from control, untreated cultures. The difference was particularly marked for the ethambutol treated cultures. Four strains, all from patients who had failed to respond to therapy with this combination, showed minimal changes in composition for all treatments. The remaining strain also showed minimal treatment-induced change, but, for this patient, therapy with the combination had proved successful. Minimum inhibitory concentrations (MICs) were determined radiometrically. All strains showed MICs < 0.5 microgram/mL for rifampicin (sensitive) and of 8 micrograms/mL for ethambutol (resistant). MIC results did not correlate with clinical response, whereas the Py-MS results correlated with clinical response for six of the seven isolates. Py-MS may have a role in predicting effective therapy for this problem group.

Ethambutol↗
PubMed1996

Antimycobacterial activities of antisense oligodeoxynucleotide phosphorothioates in drug-resistant strains.

Strains of Mycobacterium smegmatis, a mycobacterium which shares genetic sequences, grows more rapidly, and is nonpathogenic in man as compared with Mycobacterium tuberculosis, were utilized for the initial development of new antimycobacterial therapy. Drug-resistant strains of M. smegmatis which are known to arise in a manner identical to the emergence of drug-resistant strains of M. tuberculosis were isolated and utilized as models for the antimycobacterial activities of modified and unmodified oligodeoxynucleotide phosphorothioates in broth cultures. Under normal conditions, oligodeoxynucleotide phosphorothioates do not enter mycobacteria, and several strategies were successfully utilized to afford entry of oligonucleotides into the mycobacterial cells. One involved the presence of very low levels of ethambutol, which enables the entry of oligonucleotides into mycobacteria because of its induced alterations in the cell wall, and another involved the utilization of oligonucleotides covalently attached to a D-cycloserine molecule, whereby entry into the mycobacterial cell is achieved by a receptor-mediated process. Another low molecular weight, covalently attached ligand that enabled the entry and subsequent antimycobacterial activities of oligodeoxynucleotide phosphorothioates in the absence of a cell wall modifying reagent was biotin. Significant sequence-specific growth inhibition of wild-type, as well as of drug-resistant, M. smegmatis was obtained by modified oligonucleotides complementary in sequence to a specific region of the mycobacterium aspartokinase (ask) gene when utilized in combinations with ethambutol (as compared to ethambutol alone) or as D-cycloserine or biotin covalent adducts without the presence of any other cytotoxic or cytostatic agent.

Antitubercular Agents↗
PubMed1999

Altered expression profile of the surface glycopeptidolipids in drug-resistant clinical isolates of Mycobacterium avium complex.

Members of the Mycobacterium avium complex are the most frequently encountered opportunistic bacterial pathogens among patients in the advanced stage of AIDS. Two clinical isolates of the same strain, numbers 397 and 417, were obtained from an AIDS patient with disseminated M. avium complex infection before and after treatment with a regimen of clarithromycin and ethambutol. To identify the biochemical consequence of drug treatment, the expression and chemical composition of their major cell wall constituents, the arabinogalactan, lipoarabinomannan, and the surface glycopeptidolipids (GPL), were critically examined. Through thin layer chromatography, mass spectrometry, and chemical analysis, it was found that the GPL expression profiles differ significantly in that several apolar GPLs were overexpressed in the clinically resistant 417 isolate at the expense of the serotype 1 polar GPL, which was the single predominant band in the ethambutol-susceptible 397 isolate. Thus, instead of additional rhamnosylation on the 6-deoxytalose (6-dTal) appendage to give the serotype 1-specific disaccharide hapten, the accumulation of this nonextended apolar GPL probably provided more precursor substrate available for further nonsaccharide substitutions including a higher degree of O-methylation to give 3-O-Me-6-dTal and the unusual 4-O-sulfation on 6-dTal. Further data showed that this alteration effectively neutralized ethambutol, which is known to inhibit arabinan synthesis. Thus, in contrast with derived Emb-resistant mutants of Mycobacterium smegmatis or Mycobacterium tuberculosis, which are devoid of a surface GPL layer, the lipoarabinomannan from resistant 417 isolate grown in the presence of this drug was not apparently truncated.

AIDS-Related Opportunistic Infections↗
PubMed2005

Serum concentrations of antimycobacterial drugs in patients with pulmonary tuberculosis in Botswana.

BACKGROUND: We conducted a pharmacokinetic study of antimycobacterial drugs involving a cohort of patients with pulmonary tuberculosis (TB) in Gaborone, Botswana, to assess the prevalence of and risk factors for low drug concentrations in serum. METHODS: Adults participated if they had a history of cough > or =2 weeks, had abnormal chest radiograph findings, consented to testing for human immunodeficiency virus (HIV), had sputum cultures positive for Mycobacterium tuberculosis, and were receiving antituberculous therapy for >7 days. Observed maximum serum concentrations were compared with published normal ranges. RESULTS. Of 91 patients enrolled, 89 (98%) were outpatients, and 59 (68%) of 87 patients tested had HIV infection. The following numbers of patients had low serum concentrations of the following drugs: isoniazid, 27 (30%) of 90; rifampin, 71 (78%) of 91; ethambutol, 37 (41%) of 91; and pyrazinamide, 1 (1%) of 91. Low serum concentrations of both isoniazid and rifampin occurred in 23 (26%) of 90 patients. Low serum concentrations of rifampin were found in both HIV-infected and non-HIV-infected patients, and such patients were less likely to have >4 weeks of symptoms, more likely to have lymphadenopathy, and more likely to have low serum albumin levels (P<.05 for all). The associations with noncavitary pulmonary disease (P=.12) and HIV infection (P=.07) did not reach statistical significance. Delayed absorption was most common with ethambutol, followed by rifampin. CONCLUSIONS: These data, predominantly from HIV-infected patients with TB, suggest that low isoniazid, rifampin, and ethambutol concentrations are common in Botswana. In contrast, pyrazinamide usually is well absorbed.

Adult↗
PubMed1994

Treatment of disseminated disease due to the Mycobacterium avium complex in patients with AIDS.

Perhaps the most important recent advance in the field of infections due to the Mycobacterium avium complex (MAC) is the identification and development of more effective agents for the treatment and prevention of disseminated disease. These agents include clarithromycin, azithromycin, rifabutin and other rifamycins, ethambutol, clofazimine, fluoroquinolones, amikacin, and liposome-encapsulated gentamicin. Most clinicians currently use multidrug therapy to maximize efficacy and to minimize the emergence of resistance. Prospective clinical trials of multidrug regimens suggest that MAC colony counts in blood decline during therapy, usually with alleviation of clinical symptoms. The small size and short duration of these trials have not permitted an evaluation of survival or quality of life. Because the contribution of any single agent to multidrug trials is difficult to assess, short-term trials of monotherapy have been conducted recently; clarithromycin, azithromycin, ethambutol, and liposome-encapsulated gentamicin have been most active. Rifabutin and rifampin, clofazimine, amikacin, and ciprofloxacin may contribute to the efficacy of multidrug regimens. Current recommendations include the following: (1) disseminated MAC disease should be treated in patients with AIDS; (2) initial treatment should consist of at least two agents; (3) oral clarithromycin or azithromycin is the preferred first agent; (4) ethambutol is the most rational choice for the second agent; and (5) in appropriate cases, additional agents (rifampin or rifabutin, clofazimine, ciprofloxacin, or parenteral amikacin) may be added. Therapy should continue for life.

AIDS-Related Opportunistic Infections↗
PubMed1990

Quadruple-drug therapy for Mycobacterium avium-intracellulare bacteremia in AIDS patients.

The mycobacterial response was evaluated for patients with Mycobacterium avium-intracellulare complex (MAC) bacteremia treated with a quadruple regimen of rifabutin, clofazimine, isoniazid, and ethambutol. Mycobacteremia was cleared in 22 of 25 patients who received this regimen, and 18 patients experienced complete resolution of symptoms associated with MAC infection. All of the patients were immunodeficient, with a mean CD4 cell count at the time of diagnosis of MAC infection of 54.7 +/- 54.6 cells/microliters. All MAC isolates were resistant to clofazimine, isoniazid, and ethambutol. Sixteen of 24 isolates were resistant to rifabutin. Improved results of treatment may be related to the use of a higher dose of rifabutin (300-600 mg/day) compared with other studies (150-300 mg/day), earlier diagnosis and institution of treatment, and synergy between rifabutin and ethambutol. The quadruple regimen used in this study appears effective in clearing mycobacteremia and in ameliorating symptoms of infection.

Acquired Immunodeficiency Syndrome↗
PubMed1992

TLC G-65 in combination with other agents in the therapy of Mycobacterium avium infection in beige mice.

The activity of TLC G-65 (a liposomal gentamicin preparation), alone and in combination with rifapentine, clarithromycin, clofazimine and ethambutol, was evaluated in the beige mouse (C57BL/6J--bgj/bgj) model of disseminated Mycobacterium avium infection. TLC G-65 was found to be more active than amikacin. The combination of rifapentine and TLC G-65 was more active than either agent alone. The activity of clarithromycin in combination with TLC G-65 was similar to that of either agent alone. Clofazimine improved the activity of TLC G-65 with respect to the spleen, while ethambutol improved the activity with respect to the liver. Clofazimine and ethambutol enhanced the activity of TLC G-65 against bacteria in the lungs. TLC G-65 in combination with rifapentine appears to be an attractive regimen for the treatment of infections caused by bacteria in the M. avium complex.

Amikacin↗
PubMed2003

In vitro activity of C-8-methoxy fluoroquinolones against mycobacteria when combined with anti-tuberculosis agents.

OBJECTIVES: To examine the effect of first-line and second-line anti-tuberculosis agents on the ability of fluoroquinolones to kill mycobacteria. METHODS: A clinical isolate of Mycobacterium tuberculosis and a laboratory strain of Mycobacterium smegmatis were grown in liquid medium and treated with a fluoroquinolone in the presence or absence of anti-tuberculosis agents. Bacterial survival was determined by viable colony counts on agar medium. RESULTS: When moxifloxacin activity was examined in two-drug combinations containing traditional anti-tuberculosis agents, activity was greater than either compound alone with isoniazid, capreomycin and low, but not high, concentrations of rifampicin. Cycloserine contributed no additional activity, and ethambutol interfered with the lethal action of moxifloxacin and gatifloxacin. Experiments with M. smegmatis confirmed that both rifampicin and ethambutol reduce fluoroquinolone lethality. Moreover, ethambutol increased the recovery of fluoroquinolone-resistant mutants newly created by ethyl methanesulphonate treatment. CONCLUSIONS: The intrinsic bactericidal activity of C-8-methoxy fluoroquinolones can be adversely affected by some agents currently used for treatment of tuberculosis.

Anti-Bacterial Agents↗
PubMed1990

In vitro susceptibility of Mycobacterium avium complex to the new fluoroquinolone sparfloxacin (CI-978; AT-4140) and comparison with ciprofloxacin.

We tested the activity of the new fluoroquinolone sparfloxacin (CI-978; AT 4140) against 30 strains of Mycobacterium avium complex (MAC) isolated from patients with acquired immune deficiency syndrome. MICs of sparfloxacin (range, less than or equal to 0.06 to 4 micrograms/ml) were lower than MICs of ciprofloxacin for all 30 strains, and MBCs for acid-fast bacteria were lower for 28 of the 30 strains. In synergism experiments using 10 strains of MAC, fractional inhibitory concentration indices revealed that the combination of sparfloxacin plus ethambutol was synergistic against 9 strains, and the three-drug combination of sparfloxacin plus ethambutol plus rifampin was synergistic against all strains. In the absence of ethambutol, the combination of sparfloxacin plus rifampin appeared to be antagonistic against three of the MAC strains.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Combined versus single antituberculosis drugs on the in vitro sensitivity patterns of non-tuberculous mycobacteria.

Drug sensitivity tests were performed for ethambutol, rifampicin, streptomycin, and isoniazid both alone and in paired combinations, on 16 strains of Mycobacterium avium intracellulare, seven strains of Mycobacterium xenopi, and eight strains of Mycobacterium malmoense. Most strains were resistant to the individual drugs, but all strains of M malmoense, 86% of M xenopi, and 31% of M avium intracellulare were completely suppressed by the lowest concentrations of ethambutol and rifampicin when the two drugs were combined in vitro. Streptomycin combined with ethambutol or with rifampicin in the lowest combined concentrations suppressed 50% and 62% respectively of strains of M malmoense. All strains of M xenopi were suppressed by the lowest combined concentrations of streptomycin with rifampicin. Combinations with isoniazid were less effective. It is postulated that similar effects in vivo might account for the satisfactory clinical response seen in patients with disease caused by these mycobacteria who have received treatment with combinations of standard antituberculosis drugs despite in vitro resistance to the individual agents.

Antitubercular Agents↗
PubMed1987

Proficiency testing of conventional drug susceptibility tests of Mycobacterium tuberculosis.

Proficiency testing of indirect drug susceptibility tests of Mycobacterium tuberculosis was begun in 1985 by the Laboratory Centre for Disease Control (LCDC) with the participation of Provincial Public Health Laboratories in Canada. Comparable sets of 60 cultures of Mycobacterium tuberculosis representing 30 strains were distributed by LCDC to the participating laboratories to be tested for drug susceptibility against isoniazid, streptomycin, rifampin, and ethambutol using conventional methodologies. Intralaboratory agreement values determined by comparing results obtained on sets of duplicate cultures were high and were found to vary little from drug to drug and from laboratory to laboratory. Interlaboratory agreement was determined by comparing results reported by participating laboratories to those obtained by the Reference Laboratory. Agreement percentages were found to be lower for drug-resistant cultures than for drug-susceptible cultures. The reliability of drug susceptibility testing results was higher for isoniazid and rifampin, than for ethambutol and streptomycin. This study shows that the higher subsidiary drug concentrations do not compare well with main drug concentrations, especially in the case of streptomycin and ethambutol. The significance of the higher subsidiary concentrations in in vitro susceptibility testing is therefore in need of clarification. The proficiency testing results obtained in this study compare favorably with those reported in other developed countries despite the fact that a variety of testing procedures are used throughout the country.

Anti-Bacterial Agents↗
PubMed1982

Drug-resistant Mycobacterium tuberculosis in Korean isolates.

Tuberculosis is a common disease in developing countries. An increasing incidence of resistance to isoniazid (INH) and streptomycin in organisms isolated from patients who contracted their disease in these countries, particularly in the Far East, is well recognized. This drug resistance has led to the recommendation of empirically beginning a regimen in patients with tuberculosis from the Far East of INH, ethambutol, and rifampin. This report documents the increasing incidence of resistance in isolates from Korea to ethambutol and rifampin in addition to INH and streptomycin. It suggests that the empiric use of INH, ethambutol, and rifampin in this group of patients could potentially lead to resistance to all of these drugs because of a significant amount of multidrug resistance. A regimen of INH, rifampin, pyrazinamide, and capreomycin is suggested as appropriate initial therapy in these patients based on the in vitro sensitivity data presented and initial clinical experience.

Adult↗