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PubMed1976

[Treatment of new and chronic tuberculous patients with ethambutol and Rifampicin (author's transl)].

In patients with chronic pulmonary tuberculosis the results of chemotherapy between drug regimens containing ethambutol or rifampicin were compared. Patients in both groups were randomized selected. After 4 months of chemotherapy negativization was reached to 100% in the RMP-group compared to 80% of the patients in the EMB-group. In 98 chronics EMB was added to the chemotherapy regimen and resulted in 90% of negativization. In a small subgroup RMP was added to the regimen and 100% negativization could be obtained. Among 220 patients with chronic pulmonary tuberculosis, treated with RMP in 9 hospitals according to our protocoll, in 205 patients (93.2%) the excretion of bacilli was cessated. In 54 new cases treated with EMB and another combination and in 20 new cases treated additionally with RMP the sputum converted to negative in 100% of the patients. But the the negativization was reached 24 days earlier on the average in the group treated with RMP. Antituberculotic drugs are administered in our clinic according to the body weight.

Chronic Disease↗
PubMed1996

In vitro activities of rifabutin, azithromycin, ciprofloxacin, clarithromycin, clofazimine, ethambutol, and amikacin in combinations of two, three, and four drugs against Mycobacterium avium.

Multidrug therapy is recommended for treatment of Mycobacterium avium complex (MAC) bacteremia in patients with AIDS. Azithromycin, clarithromycin, rifabutin, ciprofloxacin, ethambutol, clofazimine, and amikacin have all been suggested for use in treating MAC bacteremia, but the most active combinations of these drugs have not been identified, nor has the minimum number of drugs needed for effective therapy been determined. To address the former, the in vitro bactericidal activities of all two-, three-, and four-drug combinations of these seven agents was determined by using 10 blood-derived strains of MAC isolated from patients with AIDS. The activities of the 132 drug combinations were compared by statistical analysis of survival means (analysis of variance) and further evaluated by determining the percentage of strains considered susceptible to each combination. When susceptibility was defined as a decrease in CFU of > or = 2 log10, no two- or three-drug combination and only two four-drug combinations were active against all 10 MAC strains. When a less stringent definition was applied (> or = 1 log10 decrease in CFU), 1 two-drug combinations, 9 three-drug combinations, and 31 four-drug combinations showed activity against all 10 strains. Eighteen selected drug combinations were also tested for intracellular activity in MAC-infected J774 cells. Combinations which contained amikacin as a component were considerably less active against intracellular MAC organisms than against organisms in broth. The opposite result was obtained for the combination of clarithromycin plus clofazimine.

AIDS-Related Opportunistic Infections↗
PubMed1970

Growth Inhibition of Mycobacterium tuberculosis After Single-Pulsed Exposures to Streptomycin, Ethambutol, and Rifampin.

It was reported earlier that the degree of growth inhibition of tubercle bacilli after single-pulsed isoniazid exposures is a function of the time-concentration product (TCP) of exposure rather than of either time or concentration alone (TCP = hr exposure x mug of drug/ml). In the present investigation, these time and concentration studies have been extended to streptomycin (SM), ethambutol (EMB), and rifampin (RMP). Mycobacterium tuberculosis H37Ra was grown in Sautons liquid medium at 37 C with aeration. Rapidly growing cells were harvested and resuspended at 0.5 to 0.6 mg (dry wt)/ml in fresh medium; incubation was continued in the presence of various concentrations of the appropriate drug. At time intervals, samples were diluted 1:200 into drug-free medium for turbidimetric growth assay. Minimal inhibitory concentrations of EMB, SM, and RMP were approximately 0.2, 0.02, and 0.002 mug/ml, respectively. When cells were pulsed with 0.0125 to 0.0625 mug of RMP per ml at time intervals of up to 9.5 hr, the degree of subsequent growth inhibition appeared to be a function of TCP. A similar relationship was observed when SM was tested over a range of 0.125 to 1.0 mug/ml and various time intervals of up to 8 hr. In contrast, inhibition of tubercle bacilli after EMB exposures was dependent primarily on exposure time and was affected only slightly by concentration. At any particular exposure time between 3 and 16 hr, 1.25 to 7.5 mug of EMB per ml produced similar levels of inhibition, but marked inhibition did not occur unless the exposure time exceeded 10 hr. Relationships of these latter findings to the mode of action of EMB and the potential clinical significance of the RMP, SM, and EMB data are discussed.

Journal Article↗
PubMed2004

Evaluation of the fully automated BACTEC MGIT 960 system for testing susceptibility of Mycobacterium tuberculosis to pyrazinamide, streptomycin, isoniazid, rifampin, and ethambutol and comparison with the radiometric BACTEC 460TB method.

The performance of the fully automated BACTEC MGIT 960 (M960) system for the testing of Mycobacterium tuberculosis susceptibility to streptomycin (SM), isoniazid (INH), rifampin (RMP), ethambutol (EMB), and pyrazinamide (PZA) was evaluated with 100 clinical isolates and compared to that of the radiometric BACTEC 460TB (B460) system. The agar proportion method and the B460 system were used as reference methods to resolve the discordant results for SM, INH, RMP, and EMB (a combination known as SIRE) and PZA, respectively. The overall agreements were 96.3% for SIRE and 92% for PZA. For SIRE, a total of 26 discrepancies were found and were resolved in favor of the M960 system in 8 cases and in favor of the B460 system in 18 cases. The M960 system produced 8 very major errors (VME) and 10 major errors (ME), while the B460 system showed 4 VME and 4 ME. No statistically significant differences were found. Both systems exhibited excellent performance, but a higher number of VME was observed with the M960 system at the critical concentrations of EMB and SM. For PZA, a total of eight discrepancies were observed and were resolved in favor of the M960 system in one case and in favor of the B460 system in seven cases; no statistically significant differences were found. The M960 system showed four VME and three ME. The mean times to report overall PZA results and resistant results were 8.2 and 9.8 days, respectively, for the M960 system and 7.4 and 8.1 days, respectively, for the B460 system. Statistically significant differences were found. The mean times to report SIRE results were 8.3 days for the M960 system and 8.2 days for the B460 system. No statistically significant differences were found. Twelve strains tested for SIRE susceptibility and seven strains tested for PZA susceptibility had been reprocessed because of contamination. In conclusion, the M960 system can represent a valid alternative to the B460 for M. tuberculosis susceptibility testing; however, the frequent contamination of the tests needs to be improved.

Antitubercular Agents↗
PubMed1994

Early bactericidal action of pulsed exposure to rifampicin, ethambutol, isoniazid & pyrazinamide in pulmonary tuberculosis patients.

The bactericidal action of two therapeutic regimens on Mycobacterium tuberculosis was assessed by viable counts in serial sputum samples in 49 pulmonary tuberculosis patients being treated with rifampicin (R), ethambutol (Emb), isoniazid (I) and pyrazinamide (Z) together in a single dose thrice weekly (REmbIZ3) or with REmb and IZ on alternate days (REmb3IZ3alt). In both groups of patients, there was a significant reduction (P < or = 0.02) in the colony forming units (cfu) of M. tuberculosis per ml of sputum during the first two days of treatment itself. This early bactericidal action (EBA) as well as the reduction in counts during the subsequent days of treatment were similar (P > 0.2) for both REmbIZ3 and REmb3IZ3alt regimens indicating that splitting up REmbIZ into REmb on one day and IZ on the next day in short course chemotherapy (SCC) regimens may not affect the bactericidal action of the regimens.

Antitubercular Agents↗
PubMed1975

Mutational studies of the drug-resistance of M. tuberculosis with special reference to p-aminosalicylic acid, ethambutol, isoniazid and rifampicin.

In the M. tuberculosis H37Rv and in the human tubercular strains isolated from patients, the localization of genetic determinants of drug-resistance to antitubercular chemotherapeutic drugs in current use was studied. Data obtained through the treatment of the resistanct strains with acridine dyes and ethidium bromide, and the analysis of irreversible elimination of resistance markers support the hypothesis of an extrachromosomal locus for the p-aminosalicylic acid (PAS)-resistance and confirm a chromosomal mutation for the isoniazid (INH), ethambutol (EM), rifampicin (R/AMP)-resistances, in all the levels reached in training or selected in wild strains. In the PAS-revertants recovered after treatment with mutagenic agents, a loss by degrees of resistance levels was observed. In a mycobacterial strain biresistant to PAS and streptomycin (Sm) the Authors were able to find a loss of the mono-resistance to Sm only. The significance of these results is discussed in terms of plasmid (s) having separate mutational loci for PAS- and for the aminoglycoside-resistance. These results agree with the previous studies in the field of resistance of Mycobacteria to specific drugs.

Aminosalicylic Acids↗