[Duration of the treatment of tuberculosis in 1981].
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Biomedical subjects
Publications and source records attributed to J Grosset.
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To determine whether or not low dosage prothionamide (PTH), with or without diamino diphenyl sulphone (DDS), can replace PAS or thiacetazone as the companion drug to isoniazid (INH) in the treatment of tuberculosis, two experiments have been performed in mice. In experiment I the 2-month effectiveness of 25mg/kg INH alone, INH+PTH (25mg/kg) or INH+PTH+DDS (10mg/kg) was investigated. Both PTH-containing regimens were equally effective in preventing the selection of INH-resistant mutants but PTH did not appear to add much to the bactericidal activity of INH. In experiment II the one year effectiveness of similar regimens supplemented by an initial month of streptomycin (SM) was investigated. Again PTH appeared very effective whereas DDS seemed ineffective. Therefore it seems that PTH is likely to be a good companion drug for INH when used in man at the dosage of 5mg/kg which is more or less equivalent to 25mg/kg in the mouse.
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In a first experiment mice infected intravenously with 10(6) Mycobacterium tuberculosis were randomly treated either with isoniazid (INH) + rifampicin (RMP) 25 mg/kg or with INH + RMP + pyrazinamide (PZA) or with INH + RMP + PZA + streptomycin (SM). The decrease of the viable counts (CFU) in the lungs was similar with all three regimens. In a second experiment, mice were treated for six months either with INH + RMP 25 mg/kg or INH + RMP 10 mg/kg. After a follow-up of six months, mice were killed and their lungs and spleen cultivated. Positive cultures were obtained in 7.5 p. cent of the mice treated with the high dose of RMP and 36.5 p. cent in the mice treated with the low dose (p less than 0.05). A third experiment demonstrated that, during the first two months of treatment, adding PZA to INH + RMP 10 mg/kg increased significantly the overall effectiveness of INH + RMP 10 mg/kg combination. A fourth experiment demonstrated that after three initial months of INH + RMP 10 mg/kg, RMP alone was as effective as RMP + INH or RMP + INH + PZA. It may be concluded that RMP and PZA are both active on the intracellular population of Mycobacterium tuberculosis and that RMP is the only drug to act on persisting Mycobacterium tuberculosis in extracellular lesions.
Among 244 strains of S. pneumoniae, 24% are resistant to tetracycline, 10% to sulfamethoxazole-trimethoprim (SMZ-TMP) and 1.6% to erythromycin. A low grade resistance to penicillin G is observed in two strains (MIC 0,12 and 0,3 mg/l). Clinical correlations indicate that only 48% of the S. pneumoniae isolated are undoubtedlzy responsible for bacterial infection. The serotypes isolated from blood cultures and from other specimens are not statistically different. Only 67% of the strains belonged to serotypes included in the 14-valent vaccine.
Pharmacokinetics is the study of the absorption, distribution and elimination of a drug in the body. Applied to antibiotic therapy it gives information on the concentrations of antibiotic that reach the bacteria at a given time at their site of multiplication for a given dose and route of administration. The future of an antibiotic within a body is largely related to passive transfer. This can be compared to the dialysis of molecules across a semi-permeable membrane, the passage from one side to the other being a function of the concentration of molecules in the "upstream" side, the size of the molecules and their own particular transfer speed. The final result is affected by 1) the partition coefficient itself related to the degree of aqueous and lipid solubility of the molecules, 2) the degree of ionisation of the molecules, non-ionised molecules being the only ones to be transferred, 3) protein binding as only the unbound fraction is biologically active and capable of diffusing across the membranes, 4) by the interplay of the combined phenomena of resorption, distribution and elimination. Penicillins and macrolides are the antibiotics of choice in broncho-pulmonary infections. The tetracyclines and the sulfamethoxazole-trimethoprim combination come second. The combination of a beta-lactam, an aminoglycoside and/or metronidazole are reserved for the most severe infections. The lung is a particularly well vascularised organ, the pulmonary concentrations of the antibiotic may equal the serum levels. But the concentration in the bronchial secretions only reaches 55% of the serum levels for clindamycin, 25 to 30% for aminoglycosides, minocycline and bacampicillin, 20% for cephalosporins and doxycycline and less than 10% for ampicillin and erythromycin. Only oleandomycine, spiramycin and trimethoprim are present in concentrations equal to those in the serum.
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Three methods of taking samples of bronchopulmonary secretions; transtracheal aspiration (TT), sputum collection, and fibro-aspiration, were compared in 43 patients with severe pneumopathies. There was no significant difference in the number of times a pure or dominant germ was isolated by using the three procedures in these 43 cases. In contrast, however, there was a significantly lower number of polymorphous flora and more sterile samples observed when using TT than with the other two methods. When antibiotics are given 1 to 7 days before taking the samples, there is a significant reduction in the number of cultures having a germ in the pure state.
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