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Biomedical subjects

P T Davidson

Publications and source records attributed to P T Davidson.

13 recordsLinked to original sources

Drug treatment of tuberculosis--1992.

The impact of the acquired immunodeficiency syndrome (AIDS) pandemic has made tuberculosis an increasing worldwide problem, and the effectiveness of modern chemotherapy has been blunted by the high incidence of primary drug resistance, especially in developing countries. The prospect of finding new and highly effective drugs similar to isoniazid or rifampicin is dim, yet the maximum benefits from the existing drugs which are highly effective have not been received. A 6-month regimen of isoniazid plus rifampicin, supplemented by pyrazinamide during the first 2 months, for treatment of uncomplicated tuberculosis is highly effective and the regimen of choice. Ethambutol should be added if the risk of isoniazid resistance is increased. A regimen of isoniazid, rifampicin, pyrazinamide and streptomycin for 4 months provides effective defence against smear-negative pulmonary tuberculosis. Re-treatment of multiple drug-resistant tuberculosis remains a difficult therapeutic problem. At least 3 drugs that the patient has never previously received, and that are effective according to laboratory susceptibility testing, must be used. Preventive therapy against tuberculosis is accomplished with isoniazid for 6 to 12 months, although rifampicin plus isoniazid for 3 months has been used in the United Kingdom with success. In a mouse model, rifampicin plus pyrazinamide for 2 months is more effective than isoniazid for 6 months as preventive treatment. Patient noncompliance with medication remains the biggest problem in tuberculosis control, and is a complex issue. It can only be resolved by multiple approaches. Intermittent directly observed short course chemotherapy is a major, but not the only, possible solution.

Animals

Antimycobacterial activity of some potential chemotherapeutic compounds.

Fourteen compounds were tested in vitro for activity against Mycobacterium intracellulare and other pathogenic mycobacteria. Only clofazimine and chaulmoogric acid showed significant activity against M. intracellulare. In view of known minimal side effects of clofazimine further studies are warranted for this drug in chemotherapy of M. intracellulare infections.

Clofazimine

Inhibition of Mycobacterium intracellulare by some vitamin K and coenzyme Q analogues.

Because vitamin K is present in several species of mycobacteria, and because coenzyme Q has been found to stimulate the growth of Mycobacterium tuberculosis and atypical mycobacteria, 8 quinones that can be considered to be dual analogues of vitamin K and coenzyme Q were tested for their activity against Mycobacterium intracellulare. One compound, 6-cyclo-octylamino-5,8-quinolinequinone (CQQ) exhibited considerable activity in vitro against several strains of Mycobacterium intracellulare at a concentration of 8 micrograms per ml. It has also shown evidence of bactericidal activity against growing cultures of Mycobacterium intracellulare. Time exposure studies indicated that a minimal contact period of 24 hours with a concentration of 8 micrograms of CQQ per ml is necessary for permanent inhibitory action against Mycobacterium intracellulare. At a concentration of 1 microgram per ml, CQQ inhibited Mycobacterium tuberculosis, including the rifampin-resistant strains. The drug has no activity against rapidly growing mycobacteria or organisms that are not acid-fast.

Drug Evaluation, Preclinical

Cross-resistance in M. tuberculosis to kanamycin, capreomycin and viomycin.

Drug resistant mutants to streptomycin, kanamycin, viomycin, capreomycin, and rifampicin were isolated from four strains of Mycobacterium tuberculosis. The mutants isolated from each parent were then tested for evidence of development of cross-resistance to other drugs. There was no cross-resistance between either streptomycin or rifampicin and any of the other drugs. Complete cross-resistance between viomycin and capreomycin was found. Cross-resistance between kanamycin and capreomycin, and kanamycin and viomycin was variable. A review of the medical histories of 27 patients with kanamycin-resistant tubercle bacilli indicated that cross-resistance with capreomycin and viomycin occurs, but is unpredictable. Because of this variability in cross-resistance and the fact that kanamycin is a more toxic drug than capreomycin, it is suggested that capreomycin be used in the first retreatment regimen for tuberculosis when streptomycin resistance has been demonstrated.

Capreomycin

The pathogenicity of Mycobacterium fortuitum and Mycobacterium chelonei in man: a report of seven cases.

The clinical records of 7 patients referred to the National Jewish Hospital and Research Center over a 6-year period for evaluation of an abnormal chest x-ray and repeated sputum isolates of rapidly growing mycobacteria (Runyon's Group IV) were reviewed to determine the potential pathogenicity of these organisms. Mycobacterium fortuitum was isolated from 5 patients and Mycobacterium chelonei from 2. Haemoptysis, cough and weight loss were prominent in 6. Three had rheumatoid arthritis. Although two demonstrated cutaneous anergy, lymphocyte responsiveness to PHA was normal. PPD-F was not useful in skin testing or in the in vitro evaluation of lymphocyte function. Histologic examination of the lungs of 2 patients demonstrated caseating granulomata. One patient died of massive pulmonary haemorrhage soon after intiation of therapy. Multi-drug treatment regimens generally resulted in progressive sterilization of the sutum and improvement in the appearance of the chest x-ray. We conclude that some rapidly growing mycobacteria can cause potentially fatal cavitary lung disease and that intensive anti-tuberculosis therapy may successfully alter its course.

Adult

Acquired resistance to rifampicin by Mycobacterium kansasii.

Two patients with Mycobacterium kansasii infection of the lung had organisms sensitive to rifampicin. Following treatment, essentially with rifampicin alone, the patients began to excrete organisms completely resistant to rifampicin. The ability of M. kansasii to acquire resistance to rifampicin during treatment has been clearly demonstrated. This reinforces the need to treat this infection with an adequate multiple drug regimen.

Drug Resistance, Microbial

Mycobacterium szulgai; a new pathogen causing infection of the lung.

A case of infection with a newly described scotochromogenic mycobacterial species, Mycobacterium szulgai, is presented, and all the reported cases are summarized. The disease is characterized by its predominance in middle-aged men, the occurrence of cavitary pulmonary lesions, and a good response to triple-drug therapy. Sputum samples are usually positive on smear. Drug susceptibility studies show a greater degree of susceptibility to several antituberculosis drugs than the usual scotochromogen. Mycobacterium szulgai has frequently been confused with other atypical mycobacteria, but serologic and other laboratory characteristics are distinct and should allow proper identification.

Adult