Combined chemotherapy including rifabutin for rifampicin and isoniazid resistant pulmonary tuberculosis. G.E.T.I.M. (Group for the Study and Treatment of Resistant Mycobacterial Infection).

A prospective multicentre open study has been conducted in France in order to assess the efficacy and tolerability of an antimycobacterial regimen including rifabutin in the treatment of patients with pulmonary tuberculosis due to rifampicin and isoniazid resistant bacilli. Patients were treated with daily rifabutin (450-600 mg), associated with companion drugs to which the organisms remained susceptible; in most cases the regimen included a fluoroquinolone. The duration of treatment was initially scheduled for a minimum period of 12 months after sputum culture conversion.

Antagonism between isoniazid and the combination pyrazinamide-rifampin against tuberculosis infection in mice.

Mice that had been inoculated intravenously with 6.30 log10 Mycobacterium tuberculosis H37Rv 14 days earlier were administered one of three combinations of drugs, i.e.

Activity of clarithromycin against Mycobacterium avium infection in patients with the acquired immune deficiency syndrome. A controlled clinical trial.

Disseminated Mycobacterium avium infection is common in patients with acquired immune deficiency syndrome (AIDS), but no drug studies have been reported establishing antimicrobial activity against this organism in a controlled, randomized trial. Clarithromycin, a new macrolide, has activity against M. avium in vitro and in animals, but it has not been studied in humans.

In vitro and in vivo activities of sparfloxacin (AT-4140) against Mycobacterium tuberculosis.

The in vitro and in vivo activities of sparfloxacin (AT-4140) against M. tuberculosis are reported. The MICs of sparfloxacin for 50% and 90% of 18 clinical isolates were, respectively, 0.

Rifabutin in combination with clofazimine, isoniazid and ethambutol in the treatment of AIDS patients with infections due to opportunist mycobacteria. Groupe d'Etude et de Traitement des Infections à Mycobacteries Résistantes.

96 AIDS patients with fever and either acid-fast bacilli on microscopic examination of bacteriological samples or mycobacteria isolated by culture were treated with a daily 4-drug combination of 7-10 mg/kg rifabutin, 5 mg/kg isoniazid, 20 mg/kg ethambutol and 100 mg clofazimine. 46 patients were excluded from efficacy assessment: 13 died before or within the first days of treatment, 5 had negative initial cultures, 14 had initial cultures positive for M. tuberculosis, 4 for M.

Effect of pH on the in vitro potency of clarithromycin against Mycobacterium avium complex.

Employing 7H11 agar medium at pH 6.6, the MICs of clarithromycin for 50% (MIC50) and 90% (MIC90) of 19 strains of Mycobacterium avium complex were 8 and 16 micrograms/ml, respectively. However, the MICs were 2 to 3 log2 dilutions lower in the 7H11 medium adjusted to pH 7.

Activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine compared with that of clarithromycin against multiplication of Mycobacterium avium complex within human macrophages.

The activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine against two virulent strains of the Mycobacterium avium complex isolated from patients with AIDS were evaluated in a model of intracellular infection and were compared with that of clarithromycin. Human monocyte-derived macrophages were infected with the M. avium complex at day 6 of culture.

A case of relapse with drug-susceptible M. leprae after multidrug therapy.

A male born in 1930 was diagnosed as smear-positive borderline leprosy in 1971, and was treated with dapsone and/or sulfamethoxypyridazine from 1972 to 1980 with clinical improvement. However, new skin lesions with smears strongly positive appeared in August 1980, and he was diagnosed as having downgraded to lepromatous (LL) leprosy, but the bacilli recovered from the skin biopsy were fully susceptible to both dapsone and rifampin by mouse foot pad technique. Between 1981 and 1983, the patient was treated with 24 months of rifampin 600 mg and dapsone 100 mg daily, supplemented with prothionamide 500 mg daily during the initial 3 months, and his skin lesions gradually improved during treatment with the combined regimen.

Activities of pefloxacin and ofloxacin against mycobacteria: in vitro and mouse experiments.

The minimal inhibitory concentrations for 90% of strains (MIC90) of ofloxacin against Mycobacterium tuberculosis and Mycobacterium xenopi was 2 mg/l. This was three dilutions lower than that of pefloxacin and was well within the range of drug concentrations achievable in man. The antituberculosis activities of both quinolones were independent of resistance of the strains to other antimycobacterial agents.

Effectiveness of clarithromycin and minocycline alone and in combination against experimental Mycobacterium leprae infection in mice.

As determined by the proportional bactericide method, clarithromycin had strong bactericidal activity against Mycobacterium leprae. Clarithromycin was administered to mice by gavage as 20 daily doses at dosages of 12.5 to 50 mg/kg of body weight.

Ofloxacin for the treatment of leprosy.

Among the major commercially available fluoroquinolones, ciprofloxacin was inactive against M. leprae in mice; pefloxacin was active, 50 mg/kg daily showed bacteriostatic activity but 150 mg/kg daily displayed bactericidal activity; ofloxacin was more active than pefloxacin, 50 mg/kg daily exerted the same level of bactericidal effect as pefloxacin 150 mg/kg daily, and ofloxacin 150 mg/kg displayed profound killing activity. Two clinical trials with 6 months of pefloxacin and/or ofloxacin in 31 previously untreated lepromatous patients have been completed.

Relationships between PGL-1 antigen in serum, tissue and viability of Mycobacterium leprae as determined by mouse footpad assay in multibacillary patients during short-term clinical trial.

In connection with a 56-day controlled clinical trial for comparing the therapeutic effects between pefloxacin and ofloxacin in 21 lepromatous patients, we have studied the relationships between PGL-1 antigen level in serum and in skin and serum PGL-1 antibody titre on the one hand, and the viability of Mycobacterium leprae, as measured by serial mouse footpad inoculations, and other bactericidal parameters on the other. Before and during treatment, significant correlation was found between serum PGL-1 level and the morphological index (MI), and with the number of viable organisms per mg skin tissue. However, neither serum PGL-1 antibody titre nor skin PGL-1 antigen level showed significant change during the 56-day trial.

[Norfloxacin: a broad-spectrum quinolone for superficial eye infections].

Norfloxacin is a synthetic antibiotic belonging to the fluoroquinolone class. At present, an oral formulation is available and indicated for the treatment of urinary tract infections. Because of the properties of norfloxacin, a 0.

Assessment of anti-phenolic glycolipid-I IgM levels using an ELISA for detection of M. leprae infection in populations of the South Pacific Islands.

Anti-phenolic glycolipid-I (PGL-I) IgM levels were determined in 96% of the general population of the Southern Marquesas and Maupiti, remote islands of French Polynesia, where the average annual detection rates of leprosy during the past 30 years have been 57.1 and 4.4 per 100,000, respectively.

mRNAs newly synthesized by tobacco mesophyll protoplasts are wound-inducible.

We have used 2-dimensional (2D) non-equilibrium pH gradient gel electrophoresis (NEPHGE) of in vitro synthesized proteins and northern hybridization with labelled cDNAs coding for three pathogenesis related (P.R.) proteins, to analyze the shift in mRNA content induced by the isolation and culture of tobacco mesophyll protoplasts.

Activities of clarithromycin, sulfisoxazole, and rifabutin against Mycobacterium avium complex multiplication within human macrophages.

The activities of clarithromycin, sulfisoxazole, and rifabutin against three virulent strains of Mycobacterium avium complex isolated from patients with acquired immunodeficiency syndrome were evaluated in a model of intracellular infection. Human monocyte-derived macrophages were infected at day 6 of culture with M. avium complex.

Clinical trial of pefloxacin and ofloxacin in the treatment of lepromatous leprosy.

Twenty-one previously untreated lepromatous patients were randomized into two groups and treated with either 800 mg pefloxacin (PEFLO) or 400 mg ofloxacin (OFLO) once daily. The trial consisted of two parts: monotherapy from day 0 to day 56; and combined with the World Health Organization multidrug therapy (WHO/MDT) regimen for multibacillary (MB) leprosy from day 57 to day 180. Four patients were removed from the trial because the organisms recovered from their pretreatment biopsies failed to infect mice.

[Bacteriologic basis for the treatment of tuberculosis].

To be fully effective, short-course chemotherapy for tuberculosis should take into account the slow growth rate, high oxygen requirement and high drug-resistant mutant emergence rate of Mycobacterium tuberculosis, as well as the type of the lesions observed and the specific activity of each antituberculous drug. Due to their unique sterilizing activities against bacilli that are not actively metabolizing, rifampicin and pyrazinamide are the key drugs for short-course chemotherapy. To prevent the selection of drug-resistant mutants and the occurrence of therapeutic failures, a combination of isoniazid, rifampicin, pyrazinamide and ethambutol should be given during the first two months of treatment.

Effectiveness of pefloxacin in the treatment of lepromatous leprosy.

As a first clinical trial of a fluoroquinolone derivative in leprosy, ten previously untreated lepromatous leprosy patients, about two fifths of them with primary dapsone resistance but all susceptible to rifampin, were treated with pefloxacin 400 mg twice daily for 6 months. Definite clinical improvement was observed in all ten patients as early as 2 months after beginning treatment, and the morphological index was also drastically decreased to the baseline during the same period. The rapid bactericidal effects, as measured by serial mouse foot-pad inoculations, were demonstrated to the extent that about 99% of the bacilli were killed during the first 2 months of treatment.

Tobacco Mesophyll Protoplasts Synthesize 1,3-beta-Glucanase, Chitinases, and "Osmotins" during in Vitro Culture.

Tobacco (Nicotiana tabacum) mesophyll protoplasts synthesize six basic proteins (a, a', a(1), b, b', and c) which are undetectable in the leaf and whose synthesis is reduced by auxin (Y Meyer, L Aspart, Y Chartier [1984] Plant Physiol 75: 1027-1033). Polypeptides a, a', and a(1) were shown to have similar mobilities on two-dimensional electrophoresis as one 1,3-beta-glucanase and two chitinases from tobacco mosaic virus-infected leaves. In immunoblotting experiments, polypeptide a was recognized by specific antibodies raised against the 1,3-beta-glucanase and a' and a(1) reacted with anti-chitinase antibodies.