Is PCR a useful tool for the diagnosis of tuberculosis in 1995?
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DNA, Bacterial↗
Biomedical subjects
J Grosset
Publications and source records attributed to J Grosset.
Tuberculosis caused by Mycobacterium africanum associated with involvement of the upper and lower respiratory tract, skin, and mucosa.
Cutaneous tuberculosis is rarely seen in industrialized countries and is usually caused by Mycobacterium tuberculosis. We report a case of cutaneous tuberculosis with bilateral nodular scleritis, nasal sinus invasion, and nasal septum perforation (confirmed by computed tomography scans of the sinuses), associated with pulmonary infiltrates and mediastinal adenopathy, in an African woman. Mycobacterium africanum was recovered from the sputum after 8 weeks of culture in Löwenstein-Jensen medium. To our knowledge, this is the first description of M. africanum associated with cutaneous tuberculosis and nasal sinus invasion.
Adult↗
Acquired resistance in Mycobacterium avium complex strains isolated from AIDS patients and beige mice during treatment with clarithromycin.
Clarithromycin has been reported to select clarithromycin resistant mutants of Mycobacterium avium complex (MAC) during treatment with clarithromycin in AIDS patients and beige mice. We selected resistant mutants in vitro at a frequency of 5 x 10(-9). Clarithromycin resistant strains of MAC isolated in AIDS patients and beige mice as well as derivatives selected in vitro had a unique pattern of acquired cross-resistance to macrolides and related antibiotics. In contrast, the pattern of resistance to non-macrolide antibiotics remained unchanged in clarithromycin resistant strains. A dramatic decrease in ribosome affinity for clarithromycin and erythromycin was found in clarithromycin resistant strains, but no mutation was found in the peptidyl domain of the 23S rRNA, indicating that another ribosomal modification is involved.
Acquired Immunodeficiency Syndrome↗
Selection of clarithromycin-resistant Mycobacterium avium complex during combined therapy using the beige mouse model.
Sixteen weeks of treatment with clarithromycin (CLARI) alone displayed significant bactericidal activity against Mycobacterium avium complex infection in beige mice. Only two combined regimens, CLARI combined with an initial 4 or 8 weeks of amikacin (AMIKA), displayed activity greater than that displayed by CLARI alone. Four other combined regimens, CLARI combined with ethambutol (EMB), rifabutin (RBT), or both EMB and RBT during the entire 16 weeks of treatment or with AMIKA administered in an initial 2-week course showed bactericidal activity not significantly greater than that of CLARI alone. After 16 weeks of treatment, CLARI-resistant mutants were isolated from the majority of mice that had been treated with CLARI alone, CLARI-RBT, CLARI-EMB, or CLARI-EMB-RBT, as was the case for untreated controls, but the frequencies of occurrence of mutants were significantly greater in the groups treated with these combinations or CLARI alone. On the other hand, no CLARI-resistant mutants were isolated from the mice that had been treated with the combination of CLARI plus an initial 4 or 8 weeks of AMIKA and were isolated from only a tiny proportion of mice that had been treated with CLARI plus an initial 2 weeks of AMIKA. Therefore, only treatment with CLARI combined with an initial 4 or 8 weeks of AMIKA but not combined with RBT or EMB or both, could enhance the activity of the drug treatment and prevent the selection of CLARI-resistant mutants.
Amikacin↗
Use of normal C57BL/6 mice with established Mycobacterium avium infections as an alternative model for evaluation of antibiotic activity.
Several murine models have been used to evaluate the activities of antimicrobial agents against Mycobacterium avium infection. The main model used is the beige mouse model, but beige mice are expensive and not easily available. Thus, we developed a model of infection in wild C57BL/6 mice. The drugs that exhibited some activity in a previous model of early infection were evaluated in a new model of established infection. Sparfloxacin (50 mg/kg of body weight), ethambutol (50 mg/kg), minocycline (25 mg/kg), and the inhibitor of the cortisol receptors RU-40555 (100 mg/kg) were compared with clarithromycin (50 mg/kg). Treatments were started 5 weeks after the inoculation and were continued for 21 days. Sparfloxacin and RU-40555, which exhibited a moderate activity in the model of early infection, were not effective in this model of established infection. Clarithromycin and combinations with clarithromycin kept their activities against M. avium infection, both in the spleen and in lungs. The present model of established infection of normal C57BL/6 mice is more relevant than the model of early infection for a stringent evaluation of drugs.
Animals↗
Activities of roxithromycin against Mycobacterium avium infections in human macrophages and C57BL/6 mice.
The activity of roxithromycin against three clinical isolates of Mycobacterium avium was compared with that of clarithromycin both in a model of infection of human monocyte-derived macrophages and in a model of established infection of C57BL/6 mice. In the cell culture model, roxithromycin and clarithromycin were bactericidal for strains MO-1 and N-92159 and bacteriostatic for strain N-93043. For the three strains, the differences between the intracellular activities of roxithromycin and clarithromycin were not singificant after 7 days of treatment. Mice were infected with the MO-1 strain. Drugs were given by gavage at a dosage of 200 mg/kg of body weight 6 days per week for 16 weeks starting 5 weeks after infection. At the end of treatment, clarithromycin was more effective than roxithromycin in lungs; roxithromycin was as effective as clarithromycin in spleens. Thus, the activity of roxithromycin was comparable to that of clarithromycin both in vitro and in vivo.
Animals↗
In vitro and in vivo activities of levofloxacin against Mycobacterium tuberculosis.
In tests with 18 drug-susceptible strains of Mycobacterium tuberculosis, the MIC at which 50% of the strains are inhibited by levofloxacin (LVFX) was one dilution less than that at which 50% of the strains are inhibited by ofloxacin (OFLO), but the MICs at which 90% of the strains are inhibited were similar. The in vivo activity of LVFX against M. tuberculosis was compared with the activities of isoniazid, OFLO, and sparfloxacin (SPFX). Mice were inoculated intravenously with 1.74 x 10(6) CFU of H37Rv, and treatments began the next day and were carried out six times weekly for 4 weeks. The severity of infection and effectiveness of treatment were assessed by survival rate, spleen weights, gross lung lesions, and enumeration of CFU in the spleen. In terms of CFU counts, the ranking of the anti-M. tuberculosis activities of the treatments used ran in the following order: LVFX (300 mg/kg of body weight) = SPFX (100 mg/kg) > isoniazid > SPFX (50 mg/kg) > OFLO (300 mg/kg) = LVFX (150 mg/kg) > OFLO (150 mg/kg) = LVFX (50 mg/kg). It seems, therefore, that the in vivo activity of LVFX is comparable to that produced by a twofold-greater dosage of OFLO. It is assumed that the maximal clinically tolerated dosage of LVFX is similar to that of OFLO, i.e., 800 mg daily, which is equivalent to 300 mg of LVFX per kg in mice. Because LVFX displayed powerful bactericidal activity, promising effects against human tuberculosis may be achieved if patients are treated with the maximal clinically tolerated dosage of LVFX.
Animals↗
Characterization of the Triticum durum Desf. chloroform-methanol-soluble protein family.
The CM (chloroform-methanol-soluble) proteins are low-molecular-weight cysteine-rich proteins that are found in wheat and barley endosperms. A cDNA clone encoding a Triticum durum (T. durum) CM3 protein has been isolated from a mid-maturation seed cDNA library. The T. durum CM3 protein is synthesized as a precursor including a signal peptide (SP) of 25 residues. Northern blot analysis shows that in developing seed the highest level of CM3 protein mRNA is detected at mid-maturation. The hybridization patterns obtained by Southern blot analysis indicated that T. durum CM proteins are encoded by a small multigene family. The similarity between the wheat and barley CM proteins encoded by homologous chromosomes is much higher than that between each of the three members of the T. durum family. All CM proteins contain ten cysteine residues organized in a conserved cysteine motif.
Amino Acid Sequence↗
Drug-resistant tuberculosis: laboratory issues. World Health Organization recommendations.
There is a suggestion that drug resistance rates decreased in developing countries over the period 1962-85, while recent data suggest that resistance may be increasing. The initial decrease in resistance appears to be associated with well-functioning National Tuberculosis Control Programmes (NTP), while the recently observed increase may be due either to understaffed, resource-poor programmes or to the effect of the HIV epidemic, or to both. It is possible that the HIV epidemic may overwhelm the NTP, resulting in decreased programme efficiency and ultimately increased drug resistance. Resistance surveillance appears to be a good measure of programme efficiency. For research purposes, primary drug resistance surveys should be done on a sample of relevant patients which includes and distinguishes between HIV-positive and HIV-negative patients. At this time, there is not enough information to warrant a recommendation regarding HIV testing of TB patients for surveillance purposes. In order for resistance surveys to be relevant from the public health perspective, one must know the proportion of patients presenting for treatment having previously received treatment. The meaningful denominator for drug resistance surveys from the programme evaluation perspective should be the number of patients presenting for treatment. For initial drug resistance surveys the measurement should be the number of people never having received prior TB treatment with resistant bacilli, divided by the number of new patients presenting for treatment. For acquired resistance, one should look at all patients who begin treatment with susceptible bacilli who become resistant 6 months later.
Antitubercular Agents↗
Tuberculous meningitis in France in 1990: characteristics and impact of BCG vaccination.
SETTING: France, 1990. OBJECTIVE: To measure the incidence and describe the characteristics of bacteriologically-confirmed tuberculous meningitis (TBM) and to estimate the protective efficacy of BCG vaccination in children aged less than 5 years. DESIGN: An active surveillance of TBM cases confirmed by positive cerebrospinal fluid (CSF) culture was conducted through a network of microbiology laboratories serving 99.8% of regional and district general hospitals and other large private hospitals. RESULTS: A total of 70 cases were reported: 61% were adults over 44 years, 64% were males and 77% were born in France. 7 patients were known to be infected with HIV. 6 cases were observed in children aged less than 5 years, 2 of whom had been vaccinated with BCG. 3 of the 6 children died (one had been BCG-vaccinated). Given the 80% coverage of BCG in this age group, the protective efficacy of BCG vaccination was estimated to be 87.5% (95% CI: 30-98), which indicates that 14 TBM cases may have been prevented by BCG vaccination in 1990. CONCLUSION: Results are consistent with the number of TBM cases expected on the basis of a 0.04% annual risk of infection. Current BCG vaccination policy in France still has a measurable impact on the incidence of tuberculous meningitis in children under 5 years of age. Given the probable continuous decrease of the annual risk of infection in future years, alternative policies should be considered.
AIDS-Related Opportunistic Infections↗
Chloroquine does not enhance the activity of clarithromycin against multiplication of Mycobacterium avium within human macrophages.
SETTING: Chloroquine, an alkalinizing lysosomotropic agent, enhances the intracellular activity of antibiotics against Mycobacterium tuberculosis or Coxiella burnetii. OBJECTIVE: To determine if chloroquine modifies the activity of clarithromycin, less effective at acidic pH, against intracellular Mycobacterium avium. DESIGN: The activity of clarithromycin (4 micrograms/ml) against the MO-1 strain of M. avium was evaluated within human macrophages in presence of chloroquine (5 micrograms/ml). The minimal inhibitory concentration of clarithromycin for the strain was 2 micrograms/ml. RESULTS: While clarithromycin alone did decrease the intracellular infection at day 7 of culture (P < 0.01), chloroquine alone did not impede the intracellular growth of M. avium, and did not enhance the activity of clarithromycin. CONCLUSION: Chloroquine should not improve clarithromycin treatment against M. avium infection.
Cells, Cultured↗
Selection of a gyrA mutant of Mycobacterium tuberculosis resistant to fluoroquinolones during treatment with ofloxacin.
A strain of Mycobacterium tuberculosis resistant to ofloxacin was selected in a patient with a long history of multidrug-resistant tuberculosis eventually treated by ofloxacin combined with other second-line drugs. A mutation in the gyrA gene was hypothesized to be the mechanism of acquired resistance to ofloxacin in this strain. Chromosomal DNA of strains MTB1, isolated before treatment and susceptible to ofloxacin (MIC, 1 microgram/mL), and MTB2, isolated during treatment and resistant to ofloxacin (MIC, 32 micrograms/mL), was amplified by polymerase chain reaction (PCR) using two oligonucleotide primers highly homologous to DNA sequences flanking the quinolone resistance-determining region in gyrA of mycobacteria. Comparison of the nucleotide sequences of the 150-bp fragments obtained by PCR revealed a point mutation in MTB2 leading to the substitution of histidine for aspartic acid at a position corresponding to residues involved in quinolone resistance in Escherichia coli (Asp87), Staphylococcus aureus (Glu88), and Campylobacter jejuni (Asp90).
Adult↗
Effectiveness of various antimicrobial agents against Mycobacterium avium complex in the beige mouse model.
The results of five chemotherapeutic experiments in beige mice infected with organisms of the Mycobacterium avium complex are presented. After monotherapy with various antimicrobial agents for 4 weeks, only clarithromycin, amikacin, and ethambutol displayed definite bactericidal effects; sparfloxacin and clofazimine showed modest bacteriostatic effects; and rifampin and rifabutin were totally inactive against the isolate tested. After treatment for 4 weeks, the large quantities of clofazimine that had accumulated in the organs of mice seriously interfered with the enumeration of the CFU and assessment of the efficacy of the treatment. The in vitro synergistic effects of drug combinations against M. avium complex were not confirmed in beige mice. In combination with clarithromycin, amikacin could prevent the selection of clarithromycin-resistant mutants, whereas minocycline could not.
Animals↗
Selection of a gyrA mutant of Mycobacterium tuberculosis resistant to fluoroquinolones during treatment with ofloxacin.
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Amino Acid Sequence↗
Clarithromycin and other antimicrobial agents in the treatment of disseminated Mycobacterium avium infections in patients with acquired immunodeficiency syndrome.
BACKGROUND: Disseminated infection with Mycobacterium avium is common with late-stage acquired immunodeficiency syndrome (AIDS), and no antimicrobial agent has been found to be clearly effective. METHODS: A multicenter open trial was conducted to assess the antimicrobial activity and clinical efficacy of clarithromycin--a new macrolide antibiotic--against disseminated M avium in 77 patients with late-stage AIDS. Blood cultures were taken at baseline and during treatment; side effects were also evaluated. RESULTS: Mycobacterium avium was eradicated from blood cultures in 11 (63%) of 16 evaluable patients receiving daily doses or 500 or 1000 mg, (n = 21) and in 45 of 46 (98%) of those receiving 1500 or 2000 mg (n = 56). Eradication after 2 months was influenced by continuity of drug treatment; 36 of 42 patients with no relapse had received continuous treatment vs six of 14 patients whose drug treatment had been stopped for 7 days or longer. After 2 to 7 months of treatment, acquired resistance associated with relapse was observed. Drug side effects were elevated liver enzyme levels (26%) and impaired hearing (4%). Concomitant AIDS drugs had no favorable effect on outcome and may have worsened liver toxicity. CONCLUSIONS: Clarithromycin has bacteriologic efficacy against M avium infection in late-stage AIDS, although drug resistance eventually develops. Further studies are needed to investigate safe, effective concomitant drugs.
AIDS-Related Opportunistic Infections↗
Powerful bactericidal activity of sparfloxacin (AT-4140) against Mycobacterium tuberculosis in mice.
The bactericidal activities of various monotherapies and combined regimens were compared in mice at different stages after infection with Mycobacterium tuberculosis. These therapies mimicked the initial and continuation phases of chemotherapy for human tuberculosis. As monotherapy, the bactericidal activity of sparfloxacin (SPFX) was dose related; the activity of SPFX at 100 mg/kg of body weight was comparable to that of rifampin (RMP) and was significantly greater than those of isoniazid (INH), pyrazinamide (PZA), or ofloxacin (OFLO) during both the initial and continuation phases of chemotherapy. During the initial phase, the addition of SPFX did not enhance or diminish the activities of the combinations INH-RMP-PZA or RMP-PZA; the combinations SPFX-PZA-streptomycin (SM) and SPFX-PZA-kanamycin (KANA) displayed powerful bactericidal activity. Because the area under the plasma concentration-time curve of SPFX (100 mg/kg) in mice is similar to that of SPFX (400 mg) in humans, the promising bactericidal activity displayed by SPFX in mice might be achieved in humans by administration of the drug in a clinically tolerated dosage. In addition, the combinations SPFX-PZA-SM and SPFX-PZA-KANA may be useful for the treatment of multidrug-resistant tuberculosis.
Animals↗
Efficacy of granulocyte colony-stimulating factor and RU-40555 in combination with clarithromycin against Mycobacterium avium complex infection in C57BL/6 mice.
We compared the activities of two different biological-response modifiers with that of clarithromycin against Mycobacterium avium complex infection in C57BL/6 mice. Mice were pretreated daily with clarithromycin (50 mg/kg of body weight subcutaneously [s.c.]), RU-40555 (100 mg/kg s.c.), or granulocyte colony-stimulating factor (G-CSF) at low dose (15 micrograms/kg intraperitoneally [i.p.]) or high dose (300 micrograms/kg i.p.) 3 days before intravenous challenge with 2.5 x 10(7) CFU of the MO-1 strain of M. avium complex. Mice were treated daily until sacrifice at day 1, 8, 15, or 21 after challenge, and the numbers of CFU were measured per gram of tissue in lung and spleen. Compared at day 21 with control treatment, clarithromycin significantly decreased the level of infection in spleen (P < 0.0001) and lungs (P < 0.0001). Compared with control treatment, G-CSF at low dose had no activity, but G-CSF in combination with clarithromycin was more effective than clarithromycin alone in spleen (P < 0.05) and lungs (P < 0.015). The high dose of G-CSF was as effective as the low dose. RU-40555 alone had no beneficial activity. The RU-40555-clarithromycin combination was more effective than control treatment in spleen (P = 0.0001) and lungs (P < 0.0005) and more effective than clarithromycin alone in spleen (P < 0.009) but not in lungs. Thus, our experiments suggest that clarithromycin alone or in combination with G-CSF should be further evaluated for the prophylaxis of M. avium complex infection.
Acquired Immunodeficiency Syndrome↗
Clarithromycin, minocycline, and rifabutin treatments before and after infection of C57BL/6 mice with Mycobacterium avium.
C57BL/6 mice were pretreated with rifabutin or clarithromycin alone or combined with minocycline 3 days before intravenous challenge (day 0) with Mycobacterium avium. Treatment was continued until sacrifice at days 1, 8, 15, and 21. Rifabutin or clarithromycin decreased the level of infection in both the lungs and the spleen. Rifabutin was as effective as clarithromycin in the lungs but was less [corrected] effective in the spleen. The clarithromycin-minocycline combination was as effective as clarithromycin alone.
Animals↗