Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study objective was to determine the minimum frequency of dosing for standard 4-g doses of p-aminosalicylic acid (PAS) granules. Two sequential six-patient pharmacokinetic studies are described, followed by clinical data from 40 subsequent patients. All patients had multidrug-resistant tuberculosis (MDR-TB). Serum was collected at two to three time points after dosing, and assayed by a validated high performance liquid chromatography (HPLC) assay. Data were analyzed using noncompartmental methods. In six patients, twice-daily dosing produced median serum concentrations at 4, 8, and 12 h post-dose of 25.8, 23.2, and 16.4 microgram/ml. In six patients, once-daily dosing produced median serum concentrations at 6, 12, and 24 h post-dose of 23.4, 3.7, and 0 microgram/ml. In 40 patients, twice-daily dosing produced median serum concentrations at 4 to 8 and 9 to 12 h post-dose of 24.8 and 20.6 microgram/ml. Unlike once-daily dosing, twice-daily PAS maintained serum concentrations in excess of 1 microgram/ml, the typical minimal inhibitory concentration against Mycobacterium tuberculosis, for the entire dosing interval. We now use twice-daily PAS granules for our patients with MDR-TB.
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PMID:Once-daily and twice-daily dosing of p-aminosalicylic acid granules. 1005 Dec 75

Multiple-drug-resistant Mycobacterium tuberculosis (MDR-MTB) has been well studied in hospitals or health care institutions and in human immunodeficiency virus-infected populations. However, the characteristics of MDR-MTB in the community have not been well investigated. An understanding of its prevalence and circulation within the community will help to estimate the problem and optimize the strategies for control and prevention of its development and transmission. In this study, MDR-MTB isolates from Scotland collected between 1990 and 1997 were characterized, along with non-drug-resistant isolates. The results showed that they were genetically diverse, suggesting they were unrelated to each other and had probably evolved independently. Several new alleles of rpoB, katG, and ahpC were identified: rpoB codon 525 (ACC-->AAC; Thr525Asn); katG codon 128 (CGG-->CAG; Arg128Gln) and codon 291 (GCT-->CCT; Ala291Pro); and the ahpC synonymous substitution at codon 6 (ATT-->ATC). One of the MDR-MTB isolates from an Asian patient had an IS6110 restriction fragment length polymorphism pattern very similar to that of the MDR-MTB W strain and had the same drug resistance-related alleles but did not have any epidemiological connection with the W strains. Additionally, a cluster of M. tuberculosis isolates was identified in our collection of 715 clinical isolates; the isolates in this cluster had genetic backgrounds very similar to those of the W strains, one of which had already developed multiple drug resistances. The diverse population of MDR-MTB in Scotland, along with a low incidence of drug-resistant M. tuberculosis, has implications for the control of the organism and prevention of its spread.
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PMID:Molecular evidence for heterogeneity of the multiple-drug-resistant Mycobacterium tuberculosis population in Scotland (1990 to 1997). 1007 16

Beta-lactamase activity was determined using a nitrocefin disc method on 34 Mycobacterium tuberculosis (M. tuberculosis) strains and 13 nontuberculous mycobacteria strains. In the 34 M. tuberculosis strains, 23 strains showed beta-lactamase activity. In 10 Mycobacterium avium complex strains, no beta-lactamase activity was detected. In the Mycobacterium chelonae strains, all three strains examined showed strong beta-lactamase activity. No correlation was found between beta-lactamase activity and resistance to anti-tuberculous chemotherapeutic agents. Four patients who were persistently positive for multi-drug-resistant M. tuberculosis (MDR-TB) on sputum and positive in beta-lactamase activity, were treated with penicillin/beta-lactamase inhibitor combinations. In two cases, the trials were discontinued because of diarrhea; the trials were continued in the remaining two for four months, but the MDR-TB was positive during the course of the therapy. Effectiveness of the therapy with penicillin/beta-lactamase inhibitor combinations against M. tuberculosis was obscure, although many of M. tuberculosis examined showed beta-lactamase activity.
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PMID:[A study of beta-lactamase activity of mycobacteria and clinical trial of penicillin/beta-lactamase inhibitor combinations in the treatment of drug-resistant Mycobacterium tuberculosis]. 1038 34

MDR-TB is known to be man-made-disease. Inappropriate treatment of tuberculosis is responsible for the development of MDR-TB. MDR-TB is often accompanied with the immunosuppression of the host. Given that we are unable to develop another potent anti-TB drug in near future, immunotherapy directed at combating immunosuppression and enhancing the host's own immune response is an attractive approach to supplement conventional chemotherapy for MDR-TB. Patients with AIDS and patients with abnormalities of macrophage function have frequent problems with TB. This is suggesting that the host defenses involved in protection against mycobacteria include T-cell and monocyte/macrophage functions. That is cell-mediated immunity. Diverse cytokines are known to play an important role in anti-TB cell-mediated immunity, including IL-2, IL-12, IL-18 and IFN-gamma. Various animal experiments are indicating that administration of these cytokine (s) did recover the suppressed immunity and rescued the host from death by tuberculous infection. However, we have to keep it in mind that the results obtained from animal model of mycobacterial infection on the study of pathogenesis and immune responses in TB is not always applicable to the understanding of human TB. Clinical trial of inhalation therapy with IFN-gamma showed some improvement for drug-resistant TB. Cytokine treatment, however, often gave some deleterious side effects such as high fever, malaise, general edema and even the death of the host. Clinical trials with M. vaccae have been extensively conducted by UK group. The mechanisms underlying its possible therapeutic action remain to be clarified, but when administered at an appropriate dose, it has been shown to elicit a strong Th1 immune response. From the practical view point of immunotherapy for TB, surrogate markers of disease eradication and protective immunity are urgently required. Such markers would facilitate clinical trials by providing early evidence that test compounds or vaccines are effective. Even during the era when no potent chemotherapeutic agents were available, one third of the patients with TB survived the disease and enjoyed the entire lives. Then the question is what determines the alternative: survival or death following development of drug resistant TB. Is it host immune responsiveness or virulence of the microbe, or both? Clearly much more work seems required before we are able to find some definite means to conquer MDR-TB in human.
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PMID:[Immunotherapy for MDR-TB (multi-drug resistant tuberculosis)--its feasibility]. 1042 59

The factors related to the outcome of 51 cases of multi-drug-resistant tuberculosis (MDR-TB) reported in 1994 to the French National Reference Center were retrospectively analyzed. The patients (median age, 45 yr) were mainly male (75%), foreign-born (63%), and had pulmonary involvement (95%). Sixteen percent were human immunodeficiency virus (HIV)-coinfected. The number of drugs to which the Mycobacterium tuberculosis isolates were susceptible was four. Only 82% of the patients have been hospitalized at any time (median duration, 33 d). Five patients (9%) received no antituberculosis drugs, although three had drug susceptibility results, indicating that two or more active drugs were available; 46 (91%) received drugs, including 37 who received two or more active drugs. Among the nine cases who received only one active drug, three had drug susceptibility results, indicating that two or more active drugs were available. By December 1996, 10 patients were lost before treatment completion, 24 had treatment failure, and 17 had a favorable outcome. The median survival time was 31 mo. Factors related to a poorer outcome were HIV-coinfection (hazard ratio [HR] = 41), treatment with less than two active drugs (HR = 9.9), and MDR status knowledge at the time of diagnosis (HR = 3.3). The country of birth was not associated with a poorer outcome. The management and outcome of MDR-TB in France has to be improved. A solution would be to develop a specialized unit or team for the treatment of MDR-TB, as recommended by the World Health Organization (WHO).
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PMID:Outcome of multi-drug-resistant tuberculosis in France: a nationwide case-control study. 1043 Jul 33

The indirect susceptibility test results on L-J medium for tubercle bacilli against streptomycin, isoniazid and rifampicin were read at the end of 2 wk and compared with the results at 4 wk. It was found that drug resistance could be correctly predicted in over 70 per cent of cultures including multi-drug resistant tuberculosis (MDR TB) strains at the end of 2 wk. The susceptibility to para-nitrobenzoic acid (PNB) read at 2 wk was able to distinguish non-tuberculous mycobacteria from Mycobacterium tuberculosis cultures. The early detection of resistance by this procedure requires only minimum inputs, and can benefit the majority of patients harbouring drug resistant tubercle bacilli.
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PMID:Early results from indirect drug susceptibility test for tubercle bacilli. 1064 40

Resectional surgery for tuberculosis became increasingly common in the 1940s; however, thoracoplasty remained the most popular treatment of choice until the introduction of effective antituberculosis agents. With the development of rifampin in 1966, surgery was seldom needed except for the occasional massive hemoptysis, bronchial stenosis bronchopleural fistula, or to rule out cancer. With the rise of MDR-TB and the increasing MOTT infections requiring surgery, resectional procedures are again being needed in the treatment of mycobacterial disease.
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PMID:History of resectional surgery for tuberculosis and other mycobacterial infections. 1068 31

Multi-drug-resistant tuberculosis (MDR-TB) has emerged as an obstacle to the control of tuberculosis. Recent data however, suggest that interferon-(IFN)-gamma and IFN-alpha may improve disease evolution in subjects affected with pulmonary tuberculosis caused by multi-resistant (IFN-gamma) and sensitive (IFN-alpha) strains. The mechanisms involved are not known, even though it has been reported that IFN-gamma-secreting CD4+ Th cells may possess antitubercular effects. In addition, IFN-alpha can induce IFN-gamma secretion by CD4+ Th cells, and both types of IFN may stimulate macrophage activities. The aim of this study was to explore the possibility that aerosolized IFN-alpha, administered concomitantly with conventional antitubercular chemotherapy, may improve the course of pulmonary tuberculosis. After six months of directly observed therapy (DOT), seven patients who were non-responders to a second line antitubercular therapy were given an IFN-alpha aerosol (3 MU, three times a week) for two months as adjunctive therapy. All strains were resistant to at least two first-line drugs. After IFN-alpha administration, the patients were followed up for a further six months with the same DOT. Sputum samples were collected monthly during the study period, with the exception of the IFN-alpha administration period, when the observations were performed weekly. High resolution computed tomography (HRCT) chest scans were performed before and after IFN-alpha inhalations. The analysis of the results showed that the mean number of Mycobacterium tuberculosis (Mt) had remained statistically unchanged (p = 0.80) during the first 6 months of DOT. During the following 2 months of IFN-alpha administration, 5 patients became negative (p = 0.02). After the end of treatment a progressive increase in Mt number was observed (p = 0. 02). Sputum cultures remained positive for all patients throughout the study period, although a significant decrease (p = 0.02) in the colony number per culture was observed after adjunctive treatment with IFN-alpha. After stopping administration of IFN-alpha, a significant increase (p = 0.03) in the colony number per culture was noted as well as in Mt numbers. HRCT scans were slightly improved in all patients. These preliminary data suggest that aerosolized IFN-alpha may be a promising adjunctive therapy for patients with MDR-TB. Optimal doses and schedules however, require further studies.
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PMID:Aerosolized interferon-alpha treatment in patients with multi-drug-resistant pulmonary tuberculosis. 1070 6

The line probe assay (LiPA), a rapid molecular method for detecting rifampicin resistance (RMPr) in Mycobacterium tuberculosis, correctly identified all 145 rifampicin-sensitive (RMPs) and 262 (98.5%) of 266 RMPr strains among 411 isolates collected from diverse countries. If used as a marker of multidrug-resistant tuberculosis (MDR-TB), detection of RMPr by LiPA would have detected 236 of the 240 MDR strains in this study but would have wrongly suggested the presence of MDR in 26 RMP-monoresistant isolates (sensitivity 98.3%, specificity 84.8%). Hence, the reliability of using LiPA (or any other rapid RMPr-detection method) as a surrogate marker of MDR-TB largely depends on the prevalence of RMP-monoresistance in the study population. This approach must therefore be validated in each local situation.
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PMID:Detection of rifampicin resistance in Mycobacterium tuberculosis isolates from diverse countries by a commercial line probe assay as an initial indicator of multidrug resistance. 1081 43

Information about resistant pattern of Mycobacterium tuberculosis isolates against antituberculon drugs is a very important part of tuberculosis control and indicates the directions of TB policy in each country. Poland joined WHO/IUATLD global project on drug resistance surveillance, and carried out the first prospective survey, simultaneously on primary and acquired drug resistance of tuberculosis patients according WHO/IUATLD recommendations. The programme covered the whole country, basing on cooperation between the National Reference Laboratory (NRL) with regional TB laboratories. Questionnaires and cultures were obtained from patients who excreted TB bacilli during the period from 1 November 1996 to 1 November 1997 (12 months). Drug susceptibility testing to INH, SM, EMB and RMP were performed on Lowenstein-Jensen medium according to the proportion method or/and radiometric Bactec 460 TB system. 3970 TB patients bacteriologically confirmed by culture were included in a one-year study. The male to female ratio was 2.6:1. Patients were at the age of 6 to 83 years. Majority of patients (86% males and 77% of females) was older than 35 years. Primary resistance to any drug was found in 3.6% of new cases and 2.4% of those patients who excreted monoresistant strains. No monoresistance to EMB was found. 18 patients (0.6%) were infected by MDR strains. Total resistance in new cases was for INH--2.6%, for SM--1.8%, for RMP--0.7% and for EMB--0.1%. Acquired resistance to any drug was found in 17.0% of treated. Majority of patients--7.7% excreted monoresistant strains. 7.0% were infected by MDR strains. Total resistance to INH was 14.8%, to SM--9.2%, to RMP--7.8%, and to EBM--2.5%. No correlation was found between sex and primary resistance rates. Among new cases, 3.7% of males and 3.3% of females were infected with resistant strains. However, among treated patients, males (20%) excreted resistant strains twice as much as females (9.1%). Mean age of women and men infected with primary and acquired resistant strains was similar.
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PMID:[Primary and acquired drug resistance of tuberculosis bacilli in Poland]. 1105 4


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