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British Journal of Clinical Pharmacology Oct 19801. The possibility of using minute doses of the antituberculosis drug isoniazid (INH) or of its metabolites acetylisoniazid (AcINH) or isonicotinic acid (INA) as...
1. The possibility of using minute doses of the antituberculosis drug isoniazid (INH) or of its metabolites acetylisoniazid (AcINH) or isonicotinic acid (INA) as innocuous markers for monitoring patient compliance has been investigated. 2. The ingestion of these colourless and tasteless compounds can readily be demonstrated using a sensitive and specific colorimetric method for detecting INA and its metabolite isonicotinylglycine (INAG) in the urine that is rapid and simple to perform. 3. Studies on the kinetics of the urinary elimination of INA and INAG after the ingestion of 6 mg doses of either INH, AcINH or INA by small groups of volunteers indicated the potential suitability of INH or AcINH for monitoring daily or twice-daily self-medication and the appropriateness of INA as a marker for investigating the compliance of drugs prescribed for thrice-daily ingestion. 4. More extensive studies showed that over 99% of the urine samples collected within 18h of dosage with 6 mg INH would give positive results when tested for the presence of INA and INAG, and that doses of 2-6 mg INH could readily by incorporated into capsules or tablets and used as markers for monitoring the ingestion of the antituberculosis or antileprosy drugs dapsone, thiacetazone, ethionamide or prothionamide, or the antihypertensive oxprenolol. Such doses are less than a fiftieth of the normal therapeutic INH dose used in the treatment of tuberculosis. 5. Evidence is presented that INH, AcINH and INA possess most of the characteristics that one would hope to find in a marker for monitoring compliance including very limited inter-individual variability in the rates at which they are converted to the compounds being detected in the urine.
Topics: Glycine; Half-Life; Humans; Intestinal Absorption; Isoniazid; Isonicotinic Acids; Male; Patient Compliance; Riboflavin; Self Administration; Time Factors
PubMed: 7448108
DOI: 10.1111/j.1365-2125.1980.tb01773.x -
International Journal of Infectious... May 2010Extensively drug-resistant tuberculosis (XDR-TB) has recently been identified as a major threat to global health. XDR-TB poses a risk of higher failure rates and death...
BACKGROUND
Extensively drug-resistant tuberculosis (XDR-TB) has recently been identified as a major threat to global health. XDR-TB poses a risk of higher failure rates and death during TB treatment. We report herein the outcomes of XDR-TB in patients treated with the standardized regimen in Iran.
PATIENTS AND METHODS
Between 2002 and 2006, seven patients were diagnosed with XDR-TB. All patients were treated with the standardized second-line regimen containing cycloserine, prothionamide, amikacin, and ofloxacin. First-line drugs, such as ethambutol and pyrazinamide, were added to the regimen if drug susceptibility testing showed sensitivity to these drugs.
RESULTS
Four (57.1%) patients were male. All seven patients were HIV-negative. The patient age range was 22-79 years. Of the seven cases, the final outcome was 'cure' in two (28.6%), 'relapse' in one, 'treatment failure' in one, and 'death' in two; the outcome for one patient was unknown.
CONCLUSION
Our study shows a poor prognosis in patients with XDR-TB. This indicates the necessity of detecting XDR-TB cases earlier, as well as the need to gain access to more second-line agents. This is particularly important in resource-limited settings in order to administer individualized regimens.
Topics: Adult; Aged; Antitubercular Agents; Cohort Studies; Extensively Drug-Resistant Tuberculosis; Female; Humans; Iran; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium tuberculosis; Young Adult
PubMed: 19818664
DOI: 10.1016/j.ijid.2009.07.002 -
The American Journal of Tropical... Feb 2018A Syrian asylum seeker with multidrug-resistant tuberculosis (TB) developed a bronchopleural fistula after pneumonectomy. Although screening tests were negative on...
A Syrian asylum seeker with multidrug-resistant tuberculosis (TB) developed a bronchopleural fistula after pneumonectomy. Although screening tests were negative on admission, carbapenemase-producing Enterobacteriaceae were cultured after a few months of TB treatment. Prevalence of multidrug-resistant organisms is reported to be increased in asylum seekers compared with the general Dutch population. Arduous conditions during transit and interrupted health care delivery in our patient led to multiple-resistant microorganisms that complicated treatment.
Topics: Adult; Amikacin; Carbapenem-Resistant Enterobacteriaceae; Clofazimine; Drug Monitoring; Humans; Linezolid; Male; Moxifloxacin; Netherlands; Prevalence; Prothionamide; Refugees; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Multidrug-Resistant
PubMed: 29280429
DOI: 10.4269/ajtmh.17-0544 -
Biomedical Reports Mar 2024Proteasome inhibitor bortezomib is an anticancer agent approved for treatment of multiple myeloma and mantle cell lymphoma. However, its application in other types of...
Proteasome inhibitor bortezomib is an anticancer agent approved for treatment of multiple myeloma and mantle cell lymphoma. However, its application in other types of cancer, primarily in solid tumors, is limited due to poor pharmacokinetics, inefficient tissue penetration, low stability and frequent adverse effects. In the present study, a novel micellar nano-scaled delivery system was manufactured, composed of amphiphilic poly(N-vinylpyrrolidone) nanoparticles loaded with bortezomib. Similar nanoparticles loaded with prothionamide, a drug without anticancer effect, were used as control. The size and zeta potential of the obtained polymeric micelles were measured by dynamic light scattering. Bortezomib-loaded micelles exhibited significant cytotoxic activity in monolayer tumor cell cultures (IC ~6.5 µg/ml) and in 3D multicellular tumor spheroids (IC ~8.5 µg/ml) of human glioblastoma cell lines U87 and T98G. Additionally, the toxic effects were studied in zebrafish embryos, with an estimated 50% lethal concentration of 0.1 mg/ml. Considering that bortezomib and other molecules from the class of proteasome inhibitors are potent antitumor agents, nanodelivery approach can help reduce adverse effects and expand the range of its applications for treatment of various oncological diseases.
PubMed: 38343660
DOI: 10.3892/br.2024.1725 -
Journal of Clinical Microbiology Dec 2016Our objective was to establish reference MIC quality control (QC) ranges for drug susceptibility testing of antimycobacterials, including first-line agents, second-line...
A Multilaboratory, Multicountry Study To Determine MIC Quality Control Ranges for Phenotypic Drug Susceptibility Testing of Selected First-Line Antituberculosis Drugs, Second-Line Injectables, Fluoroquinolones, Clofazimine, and Linezolid.
Our objective was to establish reference MIC quality control (QC) ranges for drug susceptibility testing of antimycobacterials, including first-line agents, second-line injectables, fluoroquinolones, and World Health Organization category 5 drugs for multidrug-resistant tuberculosis using a 7H9 broth microdilution MIC method. A tier-2 reproducibility study was conducted in eight participating laboratories using Clinical Laboratory and Standards Institute (CLSI) guidelines. Three lots of custom-made frozen 96-well polystyrene microtiter plates were used and prepared with 2× prediluted drugs in 7H9 broth-oleic acid albumin dextrose catalase. The QC reference strain was Mycobacterium tuberculosis H37Rv. MIC frequency, mode, and geometric mean were calculated for each drug. QC ranges were derived based on predefined, strict CLSI criteria. Any data lying outside CLSI criteria resulted in exclusion of the entire laboratory data set. Data from one laboratory were excluded due to higher MIC values than other laboratories. QC ranges were established for 11 drugs: isoniazid (0.03 to 0.12 μg/ml), rifampin (0.03 to 0.25 μg/ml), ethambutol (0.25 to 2 μg/ml), levofloxacin (0.12 to 1 μg/ml), moxifloxacin (0.06 to 0.5 μg/ml), ofloxacin (0.25 to 2 μg/ml), amikacin (0.25 to 2 μg/ml), kanamycin (0.25 to 2 μg/ml), capreomycin (0.5 to 4 μg/ml), linezolid (0.25 to 2 μg/ml), and clofazimine (0.03 to 0.25 μg/ml). QC ranges could not be established for nicotinamide (pyrazinamide surrogate), prothionamide, or ethionamide, which were assay nonperformers. Using strict CLSI criteria, QC ranges against the M. tuberculosis H37Rv reference strain were established for the majority of commonly used antituberculosis drugs, with a convenient 7H9 broth microdilution MIC method suitable for use in resource-limited settings.
Topics: Antitubercular Agents; Clofazimine; Fluoroquinolones; Humans; Linezolid; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Quality Control; Tuberculosis, Multidrug-Resistant
PubMed: 27654338
DOI: 10.1128/JCM.01138-16 -
Trials Sep 2014In contrast to drug-sensitive tuberculosis, the guidelines for the treatment of multi-drug-resistant tuberculosis (MDR-TB) have a very poor evidence base; current... (Randomized Controlled Trial)
Randomized Controlled Trial
Evaluation of a standardized treatment regimen of anti-tuberculosis drugs for patients with multi-drug-resistant tuberculosis (STREAM): study protocol for a randomized controlled trial.
BACKGROUND
In contrast to drug-sensitive tuberculosis, the guidelines for the treatment of multi-drug-resistant tuberculosis (MDR-TB) have a very poor evidence base; current recommendations, based on expert opinion, are that patients should be treated for a minimum of 20 months. A series of cohort studies conducted in Bangladesh identified a nine-month regimen with very promising results. There is a need to evaluate this regimen in comparison with the currently recommended regimen in a randomized controlled trial in a variety of settings, including patients with HIV-coinfection.
METHODS/DESIGN
STREAM is a multi-centre randomized trial of non-inferiority design comparing a nine-month regimen to the treatment currently recommended by the World Health Organization in patients with MDR pulmonary TB with no evidence on line probe assay of fluoroquinolone or kanamycin resistance. The nine-month regimen includes clofazimine and high-dose moxifloxacin and can be extended to 11 months in the event of delay in smear conversion. The primary outcome is based on the bacteriological status of the patients at 27 months post-randomization. Based on the assumption that the nine-month regimen will be slightly more effective than the control regimen and, given a 10% margin of non-inferiority, a total of 400 patients are required to be enrolled. Health economics data are being collected on all patients in selected sites.
DISCUSSION
The results from the study in Bangladesh and cohorts in progress elsewhere are encouraging, but for this regimen to be recommended more widely than in a research setting, robust evidence is needed from a randomized clinical trial. Results from the STREAM trial together with data from ongoing cohorts should provide the evidence necessary to revise current recommendations for the treatment for MDR-TB.
TRIAL REGISTRATION
This trial was registered with clincaltrials.gov (registration number: ISRCTN78372190) on 14 October 2010.
Topics: Antitubercular Agents; Bangladesh; Clinical Protocols; Clofazimine; Drug Administration Schedule; Drug Therapy, Combination; Ethambutol; Fluoroquinolones; Humans; Isoniazid; Kanamycin; Moxifloxacin; Prothionamide; Pyrazinamide; Research Design; Time Factors; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary
PubMed: 25199531
DOI: 10.1186/1745-6215-15-353 -
Pneumologie (Stuttgart, Germany) Jul 2014The empiric therapy of multidrug-resistant (MDR) tuberculosis (TB) after rapid molecular testing is rendered difficult by an often several weeks-long period of...
The empiric therapy of multidrug-resistant (MDR) tuberculosis (TB) after rapid molecular testing is rendered difficult by an often several weeks-long period of uncertainty, because results of susceptibility testing for second-line TB drugs are pending. The analysis of regional resistance patterns could lead to a more targeted empiric treatment for migrants depending on their country of origin. The results of the susceptibility testing from 2008 to 2013 of all mycobacteria sent to the Institute of Microbiology, working with the department of Pneumology, Heckeshorn Lung Clinic, Berlin, were reanalysed and tested for regional differences. We found 39 multidrug-resistant Mycobacterium tuberculosis strains among the examined strains. More than half of these strains tested susceptible to the following second line drugs namely, linezolid (97%), clofazimine (95%), cycloserine (95%), capreomycin (90%), p-aminosalicylic acid (82%), moxifloxacin (79%) and amikacin (79%). The proportion of strains susceptible to pyrazinamide (44%), ethambutol (28%), prothionamide (15%), rifabutin (8%) and streptomycin (8%) was lower. The mycobacterial cultures of the Chechen patients (n = 14) showed significantly different susceptibilities to amikacin (57%) and prothionamide (36%) compared to the strains from migrants of other regions. In this study, the regional differences in mycobacterial susceptibility to second line drugs suggest that the initial MDR TB therapy of migrants should be tailored to their country of origin.
Topics: Adult; Aged; Antitubercular Agents; Berlin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium tuberculosis; Prevalence; Risk Factors; Transients and Migrants; Tuberculosis, Multidrug-Resistant
PubMed: 25006843
DOI: 10.1055/s-0034-1377226 -
The Korean Journal of Gastroenterology... May 2016Anti-tuberculosis drugs can produce levels of hepatotoxicity ranging from mild elevation of aminotransferase to severe acute hepatitis. A few cases of drug-induced...
Anti-tuberculosis drugs can produce levels of hepatotoxicity ranging from mild elevation of aminotransferase to severe acute hepatitis. A few cases of drug-induced autoimmune hepatitis or the drug reaction with eosinophilia and systemic symptom (DRESS) syndrome by anti-tuberculosis medications have been reported. However, concomitant occurrence of these two disorders has not been reported. Here, we present a case of severe acute hepatitis with DRESS syndrome and autoimmune hepatitis resulting from primary standard anti-tuberculosis drugs. Both conditions were successfully treated with a systemic steroid regimen.
Topics: Alanine Transaminase; Antitubercular Agents; Cycloserine; Drug Hypersensitivity Syndrome; Drug Therapy, Combination; Eosinophilia; Ethambutol; Female; Hepatitis, Autoimmune; Humans; Isoniazid; Levofloxacin; Liver; Prothionamide; Severity of Illness Index; Tuberculosis; Young Adult
PubMed: 27206439
DOI: 10.4166/kjg.2016.67.5.267