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1.
Curr Drug Deliv ; 20(3): 306-316, 2023.
Article in English | MEDLINE | ID: mdl-35546770

ABSTRACT

BACKGROUND: Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) is a major cause of death amongst tuberculosis patients. Nanomedicine avoids some limitations of conventional drug treatment and increases therapeutic efficacy against bacterial infections. However, the effect of anti-TB drug nanoparticle (NP) compounds in anti-TB regimens against MDR-TB remains unclear. OBJECTIVE: The objective of this article is to prepare levofloxacin, linezolid, ethambutol, prothionamide, and pyrazinamide encapsulated NPs and to evaluate their therapeutic efficacy against MDR-TB in macrophages. METHODS: Drug-loaded PLGA NPs were prepared by the multiple emulsion method. The colocalization, intracellular release, and anti-TB activity of these NPs were investigated on cultured macrophages. The immune phenotype of the macrophages, including their mitochondrial membrane potential, reactive oxygen species (ROS), and nitric oxide (NO) production, was evaluated following treatment with NPs or free drug compounds. RESULTS: All drug-loaded PLGA NPs were spherical in shape, 150 to 210 nm in size, and showed 14.22% to 43.51% encapsulation efficiencies and long-duration release. Drug-loaded PLGA NPs were mainly distributed in the cytoplasm of macrophages, showed high cellular compatibility, and maintained their concentration for at least 13 days. Compared with the free drug compounds, the number of colonies after exposure to PLGA NP compounds was significantly less. The enhanced antibacterial activity of the NP compounds may be due to the enhanced levels of ROS and NO and the increased early apoptosis stress within M. tuberculosis-infected macrophages additionally. CONCLUSION: The application of PLGA NP compounds not only enhances drug efficacy but also induces innate bactericidal events in macrophages, confirming this as a promising approach for MDR-TB therapy.


Subject(s)
Mycobacterium tuberculosis , Nanoparticles , Tuberculosis, Multidrug-Resistant , Tuberculosis , Humans , Pyrazinamide/pharmacology , Pyrazinamide/therapeutic use , Prothionamide/pharmacology , Prothionamide/therapeutic use , Ethambutol/pharmacology , Ethambutol/therapeutic use , Levofloxacin/pharmacology , Linezolid/pharmacology , Linezolid/therapeutic use , Reactive Oxygen Species , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Polylactic Acid-Polyglycolic Acid Copolymer/therapeutic use , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/microbiology , Antitubercular Agents
2.
Antimicrob Agents Chemother ; 66(9): e0189321, 2022 09 20.
Article in English | MEDLINE | ID: mdl-35938799

ABSTRACT

Prothionamide, a second-line drug for multidrug-resistant tuberculosis (MDR-TB), has been in use for a few decades. However, its pharmacokinetic (PK) profile remains unclear. This study aimed to develop a population PK model for prothionamide and then apply the model to determine the optimal dosing regimen for MDR-TB patients. Multiple plasma samples were collected from 27 MDR-TB patients who had been treated with prothionamide at 2 different study hospitals. Prothionamide was administered according to the weight-band dose regimen (500 mg/day for weight <50 kg and 750 mg/day for weight >50 kg) recommended by the World Health Organization. The population PK model was developed using nonlinear mixed-effects modeling. The probability of target attainment, based on systemic exposure and MIC, was used as a response target. Fixed-dose regimens (500 or 750 mg/day) were simulated to compare the efficacies of various dosing regimens. PK profiles adequately described the two-compartment model with first-order elimination and the transit absorption compartment model with allometric scaling on clearance. All dosing regimens had effectiveness >90% for MIC values <0.4 µg/mL in 1.0-log kill target. However, a fixed dose of 750 mg/day was the only regimen that achieved the target resistance suppression of ≥90% for MIC values of <0.2 µg/mL. In conclusion, fixed-dose prothionamide (750 mg/day), regardless of weight-band, was appropriate for adult MDR-TB patients with weights of 40 to 67 kg.


Subject(s)
Prothionamide , Tuberculosis, Multidrug-Resistant , Adult , Antitubercular Agents/adverse effects , Humans , Prothionamide/therapeutic use , Tuberculosis, Multidrug-Resistant/drug therapy
3.
J Microbiol Immunol Infect ; 55(5): 917-925, 2022 Oct.
Article in English | MEDLINE | ID: mdl-34896029

ABSTRACT

BACKGROUND/PURPOSE(S): The World Health Organization (WHO) released treatment guidelines for multidrug resistant tuberculosis (MDR-TB) in 2008, with subsequent revisions in 2011; Korea disseminated corresponding guidelines in 2011 and 2014, respectively. Thus, we aimed to investigate the temporal trends of and the updated guideline's impact on the prescription patterns of anti-TB drugs. METHODS: We conducted a time-series study using Korea's nationwide healthcare database (2007-2015), where patients with TB or MDR-TB were included. Only anti-TB drugs prescribed during the intensive phase of treatment for TB (two months) or MDR-TB (eight months) were assessed. We estimated the annual utilization of TB treatment regimens and the relative difference (RD) in the proportion of MDR-TB treatment medications between the following periods: before the first Korean guideline (June 2008 to March 2011); between the first and revised guidelines (April 2011 to July 2014); after the revised guideline (August 2014 to December 2015). RESULTS: Of 3523 TB (mean age 54.1 years; male 56.8%) patients, treatment regimens for TB complied with guideline recommendations as >80% of patients received either quadruple (mean 66.8%) or triple (14.5%) therapy of first-line anti-TB drugs. Following the WHO's guideline update, prescription patterns changed accordingly among 111 MDR-TB (mean age 46.0 years; male 67.6%) patients, as use of pyrazinamide (RD +20.3%) and prothionamide (+11.5%) increased (recommended to be compulsory), and streptomycin (-43.1%) decreased (ototoxicity risks). CONCLUSIONS: Anti-TB drug prescription patterns for both TB and MDR-TB well reflected WHO's treatment guideline as well as corresponding domestic guidelines of South Korea.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Humans , Male , Middle Aged , Pyrazinamide/therapeutic use , Prothionamide/therapeutic use , Antitubercular Agents/pharmacology , Tuberculosis, Multidrug-Resistant/drug therapy , Streptomycin/therapeutic use , Republic of Korea
4.
Biomed Pharmacother ; 142: 112047, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34426260

ABSTRACT

Drug-resistant tuberculosis (DR-TB) poses a new threat to global health; to improve the treatment outcome, therapeutic vaccines are considered the best chemotherapy adjuvants. Unfortunately, there is no therapeutic vaccine approved against DR-TB. Our study assessed the therapeutic efficacy of a recombinant drug-resistant BCG (RdrBCG) vaccine in DR-TB. We constructed the RdrBCG overexpressing Ag85B and Rv2628 by selecting drug-resistant BCG strains and transformed them with plasmid pEBCG or pIBCG to create RdrBCG-E and RdrBCG-I respectively. Following successful stability testing, we tested the vaccine's safety in severe combined immune deficient (SCID) mice that lack both T and B lymphocytes plus immunoglobulins. Finally, we evaluated the RdrBCG's therapeutic efficacy in BALB/c mice infected with rifampin-resistant M. tuberculosis and treated with a second-line anti-TB regimen. We obtained M. bovis strains which were resistant to several second-line drugs and M. tuberculosis resistant to rifampin. Notably, the exogenously inserted genes were lost in RdrBCG-E but remained stable in the RdrBCG-I both in vitro and in vivo. When administered adjunct to a second-line anti-TB regimen in a murine model of DR-TB, the RdrBCG-I lowered lung M. tuberculosis burden by 1 log10. Furthermore, vaccination with RdrBCG-I adjunct to chemotherapy minimized lung tissue pathology in mice. Most importantly, the RdrBCG-I showed almost the same virulence as its parent BCG Tice strain in SCID mice. Our findings suggested that the RdrBCG-I was stable, safe and effective as a therapeutic vaccine. Hence, the "recombinant" plus "drug-resistant" BCG strategy could be a useful concept for developing therapeutic vaccines against DR-TB.


Subject(s)
Antitubercular Agents/pharmacology , BCG Vaccine/immunology , Drug Resistance, Bacterial/genetics , Mycobacterium bovis/genetics , Mycobacterium tuberculosis/drug effects , Tuberculosis, Pulmonary/prevention & control , Vaccines, Synthetic/immunology , Amikacin/pharmacology , Amikacin/therapeutic use , Animals , Antigens, Bacterial/biosynthesis , Antigens, Bacterial/genetics , Antigens, Bacterial/immunology , Antitubercular Agents/therapeutic use , BCG Vaccine/biosynthesis , BCG Vaccine/genetics , BCG Vaccine/therapeutic use , Disease Models, Animal , Levofloxacin/pharmacology , Levofloxacin/therapeutic use , Mice, Inbred BALB C , Mice, SCID , Mycobacterium bovis/chemistry , Mycobacterium bovis/drug effects , Mycobacterium tuberculosis/pathogenicity , Plasmids , Prothionamide/pharmacology , Prothionamide/therapeutic use , Pyrazinamide/pharmacology , Pyrazinamide/therapeutic use , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/pathology , Vaccines, Synthetic/biosynthesis , Vaccines, Synthetic/genetics , Vaccines, Synthetic/therapeutic use , Virulence
5.
J Pharm Sci ; 108(9): 3106-3111, 2019 09.
Article in English | MEDLINE | ID: mdl-30991038

ABSTRACT

Rifampin (RIF) has been widely used for the treatment of bacterial infections, including tuberculosis (TB). Treatment of drug-resistant TB is a global problem because of reduced drug efficacy. The present study determined the effect of RIF on MDR1 gene (P-glycoprotein, P-gp) expression in THP1 macrophages and analyzed the intracellular concentration of the anti-TB drug prothionamide in the presence of RIF. RIF treatment significantly induced MDR1 protein and mRNA levels in phorbol 12-myristate 13-acetate-stimulated THP1 macrophages (p < 0.001 and 0.01, respectively). The pregnane X receptor inhibitors resveratrol and ketoconazole significantly suppressed RIF-induced P-gp expression in THP1 macrophages (p < 0.05). RIF-treated THP1 macrophages also exhibited strong efflux of P-gp substrate, resulting in a reduced intracellular concentration of rhodamine-123 and prothionamide (p < 0.01 and 0.05, respectively). By contrast, the P-gp inhibitor cyclosporine A significantly increased intracellular concentration of rhodamine-123 and prothionamide (p < 0.001 and 0.05, respectively). The present results suggest that the usage of RIF together with P-gp-substrate drugs to treat TB may lead to deteriorated treatment efficacy because of the lower intracellular drug concentration. Further studies would be necessary to know the influence of RIF-induced P-gp induction on the treatment outcome of patients with TB.


Subject(s)
Antitubercular Agents/pharmacology , Macrophages/metabolism , Prothionamide/pharmacokinetics , Rifampin/pharmacology , ATP Binding Cassette Transporter, Subfamily B/metabolism , Antitubercular Agents/therapeutic use , Cell Line, Tumor , Drug Antagonism , Drug Resistance, Bacterial/drug effects , Drug Therapy, Combination/adverse effects , Humans , Intracellular Fluid/metabolism , Prothionamide/therapeutic use , Rifampin/therapeutic use , Tuberculosis/drug therapy , Tuberculosis/microbiology , Up-Regulation/drug effects
6.
Am J Trop Med Hyg ; 98(2): 376-378, 2018 02.
Article in English | MEDLINE | ID: mdl-29280429

ABSTRACT

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.


Subject(s)
Carbapenem-Resistant Enterobacteriaceae/drug effects , Refugees , Tuberculosis, Multidrug-Resistant/microbiology , Adult , Amikacin/therapeutic use , Carbapenem-Resistant Enterobacteriaceae/pathogenicity , Clofazimine/therapeutic use , Drug Monitoring/methods , Humans , Linezolid/therapeutic use , Male , Moxifloxacin/therapeutic use , Netherlands , Prevalence , Prothionamide/therapeutic use , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use
7.
Respir Med ; 131: 43-48, 2017 10.
Article in English | MEDLINE | ID: mdl-28947041

ABSTRACT

BACKGROUND: Rifampin (RIF) mono-resistant tuberculosis (RMR-TB) is a rare disease. Current guidelines recommend that RMR-TB be treated as multidrug-resistant TB (MDR-TB) but the evidence is scarce. METHODS: We conducted a retrospective cohort study on pulmonary TB patients to investigate the characteristics and outcomes of RMR-TB. The characteristics of RMR-TB were compared with those with adverse events to rifampin (RAE-TB). RESULTS: Forty-four RMR-TB and 29 RAE-TB patients were enrolled. RMR-TB patients showed more alcohol use, prior history of TB, and radiologically severe disease, while RAE-TB patients were older and had more comorbidities and combined extrapulmonary TB. A fluoroquinolone (FQ) was the drug most commonly added (70.5%, RMR-TB; 82.8%, RAE-TB). Median treatment duration was 453 days in RMR-TB and 371 days in RAE-TB (p = 0.001) and treatment success rates were 87.2% (34/39) and 80.0% (20/25), respectively (p = 0.586). Subanalysis of the RMR-TB group by treatment regimen (standard regimen [n = 11], standard regimen + FQ [n = 12], MDR-TB regimen [n = 21]) revealed a higher rate of radiologically severe disease in the MDR-TB subgroup, with similar treatment success rates for the subgroups (85.7% [6/7]), 91.7% [11/12], and 85.0% [17/20], respectively) despite different durations of treatment (345, 405, and 528 days, respectively). Two recurrences (33.3% [2/6]) developed only in standard regimen subgroup, suggesting that standard regimen is not enough to treat RMR-TB patients. CONCLUSIONS: The treatment outcome of RMR-TB with 1st-line drugs + FQ was comparable to that of MDR-TB regimen. Shorter treatment duration may be considered for RMR-TB patients compared with MDR-TB patients.


Subject(s)
Antitubercular Agents/therapeutic use , Rifampin/adverse effects , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy , Adult , Age Distribution , Aged , Alcohol Drinking/epidemiology , Aminosalicylic Acid/therapeutic use , Cohort Studies , Comorbidity , Cycloserine/therapeutic use , Ethambutol/therapeutic use , Female , Fluoroquinolones/therapeutic use , HIV Infections/epidemiology , Humans , Isoniazid/therapeutic use , Male , Middle Aged , Prothionamide/therapeutic use , Pyrazinamide/therapeutic use , Republic of Korea/epidemiology , Retrospective Studies , Severity of Illness Index , Treatment Outcome , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Pulmonary/epidemiology
8.
Auris Nasus Larynx ; 44(4): 404-410, 2017 Aug.
Article in English | MEDLINE | ID: mdl-27832910

ABSTRACT

OBJECTIVE: The study objectives were to determine the incidence of aminoglycoside-induced ototoxicity in institutionalized patients on intensive phase of therapy for drug-resistant Tuberculosis (DR Tb) and also to assess clinical factors which could predict the ototoxicity. METHODS: The study was a prospective analytical study among consecutive DR Tb patients who were admitted for intensive phase of therapy (of 4 months) at the DR-Tb center over a 12-month period. Patients were diagnosed as DR Tb using the Gene Xpert machine to confirm Rifampicin resistance. All eligible 70 out of 87 consenting patients were consecutively recruited into the study. Patients had baseline (admission) and serial pure tone audiometries (PTAs) performed at 4 weekly intervals until discharge after 4 months of admission. Audiometric confirmation of aminoglycoside-induced ototoxicity was done by comparing serial with baseline PTA. RESULTS: Among the 70 patients the male:female ratio was 1.7:1. Nine patients (12.9%) were retroviral-positive, and 16 patients (22.9%) were confirmed to have ototoxicity by audiometric criteria. The duration of treatment when ototoxicity was detected in the patients ranged 4-17 (Mean±SD; 9.4±3.4) weeks. Ototoxicity was detected in the audiometric low frequency ranges in 7 (43.8%) and at the high frequencies in 4 (25.0%) of the patients. Univariate analyses of clinical parameters found that age, underlying diabetes mellitus, deranged baseline PTAv >25dB HL, BMI on admission and retroviral status were significantly associated, while sex and previous drug regimen failure were not associated with ototoxicity. Multivariate adjusted logistic regression analyses, controlling for sex, revealed age (OR=1.068, p=0.018), BMI on admission (OR=0.673, p=0.012) and retroviral positivity (OR=8.822, p=0.014) of patients could significantly predict aminoglycoside-induced ototoxicity. CONCLUSION: Incidence of aminoglycoside-induced ototoxicity in DR Tb patients was 22.9%. The clinical predictors for ototoxicity were age, BMI on admission, and co-existing retroviral infection in the patients. Clinicians should consider these factors in making choices of aminoglycosides to be used during intensive phase of treatment with second line anti-Tuberculous therapy.


Subject(s)
Antitubercular Agents/therapeutic use , Hearing Loss/chemically induced , Kanamycin/adverse effects , Tuberculosis, Multidrug-Resistant/drug therapy , Adult , Age Factors , Aminoglycosides/administration & dosage , Aminoglycosides/adverse effects , Audiometry, Pure-Tone , Body Mass Index , Coinfection , Comorbidity , Cycloserine/therapeutic use , Diabetes Mellitus/epidemiology , Female , HIV Infections/epidemiology , Hearing Loss/epidemiology , Humans , Kanamycin/administration & dosage , Levofloxacin/therapeutic use , Male , Middle Aged , Nigeria/epidemiology , Prospective Studies , Prothionamide/therapeutic use , Pyrazinamide/therapeutic use , Risk Factors , Time Factors , Young Adult
10.
Korean J Gastroenterol ; 67(5): 267-271, 2016 May 25.
Article in Korean | MEDLINE | ID: mdl-27206439

ABSTRACT

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.


Subject(s)
Drug Hypersensitivity Syndrome/etiology , Ethambutol/therapeutic use , Hepatitis, Autoimmune/diagnosis , Isoniazid/therapeutic use , Tuberculosis/drug therapy , Alanine Transaminase/metabolism , Antitubercular Agents/adverse effects , Antitubercular Agents/therapeutic use , Cycloserine/therapeutic use , Drug Therapy, Combination , Eosinophilia/etiology , Ethambutol/adverse effects , Female , Hepatitis, Autoimmune/etiology , Hepatitis, Autoimmune/pathology , Humans , Isoniazid/adverse effects , Levofloxacin/therapeutic use , Liver/enzymology , Prothionamide/therapeutic use , Severity of Illness Index , Young Adult
12.
Yonsei Med J ; 56(4): 961-7, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26069117

ABSTRACT

PURPOSE: Low serum concentrations of drugs used to treat multi-drug resistant tuberculosis (MDR-TB) have occasionally been associated with treatment failure. We determined the frequencies of low serum concentrations of anti-MDR-TB drugs, and assessed the effects of these concentrations on 2-month sputum conversion. MATERIALS AND METHODS: The serum levels of moxifloxacin (MF), prothionamide (PTH), and cycloserine (CS) were determined for 89 serum samples by high-pressure liquid chromatography-tandem mass spectrometry. RESULTS: Low serum concentrations of MF, PTH, and CS below the minimal levels of the normal ranges were 83.3% (20/24), 59.2% (29/49), and 71.2% (47/66), respectively. There were no significant differences between the 2-month sputum conversion group (n=25) and the 2-month sputum non-conversion group (n=4) in median drug concentrations (µg/mL) of MF (1.46 vs. 1.60), PTH (0.91 vs. 0.70), and CS (14.90 vs. 14.90). However, a poor compliance rate was significantly greater in the 2-month sputum non-conversion group (75.0%, 3/4) than in the 2-month sputum conversion group (0%, 0/25) (p=0.001). CONCLUSION: The frequency of low serum concentrations of anti-MDR-TB drugs was substantial and might not affect the 2-month sputum conversion rate. Larger prospective studies with timely sampling are needed to investigate the role of therapeutic drug monitoring in MDR-TB.


Subject(s)
Antitubercular Agents/pharmacokinetics , Cycloserine/pharmacokinetics , Fluoroquinolones/pharmacokinetics , Prothionamide/pharmacokinetics , Sputum/microbiology , Tuberculosis, Multidrug-Resistant/drug therapy , Adult , Aged , Antitubercular Agents/blood , Antitubercular Agents/therapeutic use , Chromatography, High Pressure Liquid , Cycloserine/blood , Cycloserine/therapeutic use , Fluoroquinolones/blood , Fluoroquinolones/therapeutic use , Humans , Medication Adherence , Middle Aged , Moxifloxacin , Prothionamide/blood , Prothionamide/therapeutic use , Retrospective Studies , Tandem Mass Spectrometry , Tuberculosis, Multidrug-Resistant/blood , Young Adult
13.
Int J Tuberc Lung Dis ; 19(5): 517-24, 2015 May.
Article in English | MEDLINE | ID: mdl-25868018

ABSTRACT

SETTING: Two specialised multidrug-resistant tuberculosis (MDR-TB) treatment units in Cameroon. OBJECTIVE: To assess outcome and adverse drug events with a standardised 12-month regimen for MDR-TB among second-line drug naïve patients. DESIGN: Prospective observational study of MDR-TB patients treated with a standardised 12-month regimen including gatifloxacin, clofazimine, prothionamide, ethambutol and pyrazinamide throughout, supplemented by kanamycin and isoniazid during an intensive phase of a minimum of 4 months. Progress was monitored monthly until treatment completion and twice over one year after treatment cessation. RESULTS: Eighty-seven potentially eligible patients were lost and never treated due to delayed availability of test results. Among the 150/236 eligible and treated patients, 134 (89%) successfully completed treatment, 10 died, 5 were lost, 1 failed and none relapsed. The patients' mean age was 33.7 years (range 17-68), 73 (49%) were females, 120 (80%) had failed on previous treatment, 30 (20%) were human immunodeficiency virus seropositive, 62 (43%) had a body mass index <18.5 kg/m(2) and 41 (27%) had radiographic involvement of five or six of the six lung zones. The most important adverse drug event was hearing impairment, which occurred in 46 of 106 (43%) patients. CONCLUSIONS: These results add further evidence for the usefulness of shorter, standardised regimens among patients without second-line drug resistance.


Subject(s)
Antitubercular Agents/adverse effects , Antitubercular Agents/therapeutic use , Drug-Related Side Effects and Adverse Reactions/epidemiology , Medication Adherence/statistics & numerical data , Tuberculosis, Multidrug-Resistant/drug therapy , Adolescent , Adult , Aged , Cameroon , Clofazimine/therapeutic use , Cohort Studies , Confidence Intervals , Developing Countries , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Ethambutol/therapeutic use , Female , Fluoroquinolones/therapeutic use , Gatifloxacin , Humans , Isoniazid/therapeutic use , Kanamycin/therapeutic use , Male , Middle Aged , Odds Ratio , Prospective Studies , Prothionamide/therapeutic use , Pyrazinamide/therapeutic use , Risk Assessment , Time Factors , Treatment Outcome , Tuberculosis, Multidrug-Resistant/diagnosis , Young Adult
14.
Medicina (Kaunas) ; 49(7): 335-40, 2013.
Article in English | MEDLINE | ID: mdl-24375246

ABSTRACT

BACKGROUND AND OBJECTIVE: Since 1990, the tuberculosis incidence rate in Eastern Europe and post-Soviet republics has been increasing in many countries including Kazakhstan. This problem is particularly important in Kazakhstan regions with limited financial resources, among them - in South Kazakhstan province. The aim of this study was to investigate the main clinical and antibiotic-related economic aspects of tuberculosis treatment in South Kazakhstan province. MATERIAL AND METHODS: In total, 502 patients participated in the study. They were hospitalized to the tuberculosis dispensary of Sayram district (South Kazakhstan province) in 2007-2013. Statistical analysis included logistic regression for better treatment outcomes and analysis of antibiotic treatment costs. RESULTS: Two-thirds of patients had infiltrative tuberculosis (67%). Positive treatment outcomes were determined in 85% of cases. The patients were mostly treated with cycloserine, protionamide, capreomycin, and ofloxacin. The majority of antibiotic costs were related to the treatment with capreomycin. In case of the positive results of the test for Mycobacterium tuberculosis, antibiotic expenses were almost 3 times greater than in case of negative test results (P<0.001). CONCLUSIONS: The majority of patients had extensively drug-resistant tuberculosis. The negative results of the test for Mycobacterium tuberculosis at discharge were not related to pretreatment factors. Antibiotic-related costs were significantly higher in case of the positive results of the test of Mycobacterium tuberculosis, but were not associated with gender, residence place, hospitalization recurrence, or main blood test results before treatment.


Subject(s)
Anti-Bacterial Agents/economics , Antitubercular Agents/economics , Drug Costs , Tuberculosis, Multidrug-Resistant/economics , Tuberculosis, Pulmonary/economics , Adult , Anti-Bacterial Agents/therapeutic use , Antitubercular Agents/therapeutic use , Capreomycin/economics , Capreomycin/therapeutic use , Cycloserine/economics , Cycloserine/therapeutic use , Female , Humans , Kazakhstan/epidemiology , Male , Middle Aged , Ofloxacin/economics , Ofloxacin/therapeutic use , Prothionamide/economics , Prothionamide/therapeutic use , Treatment Outcome , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy
15.
Zhonghua Jie He He Hu Xi Za Zhi ; 36(10): 737-40, 2013 Oct.
Article in Chinese | MEDLINE | ID: mdl-24433800

ABSTRACT

OBJECTIVE: To investigate drug-induced liver injury (DILI) in tuberculosis (TB) patients treated with protionamide (Pto) and (or) para-aminosalicylic acid (PAS), and therefore to provide data for using second-line anti-tuberculosis drugs and risk prediction of liver damage. METHODS: A retrospective analysis was performed for TB patients treated with regimens containing Pto and (or) PAS in Beijing Chest Hospital during Jan. 2008 to Jan. 2013. Cases with DILI were identified, and associated factors including patients' age and gender, time of onset, severity, clinical manifestations and prognosis of DILI were analyzed. The 2 groups were compared with χ(2) test. P < 0.05 was considered to be significant. RESULTS: A total of 1714 cases were admitted, among whom 226 experienced liver damage during treatment, of which 97 cases were excluded because of underlying alcoholic liver disease, viral hepatitis B and C. Finally, 129 cases were diagnosed as having DILI, resulting in an overall incidence of 7.5% (129/1714), being 9.2% (59/641) in females, and 6.5% (70/1073) in males (χ(2) = 4.143, P < 0.05). DILI in most patients occurred between 1 week to 2 months, with 30.2% (39/129) within 2-4 weeks. 47.3% (61/129) of the patients showed no obvious clinical symptoms of hepatotoxicity. Among different regimens, combination of Pto, PAS and PZA resulted in the highest rate of DILI (20.7%, 19/92), while the rate was 9.8% (8/82) for the combination of Pto and PZA, P < 0.05. CONCLUSIONS: DILI caused by Pto and PAS should be taken into account, especially in female patients and for multi-drug combination therapy. Liver function should be monitored even in patients without related clinical manifestations for early identification and treatment, and therefore avoiding severe liver damage.


Subject(s)
Aminosalicylic Acid/adverse effects , Antitubercular Agents/adverse effects , Chemical and Drug Induced Liver Injury/epidemiology , Prothionamide/adverse effects , Adolescent , Adult , Aged , Aminosalicylic Acid/therapeutic use , Antitubercular Agents/therapeutic use , Chemical and Drug Induced Liver Injury/drug therapy , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Prothionamide/therapeutic use , Retrospective Studies , Risk Factors , Tuberculosis/drug therapy , Young Adult
16.
Microb Drug Resist ; 16(1): 81-6, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20192820

ABSTRACT

The limited experience in treating patients with extensively drug-resistant tuberculosis (XDR-TB) shows a therapeutic success rate under 50-60% and there are no publications regarding the outcome of these patients treated with standardized regimens. All multidrug-resistant tuberculosis (MDR-TB) patients hospitalized at the Masih Daneshvari Hospital in Tehran, Iran, during 2004-2007 were recruited. Drug susceptibility testing to 14 drugs (including eight second-line drugs) was performed and a standardized regimen with ofloxacin, cycloserine, prothionamide, and amikacin was administered for all patients. Outcome of the patients was studied, comparing between the MDR-TB non-XDR-TB and the XDR-TB. Fifty-one patients were included, 12 with XDR-TB criteria. Of 51, 48 were HIV negative and HIV status was unknown in three cases. All 12 were HIV negative. XDR-TB infection was significantly associated only with age (p = 0.039). The success rates for the total 51 MDR-TB, the 39 MDR-TB non-XDR-TB, and the 12 XDR-TB patients were 76.5% (39 patients), 87.2% (34 patients), and 41.7% (5 patients), respectively. Resistance to ofloxacin, ciprofloxacin, and amikacin were found to be significantly associated with unsuccessful outcome. In this setting, a standardized second-line drugs regimen produces high treatment success rates in MDR-TB patients unless XDR-TB is present.


Subject(s)
Amikacin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Cycloserine/therapeutic use , Extensively Drug-Resistant Tuberculosis/drug therapy , Mycobacterium tuberculosis/drug effects , Ofloxacin/therapeutic use , Prothionamide/therapeutic use , Tuberculosis, Pulmonary/drug therapy , Adult , Clinical Protocols , Drug Resistance, Multiple, Bacterial , Drug Therapy, Combination , Female , Humans , Iran , Male , Microbial Sensitivity Tests , Treatment Outcome
17.
Probl Tuberk Bolezn Legk ; (1): 36-40, 2009.
Article in Russian | MEDLINE | ID: mdl-19256011

ABSTRACT

The efficiency of treatment was analyzed in 142 children aged 3-14 years who had local forms of primary pulmonary tuberculosis. Therapy was performed according to regimens 3 and 1, by using individual dosage regimens depending on the extent and severity of a specific process, the presence of complications, and age-related features. In minor tuberculosis, solitary calcifications being detected without signs of the activity of tuberculous infection, the basic course of therapy was 6-8 months; it was performed using 2 drugs in individual cases. In disseminated and complicated processes, eliminated intoxication and visible X-ray inflammatory changes were observed in 58.8-61.7% of children by months 3-4 of treatment, which required a longer intensive phase, by administering 3 drugs in the continuation phase till 6-9 months.


Subject(s)
Antitubercular Agents/therapeutic use , Tuberculosis, Pulmonary/drug therapy , Adolescent , Age Factors , Antibiotics, Antitubercular/administration & dosage , Antibiotics, Antitubercular/therapeutic use , Antitubercular Agents/administration & dosage , Antitubercular Agents/adverse effects , Child , Child, Preschool , Cycloserine/administration & dosage , Cycloserine/therapeutic use , Drug Therapy, Combination , Ethambutol/administration & dosage , Ethambutol/therapeutic use , Humans , Isoniazid/administration & dosage , Isoniazid/therapeutic use , Prothionamide/administration & dosage , Prothionamide/therapeutic use , Pyrazinamide/administration & dosage , Pyrazinamide/therapeutic use , Radiography, Thoracic , Rifampin/administration & dosage , Rifampin/therapeutic use , Streptomycin/administration & dosage , Streptomycin/therapeutic use , Time Factors , Tuberculosis, Lymph Node/diagnosis , Tuberculosis, Lymph Node/drug therapy , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/diagnostic imaging
19.
Lepr Rev ; 79(4): 410-5, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19274987

ABSTRACT

The Malta Leprosy Eradication Project (MLEP) was proposed in 1971 by Freerksen with the aim of eradicating leprosy in Malta. The project involved re-treatment of all known cases in Malta as of 1972 and all new cases thereafter with a regimen consisting of Isoprodian (a combination of dapsone, prothionamide and isoniazid) and rifampicin for varying intervals depending on the severity of their disease and their response to treatment. Overall the response to therapy was excellent with an extremely low relapse rate. During the 30 years of the project the incidence of leprosy steadily decreased continuing a decline that had started at least two decades earlier and Freerksen declared the disease eradicated from Malta in 2001. Although given the long incubation period of leprosy cases may still be occasionally detected in the future, the disease has been basically eradicated at this time and there are no patients currently receiving treatment. This work was done at the leprosy clinic, Boffa Hospital, Floriana, Malta.


Subject(s)
Dapsone/therapeutic use , Isoniazid/therapeutic use , Leprostatic Agents/therapeutic use , Leprosy/drug therapy , Prothionamide/therapeutic use , Rifampin/therapeutic use , Dapsone/administration & dosage , Drug Combinations , Drug Therapy, Combination , Female , Humans , Isoniazid/administration & dosage , Leprostatic Agents/administration & dosage , Leprosy/epidemiology , Male , Malta/epidemiology , Program Evaluation , Prothionamide/administration & dosage , Rifampin/administration & dosage , Treatment Outcome
20.
Fontilles, Rev. leprol ; 25(6): 485-516, sept.-dic. 2006.
Article in Es | IBECS | ID: ibc-71505

ABSTRACT

El tratamiento de la lepra ha variado, crecido y mejorado ostensiblemente en los últimos años y ello ha ayudado a eliminar esta enfermedad como problema de Salud Pública en muchos países. Sin embargo, son necesarios aún más estudios para el desarrollo de nuevos tratamientos. La llegada de nuevas drogas al arsenal terapéutico, como el ofloxacino o la minociclian, van sin dudas a reducir el tiempo de tratamiento, así como disminuir la aparición de efectos colaterales frecuentes en los esquemas hasta ahora recomendados. La talidomida, redescubierta en la actualidad como droga muy importante, no sólo para las leprorreacciones sino además para otras muchas patologías con importante componente inmunológico/inflamatorio, es objeto de numerosas investigaciones en la actualidad. Y, sobre todo, reconocer esta enfermedad que es la lepra como la expresión de una complicada – pero cada vez mejor conocida- cascada de acontecimientos inmunológicos, ha abierto un sinfín de nuevas posibilidades en el campo de la terapéutica, los inmunomoduladores, que también desempeñan un importante papel durante los episodios reacciónales, los cuales continúan siendo, a pesar de los avances actuales, el auténtico problema para el paciente bajo tratamiento. Como esta enfermedad infecciosa, la vacuna debe ser al final el objeto de todas las investigaciones, pues con la desaparición de la susceptibilidad de la población, el resto de los tratamientos, si no existen pacientes, poco han de aportar. Nuevas vacunas están haciendo su aparición en el abanico terapéutico de la lepra, de forma aislada o sumadas a los tratamientos por vía oral. Basado en las informaciones de textos de leprología actuales, así como en búsquedas en Internet acerca de investigaciones en curso sobre los nuevos tratamientos, este trabajo intenta mostrar un estudio cuidadoso de los esquemas terapéuticos en la actualidad y de las nuevas posibilidades que están surgiendo en los campos de la Farmacología y la Inmunología


The leprosy treatment has changed, grown and improved especially in the last few years, and this factor has helped to eliminate this disease as a Public Health problema inmany countries. Since the time the leprosy patients were espelled society until our days has improved very much. Although our country still has a big problem, and yet is necessary to do more research to develop new treatments. The introduction of new drugs to the therapeutic “arsenal”, as the ofloxacín or the minocicline, no doubt will reduce the time treatment, as to reduce the appearance of side-effect in the therapeutic plans recommended until now. The thalidomide, rediscovered nowadays as a drug very valued not only for the leprosy reactions as for the many other diseases with a very important immunological component/inflammatory is a target for many recent research. And for all, recognize this disease that is the leprosy as difficult expression but after all better known as an immunological cascade happening has opened many possibilities without an end in the therapeutically area, the immunomodulators, that develop a very important role during the reaction episodes, that continue to be, besides of the modern advances, the real treatment for the patients on treatment. As an infectious disease, the vaccine has to be the main objective of all the research, because with the with draw of the population susceptibility, the rest of the therapeutic if, doesn´t exist one sick, it won´t be necessary to add very much to it. New vaccines are appearing in the therapeutically leprosy cast, alone or together with the oral treatment. Based on the papers information about modern leprosy, as in research in the internet after information about new heading treatments, this paper is willing to show a new synthesized vision of the way followed in pharmacology for the leprosy treatment, studying carefully the therapeutically plans nowadays and showing new possibilities that are being evaluated in the pharmacology and immunology areas


Subject(s)
Humans , Leprosy/diagnosis , Leprosy/therapy , Ofloxacin/therapeutic use , Minocycline/therapeutic use , Mycobacterium leprae/isolation & purification , Mycobacterium leprae/pathogenicity , Sulfones/therapeutic use , Dapsone/therapeutic use , Drug Therapy, Combination , Thalidomide/therapeutic use , Clofazimine/therapeutic use , Prothionamide/therapeutic use , Ethionamide/therapeutic use , Rifampin/therapeutic use
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