ABSTRACT
Background & objectives: The National Tuberculosis (TB) Control Programme has transitioned from thrice-weekly to daily drug treatment regimens in India. This preliminary study was conceived to compare the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) in TB patients being treated with daily and thrice weekly anti-TB treatment (ATT). Methods: This prospective observational study was undertaken in 49 newly diagnosed adult TB patients receiving either daily ATT (n=22) or thrice-weekly ATT (n=27). Plasma RMP, INH and PZA were estimated by high-performance liquid chromatography. Results: The peak concentration (Cmax) of RMP was significantly higher (RMP: 8.5 ?g/ml vs. 5.5 ?g/ml; P=0.003) and Cmax of INH was significantly lower (INH: 4.8 ?g/ml vs. 10.9 ?g/ml; P<0.001) in case of daily dosing compared to thrice-weekly ATT. Cmax of drugs and doses was significantly correlated. A higher proportion of patients had subtherapeutic RMP Cmax (8.0 ?g/ml) during thrice-weekly compared to daily ATT (78% vs. 36%; P=0.004). Multiple linear regression analysis showed that Cmax of RMP was significantly influenced by the dosing rhythm, pulmonary TB and Cmax of INH and PZA by the mg/kg doses. Interpretation & conclusions: RMP concentrations were higher and INH concentrations were lower during daily ATT, suggesting that INH doses may need to be increased in case of a daily regimen. Larger studies are, however, required using higher INH doses when monitoring for adverse drug reactions and treatment outcomes.
ABSTRACT
Objective To investigate the clinical characteristics of drug-induced liver injury caused by anti-tuberculosis drugs in newly treated pulmonary tuberculosis patients with hepatitis B virus (HBV). Methods A total of 133 patients with pulmonary tuberculosis and HBV who were treated in Zhuzhou Central Hospital from January 2018 to early January 2022 were selected, and all were treated with conventional anti-tuberculosis 2HRZE/4HR regimen. According to the liver injury, the patients were divided into liver injury group and no liver injury group. Univariate analysis was used to analyze the related factors of liver injury caused by anti-tuberculosis drugs, and multivariate logistic regression analysis was used to analyze the independent risk factors of liver injury caused by anti-tuberculosis drugs. Results Among 133 cases of newly treated pulmonary tuberculosis patients with HBV, 24 cases had liver injury caused by anti-tuberculosis drugs, accounting for 18.05%; 109 patients had no liver injury caused by anti-tuberculosis drugs, accounting for 81.95%. Univariate analysis showed that there were significant differences in smoking history, drinking history, diabetes history, hypertension history, anti-tuberculosis treatment plan, malnutrition, and use of hepatoprotective drugs between the liver injury group and the no liver injury group (P<0.05). Multivariate logistic regression analysis showed that smoking history, drinking history, diabetes history, hypertension history, PZA-containing regimen, malnutrition, and no use of hepatoprotective drugs were independent risk factors for liver injury caused by anti-tuberculosis drugs. Conclusion Smoking history, drinking history, diabetes history, hypertension history, PZA-containing regimen, malnutrition, and no use of hepatoprotective drugs are the risk factors for drug-induced liver injury caused by anti-tuberculosis drugs in newly treated pulmonary tuberculosis patients with HBV.
ABSTRACT
Drug-induced liver injury (DILI) is a liver injury caused by various drugs, herbs, or other xenobiotics, which causes abnormalities in liver tests or liver dysfunction in the absence of other causes of liver damage. The most common causative drugs are antituberculosis drugs (ATDs), anti-infective drugs, and natural herbal medicines. The diagnosis of DILI can be difficult due to the lack of specific signs, symptoms and tests and is partly a diagnosis based on exclusion. In this case report, we will discuss how to diagnosis DILI TB and causative assessment using RUCAM score. A male, 64 years old, has complained of weakness since 1 week ago and worsened since 1 day ago. The patient also felt persistent nausea for 1 week, so his eating and drinking decreased. Besides, he complained getting abdominal pain, especially in the upper right region and heartburn. The patient has been on first category of TB treatment since 20 days ago. Chest X-ray showed Lung TB with infiltrate inmultiple cavities. Abdominal ultrasound showed no abnormality. The patient was discharged from our hospital after 6 days of hospitalization. DILI remains a diagnosis of exclusion based primarily on a detailed history and judicious use of blood tests, hepatobiliary imaging, and liver biopsy. TheRoussel Uclaf causality assessment method (RUCAM)system is an assigning point for clinical, biochemical, serologic and radiologic features of liver injury. We use RUCAM score to make an assessment that show the likelihood of the hepatic injury due to a specific medication.
ABSTRACT
OBJECTIVE：To systematically evaluate the efficacy and safety of linezolid （LZD）combined with routine anti- tuberculosis drugs in the treatment of tuberculous meningitis （TBM），so as to provide evidence-based reference for clinical medi- cation. METHODS ：Retireved from PubMed ，Cochrane Library ，Embase，CNKI and Wanfang database ，randomized controlled trials（RCT）of LZD combined with routine anti-tuberculosis drugs （trial group ）versus routine anti-tuberculosis drugs （control group）were collected from the inception to Jan. 2020. After literature screening and data extraction ， the quality of the included literature were evaluated with bias risk assessment tool recommended by Cochrane system evaluator handbook 5.2. Meta-analysis was conducted by using Rev Man 5.3 software，and sensitivity analysis and publication bias analysis were performed. RESULTS ： Totally 9 RCTs involving 602 patients were included. Meta-analysis showed that total response rate [OR ＝4.05，95％CI（2.26，7.26）， P＜0.000 01]， changes of protein content of cerebrospinal fluid [MD ＝0.48，95％CI（0.20，0.77），P＝0.000 8]，changes of white blood cells count of cerebrospinal fluid [MD ＝44.43，95％CI（20.06，68.81），P＝0.000 4]，changes of cerebrospinal fluid glucose/ synchronous blood glucose [MD ＝0.09，95％CI（0.05，0.14），P＜0.000 1] of trial group were significantly higher than those of control group. There was no statistical significance in the changes of chloride content of cerebrospinal fluid [MD ＝8.08，95％CI（－0.64， 16.80），P＝0.07] and the incidence of ADR [OR ＝1.34，95％CI（0.57，3.11），P＝0.50] between 2 groups. The results of sensitivity analysis showed that there were significant differences comparison with before exclusion when the change of protein content in cerebrospinal fluid and the change of glucose/synchronous blood glucose in cerebrospinal fluid were taken as indexes ，and there was no significant difference comparison with before exclusion when the changes of white blood cell count and chloride content in cerebrospinal fluid were taken as indexes. The results of publication bias analysis showed that there was a certain publication bias in this study. CONCLUSIONS ：LZD combined with conventional anti-tuber culosis drugs is effective and safe for TBM. Because the inconsistent results of sensitivity analysis and publication bias exists in publication bias analysis ，the conclusions need to be further confirmed by more large sample and multi-center studies.
ABSTRACT
@#Tuberculosis(TB)treatment is currently falling into a gigantic dilemma-particularly with the increased frequentcy TB resistance, so the development of new anti-tuberculosis drugs is imperative and has received extensive attention. In the past decade, significant progress has been made in this field. Bedaquiline, delamanid and pretomanid have been approved for the clinical use. In addition, many other drugs and combination protocols are undergoing clinical trials. This review focuses on the new chemical entities for TB treatments from multiple perspectives, including the mechanisms of action, in vitro and in vivo pharmacological activities, pharmacokinetic properties and clinical results. Anti-tuberculosis drug research is prospected to provide a reference for drug deve-lopment.
ABSTRACT
Introduction: The occurrence of multi-drug resistance tuberculosis among tuberculosis patients has raised global public health concern, especially in Nigeria. The increase in the number of cases of resistance tuberculosis despite the effort and need to curb the menace in Nigeria led to this study. Aim of the Study: The aim was to investigate the effect of anti-Tuberculosis drugs on patients with multi-drug resistance Tuberculosis in Mainland Hospital Yaba, Lagos. Materials and Methods: This was a cross-sectional descriptive study of the already confirmed multi-drug resistance tuberculosis patients at the Mainland Hospital Yaba, Lagos .One hundred self-structured interview questionnaires were randomly administered among already confirmed mult-drug resistance tuberculosis patients at the hospital to collect bio-data information, and thereafter, received second-line anti-Tuberculosis drugs in phases for 22 months Results and Discussion: The patients received the following regimen of treatments based on their weights and ages, the selected regimens administered for 22 months comprised of two phases; first, 8 months of intensive phase of Kanamycin, levofloxacin, cycloserine, prothionamide,and pyrazinamide and second, 12 months of Levofloxacin, cycloserine, prothionamide and pyrazinamide. Post laboratory analysis was used to monitor the effectiveness of the second-line anti-Tuberculosis drugs used. Out of the 92 patients that received the drugs, 89(96.7%) were confirmed negative to multi-drug resistance tuberculosis, while 3(3.3%) were still positive. Conclusion:The anti-Tuberculosis drugs in the order used is highly recommended for the reduction if not total eradication of multi-drug resistance tuberculosis in Nigeria. Effort should be geared towards making sure that the multi-drug resistance tuberculosis patients are confined, proper regimen administered and monitored in order to reduce the rate of spread
ABSTRACT
Background & objectives: studies have shown the bactericidal potential of econazole and clotrimazole against Mycobacterium tuberculosis under in vitro and ex vivo conditions along with their synergism with conventional antituberculosis drugs. these molecules were also found to be effective against different multidrug resistant (MDR) M. tuberculosis isolates in vitro. Hence the present study was designed to evaluate the in vivo antimycobacterial potential of moxifloxacin and econazole alone and in combination against multidrug resistant tuberculosis (MDR-TB) in a mice model. Methods: Mice were infected with 2.5×107 bacilli of MDR strain of M. tuberculosis by aerosol route of infection. After four weeks of infection, chemotherapy was started orally by moxifloxacin 8.0 mg/kg body wt and econazole 3.3 mg/kg alone and in combination, as well as with four first line anti-tuberculosis drugs as a positive control. The animals were sacrificed and the lungs and spleen were excised under aspetic conditions. The tissues were homogenized with sterile normal saline, an aliquot of the homogenate was plated on Middlebrook 7H11 agar supplemented with oleate albumin dextrose catalase (OADC) and incubated at 37°C for four weeks. The number of visible and individual colonies were counted. Results: The first line anti-tuberculosis drugs (RIF+INH+EMB+PZA) after eight weeks of therapy had no impact as the bacillary load in lungs and spleens remained unchanged. However, econazole, moxifloxacin alone as well as in combination significantly reduced the bacillary load in lungs as well as in spleens of MDR-TB bacilli infected mice. Interpretation & conclusions: Co-administration of the two drugs (econazole and moxifloxacin) to MDR-TB strain JAL-7782 infected mice exhibited additive effect, the efficacy of the drugs in combination being higher as compared with ECZ or MOX alone. These results were substantiated by histopathological studies. This study suggests the utility of econazole for the treatment of MDR tuberculosis and warrants further work in this direction.
ABSTRACT
Objective: To explore the pharmaceutical care mode for drug treatment and interactions through participating in the treatment of patients using cyclosporine A combined with anti-tuberculosis ( TB) drugs. Methods: The clinical questions were pro-posed and refined, the literature evidence was retrieved in the electronic databases, the questions were answered and the procedure and mode of pharmaceutical care for the similar clinical problems was established. Results:For the patients with cyclosporine A treatment, strong anti-TB drugs should be chosen to ensure the effectiveness and decrease the drug interactions, and the concentration monitoring of cyclosporine A should be paid more attention. Conclusion: Clinical pharmacists can implement the pharmaceutical care for the pa-tients with immunosuppression and TB infection through developing anti-TB regimen, avoiding the drug interactions, improving the drug safety and so on.
ABSTRACT
Introduction: Many aspects of tuberculosis (TB) and its treatment can compromise patients' quality of life (QOL). Treatment of active TB requires prolonged therapy with multiple drugs that can lead to adverse reactions. There is considerable social stigma associated with TB, leaving the individual feeling shunned and isolated. Hence, it is necessary that for a thorough assessment of patients' health status, overall impact of TB on patient's QOL should be considered. Materials and Methods:Thirty newly diagnosed smear positive cases of pulmonary TB, of either gender were interviewed using - WHO QOL BREF, which is a 26-item scale designed by WHO. It has four domains viz.: Physical health, psychological health, social relationships, and environment. Interviews were conducted thrice: Before starting treatment, after 2 months, and after 4 months of treatment. Controls ( n = 30) were selected from the general population and interviewed using same questionnaire. Results:Before treatment, scores in all domains were significantly lower in patients than controls. Worst affected were physical domain followed by psychological. Gradual increase in scores was observed over the course of treatment, indicating positive effect of medical intervention on QOL. Despite improvements, the scores in physical and psychological domain after 4 months of treatment were still significantly lower in patients than in controls. Conclusion: Measurement of QOL in TB is essential to have an in-depth understanding of effect of disease on various dimensions of health. This would enable health care professionals to devise relevant interventions such as patient counselling which would be useful in further improving quality of TB control programs.
ABSTRACT
Genetic variants in ATP-binding cassette (ABC) transporter genes are associated with increased susceptibility to adverse drug reactions. We hypothesized that genetic variant ABC transporters (ABCB1 and ABCC2) may be candidate markers for predicting maculopapular eruption (MPE) induced by antituberculosis therapy. We compared the genotype distributions of single nucleotide polymorphisms and haplotypes in the ABCB1 and ABCC2 genes between 62 antituberculosis drug (ATD)-induced MPE cases and 159 ATD-tolerant controls using multivariate logistic regression analysis. There was no significant association between genetic polymorphisms in ABCB1 and ATD-induced MPE (P>0.05). Among seven selected SNPs of ABCC2, IVS3-49C>T in intron and I1324I were associated with ATD-induced MPE (P=0.029 and 0.036, respectively). In an analysis of the ABCC2 haplotypes (ht; -1549G>A_-24C>T_IVS3-49C>T_V417I), ht1[G-C-C-G] was significantly associated with ATD-induced MPE (P=0.032, OR=0.35, 95% CI: 0.16-0.95). No significant association between the other haplotypes and ATD-induced MPE was observed. An ABCC2 haplotype is associated with the presence of ATD-induced MPE in patients with tuberculosis and may be a genetic risk factor for the development of MPE induced by ATD.
Subject(s)
Humans , ATP-Binding Cassette Transporters , Drug-Related Side Effects and Adverse Reactions , Genotype , Haplotypes , Introns , Logistic Models , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Risk Factors , TuberculosisABSTRACT
RATIONALE: Among the first line antituberculosis (anti-TB) drugs, the major drug incriminated in the development of hepatotoxicity is isoniazid (INH). The human N-acetyl transferase2 (NAT2) gene is mainly responsible for INH metabolism. This gene exhibits a hereditarily determined polymorphism. There is presently no study on the predominant NAT2 genotype among Filipinos. There are also no Filipino studies on the incidence of hepatitis and other adverse effects of first line anti-TB drugs. OBJECTIVES: To determine the predominant NAT2 genotype and its association with the development of hepatitis among Filipino children given first line anti-TB drugs (INH, rifampicin and pyrazinamide) and to determine the incidence of hepatitis and other serious adverse reactions to these drugs. STUDY DESIGN: Prospective cohort study SETTING: Tertiary government hospital in Metro Manila STUDY POPULATION: Children on to 18 years old with pulmonary tuberculosis and normal liver function test at baseline. METHODS: Total bilirubin (TB), direct bilirubin (DB) and liver transaminases (AST and ALT) were checked routinely at baseline and at thow, four, eight and 12 weeks after starting treatment. Within the first month of treatment, blood was also taken for NAT2 genotyping. The identification of the three NAT2 polymorphisms that are associated with a slow acetylator status - 481C to T (NAT2*5), 950G to A (NAT2*6) and 857G to A (NAT2*7) was carried out by polymerase chain reaction-restriction fragment length polymorphism. All patients were followed up for a total of six months. The presense of any adverse effects like gastroinstestinal symptoms, rash, hepatitis or drug fever was also monitored. RESULTS: A total of 24 children [mean age: 5 years; 11 males] were included. Majority (96%) were diagnosed by passive detection and mean Z score was - 1.38 (1 to -3). No patient developed hepatotoxicity or any side effects to anti-TB drugs. In 23 patients who had NAT2 genotyping, 39% and 22% were alleles homozygous for the NAT2*6 and NAT2*7, respectively. There was a combination of alleles in only three (13%) subjects. CONCLUSION: NAT2*6 and NAT2*7 alleles associated with a slow acetylator status were detected among our patients although the presence of these variants did not lead to any hepatotoxicity nor any treatment-related side effects. A larger study with broader genotype analysis is needed to confirm the present findings.
Subject(s)
Humans , Male , Female , Adolescent , Child , Infant , Isoniazid , Pyrazinamide , Rifampin , Alleles , Bilirubin , Liver Function Tests , Transaminases , Antitubercular Agents , Tuberculosis, Pulmonary , Hepatitis , Polymorphism, GeneticABSTRACT
Objective To explore the therapeutic effect of Fuzbeng-Liqi mixture on hepatitis resulted from anti-tuberculosis drugs.Methods 100 inpatients of hepatitis resulted from anti-tuberculosis drugs during January 2005 to December 2007 were randomly sorted out into a treatment group and a control group.The treatment group was treated with Fuzbeng-Liqi mixture,and the control group was treated with routine drugs.The effect was analyzed by 2/2 test.Results The therapeutic effect of the treatment group markedly excelled than the control group in terms of symptoms improvement such as nausea or vomit,tiredness,icterus,bepatalgia,or augment of liver.Conclusion Fuzbeng-Liqi mixture was not only able to ameliorate the clinical manifestations of drug-induced hepatitis,but also improve hepatic function.
ABSTRACT
The value of susceptibility tests in guiding antituberculous therapy with second-line drugs remains controversial. We reanalyzed three reports regarding the relationship between in vitro susceptibility of Mycobacterium tuberculosis and the clinical outcome of in-patients treated with these drugs at the Muñiz Hospital, Buenos Aires, during the sixties. These patients had been irregularly treated with a standard regimen consisting of isoniazid, streptomycin and PAS; they developed resistance to at least the first two drugs and persisted culture-positive. Susceptibility testing to ethionamide, cycloserine and kanamycin were performed by the proportion method on Löwenstein Jensen medium. Some level of resistance was detected among isolates from patients not previously treated with these drugs, that could be due to cross resistance with previously administered first line structural analogs. However, the studies evidenced significant association between resistance to ethionamide and cycloserine and prior treatment with these drugs. Increased resistance to all three drugs was detected within the first three months of treatment. In vitro resistance to ethionamide emerged earlier and was the most frequent followed by resistance to cycloserine and kanamycin. The low frequency of resistance to kanamycin could be related to the low dosage of this drug used at that time. Simultaneous resistance to the three agents, but not to two or one drug, appeared to be a marker of treatment failure. An apparent reversion of drug resistance was observed in near 6% of patients, for whom susceptibility tests were repeated on subsequent isolates, indicating this percentage of inconsistency in reproducibility of test results.
La correlación entre resultados de pruebas de sensibilidad a drogas antituberculosas de segunda línea y evolución de los pacientes en tratamiento, aún es discutida. Se reanalizan aquí tres estudios realizados en la década del 60, sobre la relación entre resultados de pruebas de sensibilidad y tratamiento con estas drogas, en pacientes crónicos, internados en el hospital Muñiz, Buenos Aires, que habían sido tratados con el entonces régimen estándar, integrado por isoniacida, estreptomicina y PAS; se habían hecho resistentes al menos a dos de estas drogas y continuaban con cultivo positivo. La prueba de sensibilidad a etionamida, cicloserina y kanamicina se efectuó por el método de las proporciones en medio Löwenstein Jensen. Entre 4 y 13% de los pacientes previamente no tratados con estas drogas presentó cierto nivel de resistencia, fenómeno atribuido a la administración previa de drogas de primera línea con moléculas análogas. Se halló asociación significativa entre resistencia a etionamida y cicloserina, y tratamiento previo con estas drogas. La resistencia a las tres drogas fue detectada en los primeros tres meses de tratamiento, siendo la resistencia a etionamida la más frecuente, y la primera en emerger, seguida por cicloserina y kanamicina, cuya baja frecuencia en alcanzar resistencia estaría relacionada con las bajas dosis administradas. La resistencia simultánea a las tres drogas, pero no a una o dos, resultó marcadora de fracaso terapéutico. Se observó en cerca del 6% de los pacientes aparente reversión de la resistencia, en pruebas hechas en aislamientos sucesivos, interpretada como falla en la reproducibilidad de resultados.
Subject(s)
Humans , Anti-Bacterial Agents/therapeutic use , Antitubercular Agents/therapeutic use , Evidence-Based Medicine , Microbial Sensitivity Tests/standards , Mycobacterium tuberculosis/drug effects , Tuberculosis, Pulmonary/drug therapy , Argentina , Antibiotics, Antitubercular/therapeutic use , Antitubercular Agents/pharmacology , Clinical Trials as Topic , Cycloserine/therapeutic use , Drug Resistance, Microbial , Drug Therapy, Combination , Ethionamide/therapeutic use , Follow-Up Studies , Isoniazid/therapeutic use , Tuberculosis, Multidrug-Resistant , Tuberculosis, Pulmonary/microbiologyABSTRACT
Objective To analyze the drug therapeutic regimen and duration of the chemotherapy in the spinal tuberculosis in order to determine the best therapeutic regimen and duration of the spinal anti-tuberculo-sis. Methods The medication plan and duration of 890 hospitalized patients with spinal tuberculosis in our hospital from January 2001 to December 2008 were retrospectively investigated. We collected the plan of the initial treatment,retreatment,recrudescence and drug resistance. We also studied the individuation therapeutic regimen of the patients with tuberculosis at other parts or complications. On the basis of these data,we analyzed the interferential appearance that the antituberculosis drug acted on different onsets,manifestations and operations. Results In 890 patients of spinal tuberculosis,596 cases ( 67% ) were initial treatment,294 ( 33% ) were retreatment,recur cases were 110 ( 12. 3% ) ,drug resistance cases were 74( 8. 3% ) ,and those compli-cated with tuberculosis in other parts were 273 ( 30. 7% ) . The main chemotherapeutic regimen was the usual tetragenous protocol ( H12 /R12 /E9 /Z5 /S3) . The retreatment cases were given second-line drugs such as levo-floxacin. The drug resistance cases were also given second-line drugs and intravenous infusion. According to the anti-tubercle bacillus spectrum,individuation treatments were adopted,and the plan was changed in time. The medication duration continued for 9-36 months. All the 890 patients were cured. Conclusion For the treatment of spinal tuberculosis,it is significance to make a efficient and standardized anti-tuberculosis chemotherapy.