RESUMEN
Cutaneous mycobacterial infections cause substantial morbidity and are challenging to diagnose and treat. An improved understanding of the dermal immune response to mycobacteria may inspire new therapeutic approaches. We conducted a controlled human infection study with 10 participants who received 2 × 106 CFUs of Mycobacterium bovis bacillus Calmette-Guérin (Tice strain) intradermally and were randomized to receive isoniazid or no treatment. Peripheral blood was collected at multiple time points for flow cytometry, bulk RNA sequencing (RNA-seq), and serum Ab assessments. Systemic immune responses were detected as early as 8 d postchallenge in this M. bovis bacillus Calmette-Guérin-naive population. Injection-site skin biopsies were performed at days 3 and 15 postchallenge and underwent immune profiling using mass cytometry and single-cell RNA-seq, as well as quantitative assessments of bacterial viability and burden. Molecular viability testing and standard culture results correlated well, although no differences were observed between treatment arms. Single-cell RNA-seq revealed various immune and nonimmune cell types in the skin, and communication between them was inferred by ligand-receptor gene expression. Day 3 communication was predominantly directed toward monocytes from keratinocyte, muscle, epithelial, and endothelial cells, largely via the migration inhibitory factor pathway and HLA-E-KLRK1 interaction. At day 15, communication was more balanced between cell types. These data reveal the potential role of nonimmune cells in the dermal immune response to mycobacteria and the utility of human challenge studies to augment our understanding of mycobacterial infections.
Asunto(s)
Mycobacterium bovis , Piel , Humanos , Mycobacterium bovis/inmunología , Piel/inmunología , Piel/microbiología , Piel/patología , Masculino , Adulto , Isoniazida/uso terapéutico , Isoniazida/farmacología , Femenino , Tuberculosis/inmunología , Tuberculosis/microbiología , Adulto Joven , Antituberculosos/uso terapéuticoRESUMEN
BACKGROUND: Tuberculosis (TB) is a leading cause of death in patients with human immunodeficiency virus (HIV)/AIDS. About 60% of HIV-positive individuals with latent TB infection (LTBI) develop active TB. Isoniazid preventive therapy (IPT) is recommended by the World Health Organization to prevent the progression of active TB in people living with HIV/AIDS (PLWHA). However, IPT implementation has been limited in some countries like Indonesia. The objective of this study was to assess the effect of IPT administration on the incidence of active TB in HIV patients with latent TB. METHODS: This was a quasi-experimental prospective cohort study conducted in an academic hospital in Indonesia. Interferon-gamma release assay-positive HIV-TB patients were randomly divided into an IPT group (received 6 months of IPT) and a non-IPT group. The incidence of active pulmonary TB was compared between the two groups after 6 months of follow-up. RESULTS: Of the 23 eligible patients, 22 were enrolled (10 in the IPT group, 12 in the non-IPT group). The incidence of active pulmonary TB was 0% in both groups. Factors associated with the absence of TB in both groups were the use of antiretroviral therapy for >4 years and a CD4+ T lymphocyte count >200 cells/µL. IPT was found to be safe with minimal adverse effects. CONCLUSIONS: In this setting, the use of long-term antiretroviral therapy and higher CD4+ counts, rather than just IPT, were the key factors associated with preventing active TB in latent HIV-TB patients. These findings suggest that comprehensive HIV management may be more important than IPT alone for TB control in PLWHA. Further research is needed to optimize TB prevention strategies in this high-risk population.
Asunto(s)
Antituberculosos , Infecciones por VIH , Isoniazida , Tuberculosis Latente , Tuberculosis Pulmonar , Humanos , Isoniazida/uso terapéutico , Isoniazida/administración & dosificación , Tuberculosis Latente/complicaciones , Masculino , Antituberculosos/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Adulto , Femenino , Estudios Prospectivos , Tuberculosis Pulmonar/prevención & control , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/tratamiento farmacológico , Indonesia/epidemiología , Incidencia , Persona de Mediana Edad , Ensayos de Liberación de Interferón gammaRESUMEN
BACKGROUND: Tuberculosis (TB) is an airborne disease caused by Mycobacterium tuberculosis (M. tuberculosis). The world is currently facing challenges due to the spread of anti-tuberculosis drug-resistant of M. tuberculosis. Isoniazid-resistant (INH), is one of the first-line anti-tuberculosis agents that has a high resistance case. This study used Multiplex allele-specific Polymerase Chain Reaction (MAS-PCR) to detect the most common mutations associated with isoniazid resistance on inhA, katG, and ahpC gene. METHODS: This study used samples from clinical isolates of M. tuberculosis which had been tested for their antibiotic sensitivity of first-line anti-tuberculosis drugs. The DNA extraction process was carried out using the boiling method and then amplified with specific primers for inhA, katG, and ahpC genes using the MAS-PCR method. The results are then read on the electrophoretic gel with an interpretation of the mutation gene when the target gene DNA bands were absent according to the allele-specific fragments target. RESULTS: A total of 200 isolates were tested in this study consisting of isoniazid-resistant and susceptible with the largest distribution of Multi-Drug Resistant (MDR) isolates with a total of 146 isolates (73%). The most significant gene mutation was on the ahpC gene in 61 isolates (30,5%) and the combination mutation of the katG + ahpC gene in 52 isolates (26%) with sensitivity and specificity of the test reaching 87% and 42% for the detection of INH-resistant. CONCLUSION: Mutation on the ahpC gene has the highest percentage in this study. AhpC gene can be considered one of the essential genes to be tested for the cause of isoniazid-resistant. Using MAS-PCR for detecting gene mutation in isoniazid-resistant was simple and easy, it has the potential to be widely used as a rapid screening molecular test.
Asunto(s)
Antituberculosos , Proteínas Bacterianas , Catalasa , Isoniazida , Mutación , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Indonesia , Isoniazida/farmacología , Isoniazida/uso terapéutico , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Proteínas Bacterianas/genética , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Catalasa/genética , Oxidorreductasas/genética , Pruebas de Sensibilidad Microbiana , Femenino , Masculino , Adulto , Reacción en Cadena de la Polimerasa Multiplex , Farmacorresistencia Bacteriana Múltiple/genéticaRESUMEN
BACKGROUND: Among chronic condition problems, tuberculosis still represents a serious public health problem globally. OBJECTIVE: To investigate latent tuberculosis infection in patients with Crohn's disease. Retrospective, descriptive cross-sectional study of quantitative analysis. METHODS: The research was conducted on diagnosed cases of Crohn's disease at the University Hospital located in a city in Northeastern Brazil. All cases of patients with Crohn's disease undergoing isoniazid or rifampicin therapy for latent tuberculosis (LTBI) were included in the study. The data obtained were subsequently subjected to statistical analysis using the Statistical Package for the Social Sciences (SPSS) program. RESULTS: We analyzed 235 medical records, and it was observed that 56% were male, with a mean age of 42.7. Among these, 54% declared themselves as brown, 31% had completed high school, and 47% were residents of the city of Teresina. Regarding the clinical and epidemiological characteristics of the studied patients classified as having ILTB, 34% of the medical records were diagnosed by tuberculin test, 48.51% were investigated by x-ray examination, and the recent location affected the colon with 27%. CONCLUSION: Overall, the health profile of the participants in this study aligns with findings previously established in the literature, particularly studies conducted in other Brazilian states, as well as in other developing countries.
Asunto(s)
Enfermedad de Crohn , Hospitales Universitarios , Tuberculosis Latente , Humanos , Masculino , Estudios Retrospectivos , Enfermedad de Crohn/complicaciones , Femenino , Adulto , Estudios Transversales , Tuberculosis Latente/epidemiología , Tuberculosis Latente/complicaciones , Tuberculosis Latente/diagnóstico , Brasil/epidemiología , Hospitales Universitarios/estadística & datos numéricos , Persona de Mediana Edad , Adulto Joven , Adolescente , Rifampin/uso terapéutico , Anciano , Isoniazida/uso terapéutico , Antituberculosos/uso terapéuticoRESUMEN
Fluoroquinolone resistance is a major challenge in treating Multidrug-Resistant Tuberculosis globally. The GenoType MTBDRsl Ver 2.0, endorsed by the WHO, was used to characterize fluoroquinolone resistance. The fluoroquinolone resistance rates in the MDR-TB, Rifampicin-Resistant TB, and non-MDR-TB were 33%, 16.5%, and 5.4%, respectively. The most common mutation found in fluoroquinolone-resistant isolates was D94G (49.5%) in the gyrA gene. Of the 150 MDR-TB isolates, the prevalence of Extensively Drug-Resistant Tuberculosis and pre-XDR-TB was 1.33% and 30%, respectively. Among the 139 RR-TB isolates, pre-XDR-TB prevalence was 15.8%. The fluoroquinolone resistance rates were 5.12% among the 1230 isoniazid-monoresistant isolates. The study found that MDR-TB and RR-TB have higher risk of fluoroquinolone resistance than non-MDR tuberculosis. Rifampicin-resistant isolates with a mutation at codon S450L have a higher risk (RR = 12.96; 95%CI: 8.34-20.13) of developing fluoroquinolone resistance than isolates with mutations at other codons in the rpoB gene. Isoniazid-resistant isolates with a mutation at codon S315T have a higher risk (RR = 2.09; 95%CI: 1.25-3.50) of developing fluoroquinolone resistance. The study concludes that rapid diagnosis of fluoroquinolone resistance before starting treatment is urgently needed to prevent the spread and increase of resistance and to achieve better treatment outcomes in areas where it is higher.
Asunto(s)
Antituberculosos , Fluoroquinolonas , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Fluoroquinolonas/farmacología , Fluoroquinolonas/uso terapéutico , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efectos de los fármacos , Estudios Retrospectivos , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/transmisión , Tuberculosis Resistente a Múltiples Medicamentos/genética , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Masculino , Femenino , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología , Adulto , Mutación , Medición de Riesgo , Persona de Mediana Edad , Pruebas de Sensibilidad Microbiana , Rifampin/farmacología , Rifampin/uso terapéutico , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Tuberculosis Extensivamente Resistente a Drogas/microbiología , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple/genética , Isoniazida/farmacología , Isoniazida/uso terapéutico , AncianoRESUMEN
Tuberculosis (TB) preventive treatment (TPT) effectively prevents the progression from TB infection to TB disease. This study explores factors associated with TPT non-completion in Cambodia using 6-years programmatic data (2018-2023) retrieved from the TB Management Information System (TB-MIS). Out of 14,262 individuals with latent TB infection (LTBI) initiated with TPT, 299 (2.1%) did not complete the treatment. Individuals aged between 15-24 and 25-34 years old were more likely to not complete the treatment compared to those aged < 5 years old, with aOR = 1.7, p = 0.034 and aOR = 2.1, p = 0.003, respectively. Individuals initiated with 3-month daily Rifampicin and Isoniazid (3RH) or with 6-month daily Isoniazid (6H) were more likely to not complete the treatment compared to those initiated with 3-month weekly Isoniazid and Rifapentine (3HP), with aOR = 2.6, p < 0.001 and aOR = 7, p < 0.001, respectively. Those who began TPT at referral hospitals were nearly twice as likely to not complete the treatment compared to those who started the treatment at health centers (aOR = 1.95, p = 0.003). To improve TPT completion, strengthen the treatment follow-up among those aged between 15 and 34 years old and initiated TPT at referral hospitals should be prioritized. The national TB program should consider 3HP the first choice of treatment.
Asunto(s)
Antituberculosos , Isoniazida , Tuberculosis Latente , Rifampin , Humanos , Cambodia/epidemiología , Adolescente , Adulto , Femenino , Masculino , Adulto Joven , Antituberculosos/uso terapéutico , Estudios Retrospectivos , Isoniazida/uso terapéutico , Rifampin/uso terapéutico , Rifampin/análogos & derivados , Niño , Tuberculosis Latente/tratamiento farmacológico , Tuberculosis Latente/epidemiología , Tuberculosis Latente/prevención & control , Preescolar , Tuberculosis/prevención & control , Tuberculosis/epidemiología , Tuberculosis/tratamiento farmacológico , Persona de Mediana Edad , LactanteRESUMEN
BACKGROUND: Isoniazid preventive therapy (IPT) decreases risk of tuberculosis (TB) disease; impact on long-term infant growth is unknown. In a recent randomized trial (RCT), we assessed IPT effects on infant growth without known TB exposure. METHODS: The infant TB Infection Prevention Study (iTIPS) trial was a non-blinded RCT among HIV-exposed uninfected (HEU) infants in Kenya. Inclusion criteria included age 6-10 weeks, birthweight ≥2.5 kg, and gestation ≥37 weeks. Infants in the IPT arm received 10 mg/kg isoniazid daily for 12 months, while the control trial received no intervention; post-trial observational follow-up continued through 24 months of age. We used intent-to-treat linear mixed-effects models to compare growth rates (weight-for-age z-score [WAZ] and height-for-age z-score [HAZ]) between trial arms. RESULTS: Among 298 infants, 150 were randomized to IPT, 47.6% were females, median birthweight was 3.4 kg (interquartile range [IQR] 3.0-3.7), and 98.3% were breastfed. During the 12-month intervention period and 12-month post-RCT follow-up, WAZ and HAZ declined significantly in all children, with more HAZ decline in male infants. There were no growth differences between trial arms, including in sex-stratified analyses. In longitudinal linear analysis, mean WAZ (ß = 0.04 [95% CI:-0.14, 0.22]), HAZ (ß = 0.14 [95% CI:-0.06, 0.34]), and WHZ [ß = -0.07 [95% CI:-0.26, 0.11]) z-scores were similar between arms as were WAZ and HAZ growth trajectories. Infants randomized to IPT had higher monthly WHZ increase (ß to 24 months 0.02 [95% CI:0.01, 0.04]) than the no-IPT arm. CONCLUSION: IPT administered to HEU infants did not significantly impact growth outcomes in the first two years of life.
Asunto(s)
Antituberculosos , Infecciones por VIH , Isoniazida , Tuberculosis , Humanos , Isoniazida/uso terapéutico , Isoniazida/administración & dosificación , Femenino , Lactante , Masculino , Antituberculosos/uso terapéutico , Antituberculosos/administración & dosificación , Infecciones por VIH/prevención & control , Tuberculosis/prevención & control , Kenia , Preescolar , Recién NacidoRESUMEN
BACKGROUND: Tuberculosis (TB) is a leading cause of death among children living with HIV (CLHIV). Isoniazid preventive therapy (IPT) reduces the incidence of TB by 70% and mortality by 50% among CLHIV. However, in most developing countries including Tanzania, the uptake of IPT is suboptimal, below the 90% WHO-global uptake target. We assessed the factors associated with IPT uptake among CLHIV in Mwanza region, Tanzania. METHODS: This was a multicenter facility-based cross-sectional study among CLHIV aged 1 to 10 years in seven districts of Mwanza region, Tanzania from 1st November 2021 to 20th January 2022. Data were collected using a structured interview-administered questionnaire including information on children and caregivers' demographics, caregivers' health related information and children's clinical information. Our outcome variable was uptake of IPT, defined as initiation on IPT either during the time of the study or within past three years before this study We conducted modified Poisson regression to assess the association between IPT uptake and selected exposures in Stata version 15.0. RESULTS: A total of 415 CLHIV were enrolled, the median age of the children was 7 years (Interquartile range: 5-8). The uptake of IPT was 91% (n = 377). The majority of children's caregivers were HIV positive (86%, n = 387) and were aware about IPT (63.6%, n = 264). Factors associated with IPT uptake included; having an employed caregiver [Adjusted Prevalence Ratio (aPR): 1.06 95% Confidence Interval (CI): 1.00-1.13] and attending the ART clinic every month [aPR: 1.00; 95% CI: 0.87-1.00] . CONCLUSIONS: The uptake of IPT uptake among CLHIV in Mwanza, Tanzania exceeds the global WHO-target of ≥ 90%. Monthly ART clinic visits could be essential in promoting IPT uptake among CLHIV.
Asunto(s)
Antituberculosos , Infecciones por VIH , Isoniazida , Tuberculosis , Humanos , Tanzanía/epidemiología , Estudios Transversales , Isoniazida/uso terapéutico , Femenino , Masculino , Infecciones por VIH/prevención & control , Niño , Preescolar , Antituberculosos/uso terapéutico , Lactante , Tuberculosis/prevención & controlRESUMEN
BACKGROUND: Drug-resistant tuberculosis (DR-TB) is a major health problem and threatens Tuberculosis (TB) control and outcomes globally. India holds one-fourth of global DR-TB burden.1 AIMS: 1- To study drug resistance patterns and outcomes in DR-TB patients under National Tuberculosis Elimination Programme (NTEP) at a tertiary care-centre. 2- To correlate outcome of DR-TB with drug resistance patterns. METHODS: It is a retrospective study of 302 Drug Resistant Tuberculosis patients from Jan 2020 to May 2022. Common mutations of drug resistance, pyrazinamide resistance in DR-TB patients, correlation of High dose Moxifloxacin sensitivity by Line Probe Assay (LPA) and drug sensitivity test (DST), outcome of DR-TB patients with drug resistance patterns and correlation of outcome of DR-TB patients with their initial body-weight were studied. RESULTS: Kat G was the most common mutation in Isoniazid (96%) resistance for MDR TB as well as Isoniazid Mono-resistance TB (p = 0.001). 91% cases with MDR-TB were resistant to pyrazinamide. 51.2% cases had low dose Fluroquinolone resistance. 18.8% cases had low and high dose Fluroquinolone resistance. 8.5% cases had resistance to injectables. 21.7% of cases who were resistant to High dose Moxifloxacin on second line LPA were found to be sensitive on DST. Outcomes were not dependent on the LPA resistance patterns. Body-weight greater than 45 Kg at the time of initiation of treatment was associated with better outcomes (p = 0.007). CONCLUSION: DR-TB patients are resistant to pyrazinamide in nearly all cases; hence pyrazinamide is not suitable for initial replacement sequence. Second line resistance doesn't impact outcome in DR-TB patients.
Asunto(s)
Antituberculosos , Mycobacterium tuberculosis , Centros de Atención Terciaria , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Antituberculosos/uso terapéutico , India , Estudios Retrospectivos , Femenino , Masculino , Adulto , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Resultado del Tratamiento , Persona de Mediana Edad , Pruebas de Sensibilidad Microbiana , Pirazinamida/uso terapéutico , Isoniazida/uso terapéutico , Moxifloxacino/uso terapéutico , Adulto Joven , MutaciónRESUMEN
BACKGROUND: Isoniazid (INH) and Rifampicin (RIF) are two crucial drugs used in antitubercular therapy. INH is known for its potent bactericidal effects and has a relatively higher prevalence of resistance compared to RIF. However, RIF resistance has been the subject of more extensive research. On the other hand, Ethambutol (EMB) and Streptomycin (STR) resistance have not been thoroughly studied, particularly in the context of children and adolescents. To address this knowledge gap, a study was designed to investigate the resistance patterns of INH, EMB, and STR in RIF-sensitive pulmonary tuberculosis (PTB) cases among children and adolescents. METHODS: Seventy-five newly diagnosed RIF sensitive PTB cases up to 18 years of age were enrolled. Retreatment cases were excluded. Sputum/gastric aspirate sample of these patients were sent for culture in Mycobacterium Growth Indicator Tube (MGIT) followed by drug susceptibility testing and Line Probe Assay. RESULTS: INH, EMB and STR resistance among RIF sensitive PTB cases was found to be 5.7%, 0% and 0.7% respectively. RIF resistance detected by CBNAAT was found to be 8.4%. CONCLUSION: Detection of INH resistance is as important as detecting RIF resistance as prevalence of INH resistance in RIF sensitive PTB among children and adolescents up to 18 years is around 6%.
Asunto(s)
Antituberculosos , Etambutol , Isoniazida , Mycobacterium tuberculosis , Rifampin , Tuberculosis Pulmonar , Humanos , Adolescente , Rifampin/uso terapéutico , Rifampin/farmacología , Niño , Tuberculosis Pulmonar/tratamiento farmacológico , Isoniazida/uso terapéutico , Isoniazida/farmacología , Masculino , Femenino , Antituberculosos/uso terapéutico , Antituberculosos/farmacología , Etambutol/uso terapéutico , Etambutol/farmacología , Preescolar , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Estreptomicina/uso terapéutico , Estreptomicina/farmacología , India/epidemiología , Farmacorresistencia Bacteriana , Esputo/microbiologíaRESUMEN
BACKGROUND: Pharmacovigilance entails monitoring of patients for timely detection of ADR and reporting them so that more information about drug safety can be obtained. This may help in the future for dose modification or alteration of regimen. In NTEP, ADSm (Active Drug Safety monitoring) is part of pharmacovigilance. In this study we shall be studying ADRs to Anti TB drugs in DRTB. METHODOLOGY: This study is observational, retrospective and record based, of patients admitted from 2021 to 2023 in the DOTS ward of Respiratory Medicine Department of a tertiary care hospital in Goa. Data such as age, sex, regimen, date of AKT initiation and adverse effects documented has been noted and compiled. RESULTS: ADRs have been tabulated in the form of tables. Statistical analysis is done to find out the commonest ADR, time when they are likely to occur, which age and gender are most likely affected and if there are any other associated risk factors for ADRs. CONCLUSION: This study will enable in future to better monitor patients with regard to particular adverse drug reaction, patient safety and if needed to alter the regimen as early as possible.
Asunto(s)
Antituberculosos , Farmacovigilancia , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Femenino , Antituberculosos/efectos adversos , Antituberculosos/uso terapéutico , Masculino , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Adulto Joven , India/epidemiología , Adolescente , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Anciano , Isoniazida/efectos adversos , Isoniazida/uso terapéutico , Rifampin/efectos adversos , Rifampin/uso terapéutico , Factores de RiesgoRESUMEN
The emergence of drug resistant Mycobacterium tuberculosis strains increases the burden on the treatment of tuberculosis. In this study, through in-silico transcriptome analysis of drug-treated M. tuberculosis samples, novel drug targets for the treatment of drug resistance in tuberculosis were identified. Gene expression datasets of tuberculosis patients samples treated with different antibiotics (Isoniazid, Rifampicin, Pyrazinamide, Bedaquiline and Linezolid) were considered in this study. DESeq2 was used to identify the differentially regulated genes. Novel genes which were up-regulated during antibiotic treatment were identified which could be antibiotic resistance factors. Further, to understand the resistance mechanism of the novel genes, we performed gene ontology and gene network analysis for the differentially up-regulated genes. Thus, the in-silico transcriptome analysis paves way for a deeper understanding of the antibiotic resistance in M. tuberculosis.
Asunto(s)
Perfilación de la Expresión Génica , Mycobacterium tuberculosis , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Humanos , Linezolid/farmacología , Linezolid/uso terapéutico , Simulación por Computador , Pirazinamida/farmacología , Pirazinamida/uso terapéutico , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Rifampin/farmacología , Rifampin/uso terapéutico , Isoniazida/farmacología , Isoniazida/uso terapéutico , Diarilquinolinas/farmacología , Diarilquinolinas/uso terapéutico , Transcriptoma , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Farmacorresistencia Bacteriana/genéticaRESUMEN
BACKGROUND: Multi-drug resistant tuberculosis (MDR-TB) results in treatment failure and poor clinical outcomes. This study was carried out with the aim to determine the pattern of drug resistance against Mycobacterium tuberculosis towards first line ATT (anti-tubercular treatment) in sputum smear-positive patients using Line Probe Assay (LPA). METHODS: A cross sectional prospective study was carried out in a tertiary care Hospital of Meerut. A total of 898 sputum samples (on spot and early morning) collected from 449 suspected pulmonary tuberculosis patients as per RNTCP guidelines were screened by microscopy. Decontamination was done by N-acetyl-l-cysteine and sodium hydroxide. Then smear positive samples were subjected to 1st line drug susceptibility testing (DST) using LPA GenoType® MTBDRplus (HAIN Life Science) assay, a molecular method which allows rapid detection of Rifampicin (Rif) and Isoniazid (INH) resistance. RESULTS: The overall burden of MDR TB in this geographical area was 7.9 %. Mono-resistance with Rif alone was around 2.8 %. However, the mono-resistance with INH (inhA gene) and INH (katG gene) was 2.8 % and 1.1 % respectively. Drug resistance of Rif was due to mutations in rpoB gene while resistances to INH were more commonly due to mutation in inhA gene followed by katG gene. TB was more commonly seen in the age group of 30-59 years (43.8 %) and predominantly in males. CONCLUSION: Tuberculosis positivity rate is high in Western Uttar Pradesh. Burden of MDR TB in Western Uttar Pradesh was similar to National data. Line probe assay can be used as a primary method to diagnose multi drug resistant TB as done in present study which can help in earlier initiation of correct therapy.
Asunto(s)
Antituberculosos , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis Pulmonar , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , India/epidemiología , Masculino , Femenino , Adulto , Estudios Transversales , Persona de Mediana Edad , Estudios Prospectivos , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/epidemiología , Pruebas de Sensibilidad Microbiana , Adulto Joven , Esputo/microbiología , Análisis Mutacional de ADN , Rifampin/uso terapéutico , Rifampin/farmacología , Isoniazida/uso terapéutico , Isoniazida/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Proteínas Bacterianas/genética , Adolescente , Oxidorreductasas/genética , Mutación , CatalasaRESUMEN
SETTING: On a programmatic basis, a new regimen was introduced in the National Tuberculosis Elimination Programme for isoniazid monoresistant tuberculosis in a few states in India. OBJECTIVE: To describe the clinical attributes and treatment outcomes of isoniazid mono-resistant tuberculosis patients on the new 6-month levofloxacin-containing regimen in Puducherry, India. DESIGN: The study is designed as a convergent parallel mixed-methods study: a retrospective cohort study and a descriptive qualitative study. A total of 180 Hr-TB patient health records were reviewed, and in-depth interviews with 35 participants were conducted. (20 Hr-TB patients and 15 HCWs). RESULTS: Of the total 180 Hr-TB patients included, we documented unfavourable outcomes in 26.1% of cases, and the KatG gene mutation was the most common mutation observed (63.9%). A significant risk of unfavourable outcomes was associated with low adherence and positive sputum at the third-month culture report. In interviewing the stakeholders, major challenges observed were the increased pill burden, delay in diagnosis, shortage of drugs, and lack of staff. CONCLUSION: Hr-TB patients have difficulty in adhering to the 6-month levofloxacin regimen, with the need for rigorous early 3-month follow-up and assessment.
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Antituberculosos , Isoniazida , Levofloxacino , Mycobacterium tuberculosis , Humanos , India/epidemiología , Isoniazida/uso terapéutico , Antituberculosos/uso terapéutico , Masculino , Femenino , Adulto , Estudios Retrospectivos , Levofloxacino/uso terapéutico , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Resultado del Tratamiento , Persona de Mediana Edad , Tuberculosis Pulmonar/tratamiento farmacológico , Adulto Joven , Esputo/microbiología , Catalasa/genética , Cumplimiento de la Medicación/estadística & datos numéricos , Mutación , Investigación Cualitativa , Proteínas Bacterianas/genética , Farmacorresistencia BacterianaRESUMEN
INTRODUCTION: Mycobacterium tuberculosis has been extensively studied for mutations leading to drug resistance. Pyrazinamide is a drug acting on the semi-dormant bacteria that is responsible for relapse of tuberculosis. This drug helped reduce the treatment duration of tuberculosis from nine to six months. However, this drug is not being screened for resistance along with Rifampicin and Isoniazid. AIMS AND OBJECTIVES: This study aimed to estimate the proportion of pncA gene mutation among tuberculosis patients and its association between treatment outcomes, clinical characteristics, and phenotypic drug resistance. METHOD: ology: A total of 154 samples included 73 drug-resistant and 81 drug-susceptible isolates. The isolates were subjected to DNA extraction and amplification using conventional PCR. The PCR product was sequenced by the Sanger sequencing method, and phenotypic drug susceptibility testing was done using the broth dilution method. The association of this gene with the treatment outcome was done by following up with the patients till the end of the regimen. RESULTS: None of the drug susceptible tuberculosis patients showed significant non-synonymous mutations. Among the drug-resistant TB patients, seven unique significant mutations out of 73 isolates (9.6%) were distributed among Isoniazid-resistant tuberculosis and Multi-Drug Resistant Tuberculosis isolates. No association was found between the mutations and the clinical characteristics of the subjects harboring these isolates. CONCLUSION: This study estimated seven unique mutations in drug-resistant tuberculosis and none in drug-sensitive tuberculosis. Isolates harboring was not significantly associated with the participant's treatment outcome and other clinical characteristics. The pyrazinamide resistance testing by the phenotypic and genotypic methods was found to be in concordance.
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Antituberculosos , Mutación , Mycobacterium tuberculosis , Pirazinamida , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Pirazinamida/uso terapéutico , Antituberculosos/uso terapéutico , Antituberculosos/farmacología , India , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efectos de los fármacos , Masculino , Femenino , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Estudios Longitudinales , Resultado del Tratamiento , Pruebas de Sensibilidad Microbiana , Amidohidrolasas/genética , Persona de Mediana Edad , Isoniazida/uso terapéutico , Tuberculosis Pulmonar/tratamiento farmacológicoRESUMEN
BACKGROUND: Tuberculosis (TB) lymphadenitis is the most common form of extra-pulmonary TB, and the treatment duration is six months. This non-inferiority based randomized clinical trial in South India evaluated the efficacy and safety of a four-month ofloxacin containing regimen in tuberculosis lymphadenitis (TBL) patients. METHODS: New, adult, HIV-negative, microbiologically and or histopathologically confirmed superficial lymph node TB patients were randomized to either four-month oflaxacin containing test regimen [ofloxacin (O), isoniazid (H), rifampicin (R), pyrazinamide (Z) -2RHZO daily/ 2RHO thrice-weekly] or a six-month thrice-weekly control regimen (2HRZ, ethambutol/4RH). The treatment was directly observed. Clinical progress was monitored monthly during and up to 12 months post-treatment, and thereafter every three months up to 24 months. The primary outcome was determined by response at the end of treatment and TB recurrence during the 24 months post-treatment. RESULTS: Of the 302 patients randomized, 298 (98.7%) were eligible for modified intention-to-treat (ITT) analysis and 294 (97%) for per-protocol (PP) analysis. The TB recurrence-free favourable response in the PP analysis was 94.0% (95% CI: 90.1-97.8) and 94.5% (95% CI: 90.8-98.2) in the test and control regimen respectively, while in the ITT analysis, it was 92.7% and 93.2%. The TB recurrence-free favourable response in the test regimen was non-inferior to the control regimen 0.5% (95% CI: -4.8-5.9) in the PP analysis based on the 6% non-inferiority margin. Treatment was modified for drug toxicity in two patients in the test regimen, while one patient had a paradoxical reaction. CONCLUSION: The 4-month ofloxacin containing regimen was found to be non-inferior and as safe as the 6-month thrice-weekly control regimen.
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Antituberculosos , Ofloxacino , Tuberculosis Ganglionar , Humanos , Ofloxacino/administración & dosificación , Ofloxacino/efectos adversos , Ofloxacino/uso terapéutico , Adulto , Masculino , Femenino , Tuberculosis Ganglionar/tratamiento farmacológico , Antituberculosos/uso terapéutico , Antituberculosos/efectos adversos , Antituberculosos/administración & dosificación , Resultado del Tratamiento , Persona de Mediana Edad , India , Rifampin/uso terapéutico , Rifampin/administración & dosificación , Rifampin/efectos adversos , Adulto Joven , Isoniazida/uso terapéutico , Isoniazida/administración & dosificación , Isoniazida/efectos adversos , Quimioterapia Combinada , Pirazinamida/uso terapéutico , Pirazinamida/administración & dosificación , Pirazinamida/efectos adversos , Etambutol/uso terapéutico , Etambutol/administración & dosificación , Etambutol/efectos adversos , Esquema de Medicación , AdolescenteRESUMEN
Objective: To evaluate the efficacy and safety of first-line anti-tuberculosis (TB) drugs combined with linezolid in treatment of children with tuberculous meningitis (TBM). Methods: A retrospective cohort study design was performed. Eight-nine Children diagnosed as TBM during January 1st 2016 and December 31st 2023 in Department of Infectious Disease, Children's Hospital of Chongqing Medical University were enrolled in the study. According to different treatment regimens, children were divided into a group of first-line anti-tuberculous drugs (isoniazid, rifampicin, pyrazinamide, ethambutol (HRZE)) and a group of HRZE and linezolid combination (HRZEL). The efficacy and safety of the 2 regimens were compared and the relationship between linezolid drug concentration and adverse reactions were analyzed. Comparisons between groups were performed using χ2 test and Mann-Whitney U test. Results: The 89 children with TBM included 53 males and 36 females with an onset age of 4.6 (1.4, 9.6) years. There were 27 cases in the HZREL group and 62 cases in the HRZE group. Before treatment, positive rate of interferon-gamma release assays (IGRA) in HRZEL group was lower than that in HRZE group (64% (16/25) vs.92% (55/60), χ2=9.82, P<0.05), but protein level of cerebrospinal fluid (CSF) was higher than that in HRZE group (1.2 (1.0, 2.0) vs.0.8 (0.4,1.4) g/L, Z=0.32, P<0.05). By the end of the intensive phase, there were no significant differences of rates of CSF improvement and etiology negativity between HRZEL group and HRZE group (both P>0.05).The 44 TBM children with high CSF protein (>1 g/L) included 25 males and 19 females with an onset age of 6.7 (3.0, 11.8) years. There were 21 cases in the HZREL group and 23 cases in the HRZE group accordingly. Before treatment, there were no significant differences of positive rate of IGRA test and CSF protein level between the 2 groups (62% (13/21) vs. 87% (20/23), 1.7 (1.1, 2.2) vs. 1.5 (1.2, 1.9) g/L, χ2=3.67, Z=0.23, both P>0.05). There were no significant differences in CSF indicators, etiology negativity or imaging remission between the two groups by the end of intensive phase (all P>0.05). Higher frequencies of granulocytopenia, gastrointestinal symptoms as well as withdrawal or change of drugs were found in HRZEL group when compared to those in HRZE group (44% (12/27) vs. 19% (12/62), 7% (2/27) vs. 0, 33% (9/27) vs. 3% (2/62), χ2=6.01, 4.70, 15.74, all P<0.05). Conclusions: The efficacy of HRZEL regimen is similar to conventional HRZE regimen in children with TBM, but with higher adverse effect. Prudentially evaluating the pros and cons of linezolid in the usage of drug-susceptible TB and carefully monitoring of linezolid associated adverse effects is suggested.
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Antituberculosos , Quimioterapia Combinada , Linezolid , Tuberculosis Meníngea , Humanos , Tuberculosis Meníngea/tratamiento farmacológico , Estudios Retrospectivos , Masculino , Femenino , Linezolid/uso terapéutico , Linezolid/administración & dosificación , Antituberculosos/uso terapéutico , Antituberculosos/administración & dosificación , Antituberculosos/efectos adversos , Niño , Preescolar , Resultado del Tratamiento , Lactante , Rifampin/uso terapéutico , Rifampin/administración & dosificación , Etambutol/uso terapéutico , Etambutol/administración & dosificación , Pirazinamida/uso terapéutico , Pirazinamida/administración & dosificación , Isoniazida/uso terapéutico , Isoniazida/administración & dosificación , Isoniazida/efectos adversosAsunto(s)
Antituberculosos , Mycobacterium tuberculosis , Exposición Profesional , Tuberculosis Cutánea , Veterinarios , Humanos , Masculino , Antituberculosos/uso terapéutico , Mycobacterium tuberculosis/aislamiento & purificación , Piel/patología , Piel/microbiología , Tuberculosis Cutánea/diagnóstico , Tuberculosis Cutánea/tratamiento farmacológico , Tuberculosis Cutánea/microbiología , Tuberculosis Cutánea/patología , Persona de Mediana Edad , Biopsia , Isoniazida/uso terapéutico , Rifampin/uso terapéutico , Etambutol/uso terapéutico , Dermatosis de la Mano/diagnóstico , Dermatosis de la Mano/tratamiento farmacológico , Dermatosis de la Mano/microbiología , Dermatosis de la Mano/patología , Exposición Profesional/efectos adversosRESUMEN
BACKGROUND: The treatment regimen for tuberculous meningitis (TBM) remains unclear and requires optimization. There are some reports on successful adjunct intrathecal dexamethasone and isoniazid (IDI) treatment strategies for TBM, however, there is equivocal evidence on their efficacy and safety. METHODS: A comprehensive search of English and Chinese databases was conducted from inception to February 2024. A meta-analysis was performed on randomized controlled trials (RCTs) estimating the effects of adjunct IDI on conventional anti-TB (C anti-TB) treatments or C anti-TB alone. Efficacy, adverse reaction rate, cerebrospinal fluid (CSF) leukocytes, and CSF protein were used as primary outcome indicators. CSF glucose, CSF chlorides, CSF pressure, recovery time for laboratory indicators and recovery time for clinical symptoms were used as secondary outcome indicators. RESULTS: A total of 17 studies involving 1360 (IDI group vs. C anti-TB group: 392 vs. 372; higher-dose IDI group vs. lower-dose IDI group: 319 vs. 277) patients were included in our analysis. Efficacy was significantly higher (RR 1.3, 95% CI 1.2-1.4, P < 0.001) and adverse reaction rate was significantly lower in the IDI groups (RR 0.59, 95% CI 0.37-0.92, P = 0.021). Furthermore, CSF leukocytes (WMD - 29.33, 95% CI [- 40.64 to-18.02], P < 0.001) and CSF protein (WMD - 0.79, 95%CI [-0.96 to-0.61], P < 0.001) were significantly lower in the IDI groups. Recovery time indicators were all shorter in the IDI groups, fever (SMD - 2.45, 95% CI [-3.55 to-1.35], P < 0.001), coma (SMD-3.75, 95% CI [-4.33 to-3.17], P < 0.001), and headache (SMD - 3.06, 95% CI [- 4.05 to-2.07], P < 0.001), respectively. Higher-dose IDI was more effective than lower-dose IDI (RR 1.23, 95% CI 1.14-1.33, P < 0.001), with no significant difference in adverse reaction rate between the two (RR 0.82, 95%CI 0.43-1.56, P = 0.544). CONCLUSION: Adjunct IDI with C anti-TB can enhance therapeutic outcomes and reduce adverse reaction rate in adult TBM patients, with higher-dose IDI showing superior efficacy. These findings highlight the potential of IDI as an adjunctive therapy in TBM management. However, more high-quality RCTs from more regions should be conducted to support our results. TRIAL REGISTRATION: Retrospectively registered in PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023388860 .
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Antituberculosos , Dexametasona , Quimioterapia Combinada , Inyecciones Espinales , Isoniazida , Tuberculosis Meníngea , Humanos , Tuberculosis Meníngea/tratamiento farmacológico , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Isoniazida/administración & dosificación , Isoniazida/uso terapéutico , Isoniazida/efectos adversos , Antituberculosos/administración & dosificación , Antituberculosos/efectos adversos , Antituberculosos/uso terapéutico , Inyecciones Espinales/métodos , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto/métodosRESUMEN
This study evaluated the performance of cobas MTB and cobas MTB-RIF/INH for the diagnosis of tuberculosis and detection of rifampicin (RIF) and isoniazid (INH) resistance. Adults presenting with pulmonary tuberculosis symptoms were recruited in South Africa, Moldova, and India. Performance of cobas MTB was assessed against culture, whereas cobas MTB-RIF/INH was assessed using phenotypic drug susceptibility testing and whole-genome sequencing as composite reference standards. Xpert MTB/RIF (Xpert) or Xpert MTB/RIF Ultra (Ultra) was used as a comparator. The overall sensitivity and specificity of cobas MTB were 95% (95% CI, 93%-96%) and 96% (95% CI, 95%-97%). Among smear-negatives, the sensitivity of cobas MTB was 75% (95% CI, 66%-83%). Among participants tested with both cobas MTB and Xpert, sensitivity was 96% (95% CI, 94%-97%) for cobas MTB and 95% (95% CI, 93%-97%) for Xpert. Among participants tested with both cobas MTB and Ultra, sensitivity was 88% (95% CI, 81%-92%) for cobas MTB and 89% (95% CI, 83%-93%) for Ultra. Sensitivity and specificity of cobas MTB-RIF/INH for RIF and INH detection were 90% (95% CI, 84%-94%) and 100% (95% CI, 99%-100%), and 89% (95% CI, 84%-93%) and 99.5% (95% CI, 98%-100%), respectively. The cobas MTB and cobas MTB-RIF/INH assays exhibited high performance in a diverse population and present a suitable option for molecular detection of tuberculosis and RIF and INH resistance.