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The European Respiratory Journal Nov 2017
Topics: Antitubercular Agents; Diarylquinolines; Electrocardiography; Humans; Long QT Syndrome; Tuberculosis, Multidrug-Resistant
PubMed: 29146605
DOI: 10.1183/13993003.01462-2017 -
Survey of Ophthalmology 2022Tubercular uveitis (TBU) is an inflammation/infection of the eye secondary to Mycobacterium tuberculosis infection. The difficulty in making the diagnosis has resulted... (Meta-Analysis)
Meta-Analysis Review
Tubercular uveitis (TBU) is an inflammation/infection of the eye secondary to Mycobacterium tuberculosis infection. The difficulty in making the diagnosis has resulted in variable prevalence and clinical response rates. We aimed to determine the global prevalence of TBU in uveitis patients stratified by TB high-burden countries (HBCs) and non-HBCs and by geographic regions and the clinical response of TBU to antitubercular treatment We performed a systematic review and meta-analysis of TBU studies published in PubMed, Scopus and EMBASE, up to June 30, 2020. A random effects model was used for all meta-analyses. Of 5,018 articles identified, 70 prevalence studies (65,607 uveitis and 3,166 TBU cases) and 18 clinical outcome studies (1,570 TBU cases; 1,304 responded to anti-tubercular therapy [ATT]) were analyzed. The overall weighted prevalence of TBU was 4.0% (95% CI, 3-5); in TB HBCs it was 7.0% (95% CI, 5-11), non-HBCs 3.0% (95% CI, 2-4), and sub-Saharan Africa 11.0% (95% CI, 8-15). The overall weighted clinical response was 82.0% (95% CI, 75-89). Despite the difficulty in diagnosing TBU, the prevalence is expectantly higher in HBCs, and sub-Saharan Africa and the clinical outcome is poor. Standardization of diagnostic criteria and ATT is warranted in future cohort studies.
Topics: Antitubercular Agents; Humans; Prevalence; Tuberculosis, Ocular; Uveitis
PubMed: 34626620
DOI: 10.1016/j.survophthal.2021.10.001 -
Clinical Therapeutics Nov 2020This systematic review and meta-analysis assesses the pharmacokinetic (PK) summary estimates of isoniazid (INH) between healthy volunteers and patients with tuberculosis... (Meta-Analysis)
Meta-Analysis
PURPOSE
This systematic review and meta-analysis assesses the pharmacokinetic (PK) summary estimates of isoniazid (INH) between healthy volunteers and patients with tuberculosis (TB), evaluates whether the current INH dose regimen is appropriate in patients with TB, and evaluates the impact of N-acetyl-transferase-2 (NAT2) status on the PK properties of INH.
METHODS
A systematic approach was conducted to find studies with relevant INH PK data published in the English language up to February 2018. The PK properties of INH were extracted with their respective INH dosages and were dose normalized to allow a fair comparison between healthy volunteers and patients with TB. Meta-analysis was then performed for the C and AUC estimates for all INH dosages.
FINDINGS
Ninety studies were included in this systematic review. TB status significantly affected the INH C and AUC estimates. In healthy volunteers, the dose-normalized INH C and AUC were statistically higher than those of patients with TB. No significant differences were found in dose-normalized C and AUC between adults with TB and adults with TB/HIV; however, the AUC in pediatric patients was significantly different between patients with TB and patients with TB/HIV. In addition, no significance was observed comparing the dose-normalized C and AUC of pediatric patients with TB and TB/HIV with their respective adult counterparts. Dose-normalized INH C and AUC in patients with fast and intermediate NAT2 were significantly lower than in patients with slow NAT2.
IMPLICATIONS
The current recommended dosages of INH were found to produce less drug exposure in patients with TB when compared with healthy volunteers. NAT2 polymorphism greatly impacts the PK properties of INH; hence, testing for acetylator status is highly recommended, and therapeutic drug monitoring would help reduce INH toxicity.
Topics: Adult; Antitubercular Agents; Arylamine N-Acetyltransferase; Drug Monitoring; Humans; Isoniazid; Tuberculosis
PubMed: 33032843
DOI: 10.1016/j.clinthera.2020.09.009 -
The European Respiratory Journal Mar 2023Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB drug pharmacokinetics in children and adolescents at a global level.
METHODS
We systematically searched MEDLINE, Embase and Web of Science (1990-2021) for pharmacokinetic studies of first-line anti-TB drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration-time curve from 0 to 24 h post-dose (AUC) and peak plasma concentration ( ) were assessed with random-effects models, normalised with current World Health Organization-recommended paediatric doses. Determinants of AUC and were assessed with linear mixed-effects models.
RESULTS
Of 55 eligible studies, individual patient data were available for 39 (71%), including 1628 participants from 12 countries. Geometric means of steady-state AUC were summarised for isoniazid (18.7 (95% CI 15.5-22.6) h·mg·L), rifampicin (34.4 (95% CI 29.4-40.3) h·mg·L), pyrazinamide (375.0 (95% CI 339.9-413.7) h·mg·L) and ethambutol (8.0 (95% CI 6.4-10.0) h·mg·L). Our multivariate models indicated that younger age (especially <2 years) and HIV-positive status were associated with lower AUC for all first-line anti-TB drugs, while severe malnutrition was associated with lower AUC for isoniazid and pyrazinamide. -acetyltransferase 2 rapid acetylators had lower isoniazid AUC and slow acetylators had higher isoniazid AUC than intermediate acetylators. Determinants of were generally similar to those for AUC.
CONCLUSIONS
This study provides the most comprehensive estimates of plasma exposures to first-line anti-TB drugs in children and adolescents. Key determinants of drug exposures were identified. These may be relevant for population-specific dose adjustment or individualised therapeutic drug monitoring.
Topics: Child; Adolescent; Humans; Child, Preschool; Antitubercular Agents; Isoniazid; Pyrazinamide; Ethambutol; Rifampin
PubMed: 36328357
DOI: 10.1183/13993003.01596-2022 -
The International Journal of... Jan 2017Resistance to anti-tuberculosis drugs threatens to undermine effective control of tuberculosis (TB). In areas with weak TB control and misuse of anti-tuberculosis drugs,... (Review)
Review
BACKGROUND
Resistance to anti-tuberculosis drugs threatens to undermine effective control of tuberculosis (TB). In areas with weak TB control and misuse of anti-tuberculosis drugs, hotspots of multidrug-resistant TB (MDR-TB) have appeared. The aim of this review is to determine the prevalence rate of any anti-tuberculosis drug resistance, monoresistance and MDR-TB in Ethiopia.
METHODS
A systematic review of the literature on any resistance, monoresistance and MDR-TB was conducted.
RESULTS
Of the total 468 articles found using electronic search, 14 met the eligibility criteria and were included in the review. The prevalence rate of any drug resistance, polyresistance and MDR-TB was respectively 6.7-72.9%, 0-54% and 0-46%. A higher rate of streptomycin monoresistance (1.5-20.4%) was observed.
CONCLUSION
The prevalence and distribution of drug-resistant TB remains a serious public health problem in Ethiopia. Rapid, advanced diagnostic tools should be introduced, along with strong treatment and follow-up strategies.
Topics: Antitubercular Agents; Drug Resistance, Multiple, Bacterial; Ethambutol; Ethiopia; Humans; Isoniazid; Prevalence; Public Health; Pyrazinamide; Rifampin; Streptomycin; Tuberculosis, Multidrug-Resistant
PubMed: 28157460
DOI: 10.5588/ijtld.16.0286 -
Jornal Brasileiro de Pneumologia :... 2022Multidrug-resistant tuberculosis (MDR-TB) is a life-threatening infectious disease. Treatment requires multiple antimicrobial agents used for extended periods of time.... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Multidrug-resistant tuberculosis (MDR-TB) is a life-threatening infectious disease. Treatment requires multiple antimicrobial agents used for extended periods of time. The present study sought to evaluate the treatment success rate of bedaquiline-based regimens in MDR-TB patients.
METHODS
This was a systematic review and meta-analysis of studies published up to March 15, 2021. The pooled treatment success rates and 95% CIs were assessed with the fixed-effect model or the random-effects model. Values of p < 0.05 were considered significant for publication bias.
RESULTS
A total of 2,679 articles were retrieved by database searching. Of those, 29 met the inclusion criteria. Of those, 25 were observational studies (including a total of 3,536 patients) and 4 were experimental studies (including a total of 440 patients). The pooled treatment success rate was 74.7% (95% CI, 69.8-79.0) in the observational studies and 86.1% (95% CI, 76.8-92.1; p = 0.00; I2 = 75%) in the experimental studies. There was no evidence of publication bias (p > 0.05).
CONCLUSIONS
In patients with MDR-TB receiving bedaquiline, culture conversion and treatment success rates are high even in cases of extensive resistance.
Topics: Antitubercular Agents; Diarylquinolines; Humans; Treatment Outcome; Tuberculosis, Multidrug-Resistant
PubMed: 35649043
DOI: 10.36416/1806-3756/e20210384 -
Pharmacological Research Mar 2016Tuberculosis (TB) is still one of the most difficult infectious diseases to treat, and the second most frequent cause of death due to infectious disease throughout the... (Review)
Review
Tuberculosis (TB) is still one of the most difficult infectious diseases to treat, and the second most frequent cause of death due to infectious disease throughout the world. The number of cases of multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB), which are characterised by high mortality rates, is increasing. The therapeutic management of children with MDR- and XDR-TB is complicated by a lack of knowledge, and the fact that many potentially useful drugs are not registered for pediatric use and there are no formulations suitable for children in the first years of life. Furthermore, most of the available drugs are burdened by major adverse events that need to be taken into account, particularly in the case of prolonged therapy. This document describes the recommendations of a group of scientific societies on the therapeutic approach to pediatric MDR- and XDR-TB. On the basis of a systematic literature review and their personal clinical experience, the experts recommend that children with active TB caused by a drug-resistant strain of Mycobacterium tuberculosis should always be referred to a specialised centre because of the complexity of patient management, the paucity of pediatric data, and the high incidence of adverse events due to second-line anti-TB treatment.
Topics: Antitubercular Agents; Child; Extensively Drug-Resistant Tuberculosis; Humans; Mycobacterium tuberculosis; Practice Guidelines as Topic; Tuberculosis, Multidrug-Resistant
PubMed: 26821118
DOI: 10.1016/j.phrs.2016.01.020 -
The Cochrane Database of Systematic... Mar 2017Corticosteroids used in addition to antituberculous therapy have been reported to benefit people with tuberculous pleurisy. However, research findings are inconsistent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Corticosteroids used in addition to antituberculous therapy have been reported to benefit people with tuberculous pleurisy. However, research findings are inconsistent and raise doubt as to whether such treatment is worthwhile. There is also concern regarding the potential adverse effects of corticosteroids, especially in HIV-positive people.
OBJECTIVES
To evaluate the effects of adding corticosteroids to drug regimens for tuberculous pleural effusion.
SEARCH METHODS
In April 2016, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library), MEDLINE, Embase, LILACS, Current Controlled Trials, and the reference lists of articles identified by the literature search.
SELECTION CRITERIA
Randomized controlled trials (RCTs) and quasi-RCTs that compared any corticosteroid with no treatment, placebo, or other active treatment (both groups should have received the same antituberculous drug regimen) in people diagnosed with tuberculous pleurisy.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the search results, extracted data from the included trials, and assessed trial methodological quality using the Cochrane 'Risk of bias' tool. We analysed the data using risk ratios (RR) with 95% confidence intervals (CIs). We applied the fixed-effect model in the absence of statistically significant heterogeneity.
MAIN RESULTS
Six trials with 590 participants met the inclusion criteria, which were conducted in Asia (three trials), Africa (two trials), and Europe (one trial). Two trials were in HIV-negative people, one trial was in HIV-positive people, and three trials did not report HIV status.Corticosteroids may reduce the time to resolution of pleural effusion. Risk of residual pleural effusion on chest X-ray was reduced by 45% at eight weeks (RR 0.54, 95% CI 0.37 to 0.78; 237 participants, 2 trials, low certainty evidence), and 65% at 24 weeks (RR 0.35, 95% CI 0.18 to 0.66; 237 participants, 2 trials, low certainty evidence).Compared with control, corticosteroids may reduce the risk of having pleural changes (such as pleural thickening or pleural adhesions), on chest X-ray at the end of follow-up by almost one third (RR 0.72, 95% CI 0.57 to 0.92; 393 participants, 5 trials,low certainty evidence), which translates to an absolute risk reduction of 16%.One trial reported deaths in people that were HIV-positive, with no obvious difference between the groups; the trial authors' analysis suggests that the deaths observed in this trial were related to HIV disease rather than pleural TB (RR 0.91, 95% CI 0.64 to 1.31; 197 participants, 1 trial).We found limited data on long-term functional respiratory impairment on 187 people in two trials, which reported that average percentage predicted forced vital capacity was similar in the group receiving prednisolone and in the control group (very low certainty evidence).The risk of adverse events that led to discontinuation of the trial drug was higher in people with pleural TB receiving corticosteroids (RR 2.78, 95% CI 1.11 to 6.94; 587 participants, 6 trials, low certainty evidence). The trial in HIV-positive people reported on six different HIV-related infections, with no obvious differences. However, cases of Kaposi's sarcoma were only seen in the corticosteroid group (with 6/99 cases in the steroid group compared to 0/98 in the control group) (very low certainty evidence).
AUTHORS' CONCLUSIONS
Long-term respiratory function is potentially the most important outcome for assessing the effects of adjunctive treatments for people with pleural TB. However, the information on the impact of pleural TB on long-term respiratory function is unknown and could be eclipsed by other risk factors, such as concurrent pulmonary TB, smoking, and HIV. This probably needs to be quantified to help decide whether further trials of corticosteroids for pleural TB would be worthwhile.
Topics: Adrenal Cortex Hormones; Antitubercular Agents; HIV Seronegativity; HIV Seropositivity; Humans; Pleura; Randomized Controlled Trials as Topic; Tuberculosis, Pleural; Tuberculosis, Pulmonary
PubMed: 28290161
DOI: 10.1002/14651858.CD001876.pub3 -
Annals of Internal Medicine Jul 2008Despite the increasing prevalence of drug-resistant tuberculosis, most low- and middle-income countries use standardized regimens, without assessment of drug... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite the increasing prevalence of drug-resistant tuberculosis, most low- and middle-income countries use standardized regimens, without assessment of drug susceptibility.
PURPOSE
To perform a systematic review and meta-analysis of the effect of initial drug resistance and treatment regimen on tuberculosis treatment outcomes.
DATA SOURCES
PubMed, the Cochrane Central Database of Clinical Trials, and EMBASE were searched for studies published in English from 1965 to June 2007. Additional studies were identified from cited references.
STUDY SELECTION
Randomized, controlled trials and cohort studies of standardized treatment of previously untreated patients with culture-confirmed pulmonary tuberculosis. Drug-susceptibility testing was done on pretreatment isolates from all patients and from patients with treatment failure or relapse.
DATA EXTRACTION
Two authors reviewed the studies for methods, initial drug resistance, treatment regimens, and outcomes.
DATA SYNTHESIS
Pooled cumulative incidences were computed with random-effects meta-analyses. Association between risk factors and outcomes were determined by using stratified analyses. The cumulative incidence of acquired drug resistance with initially pan-sensitive strains was 0.8% (95% CI, 0.5% to 1.0%) compared with 6% (CI, 4% to 8%) with initially single drug-resistant strains and 14% (CI, 9% to 20%) with initially polydrug-resistant strains. Failure and relapse were most strongly associated with initial drug resistance. Failure was also associated with shorter duration of rifampin therapy and nonuse of streptomycin, whereas the rate of relapse was higher with shorter duration of rifampin therapy and nonuse of pyrazinamide.
LIMITATIONS
Few studies included HIV-infected persons, and treatment outcomes were pooled despite considerable heterogeneity.
CONCLUSION
Treatment outcomes were substantially worse in the presence of initial drug resistance, which has important implications in resource-limited settings in which drug resistance is prevalent.
Topics: Antitubercular Agents; Drug Resistance, Bacterial; Humans; Mycobacterium tuberculosis; Treatment Outcome; Tuberculosis, Pulmonary
PubMed: 18626051
DOI: 10.7326/0003-4819-149-2-200807150-00008 -
The International Journal of... Nov 2017To reduce transmission and improve patient outcomes, rapid diagnosis and treatment of rifampicin-resistant tuberculosis (RR-TB) is required. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To reduce transmission and improve patient outcomes, rapid diagnosis and treatment of rifampicin-resistant tuberculosis (RR-TB) is required.
OBJECTIVE
To conduct a systematic review and meta-analysis assessing time to treatment for RR-TB and variability using diagnostic testing methods and treatment delivery approach.
DESIGN
Studies from 2000 to 2015 reporting time to second-line treatment initiation were selected from PubMed and published conference abstracts.
RESULTS
From 53 studies, 83 cohorts (13 034 patients) were included. Overall weighted mean time to treatment from specimen collection was 81 days (95%CI 70-91), and was shorter with ambulatory (57 days, 95%CI 40-74) than hospital-based treatment (86 days, 95%CI 71-102). Time to treatment was shorter with genotypic susceptibility testing (38 days, 95%CI 27-49) than phenotypic testing (108 days, 95%CI 98-117). The mean percentage of diagnosed patients initiating treatment was 76% (95%CI 70-83, range 25-100).
CONCLUSION
Time to second-line anti-tuberculosis treatment initiation is extremely variable across studies, and often unnecessarily long. Reduced delays are associated with genotypic testing and ambulatory treatment settings. Routine monitoring of the proportion of diagnosed patients initiating treatment and time to treatment are necessary to identify areas for intervention.
Topics: Ambulatory Care; Antitubercular Agents; Genotype; Hospitalization; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Rifampin; Time-to-Treatment; Tuberculosis, Multidrug-Resistant
PubMed: 29037299
DOI: 10.5588/ijtld.17.0230