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The Indian Journal of Tuberculosis Oct 2023Drug-induced thrombocytopenia is a known adverse event of several drugs. Antitubercular therapy (ATT) is rarely reported but important cause of thrombocytopenia. The... (Review)
Review
INTRODUCTION
Drug-induced thrombocytopenia is a known adverse event of several drugs. Antitubercular therapy (ATT) is rarely reported but important cause of thrombocytopenia. The present review aimed to understand the profile of thrombocytopenia caused by first-line ATT i.e. isoniazid, rifampicin, pyrazinamide, and ethambutol.
MATERIALS AND METHODS
We screened case reports, case series, and letter-to-editor from databases, like Pubmed/MEDLINE, Ovid, and EMBASE from 1970 to 2021. The PRISMA guidelines were followed in the present systematic review.
RESULTS
Categorical data were expressed as n (%) and quantitative data were expressed as median (IQR). After applying the inclusion/exclusion criteria, 17 case reports and 7 letters to the editor were selected for the present review. Rifampicin was most frequently associated with thrombocytopenia (65%). A median (IQR) drop to 20,000 (49,500) platelets/mm3 was observed. Anti-rifampicin associated antibodies and anti-dsDNA positivity were found in six studies. Except for two, all patients responded to symptomatic treatment.
DISCUSSION
ATT-induced thrombocytopenia can be life-threatening and require hospitalization. Clinicians should be aware of the association of ATT with thrombocytopenia and should take appropriate measures for patient management.
CONCLUSION
This review provides clinicians a comprehensive picture of adverse effects and their management in ATT induced thrombocytopenia.
Topics: Humans; Rifampin; Antitubercular Agents; Pyrazinamide; Isoniazid; Thrombocytopenia
PubMed: 37968056
DOI: 10.1016/j.ijtb.2023.04.029 -
International Journal of Antimicrobial... Sep 2023Pyrazinamide (PZA) is a first-line antituberculosis drug with potent sterilising activity. Variability in drug exposure may translate into suboptimal treatment... (Review)
Review
Pyrazinamide (PZA) is a first-line antituberculosis drug with potent sterilising activity. Variability in drug exposure may translate into suboptimal treatment responses. This systematic review, conducted according to PRISMA guidelines, aimed to evaluate the concentration-effect relationship. In vitro/in vivo studies had to contain information on the infection model, PZA dose and concentration, and microbiological outcome. Human studies had to present information on PZA dose, measures of drug exposure and maximum concentration, and microbiological response parameter or overall treatment outcome. A total of 34 studies were assessed, including in vitro (n = 2), in vivo (n = 3) and clinical studies (n = 29). Intracellular and extracellular models demonstrated a direct correlation between PZA dose of 15-50 mg/kg/day and reduction in bacterial count between 0.50-27.7 log CFU/mL. Consistent with this, higher PZA doses (>150 mg/kg) were associated with a greater reduction in bacterial burden in BALB/c mice models. Human pharmacokinetic studies displayed a linear positive correlation between PZA dose (i.e. 21.4-35.7 mg/kg/day) and drug exposure (AUC range 220.6-514.5 mg·h/L). Additionally, human studies confirmed a dose-effect relationship, with an increased 2-month sputum culture conversion rate at AUC/MIC targets of 8.4-11.3 with higher exposure/susceptibility ratios leading to greater efficacy. A 5-fold variability in AUC was observed at PZA dose of 25 mg/kg. A direct concentration-effect relationship and increased treatment efficacy with higher PZA exposure to susceptibility ratios was observed. Taking into account variability in drug exposure and treatment response, further studies on dose optimisation are justified.
Topics: Animals; Mice; Humans; Pyrazinamide; Mycobacterium tuberculosis; Tuberculosis; Antitubercular Agents; Mice, Inbred BALB C; Microbial Sensitivity Tests
PubMed: 37419292
DOI: 10.1016/j.ijantimicag.2023.106914 -
Annals of Medicine Dec 2024The Directly Observed Treatment-Short Course (DOTS) Programme was implemented by WHO and includes a combination of four anti-tuberculosis (TB) drugs (isoniazid,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The Directly Observed Treatment-Short Course (DOTS) Programme was implemented by WHO and includes a combination of four anti-tuberculosis (TB) drugs (isoniazid, pyrazinamide, ethambutol and rifampicin) for a period of six months to eradicate the TB infection completely. Diabetes mellitus (DM) is recognized as one of a strong contributor of TB according to World Health Organization (WHO). The presence of diabetes mellitus type 2 (DM type 2) makes TB treatment complicated. Thus, the objective of the current meta-analysis was to identify and quantify the impact of type 2 DM on treatment outcomes of TB patients treated under the DOTS Programme.
METHODS
This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Through a systematic review of relevant literature, we focused on studies investigating treatment outcomes including extended treatment duration and recurrence for individuals with both TB and DM undergoing DOTS therapy. The extracted information included study designs, sample sizes, patient characteristics and reported treatment results.
RESULTS
In 44 studies from different parts of the world, the pooled HR for the impact of DM on extended treatment duration and reoccurrence were HR 0.72, 95% CI 0.56-0.83, < .01 and HR 0.93, 95% CI 0.70-1.04, = .08, respectively. The pooled HR for impact of DM on composite TB treatment outcomes was calculated as 0.76 (95% CI 0.60-0.87), < .01 with an effect size of 41.18. The heterogeneity observed among the included studies was moderate ( = 55.79%).
CONCLUSIONS
A negative impact of DM was found on recurrence and extended treatment duration in TB patients treated with DOTS therapy. DM type 2 is responsible for the TB treatment prolongation and TB recurrence rates. By implementing effective management strategies and advancing research, the challenges can be mitigated, arising due to the complex interaction between DM and TB.
Topics: Humans; Tuberculosis; Diabetes Mellitus, Type 2; Comorbidity; Isoniazid; Ethambutol; Diabetes Mellitus
PubMed: 38346381
DOI: 10.1080/07853890.2024.2313683 -
Clinical Microbiology and Infection :... Feb 2024Contacts of patients with multidrug-resistant tuberculosis (MDR-TB) are at risk of developing TB disease. Tuberculosis preventive treatment (TPT) is an intervention that... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Contacts of patients with multidrug-resistant tuberculosis (MDR-TB) are at risk of developing TB disease. Tuberculosis preventive treatment (TPT) is an intervention that can potentially reduce this risk.
OBJECTIVES
To evaluate the effectiveness and safety of TPT for contacts of patients with MDR-TB.
DATA SOURCES
EMBASE, PubMed, Web of Science, and the Cochrane Library were searched for eligible studies on 24 July 2023, without start date restrictions.
STUDY ELIGIBILITY CRITERIA
We included studies that compared TPT with no treatment in contacts of patients with MDR-TB and reported outcomes of progression to TB disease.
PARTICIPANTS
Contacts of patients with MDR-TB.
INTERVENTIONS
TPT.
ASSESSMENT OF RISK OF BIAS
A modified version of the Newcastle-Ottawa Scale was used.
METHODS OF DATA SYNTHESIS
Random-effects meta-analysis was utilized to calculate the relative risk for disease progression to TB in contacts of patients with MDR-TB who received TPT compared to those who did not. Additionally, completion, adverse effect, and discontinued rates were assessed.
RESULTS
Involving 1105 individuals from 11 studies, the pooled relative risk for disease progression in contacts receiving TPT versus those without treatment was 0.34 (95% CI: 0.16-0.72). Subgroup analysis indicated a lower pooled relative risk for regimens based on the drug-resistance profile of the index patients with TB compared to uniform treatment regimens (0.22 [95% CI: 0.06-0.84] vs. 0.49 [95% CI: 0.17-1.35]), although not statistically significant. The pooled completed rate was 83.8%, adverse effect rate was 22.9%, and discontinued rate was 6.5%. After excluding the levofloxacin and pyrazinamide regimen study, the completed rate increased to 88.0%, and adverse effects and discontinued rates decreased to 8.0% and 4.0%, respectively.
DISCUSSION
TPT reduces TB disease progression risk in contacts of patients with MDR-TB. Tailored TPT regimens based on drug-resistance profiles may offer additional benefits. Furthermore, efforts to improve completed rates and manage adverse effects are essential for optimizing effectiveness and safety.
Topics: Humans; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Pyrazinamide; Levofloxacin; Drug-Related Side Effects and Adverse Reactions; Disease Progression
PubMed: 37741621
DOI: 10.1016/j.cmi.2023.09.015 -
EClinicalMedicine Oct 2023Tuberculosis (TB) is the leading infectious cause of death globally. Several preventive measures are employed to prevent TB, yet there is a paucity of evidence on the...
BACKGROUND
Tuberculosis (TB) is the leading infectious cause of death globally. Several preventive measures are employed to prevent TB, yet there is a paucity of evidence on the effectiveness of these interventions. Therefore, this study aimed to identify the most effective interventions for reducing TB incidence.
METHODS
A systematic search was undertaken across five relevant databases including PubMed, SCOPUS, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to February 22, 2023. Bayesian network meta-analysis (NMA) was conducted to compare the effectiveness of preventive interventions including preventive therapy, nutritional intervention, targeted screening, and vaccination in reducing TB incidence. Subgroup analysis was conducted to investigate the effectiveness of TB preventive treatments.
FINDINGS
Overall 82 articles were included in the NMA. Preventive therapy (OR = 0.44, 95% CrI 0.36-0.52), BCG vaccination (OR = 0.62, 95% CrI 0.39-0.98) and TB candidate vaccines (OR = 0.67, 95% CrI 0.46-0.98) were more effective than placebo or no intervention. When all active interventions were considered, preventive therapy ranked as the best intervention. Of the preventive treatments, isoniazid (OR = 0.46, 95% CrI 0.35-0.55), isoniazid plus rifampicin (OR = 0.56, 95% CrI 0.32-0.97), isoniazid plus rifapentine (OR = 0.49, 95% CrI 0.29-0.83), isoniazid plus ethambutol (OR = 0.39, 95% CrI 0.15-0.99), isoniazid plus streptomycin (OR = 0.12, 95% CrI 0.02-0.55), rifampicin (OR = 0.41, 95% CrI 0.18-0.92), and rifampicin plus pyrazinamide (OR = 0.51, 95% CrI 0.29-0.87) surpassed placebo/none.
INTERPRETATION
Our study suggested that when all available preventive interventions are considered, preventive therapy is likely the most effective intervention. Within TB preventive treatments, isoniazid plus streptomycin is likely ranked at the top. This comparative study provides important information for policymakers and stakeholders, enabling them to make informed decisions on preventive strategies, whilst considering local resources and capacity constraints.
FUNDING
Curtin University strategic scholarship and Australian National Health and Medical Research Council, through an Emerging Leadership Investigator grant.
PubMed: 37731939
DOI: 10.1016/j.eclinm.2023.102209 -
Journal of Chemotherapy (Florence,... Nov 2023Pyrazinamide (PZA) is an essential first-line tuberculosis drug for its unique mechanism of action active against multidrug-resistant-TB (MDR-TB). Thus, the aim of... (Meta-Analysis)
Meta-Analysis Review
Pyrazinamide (PZA) is an essential first-line tuberculosis drug for its unique mechanism of action active against multidrug-resistant-TB (MDR-TB). Thus, the aim of updated meta-analysis was to estimate the PZA weighted pooled resistance (WPR) rate in M. tuberculosis isolates based on publication date and WHO regions. We systematically searched the related reports in PubMed, Scopus, and Embase (from January 2015 to July 2022). Statistical analyses were performed using STATA software. The 115 final reports in the analysis investigated phenotypic PZA resistance data. The WPR of PZA was 57% (95% CI 48-65%) in MDR-TB cases. According to the WHO regions, the higher WPRs of PZA were reported in the Western Pacific (32%; 95% CI 18-46%), South East Asian region (37%; 95% CI 31-43%), and the Eastern Mediterranean (78%; 95% CI 54-95%) among any-TB patients, high risk of MDR-TB patients, and MDR-TB patients, respectively. A negligible increase in the rate of PZA resistance were showed in MDR-TB cases (55% to 58%). The rate of PZA resistance has been rising in recent years among MDR-TB cases, underlines the essential for both standard and novel drug regimens development.
Topics: Humans; Pyrazinamide; Mycobacterium tuberculosis; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Drug Resistance, Multiple, Bacterial; Amidohydrolases; Mutation; Microbial Sensitivity Tests; Tuberculosis
PubMed: 37211822
DOI: 10.1080/1120009X.2023.2214473 -
The Journal of Infectious Diseases May 2024For simultaneous prediction of phenotypic drug susceptibility test (pDST) for multiple antituberculosis drugs, the whole genome sequencing (WGS) data can be analyzed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
For simultaneous prediction of phenotypic drug susceptibility test (pDST) for multiple antituberculosis drugs, the whole genome sequencing (WGS) data can be analyzed using either a catalog-based approach, wherein 1 causative mutation suggests resistance, (eg, World Health Organization catalog) or noncatalog-based approach using complicated algorithm (eg, TB-profiler, machine learning). The aim was to estimate the predictive ability of WGS-based tests with pDST as the reference, and to compare the 2 approaches.
METHODS
Following a systematic literature search, the diagnostic test accuracies for 14 drugs were pooled using a random-effect bivariate model.
RESULTS
Of 779 articles, 44 with 16 821 specimens for meta-analysis and 13 not for meta-analysis were included. The areas under summary receiver operating characteristic curve suggested test accuracy was excellent (0.97-1.00) for 2 drugs (isoniazid 0.975, rifampicin 0.975), very good (0.93-0.97) for 8 drugs (pyrazinamide 0.946, streptomycin 0.952, amikacin 0.968, kanamycin 0.963, capreomycin 0.965, para-aminosalicylic acid 0.959, levofloxacin 0.960, ofloxacin 0.958), and good (0.75-0.93) for 4 drugs (ethambutol 0.926, moxifloxacin 0.896, ethionamide 0.878, prothionamide 0.908). The noncatalog-based and catalog-based approaches had similar ability for all drugs.
CONCLUSIONS
WGS accurately identifies isoniazid and rifampicin resistance. For most drugs, positive WGS results reliably predict pDST positive. The 2 approaches had similar ability.
CLINICAL TRIALS REGISTRATION
UMIN-ID UMIN000049276.
Topics: Antitubercular Agents; Whole Genome Sequencing; Mycobacterium tuberculosis; Humans; Microbial Sensitivity Tests; Phenotype; Tuberculosis, Multidrug-Resistant; Drug Resistance, Bacterial; Rifampin; Isoniazid
PubMed: 37946558
DOI: 10.1093/infdis/jiad480 -
BMJ Open Sep 2023To evaluate the efficacy of antituberculosis therapy on pregnancy outcomes in infertile women with genital tuberculosis.
OBJECTIVES
To evaluate the efficacy of antituberculosis therapy on pregnancy outcomes in infertile women with genital tuberculosis.
DESIGN
Systematic review.
DATA SOURCES
We searched in PubMed/MEDLINE, CENTRAL and EMBASE up to 15 January 2023. Additionally, we manually search the reference lists of included studies.
ELIGIBILITY CRITERIA
We included randomised controlled trials (RCT), non-RCTs (non-RCT) and cohort studies that evaluated the effects of antituberculosis treatment on pregnancy outcomes in infertile women with genital tuberculosis compared with not receiving antituberculosis treatment or receiving the treatment for a shorter period.
DATA EXTRACTION AND SYNTHESIS
Two independent reviewers extracted data. We used Cochrane Risk of Bias 1.0 and Risk Of Bias In Non-randomised Studies tools for risk of bias assessment and meta-analysis was not performed. We used Grading of Recommendations, Assessment, Development and Evaluations approach to assess the certainty of the evidence.
RESULTS
Two RCTs and one non-RCT were included. The antituberculosis regimens were based on isoniazid, rifampicin, pyrazinamide and ethambutol for 6-12 months. In women without structural damage, very low certainty of evidence from one RCT showed that the antituberculosis treatment may have little to no effect on pregnancy, full-term pregnancy, abortion or intrauterine death and ectopic pregnancy, but the evidence is very uncertain. In women with structural damage, very low certainty of evidence from one non-RCT showed that the antituberculosis treatment may reduce the pregnancy rate (297 fewer per 1000, 95% CI -416 to -101), but the evidence is very uncertain. In addition, very low certainty of evidence from one RCT compared a 9-month vs 6-month antituberculosis treatment regimen showed similar effects between the schemes, but the evidence is very uncertain. Two RCTs reported that no adverse events of antituberculosis treatment were noted or were similar in both groups.
CONCLUSION
The effect of antituberculosis treatment on pregnancy outcomes in infertile women with genital tuberculosis is very uncertain.
PROSPERO REGISTRATION NUMBER
CRD42022273145.
Topics: Female; Pregnancy; Humans; Pregnancy Outcome; Stillbirth; Infertility, Female; Antitubercular Agents; Tuberculosis; Genitalia
PubMed: 37758670
DOI: 10.1136/bmjopen-2022-070456