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Open Forum Infectious Diseases Jun 2022Before August 2021, the only regimen recommended by the World Health Organization (WHO) to treat pediatric drug-susceptible tuberculous meningitis was a 12-month regimen...
BACKGROUND
Before August 2021, the only regimen recommended by the World Health Organization (WHO) to treat pediatric drug-susceptible tuberculous meningitis was a 12-month regimen consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide (2HRZE/10HR). The comparative effectiveness of shorter regimens is unknown.
METHODS
To inform a WHO guideline update, we undertook a systematic review and meta-analysis to evaluate outcomes from regimens of 6- to less than 12-months' duration that included, at a minimum, isoniazid, rifampicin, and pyrazinamide. We included studies that applied rigorous diagnostic criteria and reported outcomes for ≥10 children or adolescents. Using generalized linear mixed models, we estimated the random effects pooled proportions of patients with key outcomes.
RESULTS
Of 7 included studies, none compared regimens head-to-head. Three studies (724 patients) used a 6-month intensive regimen, which includes isoniazid and rifampicin at higher doses, pyrazinamide, and ethionamide instead of ethambutol (6HRZEto). Outcomes for this versus the 12-month regimen (282 patients, 3 studies) were, respectively, as follows: death, 5.5% (95% confidence interval [CI], 2.1%-13.4%) vs 23.9% (95% CI, 17.5%-31.7%); treatment success (survival with or without sequelae), 94.6% (95% CI, 73.9%-99.1%) vs 75.4% (95% CI, 68.7%-81.1%); and neurological sequelae among survivors, 66.0% (95% CI, 55.3%-75.3%) vs 36.3% (95% CI, 30.1%-43.0%). Relapse did not occur among 148 patients followed-up for 2 years after completing the 6-month intensive regimen.
CONCLUSIONS
Our findings are limited by the small number of studies and substantial potential for confounding. Nonetheless, the 6HRZEto regimen was associated with high treatment success and is now recommended by WHO as an alternative to the 12-month regimen.
PubMed: 35673608
DOI: 10.1093/ofid/ofac108 -
Oman Medical Journal Jan 2022This systematic review explores the effectiveness and safety of a short-term regimen (STR) in treating multidrug-resistant tuberculosis (MDR-TB). We use several cohort... (Review)
Review
This systematic review explores the effectiveness and safety of a short-term regimen (STR) in treating multidrug-resistant tuberculosis (MDR-TB). We use several cohort studies which were searched using standardized Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The keywords were used based on problem, intervention, comparison, and outcome consisted of MDR-TB and STR. Seven cohort studies were selected from 314 studies. The result showed that STR has better therapeutic efficacy and shorter duration than the 2011 World Health Organization regimen for MDR-TB with success rates above 50% in respective studies. The most effective regimen was kanamycin-high-dose isoniazid-clofazimine-ethambutol-prothionamide-pyrazinamide-gatifloxacin in the intensive phase for four months and clofazimine-ethambutol-pyrazinamide-gatifloxacin-prothionamide in the continuation phase for eight months. Gastrointestinal problems, ototoxicity, dysglycemia, and liver problems were the most reported side effects. STR provides good effectiveness in MDR-TB treatment in terms of treatment success rate and short therapy duration.
PubMed: 35211341
DOI: 10.5001/omj.2021.64 -
BMC Infectious Diseases Sep 2021Tuberculosis (TB) is one of the most contagious infectious diseases worldwide. Currently, drug-resistant Mycobacterium tuberculosis (Mtb) isolates are considered as one... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tuberculosis (TB) is one of the most contagious infectious diseases worldwide. Currently, drug-resistant Mycobacterium tuberculosis (Mtb) isolates are considered as one of the main challenges in the global TB control strategy. Rapid detection of resistant strains effectively reduces morbidity and mortality of world's population. Although both culture and conventional antibiotic susceptibility testing are time-consuming, recent studies have shown that high resolution melting (HRM) assay can be used to determine the types of antibiotic resistance. In the present meta-analysis, we evaluated the discriminative power of HRM in detecting all drug-resistance cases of TB.
METHODS
A systematic search was performed using databases such as Cochrane Library, Scopus, PubMed, Web of Science, and Google Scholar. Related studies on the effect of HRM in the diagnosis of drug-resistant (DR) TB cases were retrieved by April 2021. We used Meta-Disc software to evaluate the pooled diagnostic sensitivity and specificity of HRM for the detection of each type of drug-resistant cases. Finally, diagnostic value of HRM was characterized by summary receiver operating characteristic (SROC) curve and the area under the curve (AUC) method.
RESULTS
Overall 47 studies (4,732 Mtb isolates) met our criteria and were included in the present meta-analysis. Sensitivity, specificity, and AUC of HRM were measured for antibiotics such as isoniazid (93%, 98%, 0.987), rifampin (94%, 97%, 0963), ethambutol (82%, 87%, 0.728), streptomycin (82%, 95%, 0.957), pyrazinamide (72%, 84%, 0.845), fluoroquinolones (86%, 99%, 0.997), MDR-TB (90%, 98%, 0.989), and pan-drug-resistant TB (89%, 95%, 0.973).
CONCLUSIONS
The HRM assay has high accuracy for the identification of drug-resistant TB, particularly firs-line anti-TB drugs. Therefore, this method is considered as an alternative option for the rapid diagnosis of DR-TB cases. However, due to heterogeneity of included studies, the results of HRM assays should be interpreted based on conventional drug susceptibility testing.
Topics: Antitubercular Agents; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Rifampin; Sensitivity and Specificity; Tuberculosis, Multidrug-Resistant
PubMed: 34551717
DOI: 10.1186/s12879-021-06708-1 -
Clinical Microbiology and Infection :... Jan 2022Outcomes of treatment of tuberculosis patients with regimens including pretomanid have not yet been systematically reviewed. (Review)
Review
BACKGROUND
Outcomes of treatment of tuberculosis patients with regimens including pretomanid have not yet been systematically reviewed.
OBJECTIVES
To appraise existing evidence on efficacy and safety of pretomanid in tuberculosis.
DATA SOURCES
Pubmed, clinicaltrials.gov. and Cochrane library.
STUDY ELIGIBILITY CRITERIA
Quantitative studies presenting original data on clinical efficacy or safety of pretomanid.
PARTICIPANTS
Patients with tuberculosis.
INTERVENTIONS
Treatment with pretomanid or pretomanid-containing regimens in minimum one study group.
METHODS
Two authors independently extracted data and assessed risk of bias. Data on efficacy (early bactericidal activity, bactericidal activity, end-of-treatment outcomes and acquired resistance) and safety were summarized in tables. Mean differences in efficacy outcomes between regimens across studies were calculated.
RESULTS
Eight studies were included; four randomized controlled trials on 2-week early bactericidal activity in rifampicin-susceptible tuberculosis, three trials with randomized rifampicin-susceptible tuberculosis arms and a single rifampicin-resistant tuberculosis arm (two on 8-week bactericidal activity, one on end-of-treatment outcomes), one single-arm trial with end-of-treatment outcomes in highly resistant tuberculosis. Activity of pretomanid-moxifloxacin-pyrazinamide was superior to standard treatment on daily change in colony-forming units at days 0-2, 0-56 and 7-56 and time to culture conversion in rifampicin-susceptible tuberculosis (hazard ratio: 1.7; 95% CI 1.1-2.7), but not at end of treatment in one study. This study was stopped due to serious hepatotoxic adverse events, including three deaths, in 4% (95% CI 2-8) patients on pretomanid-moxifloxacin-pyrazinamide and none in controls. In patients with uncomplicated rifampicin-resistant tuberculosis on pretomanid-moxifloxacin-pyrazinamide treatment, 91% (95% CI 59-100) had favourable end-of-treatment outcomes. In patients with highly resistant tuberculosis, 90% (95% CI 83-95) on pretomanid-bedaquiline-linezolid had favourable outcomes six months after treatment, but linezolid-related toxicity was frequent. No acquired resistance to pretomanid was reported.
CONCLUSIONS
Evidence suggests an important role for pretomanid in rifampicin-resistant and highly resistant tuberculosis. Trials comparing pretomanid to existing core and companion drugs are needed to further define that role.
Topics: Antitubercular Agents; Humans; Linezolid; Moxifloxacin; Nitroimidazoles; Pyrazinamide; Randomized Controlled Trials as Topic; Rifampin; Tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 34400340
DOI: 10.1016/j.cmi.2021.08.007 -
Annals of Palliative Medicine Jun 2021Isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) are the four most common drugs for the first-line treatment of tuberculosis (TB). Although... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) are the four most common drugs for the first-line treatment of tuberculosis (TB). Although chemotherapy drugs are widely used in the treatment of TB, and achieved good results, but the side effects, especially anti-tuberculosis drug-induced liver injury (ATDILI), cannot be overlooked. Many researchers have made efforts to uncover the association of cytochrome P450 (CYP) enzyme genetic polymorphisms with ATDILI. In this study, we systematically reviewed and meta-analyzed the relationship between CYP polymorphism and susceptibility to ATDILI.
METHODS
We carried out literature searches of PubMed, Ovid, the Cochrane Library, Web of Science and Chinese National Knowledge Infrastructure (CNKI). Medical Subject Headings (MeSH) terms including "cytochrome P450 enzyme", "drug-induced liver injury", "polymorphism", "tuberculosis", and "hepatotoxicity" were used as keywords for our searches.
RESULTS
The pooled odds ratio (OR) of all studies for CYP2E1 to the risk of ATDILI was 1.18 [95% confidence interval (CI): 0.82-1.71]. The articles in this meta-analysis were observed to be mildly heterogeneous. Further subgroup analysis revealed that the patients who receiving a four-drug protocol (INH + RIF + PZA + EMB) or three-drug protocol (INH + RIF + PZA) regimens showed a higher risk of ATDILI than those who receiving INH alone. However, subgroup analyses according to participants' ethnic origin, study type, and the definition of ATDILI produced no statistically significant results. Associations between other genes in the CYP family and ATDILI were indistinct and equivocal.
DISCUSSION
Our meta-analysis has uncovered an association between CYP2E1 RsaI/PstI polymorphisms and ATDILI, especially among patients who receive a four-drug (INH + RIF + PZA + EMB) or three-drug (INH + RIF + PZA) anti-TB treatment regimen.
Topics: Antitubercular Agents; Chemical and Drug Induced Liver Injury; Cytochrome P-450 Enzyme System; Humans; Polymorphism, Genetic; Tuberculosis
PubMed: 34154362
DOI: 10.21037/apm-21-1224 -
Iranian Journal of Basic Medical... Apr 2021This updated systematic review and meta-analysis follows two aims: 1) to assess antibiotic resistance in Iran from 2013 to 2020 and, 2) to assess the trend of... (Review)
Review
This updated systematic review and meta-analysis follows two aims: 1) to assess antibiotic resistance in Iran from 2013 to 2020 and, 2) to assess the trend of resistance from 1999 to 2020. Several national and international databases were systematically searched through MeSH extracted keywords to identify 41 published studies addressing drug-resistant in Iran. Meta-analysis was done based on the PRISMA protocols using Comprehensive Meta-Analysis software. The average prevalence of resistance to first- and second-line anti-TB drugs, multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in new and previously treated tuberculosis (TB) cases in Iran during 2013-2020 were as follows: isoniazid 6.9%, rifampin 7.9%, ethambutol 5.7%, pyrazinamide 20.4%, -aminosalicylic acid 4.6%, capreomycin 1.7%, cycloserine 1.8%, ethionamide 11.3%, ofloxacin 1.5%, kanamycin 3.8%, amikacin 2.2%, MDR-TB 6.3% and XDR-TB 0.9%. Based on the presented data, resistance to first- and second-line anti-TB drugs, as well as MDR-TB, was low during 2013-2020 in Iran. Furthermore, there was a declining trend in TB drug resistance from 1999 to 2020. Hence, to maintain the current decreasing trend and to control and eliminate TB infection in Iran, continuous monitoring of resistance patterns is recommended.
PubMed: 34094023
DOI: 10.22038/IJBMS.2021.48628.11161 -
Clinical Pharmacology : Advances and... 2021Tuberculosis remains the major public health problem besides tremendous efforts to combat it. Most tuberculosis patients are treated with a standard dose of first-line...
BACKGROUND
Tuberculosis remains the major public health problem besides tremendous efforts to combat it. Most tuberculosis patients are treated with a standard dose of first-line anti-TB drugs. The cure rate, however, varies from patient to patient. Various factors have been related to anti-TB treatment failure. In recent years, studies associating lower plasma concentrations of anti-TB drugs with poor treatment outcomes are emerging although the results are inconclusive.
OBJECTIVE
Investigate the impact of first-line anti-tubercular drugs pharmacokinetics on treatment outcome.
METHODS
A systematic search of Pubmed, EMBASE, Web of Science, and the Cochrane Library for articles published in the English language between January 2010 to June 2020 was conducted to identify eligible studies describing associations of first-line anti-tubercular drug pharmacokinetics with treatment outcomes. The primary outcomes considered were pharmacokinetics parameter results and its association with treatment outcome.
RESULTS
The search identified 1754 articles of which twelve articles; ten prospective observational studies and two controlled clinical trials fulfilled the eligibility criteria. The majority of the studies showed target concentrations for the first-line anti-tubercular drugs below the current standard range. Among the twelve studies, eleven studies assessed rifampicin pharmacokinetics of which eight reported association of drug concentration and treatment outcomes. Similarly, four out of eight and three out of seven reported drug concentration and treatment outcome association for isoniazid and pyrazinamide, respectively. Despite the low plasma concentration, a favorable treatment outcome was achieved for the bulk of the patients. Irrespective of the inconsistency, an increase in exposure to rifampicin improved the outcome, and lower rifampicin, isoniazid, and pyrazinamide concentration are associated with poor outcome. No data are available for ethambutol associating its pharmacokinetics with treatment outcomes.
CONCLUSION
The pharmacokinetics of first-line antitubercular drugs can influence treatment outcomes. Further controlled clinical studies are, however, required to establish these relationships.
PubMed: 33469389
DOI: 10.2147/CPAA.S289714 -
The International Journal of... Jan 2020Low serum concentrations of first-line tuberculosis (TB) drugs have been widely reported. However, the impact of low serum concentrations on treatment outcome is less... (Meta-Analysis)
Meta-Analysis
Low serum concentrations of first-line tuberculosis (TB) drugs have been widely reported. However, the impact of low serum concentrations on treatment outcome is less well studied. A systematic search of MEDLINE/Pubmed and the Cochrane Central Register of Controlled Trials up to 31 March 2018 was conducted for articles describing drug concentrations of first-line TB drugs and treatment outcome in adult patients with drug-susceptible TB. The search identified 3073 unique publication abstracts, which were reviewed for suitability: 21 articles were acceptable for inclusion in the qualitative analysis comprising 13 prospective observational cohorts, 4 retrospective observational cohorts, 1 case-control study and 3 randomised controlled trials. Data for meta-analysis were available for 15 studies, 13 studies of rifampicin (RMP), 10 of isoniazid (INH), 8 of pyrazinamide (PZA) and 4 of ethambutol (EMB). This meta-analysis revealed that low PZA concentration appears to increase the risk of poor outcomes (8 studies, = 2727; RR 1.73, 95%CI 1.10-2.72), low RMP concentrations may slightly increase the risk of poor outcomes (13 studies, = 2753; RR 1.40, 95%CI 0.91-2.16), whereas low concentrations of INH (10 studies, = 2640; RR 1.32, 95%CI 0.66-2.63) and EMB (4 studies, = 551; RR 1.12, 95%CI 0.41-3.05) appear to make no difference to treatment outcome. There was no significant publication bias or between-study heterogeneity in any of the analyses. The potential clinical impact of low concentrations of PZA and RMP warrants further evaluation. Also, comprehensive assessments of the complex pharmacokinetic-pharmacodynamic relationships in the treatment of TB are urgently needed.
Topics: Adult; Antitubercular Agents; Case-Control Studies; Humans; Isoniazid; Observational Studies as Topic; Pharmaceutical Preparations; Pyrazinamide; Retrospective Studies; Treatment Outcome; Tuberculosis
PubMed: 32005307
DOI: 10.5588/ijtld.19.0025 -
The Cochrane Database of Systematic... Dec 2019Tuberculosis causes more deaths than any other infectious disease worldwide, with pulmonary tuberculosis being the most common form. Standard first-line treatment for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tuberculosis causes more deaths than any other infectious disease worldwide, with pulmonary tuberculosis being the most common form. Standard first-line treatment for drug-sensitive pulmonary tuberculosis for six months comprises isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE) for two months, followed by HRE (in areas of high TB drug resistance) or HR, given over a four-month continuation phase. Many people do not complete this full course. Shortened treatment regimens that are equally effective and safe could improve treatment success.
OBJECTIVES
To evaluate the efficacy and safety of shortened treatment regimens versus the standard six-month treatment regimen for individuals with drug-sensitive pulmonary tuberculosis.
SEARCH METHODS
We searched the following databases up to 10 July 2019: the Cochrane Infectious Diseases Group Specialized Register; the Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE (PubMed); Embase; the Latin American Caribbean Health Sciences Literature (LILACS); Science Citation Index-Expanded; Indian Medlars Center; and the South Asian Database of Controlled Clinical Trials. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform, ClinicalTrials.gov, the Clinical Trials Unit of the International Union Against Tuberculosis and Lung Disease, the UK Medical Research Council Clinical Trials Unit, and the Clinical Trials Registry India for ongoing trials. We checked the reference lists of identified articles to find additional relevant studies.
SELECTION CRITERIA
We searched for randomized controlled trials (RCTs) or quasi-RCTs that compared shorter-duration regimens (less than six months) versus the standard six-month regimen for people of all ages, irrespective of HIV status, who were newly diagnosed with pulmonary tuberculosis by positive sputum culture or GeneXpert, and with presumed or proven drug-sensitive tuberculosis. The primary outcome of interest was relapse within two years of completion of anti-tuberculosis treatment (ATT).
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, extracted data, and assessed risk of bias for the included trials. For dichotomous outcomes, we used risk ratios (RRs) with 95% confidence intervals (CIs). When appropriate, we pooled data from the included trials in meta-analyses. We assessed the certainty of evidence using the GRADE approach.
MAIN RESULTS
We included five randomized trials that compared fluoroquinolone-containing four-month ATT regimens versus standard six-month ATT regimens and recruited 5825 adults with newly diagnosed drug-sensitive pulmonary tuberculosis from 14 countries with high tuberculosis transmission in Asia, Africa, and Latin Ameria. Three were multi-country trials that included a total of 572 HIV-positive people. These trials excluded children, pregnant or lactating women, people with serious comorbid conditions, and those with diabetes mellitus. Four trials had multiple treatment arms. Moxifloxacin replaced ethambutol in standard four-month, daily or thrice-weekly ATT regimens in two trials; moxifloxacin replaced isoniazid in four-month ATT regimens in two trials, was given daily in one trial, and was given with rifapentine instead of rifampicin daily for two months and twice weekly for two months in one trial. Moxifloxacin was added to standard ATT drugs for three to four months in one ongoing trial that reported interim results. Gatifloxacin replaced ethambutol in standard ATT regimens given daily or thrice weekly for four months in two trials. Follow-up ranged from 12 months to 24 months after treatment completion for the majority of participants. Moxifloxacin-containing four-month ATT regimens Moxifloxacin-containing four-month ATT regimens that replaced ethambutol or isoniazid probably increased the proportions who experienced relapse after successful treatment compared to standard ATT regimens (RR 3.56, 95% CI 2.37 to 5.37; 2265 participants, 3 trials; moderate-certainty evidence). For death from any cause, there was probably little or no difference between the two regimens (2760 participants, 3 trials; moderate-certainty evidence). Treatment failure was rare, and there was probably little or no difference in proportions with treatment failure between ATT regimens (2282 participants, 3 trials; moderate-certainty evidence). None of the participants given moxifloxacin-containing regimens developed resistance to rifampicin, and these regimens may not increase the risk of acquired resistance (2282 participants, 3 trials; low-certainty evidence). Severe adverse events were probably little or no different with moxifloxacin-containing four-month regimens that replaced ethambutol or isoniazid, and with three- to four-month regimens that augmented standard ATT with moxifloxacin, when compared to standard six-month ATT regimens (3548 participants, 4 trials; moderate-certainty evidence). Gatifloxacin-containing four-month ATT regimens Gatifloxacin-containing four-month ATT regimens that replaced ethambutol probably increased relapse compared to standard six-month ATT regimens in adults with drug-sensitive pulmonary tuberculosis (RR 2.11, 95% CI 1.56 to 2.84; 1633 participants, 2 trials; moderate-certainty evidence). The four-month regimen probably made little or no difference in death compared to the six-month regimen (1886 participants, 2 trials; moderate-certainty evidence). Treatment failure was uncommon and was probably little or no different between the four-month and six-month regimens (1657 participants, 2 trials; moderate-certainty evidence). Acquired resistance to isoniazid or rifampicin was not detected in those given the gatifloxacin-containing shortened ATT regimen, but we are uncertain whether acquired drug resistance is any different in the four- and six-month regimens (429 participants, 1 trial; very low-certainty evidence). Serious adverse events were probably no different with either regimen (1993 participants, 2 trials; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Evidence to date does not support the use of shortened ATT regimens in adults with newly diagnosed drug-sensitive pulmonary tuberculosis. Four-month ATT regimens that replace ethambutol with moxifloxacin or gatifloxacin, or isoniazid with moxifloxacin, increase relapse substantially compared to standard six-month ATT regimens, although treatment success and serious adverse events are little or no different. The results of six large ongoing trials will help inform decisions on whether shortened ATT regimens can replace standard six-month ATT regimens. 9 December 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (10 Jul, 2019) were included.
Topics: Antitubercular Agents; Clinical Protocols; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Humans; Randomized Controlled Trials as Topic; Tuberculosis, Pulmonary
PubMed: 31828771
DOI: 10.1002/14651858.CD012918.pub2 -
Clinical and Molecular Hepatology Apr 2020Drug induced liver injury (DILI) may be different in the East compared to the West due to differing disease prevalence, prescribing patterns and pharmacogenetic... (Meta-Analysis)
Meta-Analysis
Drug induced liver injury (DILI) may be different in the East compared to the West due to differing disease prevalence, prescribing patterns and pharmacogenetic profiles. To review existing literature on causative agents of DILI in the East compared to the West, a comprehensive literature search was performed on electronic databases: MEDLINE/PubMed, Embase, Cochrane Library and China National Knowledge Infrastructure without language restrictions. Studies which involve patients having DILI and reported the frequency of causative agents were included. A random effects model was applied to synthesize the current evidence using prevalence of class-specific and agent-specific causative drugs with 95% confidence intervals. Of 6,914 articles found, 12 showed the distribution of drugs implicated in DILI in the East with a total of 33,294 patients and 16 in the West with a total of 26,069 DILI cases. In the East, the most common agents by class were anti-tuberculosis drugs (26.6%), herbal and alternative medications (25.3%), and antibiotics (15.7%), while in the West, antibiotics (34.9%), cardiovascular agents (17.3%), and non-steroidal anti-inflammatory drugs (12.5%) were the commonest. For individual agents, the most common agents in the East were isoniazid-rifampicin-pyrazinamide (25.4%), phenytoin (3.5%), and cephalosporin (2.9%) while in the West, amoxicillin-potassium clavulanate combination acid (11.3%), nimesulide (6.3%), and ibuprofen (6.1%) were the commonest. There was significant heterogeneity due to variability in single-centre compared to multi-centre studies. Differences in DILI in the East versus the West both in drug classes and individual agents are important for clinicians to recognize.
Topics: Anti-Bacterial Agents; Antitubercular Agents; Cardiovascular Agents; Chemical and Drug Induced Liver Injury; Databases, Factual; Humans; Medicine, Traditional; Risk Assessment
PubMed: 31816676
DOI: 10.3350/cmh.2019.1003