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Deutsches Arzteblatt International Oct 2019Around 10 million people worldwide contract tuberculosis every year. According to the World Health Organization (WHO), approximately one-quarter of the world's... (Review)
Review
BACKGROUND
Around 10 million people worldwide contract tuberculosis every year. According to the World Health Organization (WHO), approximately one-quarter of the world's population is latently infected with Mycobacterium tuberculosis. In Ger- many, the incidence of tuberculosis was in decline over several decades but rose in 2015 to 7.3 new cases per 100 000 persons. In 2018, a total of 5429 new cases were documented, corresponding to 6.5 new cases per 100 000 persons.
METHODS
This article is based on literature retrieved by a selective search in PubMed and on the authors' clinical experience.
RESULTS
Tuberculosis involves the lungs in almost 75% of patients but can generally involve any organ. In Germany, the majority of patients come from high-incidence countries. If a patient's differential diagnosis includes tuberculosis, the main tests for the detection of the pathogen in sputum and tissue samples are culture (the gold standard), microscopy, and nucleic acid amplification tests. Imaging studies are also used for diagnosis and follow-up. The standard treatment consists of a combination of isoniazid, rifampicin, ethambutol, and pyrazinamide, followed by a combination of isoniazid and rifampicin only. Liver damage is one of the more common adverse effects of this treatment, arising in 2.4% of patients. Multidrug-resistant tuberculosis, which is rare in Germany (around 100 cases per year), should be treated in special- ized centers.
CONCLUSION
Rapid diagnosis and targeted treatment are essential to prevent an unfavorable course of the disease as well as its transmission to other individuals. In patients presenting with unclear symptoms, tuberculosis should always be considered as a differential diagnosis. The diagnosis of latent tuberculosis and decision-making regarding its treatment are difficult because of the lack of specific biomarkers and of relevant data from clinical trials.
Topics: Antitubercular Agents; Diagnosis, Differential; Drug Therapy, Combination; Germany; Humans; Tuberculosis
PubMed: 31755407
DOI: 10.3238/arztebl.2019.0729 -
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 -
Drug Metabolism and Disposition: the... Aug 2021Pyrazinamide (PZA) is an important component of a standard combination therapy against tuberculosis. However, PZA is hepatotoxic, and the underlying mechanisms are... (Review)
Review
Pyrazinamide (PZA) is an important component of a standard combination therapy against tuberculosis. However, PZA is hepatotoxic, and the underlying mechanisms are poorly understood. Biotransformation of PZA in the liver was primarily suggested behind its hepatoxicity. This review summarizes the knowledge of the key enzymes involved in PZA metabolism and discusses their contributions to PZA hepatotoxicity. SIGNIFICANCE STATEMENT: This review outlines the current understanding of PZA metabolism and hepatotoxicity. This work also highlights the gaps in this field, which can be used to guide the future studies on PZA-induced liver injury.
Topics: Antitubercular Agents; Chemical and Drug Induced Liver Injury; Humans; Liver; Pyrazinamide; Tuberculosis
PubMed: 34074731
DOI: 10.1124/dmd.121.000389 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Dec 2022Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the... (Review)
Review
Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including mutations in isoniazid resistance, mutations in rifampin resistance, mutations in pyrazinamide resistance, and mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.
Topics: Humans; Pyrazinamide; Isoniazid; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Mycobacterium tuberculosis; Tuberculosis; Rifampin; Mutation; Drug Resistance, Multiple, Bacterial
PubMed: 36915970
DOI: 10.3724/zdxbyxb-2022-0454 -
The Pan African Medical Journal 2022Purulent pericarditis is an infection of the pericardial space that produces pus that is found on gross examination of the pericardial sac or on the tissue microscopy....
Purulent pericarditis is an infection of the pericardial space that produces pus that is found on gross examination of the pericardial sac or on the tissue microscopy. In this case report, we will discuss a 31-year-old male who presented with a chief complaint of low-grade fevers, dry cough and difficulty breathing for about two weeks which preceded after removing of dental also two weeks prior. He was admitted and treated as COVID-19 in the isolation ward, he later developed cardiac tamponade and during pericardiocentesis thick pus was discharged. Pus culture and Gene Xpert tests were all negative. After his condition improved, the patient was transferred to the general ward with the pericardial window still discharging pus. Pericardiectomy was chosen as definitive management. The key takeaway in this report is that Empirical treatment with RHZE (rifampin, isoniazid, pyrazinamide, and ethambutol) in resource-limited settings is recommended due to difficulty in identifying the exact cause at a required moment.
Topics: Adult; COVID-19; Ethambutol; Humans; Isoniazid; Male; Mediastinitis; Pericarditis; Pericardium; Pyrazinamide; Rifampin; Sclerosis; Suppuration
PubMed: 36160276
DOI: 10.11604/pamj.2022.42.145.34018 -
Open Forum Infectious Diseases Nov 2022Female genital tuberculosis (FGTB) is an important cause of morbidity and infertility worldwide. most commonly spreads to the genital tract from a focus elsewhere in... (Review)
Review
Female genital tuberculosis (FGTB) is an important cause of morbidity and infertility worldwide. most commonly spreads to the genital tract from a focus elsewhere in the body and affects the bilateral fallopian tubes and/or endometrium. Many patients with FGTB have indolent disease and are only diagnosed after evaluation for infertility. Women may present with menstrual irregularities, lower abdominal or pelvic pain, or abnormal vaginal discharge. Given the low sensitivity of diagnostic tests, various composite reference standards are used to diagnose FGTB, including some combination of endoscopic findings, microbiological or molecular testing, and histopathological evidence in gynecological specimens. Early treatment with a standard regimen of a 2-month intensive phase with isoniazid, rifampin, ethambutol, and pyrazinamide, followed by a 4-month continuation phase with isoniazid and rifampin, is recommended to prevent irreversible organ damage. However, even with treatment, FGTB can lead to infertility or pregnancy-related complications, and stigma is pervasive.
PubMed: 36447614
DOI: 10.1093/ofid/ofac543