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Respiratory Research Jun 2024Tuberculosis (TB) remains the second leading cause of death from a single infectious agent and long-term medication could lead to antituberculosis drug-induced liver...
Tuberculosis (TB) remains the second leading cause of death from a single infectious agent and long-term medication could lead to antituberculosis drug-induced liver injury (ATB-DILI). We established a prospective longitudinal cohort of ATB-DILI with multiple timepoint blood sampling and used untargeted metabolomics to analyze the metabolic profiles of 107 plasma samples from healthy controls and newly diagnosed TB patients who either developed ATB-DILI within 2 months of anti-TB treatment (ATB-DILI subjects) or completed their treatment without any adverse drug reaction (ATB-Ctrl subjects). The untargeted metabolome revealed that 77 metabolites (of 895 total) were significantly changed with ATB-DILI progression. Among them, levels of multiple fatty acids and bile acids significantly increased over time in ATB-DILI subjects. Meanwhile, metabolites of the same class were highly correlated with each other and pathway analysis indicated both fatty acids metabolism and bile acids metabolism were up-regulated with ATB-DILI progression. The targeted metabolome further validated that 5 fatty acids had prediction capability at the early stage of the disease and 6 bile acids had a better diagnostic performance when ATB-DILI occurred. These findings provide evidence indicating that fatty acids metabolism and bile acids metabolism play a vital role during ATB-DILI progression. Our report adds a dynamic perspective better to understand the pathological process of ATB-DILI in clinical settings.
Topics: Humans; Antitubercular Agents; Male; Metabolomics; Female; Chemical and Drug Induced Liver Injury; Longitudinal Studies; Adult; Middle Aged; Biomarkers; Prospective Studies; Predictive Value of Tests; Tuberculosis; Bile Acids and Salts
PubMed: 38907347
DOI: 10.1186/s12931-024-02837-8 -
BMC Infectious Diseases Jun 2024To determine the relationship of Neutrophil Lymphocyte Ratio (NLR), Monocyte Lymphocyte Ratio (MLR), and Neutrophil Monocyte Ratio (NMR) with treatment response in...
Relationship of neutrophil lymphocyte ratio, monocyte lymphocyte ratio and neutrophil monocyte ratio with treatment response in pulmonary tuberculosis patients during intensive phase treatment.
OBJECTIVE
To determine the relationship of Neutrophil Lymphocyte Ratio (NLR), Monocyte Lymphocyte Ratio (MLR), and Neutrophil Monocyte Ratio (NMR) with treatment response in Pulmonary Tuberculosis (PTB) patients during intensive phase treatment (IPT).
METHODS
This analytical cross-sectional study was conducted at Ojha Institute of Chest Diseases (OICD), Dow University of Health Sciences, from February to December 2021. 100 patients were enrolled using purposive sampling technique. Both male and female of age 18 and above, rifampicin sensitive newly diagnosed cases of PTB by Acid Fast Bacilli (AFB) microscopy and Gene Xpert MTB/RIF were included. SPSS version 26 was used to analyze data. Numerical data was expressed in median and interquartile range and categorical data was expressed in frequencies and percentages.
RESULTS
Out of total 100 patients, 81% (n = 81) showed treatment response with negative AFB Sputum Smear Microscopy (SSM) after 2nd month. Out of 81% (n = 81) of the patients who achieved treatment response, 83.9% (n = 68) also had decreased NLR, 85.2% (n = 69) had decreased MLR and 83.9% (n = 68) had decreased NMR from baseline. However 19% (n = 19) did not achieved treatment response with positive AFB SSM after 2nd month of ATT (Anti tuberculosis treatment), among them 10.52% (n = 2) were INH resistant with no decrease in all the ratios after 2nd month.
CONCLUSION
Leukocyte ratios decreased significantly from baseline as PTB was treated in patients who achieved treatment response with negative AFB SSM after two months of ATT and hence these ratios could be used as markers to monitor the treatment response.
Topics: Humans; Male; Female; Tuberculosis, Pulmonary; Adult; Neutrophils; Cross-Sectional Studies; Lymphocytes; Monocytes; Middle Aged; Antitubercular Agents; Treatment Outcome; Young Adult; Sputum; Adolescent; Rifampin
PubMed: 38907220
DOI: 10.1186/s12879-024-09454-2 -
Indian Journal of Ophthalmology Jul 2024
Topics: Humans; Ethambutol; Antitubercular Agents; Male; Female; Adult; Electroretinography; Middle Aged; Visual Acuity; Tomography, Optical Coherence
PubMed: 38905470
DOI: 10.4103/IJO.IJO_494_23 -
Indian Journal of Ophthalmology Jul 2024
Comparative Study
Topics: Humans; Intravitreal Injections; Administration, Oral; Rifampin; Central Serous Chorioretinopathy; Vascular Endothelial Growth Factor A; Propranolol; Angiogenesis Inhibitors; Adrenergic beta-Antagonists
PubMed: 38905466
DOI: 10.4103/IJO.IJO_2774_23 -
Medicine Jun 2024Tuberculosis of the long tubular bones in children's extremities is infrequent, particularly in the ulna. Early diagnosis poses significant challenges. This report... (Review)
Review
RATIONALE
Tuberculosis of the long tubular bones in children's extremities is infrequent, particularly in the ulna. Early diagnosis poses significant challenges. This report presents a case involving a 2-year-old child with tuberculosis of the ulnar bone, accompanied by a comprehensive review of pertinent literature. The purpose of this study is to share diagnostic and therapeutic experiences and provide potentially valuable insights.
PATIENT CONCERNS
In this case, the patient exhibited complete destruction and expansion of the ulnar bone, resulting in a forearm size considerably greater than normal. Concerns were raised about the irreversible deformation of the ulna, the potential for a malignant bone tumor, and its impact on forearm function, potentially endangering the patient's life.
DIAGNOSES
The diagnosis was confirmed as tuberculosis of the ulnar bone.
INTERVENTIONS
The patient underwent surgery to remove the affected ulnar tissue and received anti-tuberculosis medication.
OUTCOMES
Subsequent to treatment, the destruction and expansion of the ulnar bone resolved, with the return of normal ulnar morphology and bone structure.
LESSONS
Even in the absence of typical symptoms like fever, weight loss, and loss of appetite, extensive destruction and expansion of a long tubular bone should prompt vigilant consideration of bone tuberculosis.
Topics: Child, Preschool; Humans; Antitubercular Agents; Tuberculosis, Osteoarticular; Ulna
PubMed: 38905359
DOI: 10.1097/MD.0000000000038611 -
Cureus May 2024Toxic epidermal necrolysis (TEN) is a severe and potentially fatal adverse drug reaction. This case report presents a 19-year-old male with pulmonary tuberculosis...
Toxic epidermal necrolysis (TEN) is a severe and potentially fatal adverse drug reaction. This case report presents a 19-year-old male with pulmonary tuberculosis undergoing anti-tubercular therapy who developed TEN. The patient had multiple comorbidities including type 1 diabetes mellitus and multisystem atrophy. ChatGPT was utilized alongside conventional methods to assess causality. While conventional scoring systems estimated mortality at 58.3% (SCORTEN) and 12.3% (ABCD-10), ChatGPT yielded divergent scores. Causality assessment using WHO-Uppsala Monitoring Centre (UMC) and Naranjo's scale indicated rifampicin and isoniazid as probable causative agents. However, ChatGPT provided ambiguous results. The study underscores the potential of AI in pharmacovigilance but emphasizes caution due to discrepancies observed. Collaborative utilization of artificial intelligence (AI) with clinical judgment is advocated to enhance diagnostic accuracy and treatment decisions in adverse drug reactions. This case highlights the importance of integrating AI into drug safety systems while acknowledging its limitations to ensure optimal patient care.
PubMed: 38903274
DOI: 10.7759/cureus.60638 -
Nature Communications Jun 2024Novel therapeutic strategies against difficult-to-treat bacterial infections are desperately needed, and the faster and cheaper way to get them might be by repurposing...
Novel therapeutic strategies against difficult-to-treat bacterial infections are desperately needed, and the faster and cheaper way to get them might be by repurposing existing antibiotics. Nanodelivery systems enhance the efficacy of antibiotics by guiding them to their targets, increasing the local concentration at the site of infection. While recently described nanodelivery systems are promising, they are generally not easy to adapt to different targets, and lack biocompatibility or specificity. Here, nanodelivery systems are created that source their targeting proteins from bacteriophages. Bacteriophage receptor-binding proteins and cell-wall binding domains are conjugated to nanoparticles, for the targeted delivery of rifampicin, imipenem, and ampicillin against bacterial pathogens. They show excellent specificity against their targets, and accumulate at the site of infection to deliver their antibiotic payload. Moreover, the nanodelivery systems suppress pathogen infections more effectively than 16 to 32-fold higher doses of free antibiotics. This study demonstrates that bacteriophage sourced targeting proteins are promising candidates to guide nanodelivery systems. Their specificity, availability, and biocompatibility make them great options to guide the antibiotic nanodelivery systems that are desperately needed to combat difficult-to-treat infections.
Topics: Anti-Bacterial Agents; Bacteriophages; Nanoparticles; Drug Delivery Systems; Viral Proteins; Animals; Mice; Rifampin; Humans; Ampicillin; Bacterial Infections
PubMed: 38902231
DOI: 10.1038/s41467-024-49603-4 -
Molecules (Basel, Switzerland) May 2024Kallopterolides A-I (-), a family of nine diterpenoids possessing either a cleaved pseudopterane or a severed cembrane skeleton, along with several known compounds were...
Kallopterolides A-I (-), a family of nine diterpenoids possessing either a cleaved pseudopterane or a severed cembrane skeleton, along with several known compounds were isolated from the Caribbean Sea plume . The structures and relative configurations of - were characterized by analysis of HR-MS, IR, UV, and NMR spectroscopic data in addition to computational methods and side-by-side comparisons with published NMR data of related congeners. An investigation was conducted as to the potential of the kallopterolides as plausible in vitro anti-inflammatory, antiprotozoal, and antituberculosis agents.
Topics: Diterpenes; Animals; Anthozoa; Antiprotozoal Agents; Caribbean Region; Molecular Structure; Anti-Inflammatory Agents; Magnetic Resonance Spectroscopy; Antitubercular Agents
PubMed: 38893370
DOI: 10.3390/molecules29112493 -
International Journal of Molecular... Jun 2024Phenotypic susceptibility testing of the complex (MTBC) isolate requires culture growth, which can delay rapid detection of resistant cases. Whole genome sequencing...
Phenotypic susceptibility testing of the complex (MTBC) isolate requires culture growth, which can delay rapid detection of resistant cases. Whole genome sequencing (WGS) and data analysis pipelines can assist in predicting resistance to antimicrobials used in the treatment of tuberculosis (TB). This study compared phenotypic susceptibility testing results and WGS-based predictions of antimicrobial resistance (AMR) to four first-line antimicrobials-isoniazid, rifampin, ethambutol, and pyrazinamide-for MTBC isolates tested between the years 2018-2022. For this 5-year retrospective analysis, the WGS sensitivity for predicting resistance for isoniazid, rifampin, ethambutol, and pyrazinamide using Mykrobe was 86.7%, 100.0%, 100.0%, and 47.8%, respectively, and the specificity was 99.4%, 99.5%, 98.7%, and 99.9%, respectively. The predictive values improved slightly using Mykrobe corrections applied using TB Profiler, i.e., the WGS sensitivity for isoniazid, rifampin, ethambutol, and pyrazinamide was 92.31%, 100%, 100%, and 57.78%, respectively, and the specificity was 99.63%. 99.45%, 98.93%, and 99.93%, respectively. The utilization of WGS-based testing addresses concerns regarding test turnaround time and enables analysis for MTBC member identification, antimicrobial resistance prediction, detection of mixed cultures, and strain genotyping, all through a single laboratory test. WGS enables rapid resistance detection compared to traditional phenotypic susceptibility testing methods using the WHO TB mutation catalog, providing an insight into lesser-known mutations, which should be added to prediction databases as high-confidence mutations are recognized. The WGS-based methods can support TB elimination efforts in Canada and globally by ensuring the early start of appropriate treatment, rapidly limiting the spread of TB outbreaks.
Topics: Whole Genome Sequencing; Mycobacterium tuberculosis; Antitubercular Agents; Humans; Microbial Sensitivity Tests; Retrospective Studies; Drug Resistance, Bacterial; Genome, Bacterial; Ethambutol; Isoniazid; Pyrazinamide; Tuberculosis; Rifampin
PubMed: 38892433
DOI: 10.3390/ijms25116245 -
Healthcare (Basel, Switzerland) Jun 2024Tuberculosis (TB) is the top infectious killer in the world despite efforts to eliminate it. Pharmaceutical care roles are pillars of pharmacy practice, and pharmacists... (Review)
Review
Tuberculosis (TB) is the top infectious killer in the world despite efforts to eliminate it. Pharmaceutical care roles are pillars of pharmacy practice, and pharmacists are well equipped to serve a unique role in the pathway to provide education about TB. Previous systematic reviews emphasize pharmacists' role in treating TB; however, pharmacists can and do play much broader roles in overall TB elimination efforts. Five researchers searched five electronic databases (PubMed, PsychInfo, CINAHL, Academic Search Premier, and Embase). Search terms included pharmacy, pharmacist, tuberculosis, antitubercular agents, supply, distribution, and drug therapy. Inclusion criteria were studies published from 2010 through March 2023, in English or Spanish, addressed a specific TB-related role for pharmacists/pharmacies, and were peer-reviewed. Exclusion criteria included pharmacology, pharmacokinetics, clinical trials on drug efficacy, and editorials. Two researchers conducted each level of review; for discordance, a third researcher reviewed, and a decision was reached by consensus. Roles were extracted and cross-referenced with traditional pharmaceutical care steps. Of the initial 682 hits, 133 were duplicates. After further review, we excluded 514 records, leaving 37 articles for full extraction. We found nine roles for pharmacists in TB prevention and classified them as implemented, not implemented, or recommended. These roles were: (1) TB symptom screening; (2) Referring to TB care systems; (3) TB testing; (4) Dispensing TB medication correctly and/or directly observed therapy; (5) Counseling; (6) Looking to reduce socioeconomic barriers; (7) Procurement of TB medications; (8) Quality assurance of TB medications; (9) Maintaining and using pharmacy data systems. Pharmacists are well situated to play a vital role in the global fight against TB. Findings suggested pharmacists in many settings have already expanded their roles related to TB elimination beyond traditional pharmaceutical care. Still others need to increase the understanding of TB procurement and treatment, their power to improve TB care, and their contributions to data systems that serve population health. Pharmacy curricula should increase TB-related training to better equip future pharmacists to contribute to TB elimination.
PubMed: 38891212
DOI: 10.3390/healthcare12111137