-
International Journal of... Apr 2024Bedaquiline is one of the core drugs used to treat multidrug-resistant TB (MDR-TB). Delamanid is one of the companion drugs in group C which is used to complete the... (Observational Study)
Observational Study Comparative Study
Comparison of Individual Regimen Containing Bedaquiline with Delamanid and Bedaquiline without Delamanid on Efficacy and Safety in Multidrug-resistant Tuberculosis Patients: Implementation in Dr. Soetomo General Academic Hospital, Indonesia.
BACKGROUND
Bedaquiline is one of the core drugs used to treat multidrug-resistant TB (MDR-TB). Delamanid is one of the companion drugs in group C which is used to complete the treatment regimen when drugs in groups A and B can not be used. This study was conducted to analyze the efficacy and safety between individual regimens containing bedaquiline with delamanid and bedaquiline without delamanid.
METHODS
This was an observational analytic study with a retrospective design in MDR-TB patients treated with individual regimens containing bedaquiline with delamanid (bedaquiline-delamanid group) and bedaquiline without delamanid (bedaquiline group). Efficacy was measured according to the time to Acid Fast Bacilli (AFB) conversion and Mycobacterium tuberculosis culture conversion, while safety was measured specifically on QTc interval prolongation.
RESULTS
The median (range) time to AFB conversion in bedaquiline-delamanid group was faster than bedaquiline group, although there was no significant difference (1.5 (1-4) months vs. 1 (1-6) months, P=0.429), the median time to culture conversion in bedaquiline-delamanid group also faster than bedaquiline group, although there was no significant difference (1 (1-6) months vs. 2 (1-6) months, P=0.089). The incidence of QTc interval prolongation in bedaquiline-delamanid group was less than bedaquiline group, although there was no significant difference (26.9% vs. 40.3%, P=0.223).
CONCLUSIONS
Individual regimens containing bedaquiline with delamanid was proven to provide similar efficacy and safety profiles with individual regimens containing bedaquiline without delamanid. Delamanid should be preferred when selecting drugs to complete the treatment regimen when drugs in groups A and B can not be used.
Topics: Humans; Nitroimidazoles; Diarylquinolines; Oxazoles; Tuberculosis, Multidrug-Resistant; Antitubercular Agents; Retrospective Studies; Female; Adult; Male; Middle Aged; Indonesia; Treatment Outcome; Young Adult; Drug Therapy, Combination; Mycobacterium tuberculosis; Adolescent; Aged
PubMed: 38916383
DOI: 10.4103/ijmy.ijmy_88_24 -
Frontiers in Cellular and Infection... 2024is a major causative pathogen of osteomyelitis. Intracellular infections of resident bone cells including osteocytes can persist despite gold-standard clinical...
is a major causative pathogen of osteomyelitis. Intracellular infections of resident bone cells including osteocytes can persist despite gold-standard clinical intervention. The mechanisms by which intracellular evades antibiotic therapy are unknown. In this study, we utilised an infection model of human osteocytes to investigate whether antibiotic-mediated dysregulation of autophagy contributes to this phenomenon. Infected or non-infected osteocyte-like cells were exposed to combinations of rifampicin, vancomycin, and modulators of autophagy. Intracellular bacterial growth characteristics were assessed using colonyforming unit (CFU) analysis, viable bacterial DNA abundance, and the rate of escape into antibiotic-free medium, together with measures of autophagic flux. Rifampicin, alone or in combination with vancomycin, caused a rapid decrease in the culturability of intracellular bacteria, concomitant with stable or increased absolute bacterial DNA levels. Both antibiotics significantly inhibited autophagic flux. However, modulation of autophagic flux did not affect viable bacterial DNA levels. In summary, autophagy was shown to be a factor in the host-pathogen relationship in this model, as its modulation affected the growth state of intracellular with respect to both their culturability and propensity to escape the intracellular niche. While rifampicin and vancomycin treatments moderately suppressed autophagic flux acutely, this did not explain the paradoxical response of antibiotic treatment in decreasing culturability whilst failing to clear bacterial DNA and hence intracellular bacterial load. Thus, off-target effects of rifampicin and vancomycin on autophagic flux in osteocyte-like cells could not explain the persistent infection in these cells.
Topics: Autophagy; Staphylococcus aureus; Osteocytes; Anti-Bacterial Agents; Humans; Vancomycin; Rifampin; Staphylococcal Infections; Host-Pathogen Interactions; DNA, Bacterial
PubMed: 38915921
DOI: 10.3389/fcimb.2024.1403289 -
Medicina 2024
Topics: Humans; Immunocompetence; Tuberculoma; Male; Abscess; Adult; Antitubercular Agents; Female
PubMed: 38907984
DOI: No ID Found -
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