Nontuberculous mycobacteria (NTM) infections, especially those caused by Mycobacterium abscessus, are extremely difficult to treat due to the organisms’ intrinsic resistance to many antimicrobials. Myxin is a naturally occurring phenazine-5,10-dioxide antibiotic from Sorangium sp., notable for its broad-spectrum antimicrobial activity. In this study, we determined the susceptibilities of Myxin against 11 NTM reference strains and 194 clinical M. abscessus isolates using microdilution assays. Additionally, time-kill kinetic experiments were performed to distinguish the clearing efficiency of Myxin in broth. We also evaluated the efficacy of Myxin against intracellular M. abscessus in THP-1 macrophages. Checkerboard assays assessed the interactions between Myxin and eight clinically important anti-NTM antibiotics. Myxin demonstrated potent activity against M. abscessus with low MIC values (MIC 50 = 0.125 mg/L and MIC 90 = 0.5 mg/L). Treatment with 20 × MIC of Myxin in 7H9 broth resulted in up to 10 log 10 CFU/mL reduction after 4 days of incubation. Intracellular concentration-dependent bactericidal effect of Myxin was observed in THP-1 macrophages. Myxin exhibited no antagonism in combination with standard anti-NTM drugs. As such, Myxin represents a promising candidate for the treatment of M. abscessus and other NTM infections.

Nitroimidazole antibiotics, including metronidazole, tinidazole, and ornidazole, are widely used to treat anaerobic infections and parasitic diseases. While their efficacy is well-established, comprehensive safety profiles, especially for rare adverse events, remain incompletely characterized. This study aimed to systematically evaluate the safety signals of these drugs using the FDA Adverse Event Reporting System (FAERS) database from 2014 to 2024. Disproportionality analyses were performed at the System Organ Class (SOC) and Standardized MedDRA Queries (SMQ) levels to identify associations between nitroimidazole antibiotics and adverse events. A total of 17631 adverse event reports were analyzed for metronidazole, tinidazole, and ornidazole, respectively. Female patients accounted for the majority of reports (57.35%, 51.70%, and 61.11%, respectively), likely reflecting their clinical use in gynecological infections. Metronidazole exhibited the shortest median time to adverse event onset (2.5 days), while tinidazole had the longest (5.5 days). At the SOC level, all three drugs showed positive associations with gastrointestinal, nervous system, and cardiac disorders. Ornidazole displayed strong positive signals for vascular (IC025 = 18.46) and skin disorders (IC025 = 17.46), while tinidazole had weaker but notable associations with skin and blood disorders. Critically, SMQ-level analysis revealed significant signals not currently highlighted in drug labels, including acute pancreatitis, hepatic failure, fibrosis/cirrhosis, and tachyarrhythmias for tinidazole and ornidazole. These findings suggest the need for enhanced clinical monitoring of hepatic and cardiac function during treatment with these agents. Despite limitations inherent to spontaneous reporting data, this study provides valuable insights into both known and previously underrecognized risks associated with nitroimidazole antibiotics, underscoring the importance of ongoing pharmacovigilance to optimize patient safety.

not-yet-known not-yet-known not-yet-known unknown Abstract Few studies have investigated blood glucose levels and complication management in elderly patients with type 2 diabetes (T2D) at community hospitals in China. The objective of this study was to investigate the factors influencing blood glucose control in elderly patients with T2D and assess the adherence of doctors in community hospitals to the latest diabetes guidelines regarding the use of glucose-lowering medications. This study involved 1150 elderly patients (age≥65 years) with diabetes to assess blood glucose control, complications management, and adherence of medication according to the guidelines of American Diabetes Association. To evaluate blood glucose control, different glycated haemoglobin targets were assigned according to patient characteristics and health status (including comorbidities and cognitive status). Univariate and multivariate logistic regression analyses were used to investigate the factors affecting glucose control. Among the 1150 participants, 351 (30.52%) had poor glucose control. Frailty (odds ratio [OR]:0.393; 95% confidence interval [CI]:0.195-0.789; P=0.009), male sex (OR:1.472; 95% CI:1.131-1.915, P=0.004), and insulin treatment (OR:4.364; 95% CI:3.151-6.042; P<0.001) were significantly associated with poor blood glucose control in patients treated with glucose-lowering medications. The proportion of patients without frailty with poor control was higher than those with frailty (31.28% vs. 17.46%, respectively). In conclusion, blood glucose control in elderly Chinese patients with T2D is poor and influenced by frailty, sex, and insulin treatment. Hence, it is crucial to enhance the implementation of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in Chinese community hospitals and strengthen the differentiation of updated guidelines within these healthcare settings.

Myocardial injury and cardiovascular dysfunction are the most common complications in patients with sepsis, and effective therapeutic candidate is still lacking. This study aims to investigate the protective effect of oxycodone in the myocardial injury in lipopolysaccharide-induced sepsis and its related signaling pathways. Wildtype and Nrf2-knockout mice, as well as H9c2 cardiomyocytes culture treated with LPS were used as models of septic myocardial injury. In vitro model showed that oxycodone protected the cells from pyroptosis induced by LPS. In vivo model showed oxycodone pretreatment significantly attenuated myocardial pathological damage and improved cardiac function with increased ejection fraction (EF) and fractional shortening (FS) as well as decreased cardiac troponin I (cTnI), creatine kinase isoenzymes MB (CK-MB). Oxycodone also reduced the levels of inflammatory factors and oxidative stress damage induced by LPS, which involves pyroptosis-related proteins including the NLRP3, Caspase-1, ASC, and GSDMD. These changes were mediated by Nrf2 and HO-1 because Nrf2-knockout mice or Nrf2 knockdown in H9c2 cells significantly reversed the beneficial effect of oxycodone on oxidative stress, inflammatory responses and NLRP3-mediated pyroptosis. Our findings proved that oxycodone therapy reduces LPS -induced myocardial injury by suppressing NLRP3-mediated pyroptosis via the Nrf2/HO-1 signaling pathway in vivo and in vitro.

Adolescent and young adults (AYAs) belong to a unique category of patients diagnosed with acute lymphoblastic leukemia (ALL) who have better outcomes when treated with pediatric-inspired regimens. Bloodstream infections (BSIs) is a leading cause of treatment-related mortality in ALL patients. However, the epidemiology and prognostic characteristics of BSIs in ALL patients with AYAs remain unclear. In this study, we analyzed the epidemiology and prognostic factors of AYAs and compared the similarities and differences between younger and older adult patients with BSIs. We analyzed the clinical data of three comprehensive hospitals in Hunan Province, China, from January 2010 to August 2021. In this study, the clinical characteristics and pathogen distributions of AYAs patients were similar to those of adult ALL patients. Extended-spectrum beta-lactamase(ESBL)-producing bacteria were more commonly found in AYAs than in children (32.8% vs. 16.4%, P=0.09). Regarding prognostic factors, the length of hospitalization (>14 days) and renal inadequacy (creatinine≥177μmoI/L) were risk factors for 30-day mortality in AYAs with BSIs. In our study, AYAs patients with BSIs showed clinical characteristics and pathogen distributions similar to those of adult patients, but were quite different from those of children.