Antimicrobial resistance remains a public health problem of global concern with a great health and financial burden. Its recognition as a threat by political leadership has boosted the research and development of new antibiotics and particularly novel combinations of β-lactams/β-lactamase inhibitors against multidrug-resistant (MDR) Gram-negative pathogens, which remain the major concern in clinical practice. The incorporation of ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, and imipenem/cilastatin/relebactam has provided new therapeutic options in the treatment of patients with infections due to MDR pathogens. Cefiderocol along with cefepime/enmetazobactam, avibactam/aztreonam, and sulbactam/durlobactam have been recently added to these agents as therapeutic choices, particularly for metallo-β-lactamase producing Gram-negative bacteria. Currently, many combinations are being studied for their in vitro activity against both serine- and metallo-β-lactamases. However, only a few have advanced through phase 1, 2, and 3 clinical trials. Among them, in this article, we focus on the most promising combinations of cefepime/zidebactam, cefepime/taniborbactam, and imipenem/cilastatin/funobactam, which are currently under investigation in phase 3 trials.
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http://dx.doi.org/10.3390/pathogens14020168 | DOI Listing |
Blood
March 2025
Sungkyunkwan university school of medicine, Samsung Medical Center, Seoul, Korea, Republic of.
This study aimed to assess the efficacy and safety of combining cemiplimab, an anti-PD1 antibody, with isatuximab, an anti-CD38 antibody, in relapsed or refractory extranodal NK/T-cell lymphoma (R/R ENKTL). The hypothesis was that CD38 blockade could enhance the antitumor activity of PD1 inhibitors. Eligible patients received cemiplimab (250 mg on days 1 and 15) and isatuximab (10 mg/kg on days 2 and 16) intravenously every four weeks for six cycles.
View Article and Find Full Text PDFThe development of targeted therapy for patients with multiple myeloma (MM) is hampered by the low frequency of actionable genetic abnormalities. Gain or amplification of chromosome 1q (1q+) is the most frequent arm-level copy number gain in patients with MM and is associated with higher risk of progression and death despite recent therapeutic advances. Thus, developing targeted therapy for MM patients with 1q+ stands to benefit a large portion of patients in need of more effective management.
View Article and Find Full Text PDFJ Agric Food Chem
March 2025
State Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China.
To discover novel structural nematicides, 79 amide compounds containing 1,2,4/1,3,4-oxadiazole moiety were designed, synthesized, and evaluated for nematicidal efficacy against second-stage juveniles of (). Notably, some compounds exhibited superior nematicidal efficacy, for example, the LC values of compounds , , , , , , , and were 7.4, 31.
View Article and Find Full Text PDFJ Med Chem
March 2025
State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine; Shanghai Frontiers Science Center of TCM Chemical Biology; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
The anticancer agent irinotecan often induces severe delayed-onset diarrhea, inhibiting human carboxylesterase 2A (hCES2A) can significantly alleviate irinotecan-triggered gut toxicity (ITGT). This work presents an efficient workflow for design and developing novel efficacious hCES2A inhibitors. A well-training machine learning model identified as a lead compound, while compound was developed as a novel time-dependent hCES2A inhibitor (IC = 0.
View Article and Find Full Text PDFSkin Therapy Lett
March 2025
Center for Clinical Studies, Webster, TX, USA.
Psoriatic arthritis (PsA) is a chronic, inflammatory disease with heterogeneous clinical features. The pathogenesis of PsA involves a complex interplay of genetic, immunologic, and environmental factors, leading to the activation of the immune system and subsequent inflammation. Over the past decade, the understanding of the immune mechanisms underlying PsA has advanced significantly, particularly regarding the role of the interleukin-23/T helper 17 pathway in the disease process.
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