Objectives: Physicians must leverage several factors when making antibiotic therapy decisions, including route of administration and duration of therapy. Oral administration provides several potential advantages including increased accessibility, prevention of hospitalizations and earlier discharges. Sulopenem-a broad-spectrum, synthetic penem β-lactam agent-uniquely possesses both oral and IV formulations along with noted stability among antimicrobial-resistant subsets. This study evaluated the in vitro activity of sulopenem and comparator agents against contemporary Enterobacterales and anaerobic clinical isolates predominantly from patients with bloodstream, intra-abdominal and urinary tract infections.
Methods: A contemporary collection of 1647 Enterobacterales and 559 anaerobic isolates was assembled from medical centres in Europe and the USA. Isolates were susceptibility tested using the CLSI reference methods: broth microdilution for Enterobacterales and agar dilution for anaerobes.
Results: Sulopenem demonstrated potent in vitro antimicrobial activity (MIC50/90, 0.03/0.25 mg/L) against Enterobacterales isolates regardless of infection type, inhibiting 99.2% of isolates at ≤1 mg/L. This activity was conserved against resistant phenotypes including ESBL-phenotype Escherichia coli (MIC50/90, 0.03/0.06 mg/L) and ESBL-phenotype Klebsiella pneumoniae (MIC50/90, 0.06/1 mg/L). Sulopenem maintained activity against ciprofloxacin-, nitrofurantoin- and trimethoprim/sulfamethoxazole-non-susceptible subsets (MIC50/90, 0.03-0.06/0.12-0.5 mg/L). Against anaerobic isolates, sulopenem (98.9% inhibited at ≤4 mg/L) and meropenem [98.4% susceptible (CLSI)] were the most active compounds tested.
Conclusions: The potent in vitro activity of sulopenem against this large collection of recent Enterobacterales and anaerobic clinical isolates from multiple infection types supports its further clinical evaluation in the treatment of intra-abdominal and urinary tract infections.
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http://dx.doi.org/10.1093/jac/dkad099 | DOI Listing |
Blood Coagul Fibrinolysis
December 2024
Department of Hematology, The Second Affiliated Hospital, Chongqing Medical University, Jiangnan, Chongqing, China.
Background: Congenital factor VII (FVII) deficiency is a genetic disorder characterized by decreased FVII activity, which sometimes leads to fatal bleeding. Numerous variants have been found in FVII deficiency, but mutations vary among patients. Each mutation deserves further exploration for each patient at risk of bleeding.
View Article and Find Full Text PDFIn this study, we have designed and developed a cationic bolaform C12-(2,3-dihydroxy-N, N-dimethyl-N-(2-ureidoethyl)propan-1-aminium chloride)2 (C12(DDUPAC)2) that is derived from biocompatible molecules. The bolaform C12(DDUPAC)2 has hydroxyl (OH) functionality at both the cationic head groups. The impact of head group structure on the self-assembly and effectiveness of gene transfection and antimicrobial activity was investigated and compared with that of the hydrochloride salt C12-(N, N-dimethyl-N-(2-ureidoethan-1-aminium chloride)2 (C12(DUAC)2) of its precursor molecule.
View Article and Find Full Text PDFIUBMB Life
January 2025
Department of General Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Tamoxifen (TAM) is employed to treat premenopausal ER-positive breast cancer patients, but TAM resistance is the main reason affecting its efficacy. Thus, addressing TAM resistance is crucial for improving therapeutic outcomes. This study explored the potential role of Tinagl1, a secreted extracellular matrix protein, whose expression is compromised in TAM-resistant MCF-7 breast cancer cells (MCF-7R).
View Article and Find Full Text PDFImmunol Invest
January 2025
Department of Respiratory Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China.
Introduction: T helper 17 (Th17) cells have a significant effect in the pathogenesis of asthma, and signal transducer and activator of transcription 3 (STAT3) pathway activation is critical for Th17 cell differentiation. Timosaponin A-III (TA3) was reported to inhibit the STAT3 pathway. Here, we investigated whether TA3 improved asthma by inhibiting the STAT3 pathway.
View Article and Find Full Text PDFEmerg Microbes Infect
January 2025
College of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou, China.
Phages demonstrate remarkable promise as antimicrobial agents against antibiotic-resistant bacteria. However, the emergence of phage-resistant strains poses challenges to their effective application. In this paper, we presented the isolation of a phage adaptive mutant that demonstrated enhanced and sustained antibacterial efficacy through the co-evolution of () 111-2 and phage ZX1Δint .
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