Phosphonate and phosphonoamidate derivatives of benzylphosphonic acids were synthesized as potential inhibitors of penicillin acylase (EC 3.5.1.11) proceeding from the concept of transition-state analogues. The compounds obtained are not the substrates of the enzyme and they are stable under conditions of enzyme activity testing.
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World J Gastroenterol
January 2025
Department of Gastroenterology, Peking University First Hospital, Beijing 100034, China.
Background: A dual therapy regimen containing amoxicillin is a common treatment option for the eradication of (). While substantial research supports the efficacy and safety of vonoprazan and amoxicillin (VA) dual therapy in the general population, there is still a lack of studies specifically focusing on its safety in elderly patients.
Aim: To evaluate efficacy and safety of VA dual therapy as first-line or rescue treatment for in elderly patients.
β-Lactams are the most widely used antibiotics for the treatment of bacterial infections because of their proven track record of safety and efficacy. However, susceptibility to β-lactam antibiotics is continually eroded by resistance mechanisms. Emerging multidrug-resistant (MDR) strains possessing altered alleles (encoding PBP2) pose a global health emergency as they threaten the utility of ceftriaxone, the last remaining outpatient antibiotic.
View Article and Find Full Text PDFPLoS Pathog
December 2024
Servicio de Microbiología and Unidad de Investigación, Hospital Universitario Son Espases, Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain.
Neisseria gonorrhoeae exhibits alarming antibiotic resistance trends and poses a significant challenge in therapeutic management. This study aimed to explore the association of penA alleles with penicillin-binding protein (PBP) occupancy patterns and reduced outer membrane permeability, impacting susceptibility to last-line cephalosporins and potential β-lactam candidates. The whole genome sequence, the MICs and PBP IC50s were determined for 12 β-lactams and β-lactamase inhibitors in 8 clinical isolates with varying β-lactam sensitivity, 2 ATCC, and 3 WHO cephalosporin-resistant reference strains.
View Article and Find Full Text PDFAntimicrob Agents Chemother
December 2024
Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA.
() presents significant clinical challenges. This study evaluated the synergistic effects of a β-lactam and β-lactamase inhibitor combination against and explored the underlying mechanisms. Synergy was assessed through MIC tests and time-kill studies, and binding affinities of nine β-lactams and BLIs to eight target receptors (L,D-transpeptidases [LDT] 1-5, D,D-carboxypeptidase, penicillin-binding protein [PBP] B, and PBP-lipo) were assessed using mass spectrometry and kinetic studies.
View Article and Find Full Text PDFBMC Microbiol
December 2024
Microbial Biotechnology Research Center, Iran University of Medical Sciences, Tehran, Iran.
Objective: The foodborne pathogen Salmonella enterica serovar Typhimurium causes self-limiting gastroenteritis in humans and is difficult to eliminate due to its ability to adhere to surfaces and form biofilms that exhibit high resistance to antimicrobial agents. To explore alternative strategies for biofilm treatment, it is essential to investigate novel agents that inhibit Salmonella biofilms.
Method: In this study, we investigated the minimum biofilm inhibitory concentrations (MBICs) and minimum biofilm eradication concentrations (MBECs) of nafcillin and diosmin, both previously identified as Lon protease inhibitors, against biofilms formed by S.
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