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Development of Novel Bacterial Topoisomerase Inhibitors Assisted by Computational Screening.
ACS Med Chem Lett
August 2024
Division of Medicinal Chemistry and Pharmacognosy, Department of Chemistry and Biochemistry, Microbial Infection and Immunity, Division of Outcomes and Translational Sciences, Department of Microbiology, and Division of Pharmaceutics and Pharmacology, The Ohio State University, Columbus, Ohio 43210, United States.
Multidrug-resistant bacterial infections pose an ever-evolving threat to public health. Since the outset of the antibacterial age, bacteria have developed a multitude of diverse resistance mechanisms that suppress the effectiveness of current therapies. New drug entities, such as Novel Bacterial Topoisomerase Inhibitors (NBTIs), can circumvent this major issue.
View Article and Find Full Text PDFComparative in vitro efficacy of antibiotics against the intracellular reservoir of Staphylococcus aureus.
J Antimicrob Chemother
October 2024
Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA.
Unlabelled: Staphylococcus aureus (SA) is a leading cause of bloodstream infection. The liver represents the sentinel immune organ for clearance of bloodstream pathogens and eradication of intracellular SA from liver-resident macrophages (Kupffer cells, KCs) eliminates the likely pathogenic reservoir that contributes to persistent bacteraemia.
Objectives: We assessed antimicrobial activity at phagolysosome-mimicking pH, intracellular penetration, and SA eradication within KCs in vitro for clinically prescribed antistaphylococcal agents alone or in combination: vancomycin, daptomycin, ceftaroline, ceftobiprole, oritavancin, oxacillin, cefazolin; rifampin and fosfomycin.
Dilution of humoral immunity: Results from a natural history study of healthy total knee arthroplasty patients.
J Orthop Res
December 2024
Department of Orthopaedic Surgery, Virginia Commonwealth University, Richmond, Virginia, USA.
The incidence of prosthetic joint infection (PJI) following elective primary total knee arthroplasty (TKA) is very low but serious risk remains. To identify unknown risk factors, we completed a natural history study of IgG specific for Staphylococcus aureus antigens previously phenotyped as protective (anti-Atl) and pathogenic (anti-Isd). Twenty-five male and 25 female optimized patients 50-85 years of age and BMI 24-39 undergoing primary TKA were prospectively enrolled.
View Article and Find Full Text PDFAcute kidney injury in Staphylococcus aureus bacteraemia: a recurrent events analysis.
Clin Microbiol Infect
October 2024
Department of Internal Medicine, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands.
Article Synopsis
- The study aimed to identify risk factors for acute kidney injury (AKI) and assess its impact on mortality in patients with Staphylococcus aureus bacteraemia (SAB), considering variables like recurrent AKI episodes and competing risks.
- A total of 453 patients were analyzed, revealing that 43% experienced AKI episodes, with age, comorbidity, septic shock, persistent bacteraemia, and vancomycin therapy linked to an increased AKI risk.
- The findings highlighted that AKI significantly raises the risk of 90-day mortality in SAB patients, indicating a worse clinical outcome than previously understood, especially in those treated with vancomycin.
Genomic investigation and clinical correlates of the β-lactam: NaHCO responsiveness phenotype among methicillin-resistant isolates from a randomized clinical trial.
Antimicrob Agents Chemother
July 2024
Victorian Infectious Diseases Service, The Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
NaHCO responsiveness is a novel phenotype where some methicillin-resistant (MRSA) isolates exhibit significantly lower minimal inhibitory concentrations (MIC) to oxacillin and/or cefazolin in the presence of NaHCO. NaHCO responsiveness correlated with treatment response to β-lactams in an endocarditis animal model. We investigated whether treatment of NaHCO-responsive strains with β-lactams was associated with faster clearance of bacteremia.
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