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The incidence of heterogeneous vancomycin-intermediate (hVISA) infection is increasing and is associated with vancomycin treatment failures. However, studies investigating the risk factors for treatment failure in hVISA infection are limited. Patients with hVISA bacteremia treated with vancomycin over 7 days between August 2008 and June 2020 were enrolled in this study. Clinical and microbiological characteristics were compared between vancomycin treatment failure and success groups to identify the risk factors for vancomycin treatment failure. Among the 180 patients with hVISA bacteremia, 102 patients treated with vancomycin over 7 days were included. Vancomycin treatment failed in 80 (78%) patients. Patients in the vancomycin treatment failure group were older ( < 0.001) and more frequently had solid cancer ( = 0.04) than those in the vancomycin treatment success group. Solid organ transplantation (SOT) was more frequent ( < 0.001) in the vancomycin treatment success group. The Charlson comorbidity index ( = 0.01) and Acute Physiology and Chronic Health Evaluation II scores ( < 0.001) were higher in the vancomycin treatment failure group. In multivariate analysis, independent risk factors for vancomycin treatment failure were old age and severity of bacteremia. SOT and vancomycin minimal inhibitory concentration (MIC) ≤ 1.0 mg/L using the broth microdilution (BMD) method were associated with successful vancomycin treatment. Old age and infection severity were independent risk factors for vancomycin treatment failure. Vancomycin MIC using the BMD method is an important risk factor for vancomycin treatment failure, and its use should be considered in hVISA bacteremia.IMPORTANCEIn this study, we assessed the clinical and microbiological characteristics of heterogeneous vancomycin-intermediated (hVISA) bacteremia and identified risk factors for vancomycin treatment failure. We found that advanced age and severity of infection were independent risk factors for vancomycin treatment failure. On the other hand, solid organ transplantation and a low vancomycin minimal inhibitory concentration were associated with successful vancomycin treatment. This study highlights the importance of vancomycin minimal inhibitory concentration in hVISA bacteremia.
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http://dx.doi.org/10.1128/spectrum.00333-24 | DOI Listing |
Farm Hosp
September 2025
Servicio de Farmacia, Hospital Universitario de Toledo, Toledo, Spain.
Objective: To standardize the drug dilutions administered intravenously in a Pediatric Intensive Care Unit and to characterize these dilutions based on their pH, osmolarity, and vesicant nature. This aims to guide the selection of the most appropriate vascular access device, minimizing associated complications, and preserving the patient's venous capital.
Methods: Through a consensus between Pharmacy and Pediatric Services, the most frequently administered intravenous drugs in the Pediatric Intensive Care Unit were selected.
Cell Metab
August 2025
Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA. Electronic address:
Diet and obesity contribute to insulin resistance and type 2 diabetes, in part via the gut microbiome. To explore the role of gut-derived metabolites in this process, we assessed portal/peripheral blood metabolites in mice with different risks of obesity/diabetes, challenged with a high-fat diet (HFD) + antibiotics. In diabetes/obesity-prone C57BL/6J mice, 111 metabolites were portally enriched and 74 were peripherally enriched, many of which differed in metabolic-syndrome-resistant 129S1/129S6 mice.
View Article and Find Full Text PDFBioorg Med Chem
September 2025
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo 11566, Egypt. Electronic address:
With the continued upsurge of antibiotic resistance and reduced susceptibility to almost all frontline antibiotics, there is a pressing need for the development of new, effective, and safe alternatives. In this study, a scaffold-hopping strategy was utilized to develop a novel class of penicillin-binding protein 2a (PBP2a) inhibitors, centered around a 4H-chromen-4-one core structure. These newly designed compounds demonstrated strong antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and other drug-resistant gram-positive pathogens.
View Article and Find Full Text PDFEur J Med Chem
September 2025
Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan Province, China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan Province,
Methicillin-resistant Staphylococcus aureus (MRSA) is a major global health threat owing to its multi-drug resistance, creating an urgent need for novel antibiotics. This study focused on developing anti-MRSA agents by designing and synthesizing 30 xanthotoxin-pyridine quaternary ammonium derivatives, followed by evaluating their antibacterial activity and dissecting their mechanism of action against MRSA. Among all derivatives, III13 demonstrated as the most promising candidate: it exhibited potent anti-MRSA activity (MIC = 1 μg/mL), low cytotoxicity, minimal hemolysis, rapid bactericidal effects, and the ability to disrupt biofilms.
View Article and Find Full Text PDFACS Synth Biol
September 2025
Jiangsu Key Laboratory for Food Quality and Safety, State Key Laboratory Cultivation Base of Ministry of Science and Technology, Institute of Food Safety and Nutrition, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China.
Anti-idiotypic antibodies (Anti-Ids) possess the properties to mimic the structure and biological activity of an antigen, which can be utilized for preventing and monitoring hazards. In this study, Nb4Mutant6-Anti-Id, which mimics the structure and antibacterial activity of vancomycin, was designed based on phage display antibody library screening and mutagenesis technology. The affinity of Nb4Mutant6-Anti-Id for the coated antigens of Van-pAbs F(ab)2 and inactivated cells was 6.
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