Antibacterial agents(National Technical University of Athens)

Bacterial biofilms attach to various surfaces and represent an important clinical and public health problem, as they are highly recalcitrant and are often associated with chronic, nonhealing diseases and healthcare-associated infections. Antibacterial agents are often not sufficient for their elimination and have to be combined with mechanical removal. Mechanical forces can be generated by actuating nonspherical (anisotropic) magnetically responsive nanoparticles in a rotating magnetic field. We have thus prepared anisotropic superparamagnetic nanochains in the size range of 0.5-1 μm by magnetically assembling several iron oxide nanoparticle clusters and coating them with a layer of silica with different shell morphologies: smooth, moderately rough, and highly rough. The silica surface was additionally functionalized with carboxylic groups to increase colloidal stability. The efficacy of the nanochains in biofilm removal was studied systematically with three different model nonpathogenic bacterial species Escherichia coli, Lactococcus lactis, and Pseudomonas fragi; two different magnetic field strengths; two stirring speeds; and two treatment durations. All bacterial species were engineered to express fluorescent proteins to enable quantification of biofilm removal by colony-forming unit count and fluorescence measurements. Nanochains removed >90% of Gram-negative E. coli and P. fragi with a stronger magnetic field, and <90% of Gram-positive L. lactis with a weaker magnetic field. Surface roughness of nanochains, duration, and stirring speed also affected removal, but the effect could not be generalized. In contrast to their effects on biofilms, the functionalized nanochains showed no toxicity to Caco-2 intestinal epithelial cells, regardless of whether magnetomechanical force was employed or not. In summary, we demonstrated that remotely controlled spatial movement of nanoparticles can generate sufficient mechanical forces to disperse attached biofilms while retaining safety in an epithelial cell model.

Evidence supporting antibiotic administration within 3 hours in sepsis without shock is limited. Therefore, we conducted a systematic review and meta-analysis to determine whether the timing of antibiotic initiation influences mortality in patients with sepsis or septic shock. We comprehensively searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and the Korean Medical Database from inception to November, 2022, using the keywords “sepsis,” “septic shock,” “anti-bacterial agents,” “time to treatment,” and “time factors.” Two reviewers independently performed eligibility screening and full-text review. Thirteen studies including 79,246 patients were analyzed: five prospective, seven retrospective, and one retrospective case–control study. In overall sepsis cases, mortality did not differ significantly between patients who received antibiotics within 1 hour and those in the delayed group but was significantly lower in those who received antibiotics within 3 hours than in those in the delayed group. In patients with septic shock, mortality was significantly lower in groups that received antibiotics within both 1 and 3 hours than in the delayed group. In septic shock, administration of antibiotics within 1 hour of diagnosis reduces mortality. In patients with sepsis, antibiotic administration within 3 hours, but not necessarily within 1 hour, was associated with reduced mortality.