triamcinolone acetonide + moxifloxicin + vancomycin

The Osteogenic Effect of Local Delivery of Vancomycin and Tobramycin on Bone Marrow Stromal Cells [Retraction].

[This retracts the article DOI: 10.2147/IDR.S261767.].

Antimicrobial susceptibility of Enterococcus and Bacillus species isolated from commercial probiotic products indicated for use in cattle.

Branco-Lopes Rúbia R, Okello Emmanuel E, Tonooka Karen K, Okella Hedmon H et al.

Assessment of antimicrobial resistance is an important component of probiotic safety evaluation, particularly as the use of these products increases on commercial dairy farms. Because microbial feed additives should not contribute to the dissemination of antimicrobial resistance (AMR), characterizing the antimicrobial susceptibility of microorganisms used in commercial probiotic products is critical. The objective of this study was to evaluate the phenotypic antimicrobial susceptibility of Enterococcus spp. and Bacillus spp. isolated from commercially available cattle probiotics. Cattle probiotic products labeled to contain at least 1 Enterococcus spp. or Bacillus spp. were identified through different sources. A total of 35 products were included. Phenotypic antimicrobial susceptibility of the bacterial isolates was evaluated against 16 antimicrobials using the broth microdilution method, and data were interpreted according to microbiological cut-off values. Based on 16S rRNA gene sequencing, isolates were identified as Enterococcus faecium (n = 15), and Enterococcus hirae (n = 1), Bacillus amyloliquefaciens (n = 1), Bacillus licheniformis (n = 1), Bacillus subtilis (n = 7), and Bacillus velezensis (n = 13). All Enterococcus isolates were susceptible to chloramphenicol, kanamycin, tetracycline, and vancomycin. Three isolates were resistant to erythromycin, 1 isolate was resistant to tylosin, and 1 isolate exhibited resistance to both erythromycin and tylosin. All 22 Bacillus spp. isolates were susceptible to tetracycline and vancomycin, whereas resistance was detected to chloramphenicol (n = 1) and erythromycin (n = 4). The phenotypic AMR observed in some isolates suggests a need for further investigation into the safety of commercially available probiotics, including the presence and potential transferability of AMR genes and associated mobile genetic elements.

De Novo Design of Multi-Mechanistic AIE Photosensitizer for Broad-Spectrum Bacterial Eradication.

Li Zhi-Hao ZH, Sun Yi-Qiong YQ, Li Daran D, Zhu Kai-Wei KW et al.

Antibiotic resistance poses a serious threat to human health. Inspired by the clinical practice of employing drug combinations to achieve combined effects, we hypothesized that integrating multiple mechanisms into a single molecule could address drug-resistant bacterial infections. Based on a propeller-modification strategy and dual alkyl-chain engineering, we de novo designed and synthesized a C2-symmetric propeller-shaped aggregation-induced emission photosensitizer. After iterative screening, the optimized compound MeOTDP-2 exhibits broad-spectrum antibacterial activity, enabling efficient eradication of planktonic bacteria, drug-resistant strains, polymicrobial infections, biofilms, and persister cells, with no cellular invasiveness and negligible cytotoxicity. Mechanistic studies revealed that MeOTDP-2 achieves chemo-photodynamic combined antibacterial therapy by targeting and disrupting bacterial membranes and DNA, alongside light-mediated intracellular reactive oxygen species accumulation. Furthermore, in mouse models of MRSA-induced skin abscess and full-thickness skin wound infection, MeOTDP-2 demonstrated superior therapeutic efficacy to vancomycin. This strategy, integrating dual targeting with multiple mechanisms, offers new promise for overcoming bacterial resistance.

Incyclinide exhibits potent antibacterial and anti-biofilm activity against Staphylococcus aureus.

Xi Huimin H, Yuan Junwei J, Wang Ying Y, Dai Qianbin Q et al.

Methicillin-resistant Staphylococcus aureus (MRSA) and biofilm-associated infections remain major therapeutic challenges. Here, we investigated the antibacterial activity and mechanism of Incyclinide against S. aureus. Incyclinide showed potent activity against 40 clinical isolates, with a minimum inhibitory concentration (MIC) of 2 µM for 81.25% of MSSA isolates and 91.66% of MRSA isolates. In representative MSSA and MRSA strains, 1× MIC completely inhibited planktonic growth, while time-kill assays demonstrated concentration-dependent bactericidal activity; at 8× MIC, bacterial counts decreased by 3.2 log10 CFU/mL in NCTC 8325 and 4.3 log10 CFU/mL in USA300 after 24 h. Incyclinide also markedly reduced the biomass of mature, pre-established biofilms. Proteomic profiling of Incyclinide-treated USA300 identified 59 differentially expressed proteins enriched in membrane-related functions. Transmission electron microscopy and fluorescence assays revealed severe cell envelope damage, increased membrane permeability, and membrane depolarization. Exogenous phospholipids antagonized antibacterial activity, with phosphatidylethanolamine and cardiolipin showing stronger effects than phosphatidylglycerol. In addition, resistance induction and whole-genome sequencing identified recurrent clpX mutations; clpX deletion increased the MIC from 2 to 8 µM, whereas complementation restored susceptibility. Molecular docking suggested favorable binding between Incyclinide and ClpX, with a predicted binding energy of -9.4 kcal/mol. Incyclinide also exhibited low hemolytic activity, negligible cytotoxicity toward BEAS-2B and human umbilical vein endothelial cell up to 128 µM, and significant protection in a Galleria mellonella infection model. Collectively, these findings identify Incyclinide as a promising anti-S. aureus agent with potent activity against MRSA and mature biofilms, acting primarily through membrane disruption, with ClpX potentially contributing to susceptibility.IMPORTANCEMethicillin-resistant Staphylococcus aureus (MRSA) and biofilm-associated infections pose significant clinical challenges due to limited therapeutic options. Here, we identify Incyclinide, a tetracycline derivative, as a potent anti-S. aureus agent. It exhibits potent bactericidal activity against clinical MRSA isolates and effectively eradicates mature biofilms. Mechanistically, Incyclinide disrupts membrane integrity, causing depolarization and leakage. Notably, we identify the essential chaperone ClpX as a key molecular determinant of susceptibility through genetic and docking studies. Incyclinide demonstrates a favorable safety profile and superior efficacy compared with vancomycin in a Galleria mellonella infection model. Our findings highlight Incyclinide as a promising candidate featuring a dual membrane-targeting and intracellular mechanism, offering a strategic advantage against drug-resistant and biofilm-embedded pathogens.