Bacterial sepsis is a critical and life-threatening condition resulting from a dysregulated host immune response to infection and remains one of the foremost causes of mortality worldwide. In this study, a biomimetic hybrid lipid-polymer nanocarrier (VCM-LIN-P2O NPs) was designed to target the ADAM10 and TLR2 receptor pathways through integrating linoleic acid (LIN) and poly(2-ethyl-2-oxazoline) (P2O). This engineered nanoplatform attenuates excessive inflammation via concurrent binding to ADAM10 and TLR2 while ensuring targeted delivery of vancomycin (VCM) to infection sites. The potential of LIN to competitively bind to ADAM10 and TLR2 was initially examined through molecular docking and subsequently validated using microscale thermophoresis (MST), confirming the potential ability of LIN to downregulate the inflammation associated with ADAM10 and TLR2 activation. The optimized VCM-LIN-P2O NPs displayed desirable physicochemical characteristics, excellent biocompatibility, and high stability, along with a sustained drug release profile extending up to 48 hours. Furthermore, the nanocarrier exhibited enhanced in vitro antibacterial performance compared to bare VCM, along with significant antioxidant and anti-inflammatory activity, in LPS-stimulated macrophages. In a murine MRSA-induced sepsis model, treatment with VCM-LIN-P2O NPs resulted in marked bacterial clearance from major organs and the bloodstream, accompanied by a significant reduction in TNF-α, IL-1β, and IL-18 levels, thereby alleviating organ damage. Therefore, these findings establish VCM-LIN-P2O NPs as a promising multifunctional nanoplatform for targeted antibiotic delivery and effective sepsis therapy.

Vancomycin (VAN) is widely used in sepsis but may exacerbate sepsis-associated acute kidney injury (SA-AKI). The mechanisms by which VAN aggravates renal injury in the septic context remain unclear, and early functional changes are difficult to detect using conventional biomarkers. C57BL/6 mice were subjected to lipopolysaccharide (LPS)-induced sepsis, VAN-induced nephrotoxicity, or combined injury. Renal function was continuously assessed using non-invasive percutaneous real-time glomerular filtration rate (GFR) monitoring. Conventional renal injury markers, histopathology, and transcriptomic analyses were performed at 2, 24, and 72 hours. In septic mice, VAN administration caused an early and marked decline in GFR, preceding increases in serum creatinine and blood urea nitrogen. Compared with sepsis alone, combined LPS and VAN treatment resulted in more sustained renal dysfunction and more severe tubular injury. Transcriptomic profiling identified early and persistent upregulation of Tnfrsf1a and sustained upregulation of Ccl20 in the combined injury model. Functional enrichment analyses revealed activation of inflammatory and immune-related pathways, including TNF signaling, cytokine-cytokine receptor interaction, and IgSF cell adhesion molecule signaling. Real-time GFR monitoring demonstrates that vancomycin exacerbates SA-AKI by inducing early functional impairment. Transcriptomic changes suggest that enhanced inflammatory signaling and immune cell recruitment contribute to VAN-aggravated renal injury in sepsis.

Background: Vancomycin (VAN)-induced nephrotoxicity limits its clinical application. Licorice (Glycyrrhiza uralensis Fisch.) and its bioactive constituents have been reported to protect against nephrotoxicity induced by various nephrotoxic agents. This study aimed to evaluate the protective effects of licorice against VAN-induced nephrotoxicity and to explore the underlying mechanisms both in vivo and in vitro. Methods: Seven groups of male C57BL/6 mice received different treatments for 7 consecutive days. Blood, fecal and renal tissue samples were collected for the assessment of serum creatinine, renal histopathology, mitochondrial ultrastructure, oxidative stress markers, kidney injury molecule-1 (Kim-1), short-chain fatty acids (SCFAs), and uremic toxins. In human proximal tubular epithelial cells (HK-2 cells), the effects of licorice on cell viability, oxidative stress, inflammatory markers, and mitochondrial membrane potential (MMP) were further investigated. Results: Licorice significantly attenuated VAN-induced nephrotoxicity and restored glutathione peroxidase (GSH-Px) activity while reducing malondialdehyde (MDA) levels. In addition, licorice markedly ameliorated VAN-induced renal histopathological injury, as demonstrated by hematoxylin and eosin staining and transmission electron microscopy. Licorice also reversed VAN-induced intestinal microbiota dysbiosis and increased the relative abundance of SCFA-producing bacteria, including Bacteroides. Moreover, licorice treatment increased fecal SCFA contents and modulated multiple uremic toxins in both serum and renal tissue. Consistently, licorice protected HK-2 cells against VAN-induced cytotoxicity by regulating GSH, interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and MMP. Conclusions: These findings demonstrate that licorice exerts protective effects against VAN-induced nephrotoxicity in vivo and in vitro, suggesting the potential involvement of oxidative stress, mitochondrial structure and function, inflammation, intestinal microbiota-SCFAs and uremic toxins.

Background: Anti-MRSA agents are essential for treating severe infections, yet their use is constrained by distinct toxicity profiles. However, comparative real-world data remain scarce. Methods: This nationwide pharmacovigilance study used the Japanese Adverse Drug Event Report (JADER) database (2004–2025). Disproportionality analyses (proportional reporting ratio [PRR]) were performed at the Standardized MedDRA Query and Preferred Term levels, complemented by Weibull-based time-to-onset modeling, to characterize AE patterns associated with vancomycin (VCM), teicoplanin (TEIC), arbekacin (ABK), daptomycin (DAP), linezolid (LZD), and tedizolid (TZD). Results: Distinct agent-specific AE profiles were observed. VCM showed disproportionate reporting of acute renal failure (PRR 6.66) and severe cutaneous reactions. TEIC displayed fewer renal signals but relatively higher reporting of hematologic events (PRR 3.51). ABK demonstrated high disproportionality in acute and chronic renal failure, reflecting aminoglycoside nephrotoxicity. DAP showed a high reporting signal for eosinophilic pneumonia (PRR 23.30), interstitial lung disease, and creatine kinase elevation/rhabdomyolysis, with wear-out hazard patterns suggesting a possible time-dependent reporting tendency. LZD exhibited hematopoietic signals (PRR 6.13) and additional associations with hyponatremia, lactic acidosis, and optic neuropathy, consistent with marrow suppression and mitochondrial toxicity. Weibull analysis indicated cumulative “wear-out” risks for renal, hepatic, and hematologic events, whereas hypersensitivity and many pulmonary events followed random-failure patterns. Conclusions: This large-scale JADER analysis delineated the distinct safety profiles of the six anti-MRSA agents. The key findings included DAP pulmonary and muscle toxicities, LZD hematological events, and VCM nephrotoxicity. Time-to-onset modeling indicates potential cumulative versus random risk patterns, suggesting the need for individualized monitoring and cross-validation.

Periprosthetic joint infections (PJIs) remain a serious complication following hip and knee arthroplasty, affecting 1-5% of patients in developed countries and posing significant challenges to patients, clinicians, and healthcare systems. Conventional prophylactic strategies, such as antibiotic-loaded bone cement, suffer from limited post-implantation drug release and potential compromise of mechanical integrity. To overcome these limitations, we developed a personalized, 3D-printed implant designed to integrate with the acetabular component of joint prostheses. These implants deliver either monotherapy or a combination of amphotericin B (AmB) and vancomycin (VAN), targeting both fungal and bacterial pathogens. Fabricated via fused deposition modeling using a biocompatible polyvinyl alcohol-polyethylene glycol (PVA-PEG) matrix, the implants enable passive drug loading and rapid adhesion to prosthetic surfaces within 60s, minimizing operative time. In vitro testing confirmed broad-spectrum antimicrobial activity against Candida spp. (C. albicans, C. parapsilosis, C. glabrata, C. krusei) and Staphylococcus spp. (S. aureus, S. epidermidis). VAN was released rapidly, while AmB exhibited sustained release for up to 10h, with both maintaining saturation solubility for 48h. Notably, AmB-loaded implants showed five-fold lower hemolytic toxicity compared to free drug. These results highlight the potential of 3D-printed, drug-eluting implants as a clinically viable solution for the prevention and early treatment of PJIs.

Daptomycin (DAP) or vancomycin (VAN) resistance can result in methicillin-resistant Staphylococcus aureus (MRSA) bacteremia treatment failure. Clinical trials have not yielded a clear approach to MRSA combination therapy. Furthermore, there is not a protocol approved by the Clinical Laboratory Standards Institute (CLSI) for testing most possible antibiotic combinations, and methodology used in basic research laboratories for combination testing presents significant hurdles for implementation in clinical laboratories. In response to these challenges, we developed a high-throughput antibiotic combination testing assay to measure the minimum antibiotic concentration(s) required to reach 99% growth inhibition (IC99) and used it to identify antibiotics that can be paired with DAP to restore the DAP susceptibility of DAP-resistant (DAP-R) MRSA. The IC99 recapitulated time-kill curve results and were consistent with results of single drug MIC measurements performed under CLSI conditions. Using this assay, we found that cefazolin (CFZ) restored DAP susceptibility for DAP-R MRSA with L826F and Q692E mutations in the C-terminal region of the synthase domain of the multiple peptide resistance factor MprF. CFZ also improved VAN susceptibility when used in combination with VAN against these isolates. We established the association between the L826F MprF mutation and CFZ improvement in DAP (and VAN) susceptibility using an MprF deletion strain and transcomplementation with WT MprF compared with L826F MprF. This study highlights the IC99 assay's potential for identifying antibiotic treatment for DAP-R MRSA bacteremia and suggests a probable link between MprF synthase domain mutations and CFZ's ability to improve or restore DAP or VAN susceptibility.

Genomic characterization of a vancomycin-intermediate Staphylococcus aureus (VISA) small colony variant after long-term antibiotic therapy.

This study aimed to evaluate whether polydatin (Poly) could eliminate the harmful effects of vancomycin (VCM) on the lungs of rats. Rats were administered VCM (200 mg/kg) and Poly (50 mg/kg), both separately and in combination, for a duration of 7 days. Following this, various methods were utilized to analyze proteins and pathological changes in lung tissue related to oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, and ferroptosis. It was found that Poly application significantly enhanced antioxidant enzyme activities and nonenzymatic antioxidants while decreasing VCM-induced lipid peroxidation. The study showed that VCM elevated the expression of inflammatory cytokines as well as Janus kinase 2 (JAK-2) and signal transducer and activator of transcription 3 (STAT-3), whereas Poly treatment inhibited these genes. Furthermore, VCM was found to induce apoptotic markers, but Poly offered protection to lung tissue against the harmful effects of VCM by demonstrating an antiapoptotic effect. Additionally, the increased expression of prostaglandin endoperoxide synthase 2 (PTGS2) and transferrin receptor 1 (TFR1), along with the decreased expression of glutathione peroxidase 4 (GPX4) in lung tissue induced by VCM, showed improvement following Poly administration. VCM was observed to increase, while Poly decreased the expression of endoplasmic reticulum stress markers. Overall, the findings of this study suggest that Poly has therapeutic potential in combating VCM-induced lung toxicity.

Hydrogel Microneedle Patches (HMNPs) are effective transdermal drug delivery systems designed to provide a minimally invasive and painless transfer of the incorporated payloads across the stratum corneum barrier. Herein, Chitooligosaccharide (COS) based hydrogel microneedles of four different concentrations (15%, 20%, 25% and 30% PEGDA) were developed using Polyethylene Glycol Diacrylate (PEGDA) and Carboxymethyl Chitosan (CMC) as crosslinkers and Vancomycin hydrochloride (COVAN) as the incorporated drug. Several characterization methods, such as Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), and Scanning Electron Microscopy (SEM), were performed before evaluating their efficacy as a transdermal therapeutic cargo delivery depot through mechanical testing, swelling ratio, drug release performance, and antibacterial activity. All of the tested formulations exhibited adequate compressive strength over 0.2 N per microneedle and effective penetration capabilities across the stratum corneum barrier. The 30% HMNP exhibited the highest swelling at 255% after 24 h, whereas the 25% HMNP provided the highest drug release at 83% after 48 h, indicating a Fickian diffusion-induced drug release mechanism. This was confirmed by fitting drug release data into mass transfer models, where all formulations except the 30% HMNP's drug release data fit the Korsmeyer-Peppas model. Except for the 20% HMNP, all HMNPs exhibited significantly greater antibacterial activity against a gram-positive bacterium, B.cereus, compared to vancomycin alone. Such efficacy establishes the HMNPs as potential transdermal drug delivery systems (TDDS) in the treatment of gram-positive bacteria-induced diseases such as cellulitis, folliculitis, etc.

Antimicrobial susceptibility of Clostridioides difficile. An Argentinian multicenter study of isolates from human patients.

Sinapic acid attenuates vancomycin-induced hepatotoxicity in rats via modulation of ER stress (CHOP, IRE1, ATF-6, PERK), apoptotic pathways (caspase-3, Bax/Bcl-2, Apaf-1, cytochrome-c), and antioxidant defenses.

Development of inhalable extra-fine particles of vancomycin for the treatment of pulmonary methicillin-resistant Staphylococcus aureus infections.

A smartphone-integrated portable fluorescent biosensor for on-site detection of antibiotics.

This study presents the results of an investigation into the interactions between innovative ophthalmic formulations and commercially available low-density polyethylene (LDPE) containers. The newly developed formulations are self-emulsifying oils (SEOs) containing suspended drug particles, designed to form an emulsion immediately upon contact with tear fluid. Physicochemical and mechanical properties of the containers were evaluated. Interactions between 6 different LDPE containers and the SEO matrix (oil "O" and surfactant Tween 20 "T") were investigated, and the impact of the SEO formulations on the mechanical properties of the containers was assessed. The study aimed to identify potential interactions between SEO components and the packaging that may occur during storage under stress conditions, based on changes in morphology, structure, thermal behavior, and mechanical strength. The SEO carrier was prepared by mixing Miglyol® 812 with Tween® 20 at a concentration of 5% w/w, followed by sterile filtration. The suspensions were compounded aseptically using sterile, micronized sodium cefuroxime (CEF) and vancomycin hydrochloride (VAN) at a concentration of 5% w/w, along with sodium citrate (2% w/w). In accordance with stability testing guidelines, stress stability studies were conducted in a climatic chamber at 40°C/75% relative humidity and 60°C/75% relative humidity. To detect structural and physicochemical changes, advanced analytical techniques were employed, including Fourier-transform infrared (FTIR) and near-infrared (NIR) spectroscopy for the assessment of structural alterations and potential degradation, differential scanning calorimetry (DSC) for thermal analysis, and X-ray diffraction (XRD) for evaluation of material crystallinity. The mechanical strength of packaging material fragments after contact with the formulations was evaluated using a TA.XTplus texture analyzer. The experiments indicated potential migration (e.g., of plasticizers and residual monomers), as well as adsorption or absorption of excipient components. Subtle interactions were observed, accompanied by negligible changes in the mechanical strength of the packaging material. The study confirmed the necessity of comprehensive compatibility testing between ophthalmic formulations and their packaging materials. A thorough understanding of these interactions is essential to ensure product stability, safety, and quality during storage and use.

Background/Objectives: In the area of pharmacology and clinical research, it is necessary to use versatile technologies able to quantify last-line antibiotic molecules with high specificity and sensitivity. This article describes the development of two types of immunosensors based on amperometric and surface plasmon resonance (SPR) measurements and their applicability in the measurement/assessment of therapeutic drug monitoring (TDM) of four last-line antibiotics such as vancomycin, colistin, daptomycin and meropenem in human plasma. In this study, ligand immobilization by preconcentration assays, sensor surface regeneration, determination of sensitivity and correlation of plasma sample quantification results by HPLC were considered. Results: In the case of the electrochemical biosensor the IC50 values obtained were 3.49 μg/L for vancomycin (VAN), 5.44 μg/L for colistin (COL), 0.82 μg/L for meropenem (MER) and 5.10 μg/L for daptomycin (DAP). For the SPRi biosensor the LODs achieved were 19 ng/mL for VAN, 9 μg/L for COL, 12 μg/L for MER and 12.3 μg/L for DAP. Finally, both electrochemical biosensor and the SPRi optical biosensor showed that for the four antibiotics the standard deviations were less than 10% with respect to the HPLC results, with ranges for VAN between ~5-6 µg/mL, for COL ~0.2-0.7 µg/mL, for MER ~4.5-5.5 µg/mL and for DAP ~0.09-0.65 µg/mL. Conclusions: These kinds of biosensors provide a precise and sensitive strategy, together with real-time determination, to quantify last-line antibiotics, with working ranges like those shown by robust techniques such as HPLC and great potential for the clinic.

Linezolid (LZD) is an effective alternative to vancomycin (VCM) for the treatment of methicillin-resistant Staphylococcus-associated infective endocarditis (IE), including cases involving prosthetic materials. However, the prolonged use often leads to thrombocytopenia, thus highlighting the importance of therapeutic drug monitoring (TDM) for dose optimization. We herein present the case of slowly progressive methicillin-resistant Staphylococcus epidermidis IE affecting a mitral annuloplasty ring in a 69-year-old afebrile patient whose only manifestation was a recurrent cerebral embolism. TDM-guided LZD dose adjustments using rapid high-performance liquid chromatography enabled the successful completion of a six-week antibiotic course while preventing severe thrombocytopenia and ensuring no further stroke recurrence.

Comparison of renal function parameters and acute kidney injury incidence between vancomycin monotherapy and vancomycin-fosfomycin combination therapy in patients: a propensity score-matched analysis

A novel biomimetic and redox-responsive hybrid lipid polymer nanoparticle for targeting sepsis microenvironment and modulating inflammation.

Background: The current treatment strategies against Clostridioides difficile-induced colitis have severe side effects due to the non-specific distribution of drugs throughout the body. Objectives: This study introduces a novel pH-responsive, charge-reversal multilayer liposomal system combining vancomycin (VM) and berberine (BR) to achieve synergistic therapy and selective colon targeting. Methodology: Multilayered liposomes were prepared via electrostatic layer-by-layer deposition of positively charged glycol chitosan (GC) and negatively charged Eudragit S100 (ES), protecting in gastric conditions and pH-triggered charge reversal for targeted colonic drug release, followed by in vivo evaluation in a BALB/c mouse model of C. difficile–induced colitis. Results: The optimized Eudragit S100-Glycol chitosan-liposomes (ES-GC-LP) had an average vesicle size of 130.3 ±2.1 nm and a high entrapment efficiency of 71.2 ±3.6% with respect to VM. An in vivo study showed a ~60% reduction in the disease activity index compared with untreated infected controls, with marked improvement in biocompatibility and the absence of colonic inflammation when treated with ES-GC-LP. Conclusion: ES-GC-LP could be an effective oral treatment option for C. difficile-induced colitis.

Background: Antibacterial medications are crucial in the treatment of pneumonia, a major cause of death for children worldwide. to ascertain the antibacterials used for pneumonia, including their class, dosage schedule, adverse drug reactions (ADRs), selection criteria, and World Health Organization (WHO) prescription indicators. Methods: From October 2025 to December 2025 this study was conducted among 432 pediatric patients admitted with Pneumonia in JLNMCH, Bhagalpur, and Bihar. Details on antibacterial prescription with selection criteria and associated ADRs were collected. Causality, preventability and severity of ADRs were assessed. WHO prescribing indicators were calculated. Data analysed using SPSS software. Results: Ampicillin (34.6%) with a dosing regimen of 32-66 mg/kg intravenously four times a day (34.4%) and a mean treatment duration of 3.6±1.26 days was the most commonly prescribed antibacterial class, followed by aminopenicillins (61.2%). 57% of patients were administered intravenously, and 99% of patients were treated empirically. Vancomycin-induced Redman Syndrome and gentamicin and ampicillin-induced hypersensitivity reactions were the observed adverse drug events. WHO prescription indicators: 2.42 antibacterials on average per contact, 96.56% of antibacterials administered under generic names, 98.37% of encounters involving injections, and 90.9% of antibacterials from the Essential Medicines List (EML). Conclusion: The most prevalent dose regimen recommended was intravenous ampicillin 32–66 mg/kg four times a day for a mean length of 3.6±1.26 days. Aminopenicillins were the primary antibacterial class. The majority of antibacterials came from EML, were given intravenously, prescribed under generic names, and were chosen experimentally. There were three documented ADRs. Calculations were made for prescribing indicators.