A pH/enzyme dual responsive PMB spatiotemporal release hydrogel promoting chronic wound repair.

Suppressing persistent multidrug-resistant (MDR) bacterial infections and excessive inflammation is the key for treating chronic wounds. Therefore, developing a microenvironment-responsive material with good biodegradability, drug-loading, anti-infection, and anti-inflammatory properties is desired to boost the chronic wounds healing process; however, using ordinary assembly remains a defect. Herein, we propose a pH/enzyme dual-responsive polymyxin B (PMB) spatiotemporal-release hydrogel (GelMA/OSSA/PMB), namely, the amount of OSSA and PMB released from GelMA/OSSA/PMB was closely related the wound pH and the enzyme concentration changing. The GelMA/OSSA/PMB showed better biosafety than equivalent free PMB, owing to the controlled release of PMB, which helped kill planktonic bacteria and inhibit biofilm activity in vitro. In addition, the GelMA/OSSA/PMB exhibited excellent antibacterial and anti-inflammatory properties. A MDR Pseudomonas aeruginosa caused infection was effectively resolved by the GelMA/OSSA/PMB hydrogel in vivo, thereby significantly boosting wound closure during the inflammatory phase. Furthermore, GelMA/OSSA/PMB accelerated the sequential phases of wound repair.

Outer Membrane Vesicle-Coated Nanoparticle Vaccine Protects Against Acinetobacter baumannii Pneumonia and Sepsis.

The highly multidrug-resistant (MDR) Gram-negative bacterial pathogen Acinetobacter baumannii is a top global health priority where an effective vaccine could protect susceptible populations and limit resistance acquisition. Outer membrane vesicles (OMVs) shed from Gram-negative bacteria are enriched with virulence factors and membrane lipids but heterogeneous in size and cargo. We report a vaccine platform combining precise and replicable nanoparticle technology with immunogenic A. baumannii OMVs (Ab-OMVs). Gold nanoparticle cores coated with Ab-OMVs (Ab-NPs) induced robust IgG titers in rabbits that enhanced human neutrophil opsonophagocytic killing and passively protected against lethal A. baumannii sepsis in mice. Active Ab-NP immunization in mice protected against sepsis and pneumonia, accompanied by B cell recruitment to draining lymph nodes, activation of dendritic cell markers, improved splenic neutrophil responses, and mitigation of proinflammatory cytokine storm. Nanoparticles are an efficient and efficacious platform for OMV vaccine delivery against A. baumannii and perhaps other high-priority MDR pathogens.

Critically Ill Patient with Multidrug-Resistant Acinetobacter baumannii Respiratory Infection Successfully Treated with Intravenous and Nebulized Bacteriophage Therapy.

Hospitalized patients are at risk of developing serious multidrug resistant bacterial infections. This risk is heightened in patients who are on mechanical ventilation, are immunocompromised, and/or have chronic comorbidities. We report the case of a 52-year-old critically ill patient with a multidrug resistant Acinetobacter baumannii (MDR-A) respiratory infection who was successfully treated with antibiotics and intravenous and nebulized bacteriophage therapy.

Cationic chitosan@Ruthenium dioxide hybrid nanozymes for photothermal therapy enhancing ROS-mediated eradicating multidrug resistant bacterial infection.

Antibiotic resistanceand biofilm formation are the main challenges of bacterial infectious diseases, and enhancing the permeability of drugs to biofilms may be a promising strategy. Herein, we constructed a cationic chitosan coated ruthenium dioxide nanozyme (QCS-RuO2@RBT, SRT NSs)。RuO2 nanosheets (RuO2 NSs) are modified with positively charged Quaternary ammonium-chitosan (QCS) to improve biocompatibility, and enhance the interaction between RuO2 nanozymes and bacterial membranes. An antibacterial drug, [Ru(bpy)2(tip)]2+ (RBT) can be loaded onto QCS-RuO2 by π-π stacking and hydrophobic interaction. SRT NSs exhibit NIR light enhanced peroxidase-like catalytic activity, thereby effectively fighting against planktonic bacteria and damaging biofilms. In the biofilm, extracellular DNA (eDNA) was cleaved by high levels of hydroxyl radicals (•OH) catalyzed by SRT NSs, thereby disrupting the rigid biofilm. In addition, in vivo studies demonstrate that SRT NSs can significantly rescue skin wound infections and the chronic lung infection in mice caused by P. aeruginosa, and hold the same therapeutic efficacy as first-line clinically anchored anti P. aeruginosa drug ciprofloxacin. Accordingly, the research work has realized the efficient production of ·OH, and the permeability of drugs to biofilms.it provides a promising response strategy for the management of biofilm-associated infections, including chronic lung infection.

Photothermal Nano-antibiotic for Effective Treatment of Multidrug-Resistant Bacterial Infection.

Bacteria's antibiotic resistance is one of the major challenges in the treatment of infectious diseases. With increasing difficulty in discovering antibiotics, there is an urgent need to develop antibiotic-free therapeutic strategies to address this grand challenge. In this report, we developed a polypyrrole (PPy)-based photothermal nano-antibiotic (PTNA) for effective treatment of multidrug-resistant (MDR) bacterial infection. PTNA was fabricated by polymerizing pyrrole onto an anionic vesicle to integrate the cationic and photothermal properties of PPy for combinatory killing against bacteria. PTNA exhibits a strong photothermal effect in the NIR-II (1064 nm) biowindow, thus it is feasible for in vivo therapy due to deeper tissue penetration. Our in vitro experiments revealed that PTNA can significantly inhibit the growth of MDR bacteria (Salmonella typhimurium), alleviate inflammatory response of infected cells, and prevent biofilm formation. More importantly, PTNA showed a significant therapeutic effect in an S. typhimurium-infected animal disease model of acute systemic infection by inhibiting bacterial growth, lowering inflammatory responses and pathological changes, and eventually improving the survival rate of mice. Finally, PTNA had safe profiles in vitro and in vivo with no visible toxicity detected. Therefore, we believe PTNA may serve as a promising antibiotic-free antimicrobial material for the effective treatment of MDR bacterial infection.

Combating Superbug Without Antibiotic on a Postamputation Wound in a Patient with Diabetic Foot.

Diabetic foot is a kind of limb- and life-threatening complication that is difficult to treat with conventional therapy, especially when accompanied with peripheral arterial insufficiency and severe infection. We present a diabetic patient with a postamputation wound infected by multidrug-resistant Acinetobacter baumannii/haemolyticus, which was resistant to almost all antibiotics. As the clinical response to antimicrobial therapy was poor, antibiotic was discontinued. Autologous platelet-rich gel with anticoagulation, negative pressure wound therapy, and improvement of microcirculation were used successfully to eradicate infection of the superbug and achieve final wound closure.