Drug-resistant Bacterial Infections Research Articles

Polydopamine Nanocarriers with Cascade-Activated Nitric Oxide Release Combined Photothermal Activity for the Therapy of Drug-Resistant Bacterial Infections.

Antibiotic abuse leads to increased bacterial resistance, and the surviving planktonic bacteria aggregate and secrete extracellular polymers to form biofilms. Conventional antibacterial agents find it difficult to penetrate the biofilm, remove the bacteria wrapped in it, and produce an excellent therapeutic effect. In this study, a dual pH- and NIR-responsive nanocomposite (A-Ca@PDA) was developed to remove drug-resistant bacteria through a cascade of catalytic nitric oxide (NO) release and photothermal clearance. NO can melt in the outer package of the biofilm, facilitating the nanocomposites to have better permeability. Thermal therapy further inhibits the growth of planktonic bacteria. The locally generated high temperature and the burst release of NO together aggravate the biofilm collapse and bacterial death after NIR irradiation. The nanocomposites achieved a remarkable photothermal conversion efficiency of 47.5%, thereby exhibiting significant advancements in energy conversion. The nanocomposites exhibited remarkable efficacy in inhibiting multidrug-resistant (MDR) Escherichia coli and MDR Staphylococcus aureus, thus achieving an inhibition rate of >90%. Moreover, these nanocomposites significantly improved the wound-healing process in the MDR S. aureus-infected mice. Thus, this novel nanocomposite offers a novel strategy to combat drug-resistant bacterial infections.

Ta4C3 Nanosheets as a Novel Therapeutic Platform for Photothermal-Driven ROS Scavenging and Immune Activation against Antibiotic-Resistant Infections in Diabetic Wounds.

The accumulation of excessive reactive oxygen species (ROS) and recurrent infections with drug-resistant bacteria pose significant challenges in diabetic wound infections, often leading to impediments in wound healing. Addressing this, there is a critical demand for novel strategies dedicated to treating and preventing diabetic wounds infected with drug-resistant bacteria. Herein, 2D tantalum carbide nanosheets (Ta4C3 NSs) have been synthesized through an efficient and straightforward approach, leading to the development of a new, effective nanoplatform endowed with notable photothermal properties, biosafety, and diverse ROS scavenging capabilities, alongside immunogenic attributes for diabetic wound treatment and prevention of recurrent drug-resistant bacterial infections. The Ta4C3 NSs exhibit remarkable photothermal performance, effectively eliminating methicillin-resistant Staphylococcus aureus (MRSA) and excessive ROS, thus promoting diabetic wound healing. Furthermore, Ta4C3 NSs enhance dendritic cell activation, further triggering T helper 1 (TH1)/TH2 immune responses, leading to pathogen-specific immune memory against recurrent MRSA infections. This nanoplatform, with its significant photothermal and immunomodulatory effects, holds vast potential in the treatment and prevention of drug-resistant bacterial infections in diabetic wounds.

Pt-Ru bimetallic nanoclusters with peroxidase-like activity for antibacterial therapy.

Drug-resistant bacteria arising from antibiotic abuse infections have always been a serious threat to human health. Killing bacteria with toxic reactive oxygen species (ROS) is an ideal antibacterial method for treating drug-resistant bacterial infections. Here, we prepared Pt-Ru bimetallic nanoclusters (Pt-Ru NCs) with higher peroxidase (POD)-like activity than Pt monometallic nanoclusters. Pt-Ru can easily catalyze the decomposition of H2O2 to produce ·OH, thereby catalyzing the transformation of 3,3',5,5'-tetramethylbiphenylamine (TMB) to blue oxidized TMB (oxTMB). We utilized the POD-like activity of the Pt-Ru NCs for antibacterial therapy. The results showed that at doses of 40 μg/mL and 16 μg/mL, the Pt-Ru NCs exhibited extraordinary antibacterial activity against E. coli and S. aureus, demonstrating the enormous potential of Pt-Ru NCs as antibacterial agents.

Multi-mechanism antitumor/antibacterial effects of Cu-EGCG self-assembling nanocomposite in tumor nanotherapy and drug-resistant bacterial wound infections

Chemotherapy and surgery stand as primary cancer treatments, yet the unique traits of the tumor microenvironment hinder their effectiveness. The natural compound epigallocatechin gallate (EGCG) possesses potent anti-tumor and antibacterial traits. However, the tumor’s adaptability to chemotherapy due to its acidic pH and elevated glutathione (GSH) levels, coupled with the challenges posed by drug-resistant bacterial infections post-surgery, impede treatment outcomes. To address these challenges, researchers strive to explore innovative treatment strategies, such as multimodal combination therapy. This study successfully synthesized Cu-EGCG, a metal-polyphenol network, and detailly characterized it by using synchrotron radiation and high-resolution mass spectrometry (HRMS). Through chemodynamic therapy (CDT), photothermal therapy (PTT), and photodynamic therapy (PDT), Cu-EGCG showed robust antitumor and antibacterial effects. Cu+ in Cu-EGCG actively participates in a Fenton-like reaction, generating hydroxyl radicals (·OH) upon exposure to hydrogen peroxide (H2O2) and converting to Cu2+. This Cu2+ interacts with GSH, weakening the oxidative stress response of bacteria and tumor cells. Density functional theory (DFT) calculations verified Cu-EGCG’s efficient GSH consumption during its reaction with GSH. Additionally, Cu-EGCG exhibited outstanding photothermal conversion when exposed to 808 nm near-infrared (NIR) radiation and produced singlet oxygen (1O2) upon laser irradiation. In both mouse tumor and wound models, Cu-EGCG showcased remarkable antitumor and antibacterial properties.

A hydrogel dressing loaded with tea tree oil nanoemulsion accelerates methicillin-resistant Staphylococcus aureus-infected wound healing

Drug-resistant bacterial infections can easily lead to delayed wound healing and pose a serious threat to patients' health. Therefore, it was imperative to develop wound dressings to solve this problem. Herein, we developed a hydrogel based on laponite and polyacrylamide (PAAG/LAP) and loaded with tea tree oil nano-emulsion (nanoTTO) by a simple one-step mixing method via the principle of photopolymerization and its potential use and safety for MRSA-infected skin wounds. The evaluation showed that the PAAG/LAP/nanoTTO30 % hydrogel exhibited excellent compressive resistance (∼85 kPa), good biocompatibility, and great antibacterial properties against MRSA in vitro and in vivo (over 90 %). Cell migration results showed that the relative wound area ratio of the PAAG/LAP/nanoTTO30 % hydrogel treatment group (∼55.18 %) was significantly lower than that of the control group (∼68.89 %). The results of the in vivo infection rat model showed that compared with other control groups, the PAAG/LAP/nanoTTO30 % hydrogel treatment group had the lowest relative wound area ratio (8.78 %) within 12 days. Moreover, the results showed the PAAG/LAP/nanoTTO30 % hydrogel could promote MRSA-infected wound healing by directly killing bacteria and promoting angiogenesis. In conclusion, our study provided an antibacterial hydrogel dressing that does not require loading antibiotics for wounds infected by drug-resistant bacteria, expecting to achieve infected wound healing.

Photothermal/photodynamic synergistic antibacterial study of MOF nanoplatform with SnFe2O4 as the core

Drug-resistant bacterial infections cause significant harm to public life, health, and property. Biofilm is characterized by overexpression of glutathione (GSH), hypoxia, and slight acidity, which is one of the main factors for the formation of bacterial resistance. Traditional antibiotic therapy gradually loses its efficacy against multi-drug-resistant (MDR) bacteria. Therefore, synergistic therapy, which regulates the biofilm microenvironment, is a promising strategy. A multifunctional nanoplatform, SnFe2O4-PBA/Ce6@ZIF-8 (SBC@ZIF-8), in which tin ferrite (SnFe2O4, denoted as SFO) as the core, loaded with 3-aminobenzeneboronic acid (PBA) and dihydroporphyrin e6 (Ce6), and finally coated with zeolite imidazole salt skeleton 8 (ZIF-8). The platform has a synergistic photothermal therapy (PTT)/photodynamic therapy (PDT) effect, which can effectively remove overexpressed GSH by glutathione peroxidase-like activity, reduce the antioxidant capacity of biofilm, and enhance PDT. The platform had excellent photothermal performance (photothermal conversion efficiency was 55.7 %) and photothermal stability. The inhibition rate of two MDR bacteria was more than 96 %, and the biofilm clearance rate was more than 90 % (150 μg/mL). In the animal model of MDR S. aureus infected wound, after 100 μL SBC@ZIF-8+NIR (150 μg/mL) treatment, the wound area of mice was reduced by 95 % and nearly healed. The serum biochemical indexes and H&E staining results were within the normal range, indicating that the platform could promote wound healing and had good biosafety. In this study, we designed and synthesized multifunctional nanoplatforms with good anti-drug-resistant bacteria effect and elucidated the molecular mechanism of its anti-drug-resistant bacteria. It lays a foundation for clinical application in treating wound infection and promoting wound healing.

Unique aminothiazolyl coumarins as potential DNA and membrane disruptors towards Enterococcus faecalis

Aminothiazolyl coumarins as potentially new antimicrobial agents were designed and synthesized in an effort to overcome drug resistance. Biological activity assay revealed that some target compounds exhibited significantly inhibitory efficiencies toward bacteria and fungi including drug-resistant pathogens. Especially, aminothiazolyl 7-propyl coumarin 8b and 4-dichlorobenzyl derivative 11b exhibited bactericidal potential (MBC/MIC = 2) toward clinically drug-resistant Enterococcus faecalis with low cytotoxicity to human lung adenocarcinoma A549 cells, rapidly bactericidal effects and no obvious bacterial resistance development against E. faecalis. The preliminary antibacterial action mechanism studies suggested that compound 11b was able to disturb E. faecalis membrane effectively, and interact with bacterial DNA isolated from resistant E. faecalis through noncovalent bonds to cleave DNA, thus inhibiting the growth of E. faecalis strain. Further molecular modeling indicated that compounds 8b and 11b could bind with SER-1084 and ASP-1083 residues of gyrase-DNA complex through hydrogen bonds and hydrophobic interactions. Moreover, compound 11b showed low hemolysis and in vivo toxicity. These findings of aminothiazolyl coumarins as unique structural scaffolds might hold a large promise for the treatments of drug-resistant bacterial infection.

Engineering Cu nanoclusters with aggregation-induced emission for photodynamic healing of wound with drug-resistant bacteria-infection

Efforts to expedite the development of novel antimicrobial agents without drug resistance are imperative to combat drug-resistant bacterial infections. In this study, Cu nanoclusters (NCs) with aggregation-induced emission (AIE) were designed by manipulating the pH to control the aggregation of Cu(I) complexes on the surface of a Cu(0) core. The resulting Cu NCs exhibited excellent photodynamic antimicrobial activity against a wide range of bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA), through a synergistic interplay of intrinsic and photodynamic antimicrobial mechanisms. This was achieved by the copious generation of reactive oxygen species (ROS) that are lethal to bacteria. In addition to that, these Cu NCs displayed minimal cytotoxicity and excellent biocompatibility, enabling the promoted healing of MRSA-infected wounds in mice through eliminating bacterial infection, and alleviating inflammation without causing systemic harm or impairing blood and liver functions. This study represents the first successful development of AIE-featured Cu NCs-based photodynamic antimicrobials, which may shed light on the design of other AIE-featured metal NCs, contribute to a better understanding of NC’s luminescence fundamentals, and add fuels to the development of metal NCs-based nanomedicine.

Silver Nanoparticles Encapped by Dihydromyricetin: Optimization of Green Synthesis, Characterization, Toxicity, and Anti-MRSA Infection Activities for Zebrafish (Danio rerio).

To achieve the environmentally friendly and rapid green synthesis of efficient and stable AgNPs for drug-resistant bacterial infection, this study optimized the green synthesis process of silver nanoparticles (AgNPs) using Dihydromyricetin (DMY). Then, we assessed the impact of AgNPs on zebrafish embryo development, as well as their therapeutic efficacy on zebrafish infected with Methicillin-resistant Staphylococcus aureus (MRSA). Transmission electron microscopy (TEM) and dynamic light-scattering (DLS) analyses revealed that AgNPs possessed an average size of 23.6 nm, a polymer dispersity index (PDI) of 0.197 ± 0.0196, and a zeta potential of -18.1 ± 1.18 mV. Compared to other published green synthesis products, the optimized DMY-AgNPs exhibited smaller sizes, narrower size distributions, and enhanced stability. Furthermore, the minimum concentration of DMY-AgNPs required to affect zebrafish hatching and survival was determined to be 25.0 μg/mL, indicating the low toxicity of DMY-AgNPs. Following a 5-day feeding regimen with DMY-AgNP-containing food, significant improvements were observed in the recovery of the gills, intestines, and livers in MRSA-infected zebrafish. These results suggested that optimized DMY-AgNPs hold promise for application in aquacultures and offer potential for further clinical use against drug-resistant bacteria.

Oxygen vacancy-rich nickel oxide nanoplatforms for enhanced photothermal and chemodynamic therapy combat methicillin-resistant Staphylococcus aureus

Bacterial infections pose a global concern due to high fatality rates, particularly with the rise of drug-resistant bacteria and biofilm formation. There is an urgent need for innovative strategies to combat this issue. A study on chemodynamic therapy (CDT) using nanozymes in conjunction with photothermal therapy (PTT) has displayed potential in addressing drug-resistant bacterial infections. However, the effectiveness of this combined approach is limited by inadequate light absorption. This work suggests the NiOx nanoparticles enriched with oxygen vacancies enhance CDT and PTT to overcome this challenge. The presence of oxygen vacancies in NiOx can reduce the energy gap between its valence band and conduction band, facilitating oxygen adsorption. NiOx has exhibited notable antibacterial properties and complete eradication of biofilms in both laboratory and animal trials. In animal abscess models, NiOx demonstrated antibacterial and anti-inflammatory effects in the initial stages, while also promoting wound healing and tissue regeneration by influencing immune factors and encouraging collagen deposition and neovascularization. With positive biosafety and biocompatibility profiles, the oxygen vacancy-enhanced CDT and PTT therapy proposed in this article hold promise for effective sterilization, deep biofilm removal, and treatment of infections caused by drug-resistant bacteria. Statement of significanceThis study constructs oxygen vacancies NiOx nanoparticles (NiOx NPs) to improve the efficacy of photothermal therapy and chemodynamic therapy. The presence of oxygen vacancies in NiOx NPs helps bridge the energy gap between its valence band and conduction band, facilitating oxygen adsorption and improving catalytic efficiency. In both in vivo and in vitro antibacterial experiments, NiOx NPs demonstrate effective antibacterial and anti-inflammatory properties. Furthermore, it aids in wound healing and tissue regeneration by modulating immune factors, collagen deposition, and angiogenesis. This approach presents a promising collaborative strategy for utilizing nickel-based defective nanomaterials in combating deep drug-resistant bacterial infections.

Nanotechnology-driven strategies to enhance the treatment of drug-resistant bacterial infections.

The misuse of antibiotics has led to increased bacterial resistance, posing a global public health crisis and seriously endangering lives. Currently, antibiotic therapy remains the most common approach for treating bacterial infections, but its effectiveness against multidrug-resistant bacteria is diminishing due to the slow development of new antibiotics and the increase of bacterial drug resistance. Consequently, developing new a\ntimicrobial strategies and improving antibiotic efficacy to combat bacterial infection has become an urgent priority. The emergence of nanotechnology has revolutionized the traditional antibiotic treatment, presenting new opportunities for refractory bacterial infection. Here we comprehensively review the research progress in nanotechnology-based antimicrobial drug delivery and highlight diverse platforms designed to target different bacterial resistance mechanisms. We also outline the use of nanotechnology in combining antibiotic therapy with other therapeutic modalities to enhance the therapeutic effectiveness of drug-resistant bacterial infections. These innovative therapeutic strategies have the potential to enhance bacterial susceptibility and overcome bacterial resistance. Finally, the challenges and prospects for the application of nanomaterial-based antimicrobial strategies in combating bacterial resistance are discussed. This article is categorized under: Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.

Bosutinib Stimulates Macrophage Survival, Phagocytosis, and Intracellular Killing of Bacteria.

Host-acting compounds are emerging as potential alternatives to combating antibiotic resistance. Here, we show that bosutinib, an FDA-approved chemotherapeutic for treating chronic myelogenous leukemia, does not possess any antibiotic activity but enhances macrophage responses to bacterial infection. In vitro, bosutinib stimulates murine and human macrophages to kill bacteria more effectively. In a murine wound infection with vancomycin-resistant Enterococcus faecalis, a single intraperitoneal bosutinib injection or multiple topical applications on the wound reduce the bacterial load by approximately 10-fold, which is abolished by macrophage depletion. Mechanistically, bosutinib stimulates macrophage phagocytosis of bacteria by upregulating surface expression of bacterial uptake markers Dectin-1 and CD14 and promoting actin remodeling. Bosutinib also stimulates bacterial killing by elevating the intracellular levels of reactive oxygen species. Moreover, bosutinib drives NF-κB activation, which protects infected macrophages from dying. Other Src kinase inhibitors such as DMAT and tirbanibulin also upregulate expression of bacterial uptake markers in macrophages and enhance intracellular bacterial killing. Finally, cotreatment with bosutinib and mitoxantrone, another chemotherapeutic in clinical use, results in an additive effect on bacterial clearance in vitro and in vivo. These results show that bosutinib stimulates macrophage clearance of bacterial infections through multiple mechanisms and could be used to boost the host innate immunity to combat drug-resistant bacterial infections.

PH-Responsive Co-Assembled Peptide Hydrogel to Inhibit Drug-Resistant Bacterial Infection and Promote Wound Healing.

Drug-resistant bacterial infection and biofilm formation are the key inhibitors of wound healing, and new strategies are urgently needed to address these issues. In this study, we designed a pH-responsive co-assembled peptide hydrogel to inhibit Methicillin-resistant Staphylococcus aureus (MRSA) infection and promote wound healing. We synthesized a cationic short peptide (Nap-FFKKK) and a co-assembled hydrogel with curcumin at pH ∼ 7.8. The loaded curcumin was continuously released in a weak acid environment (pH ∼ 5.5). The lysine-rich cationic peptide inhibited biofilm formation in MRSA via electrostatic interaction with the negatively charged bacterial cell surface and, thus, provided a reinforcing antibacterial effect with curcumin. In vitro antibacterial experiments showed that the co-assembled system considerably reduced the minimum inhibitory concentration of curcumin against MRSA by 10-fold and promoted wound healing in a mouse model of MRSA-infected wounds. This study provides a simple and promising strategy to treat drug-resistant bacterial infections in wounds.

Poly-l-lysine modified MOF nanoparticles with pH/ROS sensitive CIP release and CUR triggered photodynamic therapy against drug-resistant bacterial infection

The challenge of drug resistance in bacteria caused by the over use of biotics is increasing during the therapy process, which has attracted great attentions of the clinicians and scientists around the world. Recently, photodynamic therapy (PDT) triggered by photosensitizer (PS) has become a promising treatment method because of its high efficacy, easy operation, and low side effect. Herein, the poly-l-lysine (PLL) modified metal-organic framework (MOF) nanoparticles, ZIF/PLL-CIP/CUR, were synthesized to allow both reactive oxygen species (ROS) responsive drug release and photodynamic effect for synergistic therapy against drug resistant bacterial infections. The PLL was modified on the shell of the zeolite imidazole framework (ZIF) by the ROS-responsive thioketal linker for controllable CIP release. CUR were encapsulated in ZIF as the photosensitizer for blue light mediated photodynamic effect to produce singlet oxygen (1O2) and superoxide anion radical (O2−) for efficient inhibition towards methicillin-resistant Staphylococcus aureus (MRSA). The charge conversion from negative charge (−4.6 mV) to positive charge (2.6 mV) was observed at pH 7.4 and pH 5.5, and 70.9 % CIP was found released at pH 5.5 in the presence of H2O2, which suggests the good biosafety at physiological pH and ROS-responsive drug release of the as-prepared nanoparticle in the bacterial microenvironment. The as-prepared nanoparticles could effectively kill MRSA and disrupt bacterial biofilm by combination of chemo- and photodynamic therapy. In mice model, the as-prepared nanoparticles exhibited excellent biosafety and synergistic effect with 98.81 % healing rate in treatment of MRSA infection, which is considered as a promising candidate in combating drug resistant bacterial infection.

A Fluorous Peptide Amphiphile with Potent Antimicrobial Activity for the Treatment of MRSA-induced Sepsis and Chronic Wound Infection.

The rising prevalence of global antibiotic resistance evokes the urgent need for novel antimicrobial candidates. Cationic lipopeptides have attracted much attention due to their strong antimicrobial activity, broad-spectrum and low resistance tendency. Herein, a library of fluoro-lipopeptide amphiphiles was synthesized by tagging a series of cationic oligopeptides with a fluoroalkyl tail via a disulfide spacer. Among the lipopeptide candidates, R6F bearing six arginine moieties and a fluorous tag shows the highest antibacterial activity, and it exhibits an interesting fluorine effect as compared to the non-fluorinated lipopeptides. The high antibacterial activity of R6F is attributed to its excellent bacterial membrane permeability, which further disrupts the respiratory chain redox stress and cell wall biosynthesis of the bacteria. By co-assembling with lipid nanoparticles, R6F showed high therapeutic efficacy and minimal adverse effects in the treatment of MRSA-induced sepsis and chronic wound infection. This work provides a novel strategy to design highly potent antibacterial peptide amphiphiles for the treatment of drug-resistant bacterial infections.

Expert Opinion on the Prescription Practice of Carbapenem Antibiotics for the Treatment of Drug-Resistant Bacterial Infections in Indian Settings

Objective: The current survey-based study aims to gather expert opinions on the prescription practice of carbapenem antibiotics for the treatment of drug-resistant bacterial infections in Indian clinical settings.
 Methods: The cross-sectional, multiple-response questionnaire-based survey involving professionals with expertise in treating pathogenic illnesses was carried out between 2022 and 2023. The questionnaire comprised 25 questions, the majority of which dealt with the use of antibiotics as monotherapy and in various combinations to treat pathogenic illnesses.
 Results: Out of 302 survey participants, 83% of them preferred meropenem medications more frequently than imipenem, biapenem, doripenem, and other antibiotics to treat pathogenic infections. For the management of multidrug-resistant (MDR), extensively drug-resistant (XDR), or pan-drug-resistant (PDR) infections, approximately 54% of the respondents preferred the administration of 1 gm of IV meropenem in 2 to 3 divided doses. About 61% of the responders suggested using IV meropenem together with colistin to treat infections. The combination of IV meropenem with β-lactams, aminoglycosides, tigecycline, colistin, and others was preferred by 91% of the respondents for the treatment of MDR, XDR, and PDR infections. For treating difficult intra-abdominal infections, meningitis, and urinary tract infections (UTIs), almost 43% of the respondents preferred meropenem in combination with sulbactam.
 Conclusion: The survey findings emphasize the prominent role of meropenem, either as a standalone treatment or in combination with other antibiotics in the management of challenging infections caused by MDR, XDR, or PDR pathogens. In specific scenarios involving difficult intra-abdominal infections, meningitis, and UTIs, clinicians recommended meropenem in combination with sulbactam antibiotics.

Nanoarchitectonics of Bimetallic Cu-/Co-Doped Nitrogen-Carbon Nanozyme-Functionalized Hydrogel with NIR-Responsive Phototherapy for Synergistic Mitigation of Drug-Resistant Bacterial Infections.

Superbug infections and transmission have become major challenges in the contemporary medical field. The development of novel antibacterial strategies to efficiently treat bacterial infections and conquer the problem of antimicrobial resistance (AMR) is extremely important. In this paper, a bimetallic CuCo-doped nitrogen-carbon nanozyme-functionalized hydrogel (CuCo/NC-HG) has been successfully constructed. It exhibits photoresponsive-enhanced enzymatic effects under near-infrared (NIR) irradiation (808 nm) with strong peroxidase (POD)-like and oxidase (OXD)-like activities. Upon NIR irradiation, CuCo/NC-HG possesses photodynamic activity for producing singlet oxygen(1O2), and it also has a high photothermal conversion effect, which not only facilitates the elimination of bacteria but also improves the efficiency of reactive oxygen species (ROS) production and accelerates the consumption of GSH. CuCo/NC-HG shows a lower hemolytic rate and better cytocompatibility than CuCo/NC and possesses a positive charge and macroporous skeleton for restricting negatively charged bacteria in the range of ROS destruction, strengthening the antibacterial efficiency. Comparatively, CuCo/NC and CuCo/NC-HG have stronger bactericidal ability against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AmprE. coli) through destroying the cell membranes with a negligible occurrence of AMR. More importantly, CuCo/NC-HG plus NIR irradiation can exhibit satisfactory bactericidal performance in the absence of H2O2, avoiding the toxicity from high-concentration H2O2. In vivo evaluation has been conducted using a mouse wound infection model and histological analyses, and the results show that CuCo/NC-HG upon NIR irradiation can efficiently suppress bacterial infections and promote wound healing, without causing inflammation and tissue adhesions.

Combating infections from drug-resistant bacteria: Unleashing synergistic broad-spectrum antibacterial power with high-entropy MXene/CDs

The growing resistance of bacteria to antibiotics has posed challenges in treating associated bacterial infections, while the development of multi-model antibacterial strategies could efficient sterilization to prevent drug resistance. High-entropy MXene has emerged as a promising candidate for antibacterial synergy with inherent photothermal and photodynamic properties. Herein, a high-entropy nanomaterial of MXene/CDs was synthesized to amplify oxidative stress under near-infrared laser irradiation. Well-exfoliated MXene nanosheets have proven to show an excellent photothermal effect for sterilization. The incorporation of CDs could provide photo-generated electrons for MXene nanosheets to generate ROS, meanwhile reducing the recombination of electron-hole pairs to further accelerate the generation of photo-generated electrons. The MXene/CDs material demonstrates outstanding synergistic photothermal and photodynamic effects, possesses excellent biocompatibility and successfully eliminates drug-resistant bacteria as well as inhibits biofilm formation. While attaining a remarkable killing efficiency of up to 99.99% against drug-resistant Escherichia coli and Staphylococcus aureus, it also demonstrates outstanding antibacterial effects against four additional bacterial strains. This work not only establishes a synthesis precedent for preparing high-entropy MXene materials with CDs but also provides a potential approach for addressing the issue of drug-resistant bacterial infections.

Leveraging Large Data, Statistics, and Machine Learning to Predict the Emergence of Resistant E. coli Infections.

Drug-resistant Gram-negative bacterial infections, on average, increase the length of stay (LOS) in U.S. hospitals by 5 days, translating to approximately $15,000 per patient. We used statistical and machine-learning models to explore the relationship between antibiotic usage and antibiotic resistance over time and to predict the clinical and financial costs associated with resistant E. coli infections. We acquired data on antibiotic utilization and the resistance/sensitivity of 4776 microbial cultures at a Kaiser Permanente facility from April 2013 to December 2019. The ARIMA (autoregressive integrated moving average), neural networks, and random forest time series algorithms were employed to model antibiotic resistance trends. The models' performance was evaluated using mean absolute error (MAE) and root mean squared error (RMSE). The best performing model was then used to predict antibiotic resistance rates for the year 2020. The ARIMA model with cefazolin, followed by the one with cephalexin, provided the lowest RMSE and MAE values without signs of overfitting across training and test datasets. The study showed that reducing cefazolin usage could decrease the rate of resistant E. coli infections. Although piperacillin/tazobactam did not perform as well as cefazolin in our time series models, it performed reasonably well and, due to its broad spectrum, might be a practical target for interventions in antimicrobial stewardship programs (ASPs), at least for this particular facility. While a more generalized model could be developed with data from multiple facilities, this study acts as a framework for ASP clinicians to adopt statistical and machine-learning approaches, using region-specific data to make effective interventions.

Prescribing antimicrobials effectively in Dentistry; Resources to support the role of the dentist in antimicrobial stewardship

Background The discovery of antibiotics revolutionised modern medicine and extended the average human lifespan by 23 years.1 Antimicrobial resistance threatens to reverse the progress that has been made. In 2019, there were 4.95 million deaths globally associated with drug-resistant bacterial infections.2 That figure may rise to as many as 50 million by 2050, making this an unprecedented global public health problem.3 The threat of a post-antibiotic era has prompted the publication of Ireland’s One Health National Action Plan on Antimicrobial Resistance (2021-2025).4 This National Action Plan advocates for the judicious use of antimicrobials to limit any unintended consequences and antimicrobial resistance. This is commonly known as Antimicrobial Stewardship. Antibiotic resistance is largely driven by the overuse and misuse of antibiotics in people, animals and in the environment.4 Dentists are responsible for approximately 10% of antibiotic prescribing in humans globally.5 With several international studies of dental antibiotic prescribing demonstrating that overprescribing occurs frequently5, dentists have an opportunity to contribute significantly to slowing the development and spread of antibiotic resistance by optimising prescribing. This article aims to show how dentists can support good antimicrobial stewardship in their practice.