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The increasing emergence and dissemination of multidrug resistant (MDR) bacterial pathogens accelerate the desires for new antibiotics. Natural products dominate the preferred chemical scaffolds for the discovery of antibacterial agents. Here, the potential of natural flavonoids from plants against MDR bacteria, is demonstrated. Structure–activity relationship analysis shows the prenylation modulates the activity of flavonoids and obtains two compounds, α‐mangostin (AMG) and isobavachalcone (IBC). AMG and IBC not only display rapid bactericidal activity against Gram‐positive bacteria, but also restore the susceptibility of colistin against Gram‐negative pathogens. Mechanistic studies generally show such compounds bind to the phospholipids of bacterial membrane, and result in the dissipation of proton motive force and metabolic perturbations, through distinctive modes of action. The efficacy of AMG and IBC in four models associated with infection or contamination, is demonstrated. These results suggest that natural products of plants may be a promising and underappreciated reservoir to circumvent the existing antibiotic resistance. Isopentenylated flavonoids such as α‐mangostin and isobavachalcone are efficacious against multidrug‐resistant Gram‐positive and Gram‐negative pathogens with permeabilized outer membrane. Both α‐mangostin and isobavachalcone display rapid bactericidal activities through distinctive modes of action by targeting bacterial membrane phospholipids. Antibacterial agents targeting membrane exert fast time‐killing dynamics with less potential to develop resistance. Targeting membrane is an alternative strategy for antibacterial therapy.

The increase in multidrug-resistant bacteria represents a true challenge in the pharmaceutical and biomedical fields. For this reason, research on the development of new potential antibacterial strategies is essential. Here, we describe the development of a green system for the synthesis of silver nanoparticles (AgNPs) bioconjugated with chitosan. We optimized a Prunus cerasus leaf extract as a source of silver and its conversion to chitosan–silver bioconjugates (CH-AgNPs). The AgNPs and CH-AgNPs were characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), ultraviolet–visible spectroscopy (UV–Vis), and zeta potential measurement (Z-potential). The cytotoxic activity of AgNPs and CH-AgNPs was assessed on Vero cells using the 3-[4.5-dimethylthiazol-2-yl]-2.5-diphenyltetrazolium bromide (MTT) cell proliferation assay. The antibacterial activity of AgNPs and CH-AgNPs synthesized using the green system was determined using the broth microdilution method. We evaluated the antimicrobial activity against standard ATCC and clinically isolated multisensitive (MS) and multidrug-resistant bacteria (MDR) Escherichia coli (E. coli), Enterococcus faecalis (E. faecalis), Klebsiella pneumonia (K. pneumoniae), and Staphylococcus aureus (S. aureus), using minimum inhibitory concentration (MIC) assays and the broth dilution method. The results of the antibacterial studies demonstrate that the silver chitosan bioconjugates were able to inhibit the growth of MDR strains more effectively than silver nanoparticles alone, with reduced cellular toxicity. These nanoparticles were stable in solution and had wide-spectrum antibacterial activity. The synthesis of silver and silver chitosan bioconjugates from Prunus cerasus leaf extracts may therefore serve as a simple, ecofriendly, noncytotoxic, economical, reliable, and safe method to produce antimicrobial compounds with low cytotoxicity.

Antimicrobial resistance is one of the biggest threats to global health as current antibiotics are becoming useless against resistant infectious pathogens. Consequently, new antimicrobial strategies are urgently required. Drug delivery systems represent a potential solution to improve current antibiotic properties and reverse resistance mechanisms. Among different drug delivery systems, solid lipid nanoparticles represent a highly interesting option as they offer many advantages for nontoxic targeted drug delivery. Several publications have demonstrated the capacity of SLNs to significantly improve antibiotic characteristics increasing treatment efficiency. In this review article, antibiotic-loaded solid lipid nanoparticle-related works are analyzed to summarize all information associated with applying these new formulations to tackle the antibiotic resistance problem. The main antimicrobial resistance mechanisms and relevant solid lipid nanoparticle characteristics are presented to later discuss the potential of these nanoparticles to improve current antibiotic treatment characteristics and overcome antimicrobial resistance mechanisms. Moreover, solid lipid nanoparticles also offer new possibilities for other antimicrobial agents that cannot be administrated as free drugs. The advantages and disadvantages of these new formulations are also discussed in this review. Finally, given the progress of the studies carried out to date, future directions are discussed.

Sepsis, caused by uncontrollable infection and inflammatory response, leads to more than 30 million infected patients and results in high morbidity worldwide every year. Currently, no efficient approaches have been developed for sepsis therapy due to antimicrobial resistance and inflammatory storm. Here, we report macrophages loaded with aggregated carbon dots (ACDs) in the lysosome, termed MCDs, to treat sepsis in immunosuppressive mice. The ACDs are constructed by negative CDs and amine‐abundant polyethyleneimine (PEI), enabling them to bear the strong antibacterial ability and enhanced photoluminescent efficacy. The ACDs are specifically located in the macrophage lysosomes, efficiently enhancing the multidrug‐resistant bacteria‐killing ability of MCDs. More importantly, the MCDs possess superior anti‐inflammatory effects such as reducing the number of pro‐inflammatory (M1) and stimulating anti‐inflammatory (M2) macrophages. These effects upregulate the inflammatory cytokines (TNF‐α, IL‐1β, IL‐4, and IL‐10), ultimately resulting in increased sepsis survival. Our work provides an intelligent approach to overcoming multidrug‐resistant bacteria‐induced infection from sepsis patients and paves a new avenue on employing nanoparticle‐loaded cells for combating inflammation‐related infection. Highly antibacterial and photoluminescent nanoparticles (ACDs), formed from carbon dots (CDs) and polyethyleneimine, are cocultured with macrophages to become localized at lysosomes. The resultant ACD‐loaded macrophages (MCDs) show a significantly enhanced multidrug‐resistant bacteria‐killing ability. They possess superior anti‐inflammatory effects, including inhibiting proinflammatory (M1) and stimulating anti‐inflammatory (M2) macrophages, therefore, improving the inflammatory cytokines and ultimately resulting in increased sepsis survival.

Green synthesis of silver nanoparticles (AgNPs) by using plants is an emerging class of nanobiotechnology. It revolutionizes all domains of medical sciences by synthesizing chemical-free AgNPs for various biomedical applications. In this report, AgNPs were successfully synthesized by using whole plant extract (WPE) and thidiazuron-induced callus extract (CE) of Linum usitatissimum. The phytochemical analysis revealed that the total phenolic and flavonoid contents were higher in CE than that in WPE. Ultraviolet-visible spectroscopy of synthesized AgNPs showed a characteristic surface plasmon band in the range of 410-426 nm. Bioreduction of CE-mediated AgNPs was completed in a shorter time than that of WPE-mediated AgNPs. Scanning electron microscopy showed that both types of synthesized AgNPs were spherical in shape, but CE-mediated AgNPs were smaller in size (19-24 nm) and more scattered in distribution than that of WPE-mediated AgNPs (49-54 nm). X-ray diffraction analysis confirmed crystalline nature (face-centered cubic) of both types of AgNPs. Fourier-transform infrared spectroscopy revealed that the polyphenols and flavonoids were mainly responsible for reduction and capping of synthesized AgNPs. Energy dispersive X-ray analysis further confirmed the successful synthesis of AgNPs. Moreover, the synthesized AgNPs were found to be stable over months with no change in the surface plasmon bands. More importantly, CE-mediated AgNPs displayed significantly higher bactericidal activity against multiple drug-resistant human pathogens than WPE-mediated AgNPs. The present work highlighted the potent role of thidiazuron in in vitro-derived cultures for enhanced biosynthesis of chemical-free AgNPs, which can be used as nanomedicines in many biomedical applications.

Antimicrobial resistance (AMR) is a global public health issue, causing an estimated 1.27 million deaths in 2019. This systematic review and meta-analysis aim to assess the burden of AMR in food animals in Pakistan, identify resistant microbes, and highlight emerging trends in multidrug resistance (MDR). The major databases were searched for articles published between 2016 and 2020 on the prevalence of AMR in food animals in Pakistan. A random-effects model was employed to pool the prevalence of antibiotic-resistant Enterobacteriaceae and non-Enterobacteriaceae pathogens. Among 1,145 studies, 35 met the inclusion criteria as evidence of AMR in food animals. Escherichia coli showed the highest resistance to ampicillin (59.5%), ciprofloxacin (49%), oxytetracycline (39%), and chloramphenicol (35%); Salmonella to ampicillin (78.4%), amoxicillin (53.9%), chloramphenicol (40%), tetracycline (39.3%), and ciprofloxacin (39%); Staphylococci to cefoxitin (53.8%) and penicillin (34.8%); and Campylobacter and Klebsiella to ciprofloxacin (50.4% and 83.3%, respectively). MDR was observed in E. coli (12/12 studies), Salmonella (7/10), Staphylococci (3/8), Campylobacter (3/3), and Klebsiella (1/3), with extensive drug resistance in E. coli (3/12), Salmonella (4/10), Campylobacter (1/3), and Klebsiella (2/2). Enterobacteriaceae showed significant resistance to tetracyclines (pooled prevalence/PPr = 0.75) and aminopenicillins (PPr = 0.74), whereas non-Enterobacteriaceae showed resistance to cephalosporins (PPr = 0.67) and aminopenicillins (PPr = 0.59), both with substantial heterogeneity. This review shows the existence of bacteria resistant to commonly used antimicrobials in food animals, potentially a threat to both human and animal health. The findings suggest the continuous monitoring of AMR and antimicrobial use (AMU) and the regulation of AMU in the food and agriculture sectors.

This study investigates the effects of piezo‐catalysts on sterilizing surfaces. The memory effects in three piezo‐catalysts, ZnO, CuO, and SiO2 are discovered, which are produced by a calcination process. After applying mechanical force to these materials, they retain an antibacterial effect for a period of days. With this discovery, it is possible to combat antibiotic‐resistant bacteria by using piezo materials on hospital floors or operating rooms that can kill bacteria just by walking on them. The results show that ZnO, CuO, and SiO2 are capable of killing bacteria even after being subjected to mechanical force for 9 days. The memory effect duration can be influenced by a variety of factors, including the calcination temperature, the storage condition after ultrasonication, the drying temperature after ultrasonication, and the solvent in which the piezo‐catalyst is ultrasonicated. When ZnO, CuO, and SiO2 are kept under a vacuum in a dark environment, the piezo effect remains almost constant for 11 days after sonication. It was discovered by Omid Amiri and co‐workers that piezo‐catalysts or piezo materials exhibit an intriguing memory effect in their ability to kill bacteria. The effect is that the piezo materials can retain their activity even days after the mechanical force has been applied. The piezo‐catalysts can preserve their ability to kill bacteria for up to 11 days, depending on the conditions.

Introduction: The growing resistance of bacteria to antibiotics is a major global public health concern. An important reservoir of this resistance is the gut microbiota. However, limited data are available on the ability of phage therapy to reduce the digestive carriage of multidrug-resistant bacteria. Materials and methods: Four novel lytic phages were isolated in vitro for efficacy against an extended-spectrum beta-lactamase-producing (ESBL) Escherichia coli strain also resistant to carbapenems through a carbapenemase OXA-48. The first step was to develop models of ESBL E. coli digestive carriage in mice. The second step was to test the efficacy of an oral and rectal phage therapy (a cocktail of four phages or microencapsulated phage) to reduce this carriage. Results: The two most intense models of digestive carriage were obtained by administering amoxicillin (0.5 g·L−1) continuously in the drinking water (Model 1) or pantoprazole (0.1 g·L−1) continuously in the drinking water, combined with amoxicillin (0.5 g·L−1), for the first 8 days (Model 2). Oral administration of the phage cocktail to Model 1 resulted in a transient reduction in the concentration of ESBL E. coli in the faeces 9 days after the bacterial challenge (median = 5.33 × 108 versus 2.76 × 109 CFU·g−1, p = 0.02). In contrast, in Model 2, oral or oral + rectal administration of this cocktail did not alter the bacterial titre compared to the control (area under the curve, AUC, 3.49 × 109; 3.41 × 109 and 3.82 × 109 for the control, oral and oral + rectal groups, respectively; p-value > 0.8 for each two-by-two group comparison), as well as the administration of an oral microencapsulated phage in Model 1 (AUC = 8.93 × 109 versus 9.04 × 109, p = 0.81). Conclusions: Oral treatment with amoxicillin promoted digestive carriage in mice, which was also the case for the addition of pantoprazole. However, our study confirms the difficulty of achieving efficacy with phage therapy to reduce multidrug-resistant bacterial digestive carriage in vivo.

This study investigated the distribution and resistance patterns of pathogens in the intensive care unit of a newly established hospital in Guizhou Province to promote the rational use of antibiotics to reduce multidrug resistance. A retrospective analysis was conducted on the distribution of pathogens and changes in drug resistance in the ICU of a newly built hospital in Guizhou Province from March 2019 to December 2023. WHONET 5.6 was used to analyze the results. A total of 2444 culture samples were received, predominantly sputum (34.66%) and blood (23.36%) samples, with a steady annual increase in specimen types. A total of 572 pathogenic strains were isolated, predominantly from respiratory specimens (54.02%), including 345 Gram-negative bacteria (60.31%), 135 Gram-positive cocci (23.60%), and 92 fungi (16.08%). The most frequent pathogens included Acinetobacter baumannii (30.77%), Candida albicans (11.71%), and Klebsiella pneumoniae (9.97%). Drug sensitivity tests indicated a fluctuating resistance rate of Acinetobacter baumannii over the past five years. Staphylococcus aureus displayed strong in vitro activity against vancomycin, tigecycline, and linezolid, with no resistant strains identified. The detection rates of carbapenem-resistant Acinetobacter baumannii (CR-AB), carbapenem-resistant Pseudomonas aeruginosa (CR-PA), methicillin-resistant Staphylococcus aureus (MRSA), and strains producing extended-spectrum beta-lactamases (ESBL) were 86.78%, 26.79%, 32.45%, 70.27%, and 23.54%, respectively. Compared with other countries in the world, China has increased its data on the prevalence of MDR pathogens and antibiotic resistance.The high resistance rate of Acinetobacter baumannii in the ICU underscores the need for effective infection control measures. Enhanced monitoring of CR-AB, ESBL-producing bacteria, and MRSA is essential, along with improved management of antibacterial drugs and the pursuit of new therapeutic options.

Objective To explore peripheral blood indicators that may serve as early indicators for multidrug‐resistant bacteria (MDR) infections in this demographic, with the goal of providing reference suggestions for the clinical prevention of MDR infections in elderly inpatients. Methods Clinical data of patients were divided into the MDR‐infected group (n = 488) and the MDR‐uninfected group (n = 233) according to the results of drug sensitivity experiments, risk factors for MDR infection, and peripheral blood indicators related to MDR infections were analyzed using univariate and multivariate logistic regression in conjunction with the construction of a Chi‐squared automatic interaction detector (CHAID) decision tree model, considering statistical significance at p < .05. Results Of 721 patients, 488 multidrug‐resistant strains were identified. Among them, with Staphylococcus spp. the most prevalent in 148 strains. The most frequent detection of MDR occurred in puncture fluid samples (167 cases). Univariate and multivariate regression analyses revealed that prolonged hospitalization, use of antibiotics preadmission, duration of antibiotics, invasive procedures or recent surgery, and coexisting lung disease were independent risk factors for contracting MDR. Subsequent analysis comparing the aforementioned influences with peripheral blood cells revealed associations between the number of antibiotic treatment days and increased neutrophil‐to‐lymphocyte ratio (NLR), platelet count‐to‐lymphocyte ratio (PLR), neutrophils, decreased lymphocytes, and increased eosinophils; preadmission antibiotic use correlated with increased PLR, NLR, neutrophils, and decreased lymphocytes; and invasive manipulation or surgery correlated with increased PLR and NLR. Conclusions Elevated NLR, PLR, neutrophils, lowered lymphocytes, and eosinophils may serve as early indicators of MDR infections in elderly hospitalized patients. The manuscript presents fresh findings indicating that peripheral blood markers may act as early indicators of multidrug‐resistant (MDR) infections in elderly hospitalized patients. Alterations in neutrophil‐to‐lymphocyte ratio (NLR) and platelet count‐to‐lymphocyte ratio (PLR), as well as neutrophils, lymphocytes, and eosinophils, may also act as early indications of MDR infections in this population.