Nano-microflora Interaction Inducing Pulmonary Inflammation by Pyroptosis.

Antimicrobial nanomaterials frequently induce inflammatory reactions within lung tissues and prompt apoptosis in lung cells, yielding a paradox due to the inherent anti-inflammatory character of apoptosis. This paradox accentuates the elusive nature of the signaling cascade underlying nanoparticle (NP)-induced pulmonary inflammation. In this study, we unveil the pivotal role of nano-microflora interactions, serving as the crucial instigator in the signaling axis of NP-induced lung inflammation. Employing pulmonary microflora-deficient mice, we provide compelling evidence that a representative antimicrobial nanomaterial, silver (Ag) NPs, triggers substantial motility impairment, disrupts quorum sensing, and incites DNA leakage from pulmonary microflora. Subsequently, the liberated DNA molecules recruit caspase-1, precipitating the release of proinflammatory cytokines and activating N-terminal gasdermin D (GSDMD) to initiate pyroptosis in macrophages. This pyroptotic cascade culminates in the emergence of severe pulmonary inflammation. Our exploration establishes a comprehensive mechanistic axis that interlinks the antimicrobial activity of Ag NPs, perturbations in pulmonary microflora, bacterial DNA release, macrophage pyroptosis, and consequent lung inflammation, which helps to gain an in-depth understanding of the toxic effects triggered by environmental NPs.

Antibacterial Nanomaterials: Mechanisms, Impacts on Antimicrobial Resistance and Design Principles.

Antimicrobial resistance (AMR) is one of the biggest threats to the environment and health. AMR rapidly invalidates conventional antibiotics, and antimicrobial nanomaterials have been increasingly explored as alternatives. Interestingly, several antimicrobial nanomaterials show AMR-independent antimicrobial effects without detectable new resistance and have therefore been suggested to prevent AMR evolution. In contrast, some are found to trigger the evolution of AMR. Given these seemingly conflicting findings, a timely discussion of the two faces of antimicrobial nanomaterials is urgently needed. This review systematically compares the killing mechanisms and structure-activity relationships of antibiotics and antimicrobial nanomaterials. We then focus on nano-microbe interactions to elucidate the impacts of molecular initiating events on AMR evolution. Finally, we provide an outlook on future antimicrobial nanomaterials and propose design principles for the prevention of AMR evolution.

Web-Based Just-in-Time Information and Feedback on Antibiotic Use for Village Doctors in Rural Anhui, China: Randomized Controlled Trial.

BACKGROUND: Excessive use of antibiotics is very common worldwide, especially in rural China; various measures that have been used in curbing the problem have shown only marginal effects. OBJECTIVE: The objective of this study was to test an innovative intervention that provided just-in-time information and feedback (JITIF) to village doctors on care of common infectious diseases. METHODS: The information component of JITIF consisted of a set of theory or evidence-based ingredients, including operation guideline, public commitment, and takeaway information, whereas the feedback component tells each participating doctor about his or her performance scores and percentages of antibiotic prescriptions. These ingredients were incorporated together in a synergetic way via a Web-based aid. Evaluation of JITIF adopted a randomized controlled trial design involving 24 village clinics randomized into equal control and intervention arms. Measures used included changes between baseline and endpoint (1 year after baseline) in terms of: percentages of patients with symptomatic respiratory or gastrointestinal tract infections (RTIs or GTIs) being prescribed antibiotics, delivery of essential service procedures, and patients' beliefs and knowledge about antibiotics and infection prevention. Two researchers worked as a group in collecting the data at each site clinic. One performed nonparticipative observation of the service process, while the other performed structured exit interviews about patients' beliefs and knowledge. Data analysis comprised mainly of: (1) descriptive estimations of beliefs or knowledge, practice of indicative procedures, and use of antibiotics at baseline and endpoint for intervention and control groups and (2) chi-square tests for the differences between these groups. RESULTS: A total of 1048 patients completed the evaluation, including 532 at baseline (intervention=269, control=263) and 516 at endpoint (intervention=262, control=254). Patients diagnosed with RTIs and GTIs accounted for 76.5% (407/532) and 23.5% (125/352), respectively, at baseline and 80.8% (417/532) and 19.2% (99/532) at endpoint. JITIF resulted in substantial improvement in delivery of essential service procedures (2.6%-24.8% at baseline on both arms and at endpoint on the control arm vs 88.5%-95.0% at endpoint on the intervention arm, P<.001), beliefs favoring rational antibiotics use (11.5%-39.8% at baseline on both arms and at endpoint on the control arm vs 19.8%-62.6% at endpoint on the intervention arm, P<.001) and knowledge about side effects of antibiotics (35.7% on the control arm vs 73.7% on the intervention arm, P<.001), measures for managing or preventing RTIs (39.1% vs 66.7%, P=.02), and measures for managing or preventing GTIs (46.8% vs 69.2%, P<.001). It also reduced antibiotics prescription (from 88.8%-62.3%, P<.001), and this decrease was consistent for RTIs (87.1% vs 64.3%, P<.001) and GTIs (94.7% vs 52.4%, P<.001). CONCLUSIONS: JITIF is effective in controlling antibiotics prescription at least in the short term and may provide a low-cost and sustainable solution to the widespread excessive use of antibiotics in rural China.

Pathways of healthcare and antibiotics use following reported gastrointestinal illness: a cross-sectional study in rural Anhui, China.

OBJECTIVE: To document the factors, and their pathways, that influence healthcare and antibiotics use following reported gastrointestinal illnesses in Anhui province, China. STUDY DESIGN: This study uses cross-sectional design, descriptive statistical analysis, pathway mapping and multivariate logistic regression modelling. SETTING: Households in 12 villages in Anhui province, China. PARTICIPANTS: A total of 3659 residents who: (1) held a registered rural residence and were actually living in the sampled villages when this study was conducted; (2) were aged 18 years and older and (3) were willing to participate and able to answer the survey questions. OUTCOME MEASURES: Planned and measured variables included the occurrence of gastrointestinal illness, professional care seeking and antibiotic use due to the illness and factors influencing these measures. RESULTS: Of the 3659 informants, 29.0% reported gastrointestinal illness episodes in the past year. Of these episodes, 50.2% led to professional care seeking and 65.4% of antibiotic use. Multivariate logistic modelling identifies that: (1) reported gastrointestinal illnesses were more frequent in north compared with middle (OR 0.569, 95% CI 0.472 to 0.686) and south (OR 0.588, 95% CI 0.492 to 0.702) Anhui, and were positively associated with age (B=0.123, p<0.05), knowledge concerning (B=0.248, p<0.05) and practice of (B=0.184, p<0.05) prevention; (2) seeking professional care and antibiotic use following the illness was linked to the severity of symptoms and geographical locations, rather than to specific pathogenic features. CONCLUSIONS: Reported gastrointestinal illnesses are quite prevalent in the sample population and a large proportion of these have resulted in professional care and antibiotics use. The factors associated with the reported illnesses and pathways of healthcare and antibiotic use, as identified in this study, should inform future research and intervention efforts.