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The occurrence of antibiotic resistance genes (ARGs) in various environments has drawn worldwide attention due to their potential risks. Previous studies have reported that a variety of substances can enhance the occurrence and dissemination of ARGs. However, few studies have compared the response of ARGs under the stress of different organic matters in biological wastewater treatment systems. In this study, seven organic pollutants were added into wastewater treatment bioreactors to investigate their impacts on the ARG occurrence in activated sludge. Based on high-throughput sequencing, it was found that the microbial communities and ARG patterns were significantly changed in the activated sludge exposed to these organic pollutants. Compared with the non-antibiotic refractory organic matters, antibiotics not only increased the abundance of ARGs but also significantly changed the ARG compositions. The increase of Gram-negative bacteria (e.g., Archangium, Prosthecobacter and Dokdonella) carrying ARGs could be the main cause of ARG proliferation. In addition, significant co-occurrence relationships between ARGs and mobile genetic elements were also observed in the sludge samples, which may also affect the ARG diversity and abundance during the organic matter treatment in the bioreactors. Overall, these findings provide new information for better understanding the ARG occurrence and dissemination caused by organic pollutants in wastewater treatment systems.

Direct discharge of aquaculture wastewater may have toxic effects, due to the presence of heavy metals, antibiotics, and even resistant pathogens, but little attention has been given. Here, tanks simulating a wild ecosystem were built to study the effects of long-term exposure to duck wastewater containing oxytetracycline (OTC) and/or arsenic (As) on the growth, physiological function, and gut microbiota evolution of Xenopus tropicalis. The results showed that duck wastewater had no apparent impact on X. tropicalis, but the impact increased significantly (P0.05) with exposure to OTC and/or As, especially the impact on body weight and growth rate. Biochemical indicators revealed varying degrees of oxidative stress damage, hepatotoxicity (inflammation, necrosis, and sinusoids), and collagen fibrosis of X. tropicalis in all treated groups after 72 days of exposure, which indirectly inhibited X. tropicalis growth. Moreover, 16S rDNA amplicon sequencing results showed that the gut microbiota structure and metabolic function were perturbed after chronic exposure, which might be the leading cause of growth inhibition. Interestingly, the abundance of intestinal resistance genes (RGs) increased with exposure time owing to the combined direct and indirect effects of stress factors in duck wastewater. Moreover, once the RGs were expressed, the resistance persisted for at least 24 days, especially that conferred by tetA. These results provide evidence of the toxic effects of DW containing OTC (0.1-4.0 mg/L) and/or As (0.3-3.5 µg/L) on amphibians and indicate that it is vital to limit the usage of heavy metals and antibiotics on farms to control the biotoxicity of wastewater.

As a new type of environmental pollutant, antibiotic resistance genes (ARGs) pose a huge challenge to global health. Horizontal gene transfer (HGT) represents an important route for the spread of ARGs. The widespread use of sulfamethazine (SM2) as a broad-spectrum bacteriostatic agent leads to high residual levels in the environment, thereby increasing the spread of ARGs. Therefore, we chose to study the effect of SM2 on the HGT of ARGs mediated by plasmid RP4 from Escherichia coli (E. coli) HB101 to E. coli NK5449 as well as its mechanism of action. The results showed that compared with the control group, SM2 at concentrations of 10 mg/L and 200 mg/L promoted the HGT of ARGs, but transfer frequency decreased at concentrations of 100 mg/L and 500 mg/L. The transfer frequency at 200 mg/L was 3.04 × 10

Lakes act as one of the reservoirs and dispersal routes of antibiotic resistance genes (ARGs) and pathogenic resistant bacteria in aquatic environments. Previous studies reported the occurrence and distribution of ARGs in lakes worldwide; however, few investigated the biogeography and diversity patterns of antibiotic resistome in the environment. To fill this gap, a large-scale data set of sediment metagenomes was collected from globally distributed lakes and characterized comprehensively using metagenomic assembly-based analysis, aiming to shed light on the biogeography and diversity patterns of ARGs in lake ecosystems from a global perspective. Our analyses showed that abundant and diverse ARGs were found in the global lake sediments, including a set of emerging ARGs such as mcr-type and carbapenem-resistant Enterobacteriaceae related genes. Most of the identified ARGs were generally associated with the commonly used antibiotics, suggesting the role of increasing antibiotic consumptions on the resistome prevalence. Spatially, the composition and diversity of ARGs varied across geographical distances and exhibited a scale-dependent distance-decay relationship. Notably, the composition of ARGs was largely shaped by bacterial community structure, and their diversities were co-governed by stochastic process (∼48%) and deterministic process (∼52%). Findings provide a valuable insight to better understand ecological mechanisms of ARGs in lake ecosystems and have important implication for the prevention and control of resistome risk.

Fe-N co-doped coral-like hollow carbon shell (Fe-N-CS) was synthesized via a simply impregnation-pyrolysis method. The Fe-N-CS showed an excellent ability for activating peroxymonosulfate (PMS), which could degrade about 93.74% tetracycline (20 mg/L) in 12 min. The Fe-N-CS/PMS system exhibited a good anti-interference capacity of various pH, inorganic anions, HA and different water qualities. More importantly, the Fe nanoparticles were anchored uniformly in the carbon layer, effectively limiting the metal leaching. The quenching tests and electron spin resonance (ESR) manifested that non-radical singlet oxygen (

The pollution of antibiotics commonly existed throughout the entire aquaculture process, but the residues of antibiotics at different aquaculture stages have rarely been studied. This study investigated the occurrence, distribution and risk assessment of antibiotics at different aquaculture stages (the non-aquaculture stage, the early aquaculture stage, the middle aquaculture stage, and the late aquaculture stage) in two typical marine aquaculture areas (Mahegang River and Dingzi Bay) surrounding the Yellow Sea. Fluoroquinolones and tetracyclines were commonly used antibiotics in the aquaculture of these areas with high detection frequencies (17% to 83%). Compared among four aquaculture stages, the highest concentration of antibiotics (9032.08 ng/L) in aquaculture ponds was detected at the late aquaculture stage. And the antibiotic pollution level of natural water was directly related to the aquaculture stages. Similarly, at the aquaculture stages, the detection frequency of antibiotics in sediments was higher than that at the non-aquaculture stage. Based on the correlation analysis, the concentration of main antibiotics in water showed a positive correlation with total nitrogen (p0.05) and chlorophyll a (p0.01), while it showed a negative correlation with salinity (p0.01) in coastal water of the Dingzi Bay. According to the risk assessment, with the development of aquaculture stages, the selection pressure of fluoroquinolones and tetracyclines on resistant bacteria had increased. And the ecological risks caused by sulfonamides and tetracyclines to aquatic organisms had also increased markedly. Overall, this study may provide a reference for formulating regulatory policies regarding antibiotic use at different aquaculture stages.

BACKGROUND: Acute respiratory infections make up a sizable percentage of emergency department (ED) visits and many result in antibiotics being prescribed. Procalcitonin has been found to reduce antibiotic use in both outpatient and critical care settings, yet remains underused in the ED. OBJECTIVE: To evaluate whether point of care molecular influenza and Respiratory Syncytial Virus (RSV) testing, procalcitonin, and a pharmacist driven educational intervention in aggregate optimizes antibiotic and antiviral prescribing in the ED setting. METHODS: A randomized trial of the Cobas Liat Flu/RSV Assay, procalcitonin, and the use of pharmacist-led education in patients 0–50 years of age being seen in the ED for Influenza Like Illness (ILI) or acute respiratory illness. The study enrolled 200 ED patients between March 2018 and April 2022 at the University of California Davis Medical Results: There was little difference in antibiotic or antiviral prescribing between the intervention and control groups in this study (39% - 32% = 7.0%, 95% CI: −6.2, 20.2, P=0.30). However, a post-hoc analysis of the use of PCT showed PCT results were used as indicated in the ED (P=0.001). CONCLUSION: Procalcitonin can be used in both adult and pediatric populations to help guide the decision of whether to treat with antibiotics in the ED setting. Pharmacist guided education may not be a driving factor.

Photooxidative removal of pharmaceuticals and organic dyes is an effective way to eliminate growing micropollutants. However, photooxidation often results in byproducts as secondary hazardous substances such as phytotoxins. Herein, we found that photooxidation of common antibiotic tetracycline hydrochloride (TCH) over a metal-free 8-hydroxyquinoline (8-HQ) functionalized carbon nitride (CN) photocatalyst significantly reduces the TCH phytotoxic effect. The phytotoxicity test of photocatalytic treated TCH-solution evaluated towards seed growth of Cicer arietinum plant model endowed natural root and shoot growth. This study highlights the conceptual insights in designing of metal-free photocatalyst for environmental remediation.

Paddy soils are potential hotspots of combined contamination with arsenic (As) and antibiotics, which may induce co-selection of antibiotic resistance genes (ARGs) and As biotransformation genes (ABGs), resulting in dissemination of antimicrobial resistance and modification in As biogeochemical cycling. So far, little information is available for these co-selection processes and specific patterns between ABGs and ARGs in paddy soils. Here, the 16S rRNA amplicon sequencing and high-throughput quantitative PCR and network analysis were employed to investigate the dynamic response of ABGs and ARGs to As stress and manure application. The results showed that As stress increased the abundance of ARGs and mobile genetic elements (MGEs), resulting in dissemination risk of antimicrobial resistance. Manure amendment increased the abundance of ABGs, enhanced As mobilization and methylation in paddy soil, posing risk to food safety. The frequency of the co-occurrence between ABGs and ARGs, the host bacteria carrying both ARGs and ABGs were increased by As or manure treatment, and remarkably boosted in soils amended with both As and manure. Multidrug resistance genes were found to have the preference to be co-selected with ABGs, which was one of the dominant co-occurring ARGs in all treatments, and manure amendment increased the frequency of Macrolide-Lincosamide-Streptogramin B resistance (MLSB) to co-occur with ABGs. Bacillus and Clostridium of Firmicutes are the dominant host bacteria carrying both ABGs and ARGs in paddy soils. This study would extend our understanding on the co-selection between genes for antibiotics and metals, also unveil the hidden environmental effects of combined pollution.

Soluble microbial products (SMPs), dissolved organic matter excreted by activated sludge, can interact with antibiotics in wastewater and natural water bodies. Interactions between SMPs and antibiotics can influence antibiotic migration, transformation, and toxicity but the mechanisms involved in such interactions are not fully understood. In this study, integrated spectroscopy approaches were used to investigate the mechanisms involved in interactions between SMPs and a representative antibiotic, trimethoprim (TMP), which has a low biodegradation rate and has been detected in wastewater. The results of liquid chromatography-organic carbon detection-organic nitrogen detection indicated that the SMPs used in the study contained 15% biopolymers and 28% humic-like substances (based on the total dissolved organic carbon concentration) so would have contained sites that could interact with TMP. A linear relationship of fluorescent intensities of tryptophan protein-like substances in SMP was observed (R

Anaphylaxis in pregnancy is a rare event, but has important implications for the pregnant patient and fetus. The epidemiology, pathophysiology, diagnosis, and treatment all carry important considerations unique to the pregnant patient. Common culprits of anaphylaxis are primarily medications, particularly antibiotics and anesthetic agents. Diagnosis can be difficult given the relative lack of cutaneous symptoms, and normal physiologic changes in pregnancy such as low blood pressure and tachycardia. Apart from patient positioning, treatment is similar to that of the general population, with a focus on prompt epinephrine administration.

Antibiotic pollution imposes urgent threats to public health and microbial-mediated ecological processes. Existing studies have primarily focused on bacterial responses to antibiotic pollution, but they ignored the microeukaryotic counterpart, though microeukaryotes are functionally important (e.g., predators and saprophytes) in microbial ecology. Herein, we explored how the assembly of sediment microeukaryotes was affected by increasing antibiotic pollution at the inlet (control) and across the outlet sites along a shrimp wastewater discharge channel. The structures of sediment microeukaryotic community were substantially altered by the increasing nutrient and antibiotic pollutions, which were primarily controlled by the direct effects of phosphate and ammonium (-0.645 and 0.507, respectively). In addition, tetracyclines exerted a large effect (0.209), including direct effect (0.326) and indirect effect (-0.117), on the microeukaryotic assembly. On the contrary, the fungal subcommunity was relatively resistant to antibiotic pollution. Segmented analysis depicted nonlinear responses of microeukaryotic genera to the antibiotic pollution gradient, as supported by the significant tipping points. We screened 30 antibiotic concentration-discriminatory taxa of microeukaryotes, which can quantitatively and accurately predict (98.7% accuracy) the in-situ antibiotic concentration. Sediment microeukaryotic (except fungal) community is sensitive to antibiotic pollution, and the identified bioindicators could be used for antibiotic pollution diagnosis.

This clinical study evaluated the antibacterial effects of calcium hydroxide associated with different vehicles during the treatment of infected teeth with apical periodontitis.Bacteriologic samples were taken from 90 necrotic root canals of teeth with apical periodontitis before (S1) and after preparation with a rotary nickel-titanium instrument system and 2.5% sodium hypochlorite irrigation (S2). The teeth were distributed in 3 groups according to the intracanal medication used, which consisted of a calcium hydroxide paste in glycerin, camphorated paramonochlorophenol/glycerin (CHPG), or 2% chlorhexidine for 1 week, and then another sample was taken (S3). The frequency of bacteria-positive cases and the reduction of bacterial counts were evaluated by quantitative real-time polymerase chain reaction.Substantial intracanal bacterial reduction was observed after preparation in the 3 groups (P .001). After calcium hydroxide paste in glycerin medication, the number of bacteria-positive cases decreased from 20/29 (69%) to 17/29 (59%); however, the mean bacterial counts increased 8.4% from S2 to S3. Medication with CHPG reduced the number of bacteria-positive cases from 17/29 (59%) to 15/29 (52%), with a significant mean S2-S3 reduction of 71% (P .05). In the chlorhexidine group, the number of bacteria-positive cases decreased from 21/30 (70%) to 17/30 (57%) after medication, with a mean S2-S3 reduction of 55%, which, however, was not statistically significant (P .05). Intergroup comparisons showed no significant differences (P .05).Comparison between the 3 calcium hydroxide pastes showed no significant differences in antibacterial effectiveness in the main root canal. However, only the CHPG paste showed a significant reduction in bacterial counts when postpreparation and postmedication samples were compared.

Klebsiella pneumoniae is a major pathogen of bacterial liver abscess in Asia. Particularly, patients with community-acquired Klebsiella pneumoniae liver abscess (CA-KPLA) tend to have a higher risk of invasive infection and pulmonary is a common invasive infectious site, making it a global clinical crisis. Therefore, considerable attention should be focused on the early prediction and active treatment strategies of such patients.The clinical data of 127 CA-KPLA cases hospitalized from January 2017 to February 2022 were collected from a single center. Risk factors were analyzed by the use of univariable and multivariable analysis. Furthermore, independent risk factors of pulmonary affection were utilized to construct a predictive nomogram.The incidence of pulmonary affection in KPLA patients was 57.5% (73/127) and the majority manifested as nodular lesions with cavities and pleural effusion in chest CT images. Based on the predictive nomogram, the SOFA score (2) was defined as the most dominant independent risk factor for the occurrence of pulmonary affection, followed by the maximum diameter of liver abscess (3 cm), multiple liver abscesses, bacteremia, and badly-controlled diabetes sequentially. The validation of this nomogram also demonstrated good discriminative ability and satisfactory consistency. Finally, early drainage of liver abscess, initial combinational antibiotics, and early Carbapenem-including antibiotic usage were established as favorable factors for therapy in pulmonary affected CA-KPLA patients.This study provided an effective model for the early prediction of pulmonary affection in patients with CA-KPLA and some rational strategies for their early therapeutic remission.

Several carbapenemases have been identified globally in Enterobacteriaceae. In Japan, IMP-type carbapenemase is the most prevalent, although cases of carbapenemase-producing Enterobacteriaceae (CPE) bacteremia are still scarce. The present case series and literature review aimed to elucidate the clinical characteristics and treatment strategies for IMP-type CPE bacteremia.Clinical data on pediatric cases of IMP-type CPE bacteremia at the Tokyo Metropolitan Children's Medical Center between 2010 and 2020 were collected, and a review of past studies of IMP-type CPE bacteremia has been provided.Five pediatric episodes of IMP-type CPE bacteremia were identified. Our review of previous literature on IMP-type CPE bacteremia revealed 24 adult patients, but no pediatric patients. All 29 cases had underlying diseases, and 23 (79%) received combination therapy. The median duration of antibiotic therapy was 14 days (interquartile range: 9-14 days). The overall mortality rate was 38% (11/29). The mortality rates associated with monotherapy and combination therapy were 67% (4/6) and 30% (7/23), respectively.We report the first case series of IMP-type CPE bacteremia in children. Our review of past studies suggests that combination therapy might lead to better survival outcomes in patients with IMP-type CPE bacteremia. Further research is needed to establish an optimal treatment strategy for IMP-type CPE bacteremia.

Hemostasis and anti-infection are crucial for emergency treatment of severe trauma. Developing functional biomaterial with efficient hemostasis, antibacterial activity and wound healing is of great social significance and clinical value to fast stop bleeding and save lives, but it is still challenged. Here we designed a series of multifunctionalized SA/PDA cryogels by using two-step cross-linking of dopamine and sodium alginate. The resulting interpenetrating network structure had good swelling ratio, excellent mechanical and shape memory properties. Compared with cotton gauze and gelatin sponge, the cryogels exhibited excellent activation of coagulation cascade, more blood cells and platelet adhesion. Due to the action of polydopamine, the cryogel also showed good antioxidant activity and photothermal antibacterial ability assisted by near-infrared radiation, as well as better wound healing performance than gelatin sponge and Tegaderm™ film. Moreover, in the tests of mouse tail docking model, rat femoral artery hemostasis model and non-compressible rabbit liver defect model, the treatment by SA/PDA cryogels presented less blood loss and shorter hemostasis time than cotton gauze and gelatin sponge. Therefore, SA/PDA cryogels with simple preparation process, low cost, and good biocompatibility would be applied in the variety of great clinical applications in bleeding control, anti-infection and wound healing, etc.

Aminoglycosides are well known, cationic antimicrobial drugs. However, biofilm-based antibiotic resistance significantly limits their efficacy. Masking the polycationic character of these drugs, followed by incorporation into self-emulsifying drug delivery systems (SEDDS) can improve biofilm eradication.Imine derivatives were synthesized via coupling with trans-cinnamaldehyde and characterized regarding degree of substitution, logP, cytotoxicity and antimicrobial efficacy on the opportunistic human pathogens Escherichia coli, Staphylococcus aureus and Candida albicans. Imines were loaded into newly developed SEDDS formulations and the antimicrobial efficacy was assessed on these pathogens in planktonic state and after biofilm formation.Successful synthesis of imine derivatives with almost entirely masked amine groups was confirmed by NMR, FT-IR, TLC and MS. Imines exhibited a marked elevation in logP value of 8 units for kanamycin and 7.7 units for tobramycin. They showed low toxicity profiles while fully preserving antimicrobial efficacy on all tested pathogens. Incorporation into SEDDS resulted in nanoemulsions, which exhibited equal antimicrobial efficacy on the model germs compared to the corresponding aminoglycosides. Moreover, the biofilm eradication assay revealed superior anti-biofilm properties of the nanoemulsions. Native aminoglycosides were largely prone to reduced microbial susceptibility due to biofilm formation, while the combination of SEDDS with iminated aminoglycosides provided overall enhanced biofilm eradication.

Bacterial prostatitis is a highly prevalent infection responsible for significant morbidity among men. The diagnosis and treatment for bacterial prostatitis remains complicated. The difficulty in diagnosis is in part owing to the paucity of high-quality evidence that guides a clinician's interpretation of patients' history, physical examination, and laboratory findings. Treatment is challenging because of the few antimicrobials capable of prostate penetration, growing antimicrobial resistance limiting effective treatment options, and the high risk of recurrence.We aimed to provide a useful resource for clinicians in effectively diagnosing and managing acute bacterial prostatitis (ABP) and chronic bacterial prostatitis (CBP).A PubMed literature search on prostatitis was performed with no restrictions on publication date.The epidemiology, pathophysiology, diagnosis, and treatment for ABP and CBP are explored using a clinical vignette as relevant context.Bacterial prostatitis can be diagnosed through a focused history and microbiological investigations. The Meares-Stamey 4-glass test or modified 2-glass test can help confirm the diagnosis if uncertainty exists. Typical uropathogens are common contributors to bacterial prostatitis but there is growing interest in exploring the role atypical and traditional non-pathogenic organisms may have. Fluoroquinolones remain first-line therapy, followed by trimethoprim-sulfamethoxazole (TMP-SMX) or doxycycline if the pathogen is susceptible. Fosfomycin has emerged as a repurposed and useful agent because of the increasing incidence of multidrug-resistant pathogens. Selection of appropriate antimicrobial regimens can be challenging and is dependent on the host, chronicity of symptoms, uropathogens' susceptibilities, antimicrobials' side effect profile, and the presence of prostatic abscesses or calcifications. ABP can typically be treated similar to other complicated urinary tract infections. However, CBP requires prolonged therapy, with a minimum of 4 weeks and up to 12 weeks of therapy.

Antibiotic exposure is associated with worse clinical outcomes in patients receiving immune checkpoint inhibitors (ICI). We analyzed antibiotic prescription patterns in lung cancer and melanoma, two malignancies in which ICI are used broadly across stages.We performed a retrospective cohort study of adults in the U.S. Veterans Affairs (VA) medical system diagnosed with lung cancer or melanoma from 2003 to 2016. We defined antibiotic exposure as receipt of a prescription for a systemic antibacterial agent between 6 months before and 6 months after cancer diagnosis. Demographics, clinical variables, prescriptions, and diagnostic codes were abstracted from the VA Corporate Data Warehouse. Antibiotic exposure was compared using t tests, Chi-square, and multivariate analyses.A total of 310,321 patients (280,068 lung cancer, 30,253 melanoma) were included in the analysis. Antibiotic exposure was more common among patients with lung cancer (42% vs. 24% for melanoma; P.001). Among antibiotic-exposed patients, those with lung cancer were more likely to receive prescriptions for multiple antibiotics (47% vs. 30% for melanoma; P.001). In multivariate analyses, antibiotic exposure was associated with lung cancer diagnosis (HR 1.50; 95% CI, 1.46-1.55), comorbidity score (HR 1.08; 95% CI, 1.08-1.09), non-white race (HR 1.11; 95% CI, 1.06-1.17), and female gender (HR 1.31; 95% CI, 1.24-1.37).Among cancer patients, antibiotics are prescribed frequently. Antibiotic exposure is more common in certain cancer types and patient populations. Given the negative effect antibiotic exposure has on immunotherapy outcomes, these observations may have clinical and healthy policy implications.

The introduction of antibacterial and hemostatic hydrogels with good mechanical properties that display desirable impacts on wound healing process is still an unmet essential for clinical wound dressings. Herein, a multifunctional hydrogel PEG-CMC-THB-PRTM was fabricated via a one-pot method combining carboxymethyl chitosan (CMC), 2,3,4-trihydroxybenzaldehyde (THB), protamine (PRTM) and 4-arm polyethylene glycol aldehyde (PEG). The hydrogel was formed by the dynamic Schiff base reaction between amino groups of carboxymethyl chitosan and aldehyde groups of 4-arm polyethylene glycol aldehyde and exhibited excellent mechanical properties. The developed hydrogel also showed outstanding effects on anti-bacteria and hemostasis through the release of PRTM. Moreover, the hydrogel could promote extracellular matrix formation and wound closure in vivo, thereby accelerating the healing of skin wound. These results suggested that the multifunctional PEG-CMC-THB-PRTM hydrogel is a promising candidate for the clinical treatment of full-thickness wounds.

In this work, a biomass composite material (CS@NC@PA-Na) was prepared from chitosan (CS), nano-cellulose (NC) and sodium phytate (PA-Na). The prepared products were characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectrometry (XPS) and X-ray diffraction (XRD). The fire/water safety and antimicrobial properties of the CS@NC@PA-Na were fully studied. The results indicated CS@NC@PA-Na (50 mg) could effectively reduce the concentration of methyl orange by 85 % under 30 min adsorption. Meanwhile, only 5 wt% CS@NC@PA-Na could increase the limiting oxygen index (LOI) value of epoxy resin composite from 24.5 to 30.1 %, and decrease the peak heat/smoke release rate by 29.5 and 33.3 %, respectively. Moreover, CS@NC@PA-Na also exhibited excellent antibacterial effect. This work provides an efficient, feasible and eco-friendly route for large-scale production of multi-functional CS-based biomass materials that could be used in the fields of fire safety and environmental conservation.

Antibacterial coatings are regarded as a necessary tool to prevent implant-related infections. Substrate-independent and widely applicable coating techniques are gaining significant interest to synthesize different types of antibacterial films, which can be relevant from a fundamental and application-oriented perspective. Plasma polymer- and polydopamine-based antibacterial coatings represent the most widely studied and versatile approaches among these coating techniques. Both single- and dual-functional antibacterial coatings can be fabricated with these approaches and a variety of dual-functional antibacterial coating strategies can still be explored in future work. These coatings can potentially be used for a wide range of different implants (material, shape, and size). However, for most implants, significantly more fundamental knowledge needs to be gained before these coatings can find real-life use.

In the United States and the United Kingdom, the roles of nurses in antimicrobial stewardship (AS) have been described in guidelines. However, in Japan, no previous studies have clarified nurses' recognition of the role of AS. Moreover, how the AS roles were implemented among nurses in Japan has not been fully clarified. The objectives of this study were to determine the perceptions of infection control nurses (ICNs) in Japan regarding the AS role of nurses and the extent of nurses' practice.A questionnaire survey of ICNs was conducted.Four hundred responses (response rate, 30.8%) were analyzed. Some of the items that have already gained consensus as the AS role of nurses were not recognized as the AS role of nurses by ICNs or had low implementation rates in Japan. Meanwhile, both recognition and implementation rates were high for the 5 types of care proposed.The reason the ICNs agreed that these 5 types of care are AS roles for nurses is that they know that such care can prevent infection and thereby obviate the need for antimicrobial administration. However, whether nurses themselves understand that these are roles for nurses in AS is unclear. To promote AS in Japan, communicating the fact that nurses already contribute to AS, strengthening nurse education, and improving staffing are desirable.

Currently, hydrogels are widely studied for wound dressings. However, wound healing is often hindered by bacterial infection. In this study, in situ cross-linked carboxymethyl chitosan (CMCS)/oxidized dextran (OD)/poly-γ-glutamic acid (γ-PGA) (COP) hydrogel was prepared for antimicrobial and hemostasis of diffuse wounds. In the COP hydrogel, γ-PGA was able to drain the surface moisture of the wound to enhance the surface adhesion. Moreover, γ-PGA could concentrate blood by absorbing plasma, and CMCS could electrostatically adsorb negative RBCs. The antibacterial properties of CMCS and OD endowed the COP hydrogel with certain antibacterial effects. In the inhibition zone experiment, an obvious inhibition zone appeared around the COP hydrogel. In vivo studies showed that the COP hydrogel significantly inhibited bacterial growth and promoted wound healing. In the rat tail diffuse hemorrhage wound model, the COP hydrogel showed superior hemostasis ability. Therefore, the multifunctional COP hydrogel is expected to find different applications in wound hemostasis and healing.

Repair of periodontal and maxillofacial bone defects is a major challenge in clinical. Guided bone regeneration (GBR) is considered one of the most effective methods. However, the efficacy of currently available GBR membranes for repair is frequently limited by their poor osteogenic potential and lack of antibacterial activity. The first step in this investigation was to construct a zinc-based zeolite-imidazolate framework loaded with copper ions (Cu@ZIF-8). Following that, a novel polycaprolactone/polylactic acid/nano-hydroxyapatite/Cu@ZIF-8 (PCL/PLA/n-HA/Cu@ZIF-8) GBR membrane was developed using a simple porogen with nonsolvent-induced phase separation (NIPS) approach. The produced membrane with asymmetric porous structure (one smooth side and one rough side) possesses hydrophilicity corresponding to the roughness of its two sides. The superior mechanical property, stability of degradation, and ion release capability of the membrane all contribute to the clinical feasibility. Additionally, in vitro biological experiments demonstrated that the PCL/PLA/n-HA/Cu@ZIF-8 membrane had favorable osteogenic and antibacterial properties, which suggests the high potential for application in the GBR procedure.

Peroxymonosulfate (PMS) driven by halloysite nanotubes (HNTs) modified with nanomanganese cobaltate (MnCo

Designed antimicrobial lipopeptides (ALPs) offer the attractive benefits of short peptide sequences and flexible tuning of amphiphilicity by altering the acyl chain length. These lipopeptides kill microbes by forming intriguing in-membrane nanostructures and causing the leakage of internal contents. However, how subtle differences in the molecular structures of the lipopeptides affect their antimicrobial efficacy and biocompatibility to host cells is still under-investigated.This work focuses on assessing changes in the acyl chain length of CHAn increase in n led to the decrease in the CAC of C

In this study, graphitic carbon nitride (CN) decorated with carbon quantum dot (CQD) and bismuth oxychlorobromide (BiOCl

Liposomes are promising targeted drug delivery systems with the potential to improve the efficacy and safety profile of certain classes of drugs. Though attractive, there are unique analytical challenges associated with the development of liposomal drugs including human dose prediction given these are multi-component drug delivery systems. In this study, we developed a multimodal imaging approach to provide a comprehensive distribution assessment for an antibacterial drug, GSK2485680, delivered as a liposomal formulation (Lipo680) in a mouse thigh model of bacterial infection to support human dose prediction. Positron emission tomography (PET) imaging was used to track the in vivo biodistribution of Lipo680 over 48 h post-injection providing a clear assessment of the uptake in various tissues and, importantly, the selective accumulation at the site of infection. In addition, a pharmacokinetic model was created to evaluate the kinetics of Lipo680 in different tissues. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) was then used to quantify the distribution of GSK2485680 and to qualitatively assess the distribution of a liposomal lipid throughout sections of infected and non-infected hindlimb tissues at high spatial resolution. Through the combination of both PET and MALDI IMS, we observed excellent correlation between the Lipo680-radionuclide signal detected by PET with the GSK2485680 and lipid component signals detected by MALDI IMS. This multimodal translational method can reduce drug attrition by generating comprehensive biodistribution profiles of drug delivery systems to provide mechanistic insight and elucidate safety concerns. Liposomal formulations have potential to deliver therapeutics across a broad array of different indications, and this work serves as a template to aid in delivering future liposomal drugs to the clinic.

Purpose This study examined the efficacy of prescribing antibiotics, specifically a single dose of vancomycin, in reducing the incidence of culture-positive and culture-negative sepsis prior to the removal of peripherally inserted central catheters (PICCs). Materials and methods We retrospectively reviewed charts of infants who had PICCs in a tertiary level hospital during the period from 2010 to 2019. The incidence of post-catheter removal clinical sepsis between the groups with or without antibiotics was compared. The antibiotic group was defined by receiving a single dose of vancomycin or any other antibiotic prior to line removal. Results We enrolled 585 PICC removal episodes in 546 infants for analysis. Antibiotics were given prior to removal in 257 cases (43.9%) and not given prior to removal in 328 cases (56.1%). There were 13 episodes of post-catheter removal clinical sepsis detected within 72 h (2.2%), 2 of which were culture-positive (0.3%). A 9.3-fold decrease in the odds for clinical sepsis was observed in the antibiotic group (p = 0.01). The incidence of post-catheter removal sepsis was decreased by a single prophylactic dose of vancomycin (p = 0.02), whereas the use of other antibiotics showed no effect (p = 0.35). Logistic regression analysis demonstrated that comorbidities with gastrointestinal diseases (p = 0.01), PICC insertion sites in the scalp and neck (p = 0.04), and no vancomycin administration prior to line removal (p = 0.02) were independent risk factors for subsequent clinical sepsis. Conclusion A single prophylactic dose of vancomycin prior to PICC line removal might reduce clinical sepsis events in infants.

Bacterial pneumonia in pregnancy is the most common fatal non-obstetrical infection and is associated with poorer maternal and fetal outcomes. Risk factors include normal physiological and anatomic changes that occur during pregnancy. In this review, we will discuss the etiological pathogens of bacterial pneumonias in pregnancy and its common complications, including both maternal and fetal outcomes. We will also review the diagnosis and management of bacterial pneumonia in the outpatient and inpatient setting and highlight the major pregnancy and lactation considerations when choosing antibiotic therapies.

In recent decades, there has been an increase in the reports of antimicrobial resistance of Listeria monocytogenes, which constitutes a serious threat to the therapeutic management of listeriosis infection. Our study profiled the antibiogram fingerprint of L. monocytogenes isolates (n = 194) recovered from common South African ready-to-eat foods. L. monocytogenes isolates recovered from foods were tested against a panel of 22 antibiotics using the disk diffusion method. Antimicrobial resistance (50%) against ceftriaxone (53.1%), trimethoprim (56.2%), streptomycin, cefotetan (59.3%), sulfamethoxazole (61.9%), vancomycin, and oxytetracyclines (62.9%) were observed. Thirty of the isolates (15.5%) were resistant against only one or two antibiotics, whereas 162 (83.5%) exhibited phenotypic multiple antibiotic resistance. Only two (1%) of the isolates did not exhibit phenotypic resistance against any antibiotics screened. Multiple antibiotic phenotypes revealed high resistance patterns, and the multiple antibiotic indices were greater than the Krumperman permissible (0.2) benchmark. Of the 44 genes screened, 22 antimicrobial resistance genes were detected among ready-to-eat food isolates, including resistance determinants that encode sulfonamides (n = 125, 64.4%), β-lactams (n = 86, 44.3%), phenicols (n = 25, 12.9), and aminoglycosides (n = 93, 47.9%) resistance. We conclude that the presence of resistant L. monocytogenes isolates harboring corresponding antimicrobial resistance genes in foods could compromise safety and constitute severe health consequences if consumed.

Proteins and polysaccharides have been frequently used in recent years to prepare environment-friendly packaging materials. However, films based on proteins or polysaccharides alone often have poor performance as packaging, so they need to be combined to improve properties. In this work, we applied enzyme technology to prepare sodium caseinate (SC)-carboxymethyl chitosan (CMC) films, incorporating epigallocatechin gallate (EGCG) as bridging molecules and antibacterial agents. SC-EGCG-CMC ternary conjugate was firstly synthesized by tyrosinase (Tyr), and the composite films were then prepared with the aid of glycerol. Under tyrosinase catalytic conditions, EGCG could cross-link with SC and CMC covalently. The effects of different concentrations of EGCG and tyrosinase on mechanical properties, water vapor permeability, antibacterial properties and free radical scavenging ability were studied. The crosslinking degree and mechanical properties were improved with the increase of EGCG and tyrosinase content. The film showed good antibacterial activity against Gram-positive bacteria. In addition, the antibacterial activity and free radical scavenging ability increased with the increase of EGCG concentration. This work provides an efficient enzymatic method to prepare films with good strength and antibacterial properties, which can be used to improve the storage quality of foods.

Bacteria have the ability to invade and survive in host cells to form intracellular bacteria (ICBs), and challenges remain in the intracellular delivery of sufficient antibiotics to remove ICBs. Herein, antimicrobial peptide of epsilon-poly-l-lysine (ePL) and nitric oxide (NO) donors are integrated into nanoparticles (NPs) for ICB treatment without using any antibiotics. ePL was grafted with dodecyl alcohol through ethyl dichlorophosphate to prepare ePL-C

Patients with cystic fibrosis (CF) often develop respiratory tract infections with pathogenic multidrug-resistant organisms (MDROs) such as methicillin-resistant Staphylococcus aureus, and a variety of gram-negative organisms that include Pseudomonas aeruginosa, Burkholderia sp., Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and nontuberculous mycobacteria (NTM). Despite the introduction of new therapies to address underlying cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, MDRO infections remain a problem and novel antimicrobial interventions are still needed. Therapeutic approaches include improving the efficacy of existing drugs by adjusting the dose based on differences in CF patient pharmacokinetics/pharmacodynamics, the development of inhaled formulations to reduce systemic adverse events, and the use of newer beta-lactam/beta-lactamase combinations. Alternative innovative therapeutic approaches include the use of gallium and bacteriophages to treat MDRO pulmonary infections including those with extreme antibiotic resistance. However, additional clinical trials are required to determine the optimal dosing and efficacy of these different strategies and to identify patients with CF most likely to benefit from these new treatment options.

It is popular that natural organics are served as green reducing and end-capping reagent for synthesis of functional nanoparticles. In this study, curcumin, a natural pigment, was employed to prepare silver nanoparticles (AgNPs) as a coloring, reducing and end-capping agent by an eco-friendly, economic and facile approach in the presence of different clay minerals, including palygorskite, montmorillonite and mixed-dimensional palygorskite clay. It was found that the phenolic hydroxyl groups or carbonyl groups of curcumin played a crucial role to reduce silver ions into AgNPs with the ginger color. Meanwhile, incorporation of clay minerals could induce the in-situ heterogeneous nucleation of AgNPs on the surface or/and interlayer of the involved clay minerals. It effectively prevented from the aggregations and resulted in uniform dispersion of AgNPs with a diameter of 30-40 nm. Furthermore, the as-prepared nanocomposites exhibited a higher antioxidant (90%) and antibacterial activity. Due to the synergistic effect of each component among the nanocompositions, the nanocomposites derived from different clay minerals were employed as multifunctional nanofillers to design functional chitosan composite films. By contrast, the chitosan composite films containing curcumin-capped AgNPs/mixed-dimensional palygorskite clay nanocomposites exhibited the best mechanical properties, antioxidant and antibacterial activities. Compared with the chitosan films, the tensile strength and elongation at break of composite films increased by 15.90 MPa and 27.27%, respectively. The inactivation rate of the composite films against Escherichia coli and Staphylococcus aureus had reached 100%. Therefore, the obtained composite film with the ginger color exhibited excellent mechanical, water resistance, antioxidant and antibacterial properties, and it was expected to develop a great potential functional packaging materials.

Antibiotic resistance is a sword of Damocles that hangs over humans. In regards to airborne antibiotic resistance genes (AARGs), critical knowledge gaps still exist in the identification of hotspots and quantification of exposure levels in different environments. Here, we have studied the profiles of AARGs, mobile genetic elements (MGEs) and bacterial communities in various atmospheric environments by high throughput qPCR and 16S rRNA gene sequencing. We propose a new AARGs exposure dose calculation that uses short-term inhalation (STI). Swine farms and hospitals were high-risk areas where AARGs standardised abundance was more abundant than suburbs and urban areas. Additionally, resistance gene abundance in swine farm worker sputum was higher than that in healthy individuals in other environments. The correlation between AARGs with MGEs and bacteria was strong in suburbs but weak in livestock farms and hospitals. STI exposure analysis revealed that occupational intake of AARGs (via PM

BACKGROUND Burkholderia cepacia complex (BCC) represents a group of multidrug-resistant gram-negative bacteria that cause infections among immunocompromised hosts. Bacteremia occurs in patients who are chronically ill and is associated with substantial morbidity and mortality. The aim of this study was to investigate the clinical characteristics and outcomes of BCC bacteremic patients without cystic fibrosis. METHODS We conducted a retrospective study at the National Taiwan University Hospital. Adults with BCC bacteremia from January 2015 to May 2019 were enrolled. The primary outcome was 14-day mortality. Multivariable logistic regression was performed for outcome analysis. RESULTS One-hundred and ninety-five patients were analyzed and their mean age was 67 years. Over 95% of the BCC isolates were susceptible to trimethoprim/sulfomethoxazole (TMP/SXT). Levofloxacin resistance rates were high, with only 25.1% of isolates being susceptible. Pairwise comparisons were made between different definitive regimens including meropenem-monotherapy, ceftazidime-monotherapy, levofloxacin-monotherapy, TMP/SXT-monotherapy, tigecycline-monotherapy as well as combination versus monotherapy. No regimen was significantly associated with survival in our study. Multivariable logistic regression showed that the Pitt bacteremia score (adjust odds ratio [aOR],1.46; 95% confidence interval [CI],1.19-1.79; p

Efforts to monitor and combat antimicrobial resistance (AMR) are typically focused on the hospital-based laboratory setting. The aim of this study was to longitudinally examine and compare trends in AMR among urine Escherichia coli isolates from a private community-based laboratory and a public hospital-based laboratory in an Australian local health district.A total of 108 262 urine E. coli isolates from a public hospital-based laboratory (N = 34 103) and a private community-based laboratory (N = 74 159) in a single health district between 2007-2019 were analysed. Linear regression was used to identify significance of change in AMR rates in both laboratories independently and detect any significant interaction of each setting in proportional change over the study period.Similar AMR trends were detected among urinary E. coli isolates in private community-based laboratory and public hospital-based laboratory settings over 12 y. AMR rates were consistently higher in the public hospital-based setting. Ampicillin was the only antibiotic for which the E. coli resistance trend did not significantly change over the time period in either laboratory setting. All other antibiotics showed a significant increase in AMR rates over time in both settings.AMR rates in both the private community-based laboratory and public hospital-based laboratory settings increased over time and were consistently higher in the public hospital-based laboratory setting. Since private laboratories handle the vast majority of pathology volumes in community outpatient settings in Australia, interventions incorporating the community-based laboratory setting are critical to addressing AMR in the community.

Emergence of the colistin resistance gene, mcr-1, has attracted worldwide attention. Despite the prevalence of mcr-1-positive Escherichia coli (MCRPEC) strains in human carriage showing a significant decrease between 2016 and 2019, genetic differences in MCRPEC strains remain largely unknown. We therefore conducted a comparative genomic study on MCRPEC strains from fecal samples of healthy human subjects in 2016 and 2019. We identified three major differences in MCRPEC strains between these two time points. First, the insertion sequence ISApl1 was often deleted and the percentage of mcr-1-carrying IncI2 plasmids was increased in MCRPEC strains in 2019. Second, the antibiotic resistance genes (ARGs), aac(3)-IVa and blaCTX-M-1, emerged and coexisted with mcr-1 in 2019. Third, MCRPEC strains in 2019 contained more virulence genes, resulting in an increased proportion of extraintestinal pathogenic E. coli (ExPEC) strains (36.1%) in MCRPEC strains in 2019 compared to that in 2016 (10.5%), implying that these strains could occupy intestinal ecological niches by competing with other commensal bacteria. Our results suggest that despite the significant reduction in the prevalence of MCRPEC strains in humans from 2016 to 2019, MCRPEC exhibits increased resistance to other clinically important ARGs and contains more virulence genes, which may pose a potential public health threat.

The intestinal microbiome provides a reservoir for antibiotic resistance genes (ARGs). The neonatal microbiome is more susceptible to disturbance from external factors than the established microbiome in later life.In this review, we systematically summarize studies which investigated the intestinal resistome in neonates.MEDLINE and Embase databases were searched.We included original studies which investigated ARGs in stool or rectal swabs in neonates using molecular diagnostics.Two authors independently extracted data, which were summarized in tables.Our search identified 2701 studies, of which 23 (22 cohorts) were included. The studies show that the neonatal intestine harbours a high abundance and variety of ARGs, even in the absence of direct antibiotic exposure. The most commonly found ARGs confer resistance to aminoglycosides, β-lactams, macrolides, tetracyclines, or multidrug resistance. There is evidence that ARGs can be transferred from mothers to neonates. Interestingly, however, compared to mothers, neonates are reported to have a higher abundance of ARGs. One likely reason for this is the bacterial phylogenetic composition with a high abundance of Gammaproteobacteria in neonatal stool. Factors that have been associated with a higher abundance of ARGs are intrapartum and neonatal antibiotic use. Breastfeeding and neonatal probiotic use have been associated with a lower abundance of ARGs. Antibiotics during pregnancy, delivery mode, or sex are reported to have little effect. However, this might be because studies were underpowered and because it is difficult to account for effect modifiers.The neonatal intestine seems to have a lower colonization resistance, which could make it easier for antibiotic-resistant populations to establish themselves. Future studies will help in the development of evidence-based interventions to modulate the abundance of ARGs in neonates, for example, by the use of pre- and probiotics and bacteriophages.

The objective of this study was to assess the in vitro activity of ceftazidime-avibactam (CAZ-AVI) and a panel of comparator agents against isolates of Enterobacter spp., Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa collected in 2018 and 2019 by different centres worldwide from patients with respiratory tract infections.Susceptibility and minimum inhibitory concentration (MIC) of all organisms were determined using broth microdilution methodology for CAZ-AVI, and a panel of comparator antimicrobial agents by a central reference laboratory according to Clinical and Laboratory Standards Institute guidelines and European Committee on Antimicrobial Susceptibility Testing guidelines.CAZ-AVI demonstrated potent antimicrobial activity against isolates of Enterobacter spp. (97.6% susceptibility, MICGram-negative respiratory isolates collected in 2018-2019 showed high susceptibility to CAZ-AVI; CAZ-AVI represents a potential treatment option against infection caused by these organisms.

Wound dressing hydrogel with multifunctional properties, including antioxidant and antimicrobial properties and appropriate mechanical, biological, and physical properties is of great interest in wound healing application and it is still a challenge. In the present study, chitooligosaccharides (COS)/ sinapic acid (SA) conjugate (COS-SA) was synthesized using H

Utilizing reactive oxygen species (ROS), which are generated by the activation of molecular oxygen (O

Objectives: The usefulness of routine microbiological testing for rationalising antibiotic use in hospitalised patients with community-acquired pneumonia (CAP) continues to be a subject of debate. We aim to determine the effect of positive microbiological testing on antimicrobial de-escalation and clinical outcomes in CAP. Methods: A retrospective analysis of a prospectively collected cohort of non-immunosuppressed adults hospitalised with CAP was performed. The primary study outcome was antimicrobial de-escalation. Secondary outcomes included 30-day case-fatality rate, adverse events, and CAP recurrence. Adjustment for confounders was performed by inverse probability weighting propensity score, logistic regression, and cause-specific Cox model. Results: Of 3677 patients with CAP, 1924 (52.3%) had any positive microbiological test. Antimicrobial de-escalation was performed in 648/1924 (33.7%) of patients with positive microbiological testing and in 179/1753 (10.2%) of those with non-positive results. When propensity score was entered into the multivariate analysis, positive microbiological testing (adjusted OR (AOR)], 2.59; 1.96-3.41) and clinical stability at day 3 (AOR 1.87; 1.45-2.10) were two of the main factors independently associated with antimicrobial de-escalation. After applying an adjusted cause-specific Cox model, antimicrobial de-escalation was not associated with a higher 30-day case-fatality rate (adjusted hazard ratio (AHR), 0.44 (95% CI, 0.14-1.43)), higher frequency of adverse events (AHR, 0.77 (95% CI, 0.53-1.12)), or CAP recurrence (AHR, 0.65 (95% CI, 0.35-1.14)). Discussion: Antimicrobial de-escalation was more often performed in hospitalised patients with CAP who had positive microbiological tests than in those with non-positive results, and it did not adversely affect relevant clinical outcomes.

Exposure of infectious biofilms to dispersants induces high bacterial concentrations in blood that may cause sepsis. Preventing sepsis requires simultaneous biofilm dispersal and bacterial killing. Here, self-targeting DCPA(2-(4-((1,5-bis(octadecenoyl)1,5-dioxopentan-2-yl)carbamoyl)pyridin-1-ium-1-yl)acetate) liposomes with complexed water were self-assembled with ciprofloxacin loaded in-membrane and PEGylated as a lipid-membrane component, together with bromelain loaded in-core. Inside biofilms, DCPA-H2O and PEGylated ciprofloxacin became protonated, disturbing the balance in the lipid-membrane to cause liposome-burst and simultaneous release of bromelain and ciprofloxacin. Simultaneous release of bromelain and ciprofloxacin enhanced bacterial killing in Staphylococcus aureus biofilms as compared with free bromelain and/or ciprofloxacin. After tail-vein injection in mice, liposomes accumulated inside intra-abdominal staphylococcal biofilms. Subsequent liposome-burst and simultaneous release of bromelain and ciprofloxacin yielded degradation of the biofilm matrix by bromelain and higher bacterial killing without inducing septic symptoms as obtained by injection of free bromelain and ciprofloxacin. This shows the advantage of simultaneous release from liposomes of bromelain and ciprofloxacin inside a biofilm.

The preparation of hydrogel-based wearable sensors for underwater application with high mechanical properties and electrical conductivity is an urgent challenge. Here, a supramolecular hydrogel based on polyionic liquids was designed and prepared for underwater sensing. The introduction of functional ionic liquid structures effectively increased the supramolecular interaction in the hydrogel network, which made the hydrogel successfully resist the interference of external water molecules. Depending on the effect of charge and hydrophobic interactions, this supramolecular hydrogel sensor exhibited high tensile (759 %), high tensile strength (0.23 MPa), high sensitivity (GF = 10.76) and extensive antibacterial properties, even in seawater environment. The obtained hydrogel sensor successfully monitored the swimming posture, which was helpful to digitally reflect the limb movement of athletes during underwater sports. This work made progress in the field of underwater wearable sensors based on hydrogels, and this design of multifunctional hydrogel provided a new idea for the development of functional sensors.

The increasing morbidity of oral diseases, such as dental caries, periodontitis and oral cancer, has greatly compromised the life quality of humans. With the rapid development of biomaterials and nanotechnology, various biomaterials-based systems have been reported to treat oral diseases. As the biocompatible, biodegradable and bioadhesive polysaccharide biomaterials, chitosan and its derivatives have also been widely used for the oral disease therapy, either as the antibacterial agents, drug delivery carriers or tissue engineering scaffolds. It has been well demonstrated that chitosan can significantly enhance the therapy efficacy for various oral diseases, due to its intrinsic antibacterial activity and controlled drug release feature. Herein, we aim to provide a comprehensive understanding of the biological functions of chitosan, such as antimicrobial, anticancer and remineralization activity, and summarize the applications of chitosan-based therapeutic systems in treating the typical oral diseases, including dental caries, endodontic diseases, periodontal diseases, oral cancer, oral and maxillofacial surgery, and oral mucosal diseases. In addition, the concerns and possible solutions of the clinical use of chitosan are also discussed.

Intestinal enteritis is a main issue in crucian carp production which results in massive economic loss. Traditional antibiotics used for disease prevention of crucian carp (Carassius carassius) have been banned, thus an alternative approach needs to be identified. In this study, the bioactive peptide was evaluated as a diet supplement for preventing intestinal inflammation in crucian carp. Intestinal inflammation was induced by intrarectal administration of a 2,4,6-trinitrobenzene sulfonic acid (TNBS) solution. The fish samples were fed with different diets for 14 days. The disease activity index (DAI), which included, fish swimming, food intake, anal inflammation, body surface, and ascites was determined daily. Intestine segments were stained with haematoxylin and eosin (H.E.) for histopathological analysis. The expression of cytokines, including interleukin-1β (IL-1β), interleukin-8 (IL-8), tumor necrosis factor α (TNF-α), and myeloperoxidase (MPO) in crucian carp were determined. In TNBS-induced groups, the DAI scores were dramatically increased compared to the control group. The histopathological analysis showed that the damage of the fish intestine after the injection of TNBS. The relative expression levels of pro-inflammation cytokines (TNF-α, IL-1β, IL-8, MPO) were significantly increased compared to the control group on day 1. In the TNBS-induced group feed with a diet supplemented with bioactive peptide, the symptoms of intestinal inflammation were relieved on day 3 and the mRNA expression levels of pro-inflammation cytokines (TNF-α, IL-1β, IL-8, MPO) were reduced compared to day 1. On day 7, the fish samples enrofloxacin group and bioactive peptide group were recovered from TNBS-induced intestinal inflammation. This study showed that the fish diet supplemented with bioactive peptide could help to prevent and recover from intestinal inflammation. Thus, the bioactive peptide can be used as a replacement for antibiotics to prevent disease in aquaculture production.

Effective treatment of pneumonia requires timely administration of appropriate antimicrobials but standard diagnostic tests take around 48 h to generate results. Highly accurate, rapid molecular tests have been developed for identifying organisms in lower respiratory tract samples, however their impact on antibiotic use is unknown. The aim of this study was to assess the impact of syndromic molecular point-of-care testing compared to conventional diagnostic testing, on antibiotic use.In this pragmatic, randomised controlled trial, we enrolled critically ill adults with pneumonia. Patients were assigned (1:1) to molecular testing of samples at the point-of-care or routine clinical care. The primary outcome was the proportion of patients who received results-directed antimicrobial therapy.200 patients were randomly assigned to point-of-care testing (n = 100) or the control group (n = 100). 85 patients had community acquired pneumonia (42 in the mPOCT group and 43 in the control group), 69 hospital acquired pneumonia (30 in mPOCT and 39 in control) and 46 ventilator associated pneumonia (28 in mPOCT and 18 in control). The median [IQR] time to results was 1.7 [1.6-1.9] hours for point-of-care testing and 66.7 [56.7-88.5] hours for standard diagnostics (difference of -65.0 h, 95%CI -68.0 to -62.0; p 0.0001). 71 (71%) patients in the point-of-care testing arm had pathogens detected compared to 51 (51%) in the control arm (difference of 20%, 95%CI 7 to 33; p = 0.004). 80 (80%) of patients in the point-of-care group received results-directed therapy, compared with 29 (29%) of 99 in the control group (difference of 51%, 95%CI 39-63; p 0.0001). Time to results-directed therapy was 2.3 [1.8-7.2] hours in the mPOCT group and 46.1 [23.0-51.5] hours in the control group (difference of -43.8 h, 95% CI -48.9 to -38.6; p 0.0001). 42 (42%) patients in mPOCT group had antibiotics de-escalated compared with 8 (8%) of 98 in the control group (difference of 34%, 95%CI 23-45; p 0.0001). Time to de-escalation was 4.8 [2.4-13.0] hours in the mPOCT group compared with 46.5 [26.3-48.6] hours in the control group (difference of -41.4 h, 95%CI -53 to -29.7; p 0.0001). There was no major difference in antibiotic duration or in clinical or safety outcomes between the two groups.Use of molecular point-of-care testing in patients with pneumonia returned results more rapidly and identified more pathogens than conventional testing. This was associated with improvements in appropriate antimicrobial use and appeared safe.