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Although public–private collaboration abounds in addressing societal grand challenges, little is known about its performance relative to private-sector collaboration. Drawing from the innovation collaboration literature, and qualitative insights from interviews and contracts, we argue that collaboration risk impairs task performance of public–private versus private–private collaboration. We attribute this to two collaboration risk mechanisms: cooperation problems arising from misaligned social versus economic incentives, and coordination problems due to differences in organizational governance and processes. We test our hypotheses using the development history of 2,496 antimicrobial drugs from 1995–2019. After accounting for endogenous selection into collaboration, we find that public–private collaboration is less effective than private–private collaboration. However, this performance gap reduces for innovation tasks under high technological uncertainty (i.e., in the discovery stage and for developing new drug action mechanisms). To probe the distinctive cooperation and coordination mechanisms, we also examine innovation task efficiency. Findings reveal a wider gap in task effectiveness but not efficiency between public–private and private–private collaboration, suggesting more significant cooperation than coordination problems. Our theoretical and practical insights pertain to whether, when, and how public–private and private–private collaboration offer viable pathways for socially beneficial innovation tasks. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the effectiveness of coating of abutments with antimicrobial agents and their influence on the physicochemical and biologic properties of the coated materials. Materials and Methods: This work was registered in Open Science Framework (osf.io/6tkcp) and followed the PRISMA protocols. A search of two independent reviewers of articles published up to October 29, 2021, was performed in the Embase, PubMed, Science Direct, and Scopus databases. Results: The databases found a total of 1,474 references. After excluding the duplicates, 1,050 remained. After reading the titles and abstracts and applying the inclusion criteria, 13 articles remained and were read in full. A total of 8 articles were included in this systematic review. Different antimicrobial agents have been used to coat abutments, including graphene oxide, polydopamine, titanium and zirconium nitride, lactoferrin, tetracycline, silver, and doxycycline with varied release times. Titanium-coated silver showed a better antimicrobial agent release time of up to 28 days. Chemical analysis confirmed the presence of antimicrobials on the surface after coating. Different pathogenic microorganisms, such as Streptococcus sanguinis, Streptococcus oralis, and Staphylococcus aureus, were inhibited when in contact with the coated surface. Conclusions: This review showed that there is still no consensus on which is the better antimicrobial agent and which coated materials have the better performance. However, the association of surface coating of abutments with antimicrobials is feasible and can benefit many patients, which can support their clinical use to favor the healing process and prevent infections that can lead to treatment failure with dental implants. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the possible antimicrobial activity of glycine air polishing by comparing peri-implant microbiota before and after treatment. Materials and Methods: A total of 15 patients who received implant-supported full-arch fixed rehabilitations were included. After prosthesis removal (T0), Plaque Index (PI), probing depth (PD), and bleeding on probing (BOP) were recorded. In each hemiarch, the implant with the highest PD score was selected for microbiologic sample collection from the peri-implant sulcus (T0). All patients received two different hygienic protocols (randomly administered, one per each hemiarch): glycine air-polishing (G) and cleansing with cotton pellets soaked in saline (C). At 7 days (T1) and 3 months (T2) after the intervention, PI and BOP were recorded, and new microbiologic samples were taken. Traditional polymerase chain reaction (PCR) and quantitative PCR real-time were employed for microbiologic analysis to investigate how the presence of different bacterial species varied according to the hygienic treatment performed. Results: Treatment G provided a significantly higher PI score reduction around implants compared to treatment C (P = .015). No statistical difference was found in the microbial population around G and C implant sites, with Tannerella forsythia being the most commonly detected bacterial species in both G and C groups. No statistical differences were found between the antimicrobial activity of treatments C and G. Conclusions: Glycine powder air polishing is a valid method for professional hygienic care of implants and was more effective in PI reduction compared to the control treatment. However, its antimicrobial efficacy cannot be confirmed by the outcomes of the present study. [ABSTRACT FROM AUTHOR]

Host-directed therapy (HDT) is an emerging approach to overcome antimicrobial resistance in pathogenic microorganisms. Specifically, HDT targets host-encoded factors required for pathogen replication and survival without interfering with microbial growth or metabolism, thereby eliminating the risk of resistance development. By applying HDT and a drug repurposing approach, we demonstrate that (R)-DI-87, a clinical-stage anticancer drug and potent inhibitor of mammalian deoxycytidine kinase (dCK), mitigates Staphylococcus aureus abscess formation in organ tissues upon invasive bloodstream infection. Mechanistically, (R)-DI-87 shields phagocytes from staphylococcal death-effector deoxyribonucleosides that target dCK and the mammalian purine salvage pathway-apoptosis axis. In this manner, (R)-DI-87-mediated protection of immune cells amplifies macrophage infiltration into deep-seated abscesses, a phenomenon coupled with enhanced pathogen control, ameliorated immunopathology, and reduced disease severity. Thus, pharmaceutical blockade of dCK represents an advanced anti-infective intervention strategy against which staphylococci cannot develop resistance and may help to fight fatal infectious diseases in hospitalized patients.

The growing concerns regarding foodborne illnesses related to fresh produce accentuate the necessity for innovative material solutions, particularly on surfaces that come into close contact with foods. This study introduces a sustainable, efficient, and removable antimicrobial and antifouling coating ideally suited for hydrophobic food-contact surfaces such as low-density polyethylene (LDPE). Developed through a crosslinking reaction involving tannic acid, gelatin, and soy protein hydrolysate, these coatings exhibit proper stability in aqueous washing solutions and effectively combat bacterial contamination and prevent biofilm formation. The unique surface architecture promotes the formation of halamine structures, enhancing antimicrobial efficacy with a rapid contact killing effect and reducing microbial contamination by up to 5 log10 cfu·cm-2 against both Escherichia coli (Gram-negative) and Listeria innocua (Gram-positive). Notably, the coatings are designed for at least five recharging cycles under mild conditions (pH6, 20 ppm free active chlorine) and can be easily removed with hot water or steam to refresh the depositions. This removal process not only conveniently aligns with existing sanitation protocols in the fresh produce industry but also facilitates the complete eradication of potential developed biofilms, outperforming uncoated LDPE coupons. Overall, these coatings represent sustainable, cost-effective, and practical advancements in food safety and are promising candidates for widespread adoption in food processing environments.

The transmission of antimicrobial resistant bacteria in the urban environment is poorly understood. We utilized genomic sequencing and phylogenetics to characterize the transmission dynamics of antimicrobial resistant Escherichia coli (AMR-Ec) cultured from putative canine (caninep) and human feces present on urban sidewalks in San Francisco, California. We isolated a total of fifty-six AMR-Ec isolates from human (n = 20) and caninep (n = 36) fecal samples from the Tenderloin and South of Market (SoMa) neighborhoods of San Francisco. We then analyzed phenotypic and genotypic antimicrobial resistance (AMR) of the isolates, as well as clonal relationships based on cgMLST and single nucleotide polymorphisms (SNPs) of the core genomes. Using Bayesian inference, we reconstructed the transmission dynamics between humans and caninesp from multiple local outbreak clusters using the marginal structured coalescent approximation (MASCOT). Our results provide evidence for multiple sharing events of AMR-Ec between humans and caninesp. In particular, we found one instance of likely transmission from caninesp to humans as well as an additional local outbreak cluster consisting of one caninep and one human sample. Based on this analysis, it appears that non-human feces act as an important reservoir of clinically relevant AMR-Ec within the urban environment for this study population. This work showcases the utility of genomic epidemiology to reconstruct potential pathways by which antimicrobial resistance spreads.

Purpose: To verify the parameters and characteristics evaluated in 3D-printed complete denture (CD) bases and how they influence CD properties. Materials and Methods: This work was registered in Open Science Framework (osf.io/4um6v) and followed the PRISMA Extension for Scoping Reviews. A search of peer-reviewed articles published up to April 9, 2020, was performed on the PubMed, LILACS, Cochrane Library, and Science Direct databases. The review question based on the PCC (population, concept, and context) was: What printing parameters and characteristics of CD bases can influence their properties? Results: The database search resulted in 1,945 articles, and the initial screening was carried out in 1,390 articles, 17 of which were selected for inclusion in this review. The present authors verified that cleaning the prosthesis with alcohol after printing followed by a postcuring cycle influences biocompatibility and residual monomers. The printing angle influences physicomechanical properties, microbial adhesion, and tissue adaptation. Accuracy is influenced by layer thickness and manufacturing technique, which also influences retention and tissue adaptation. The incorporation of antimicrobial agents influences physicomechanical properties and antimicrobial activity. The method of union between the denture base and teeth influences mechanical strength. Conclusions: Printed denture bases showed good adaptation to tissues and accuracy with 100-µm layer thickness, but the base must be cleaned in ethanol followed by postcuring for better biocompatibility. Nano- and microparticles can be added to provide antimicrobial activity and better resistance. The printing angle and mechanical properties must be better evaluated. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the applica.on of chitosan as a cleanser in the control of biofilm forma.on on cobalt-chromium (Co-Cr) alloy and acrylic resin surfaces. Materials and Methods: In total, 172 Co-Cr discs and 172 acrylic resin discs (14 mm x 3 mm) were contaminated with Streptococcus mutans, Staphylococcus aureus, Candida albicans, or Candida glabrata and incubated for 48 hours. Then, specimens were randomly divided into groups and immersed in the following solu.ons for 15 minutes: solu.on without chitosan (WC/control); chitosan solu.on (CH: 5 mg/mL); chitosan nanopar.cle solu.on (CN: 3.8 mg/mL); and effervescent tablet (ET). Biofilm recovery rates (n = 9) were evaluated by coun.ng the colony-forming units (CFU/mL). Biofilm morphology was evaluated using scanning electron microscopy (SEM). Data were compared using the Kruskal-Wallis or ANOVA tests followed by the Tukey post hoc test. Results: For acrylic resin, ET showed the lowest number of CFU for S aureus and S mutans (P < .001). CH exhibited intermediate values for S mutans, S aureus, and C albicans; CN exhibited intermediate values for S mutans and S aureus. For C glabrata, there was no sta.s.cal difference between the solu.ons (P = .264). For Co-Cr, ET showed the highest level of an.microbial ac.on against all microorganisms (P < .001), and CH showed an intermediate level of ac.on against S mutans and S aureus. Against C albicans and C glabrata, there was no significant difference among CH, CN, and WC. Conclusions: Although ET had a broader spectrum of an.microbial ac.on, CH showed promise as a denture cleanser. [ABSTRACT FROM AUTHOR]

This study aimed to investigate how the presence of co-morbid conditions influenced antimicrobial usage as presumptive prophylaxis for suspected bacteremia in dogs and cats undergoing dental treatments at primary care veterinary clinics in the United States. In 2020, data was collected from 1076 veterinary clinics across 44 US states. A total of 681,541 general anesthesia dental procedures were conducted on 592,472 dogs and 89,069 cats. This revealed that systemic antimicrobials were administered in 8.8% of dog procedures and 7.8% of cat procedures in the absence of concurrent periodontal disease or extractions. Cefpodoxime, clindamycin, and amoxicillin-clavulanate were the most frequently used antimicrobials in dogs, while cefovecin, amoxicillin-clavulanate, and clindamycin topped the list for cats. Dogs with cardiovascular, hepato-renal, and endocrine co-morbidities, as well as those undergoing concurrent removal of cutaneous or subcutaneous neoplasia, displayed higher antimicrobial use. Similarly, cats with endocrine or hepato-renal disease, retroviral infection (i.e., feline leukemia virus (FeLV), feline immunodeficiency virus (FIV)), and concurrent removal of cutaneous or subcutaneous neoplasia exhibited increased antimicrobial use. Dogs with hepato-renal abnormalities had longer treatment durations compared to those without (10.1 vs. 9.6 days). Conversely, cats with concurrent removal of cutaneous or subcutaneous neoplasia had shorter durations of treatment as compared to those that did not have this procedure performed (8.4 vs 9.2 days). The findings of this study underscore the necessity for further research and collaboration within the veterinary community to develop evidence-based guidelines, promoting responsible antimicrobial use, and advancing the field of veterinary dentistry for enhanced patient outcomes.

The objective of this study was to evaluate the impact of dietary zinc supplementation in pre-weaned dairy calves on the phenotypic antimicrobial resistance (AMR) of fecal commensal bacteria. A repository of fecal specimens from a random sample of calves block-randomized into placebo (n = 39) and zinc sulfate (n = 28) groups collected over a zinc supplementation clinical trial at the onset of calf diarrhea, calf diarrheal cure, and the last day of 14 cumulative days of zinc or placebo treatment were analyzed. Antimicrobial susceptibility testing was conducted for Enterococcus spp. (n = 167) and E. coli (n = 44), with one representative isolate of each commensal bacteria tested per sample. Parametric survival interval regression models were constructed to evaluate the association between zinc treatment and phenotypic AMR, with exponentiated accelerated failure time (AFT) coefficients adapted for MIC instead of time representing the degree of change in AMR (MIC Ratio, MR). Findings from our study indicated that zinc supplementation did not significantly alter the MIC in Enterococcus spp. for 13 drugs: gentamicin, vancomycin, ciprofloxacin, erythromycin, penicillin, nitrofurantoin, linezolid, quinupristin/dalfopristin, tylosin tartrate, streptomycin, daptomycin, chloramphenicol, and tigecycline (MR = 0.96-2.94, p > 0.05). In E. coli, zinc supplementation was not associated with resistance to azithromycin (MR = 0.80, p > 0.05) and ceftriaxone (MR = 0.95, p > 0.05). However, a significant reduction in E. coli MIC values was observed for ciprofloxacin (MR = 0.17, 95% CI 0.03-0.97) and nalidixic acid (MR = 0.28, 95% CI 0.15-0.53) for zinc-treated compared to placebo-treated calves. Alongside predictions of MIC values generated from these 17 AFT models, findings from this study corroborate the influence of age and antimicrobial exposure on phenotypic AMR.

In recent years, compounds from the Schiff base group have been intensively studied for their biological activities. Accordingly, a series of Schiff bases were synthesized from substituted aromatic aldehydes (5-chlorosalicylaldehyde) and differently substituted aromatic amines and their antimicrobial activities were evaluated. The molecular identity of compounds was confirmed using various spectroscopic techniques, such as IR and NMR spectroscopy and elemental analysis, and the molecular structure of compound 3k was determined by single-crystal X-ray analysis. The antimicrobial activity of 3a–3k compounds was examined in sixteen microorganisms (five species of bacteria and eleven species of fungi) using the microdilution method. Regarding antibacterial activity, a remarkable MIC value (0.0098 mg mL−1) and, therefore, the best activity was displayed against Proteus mirabilis for 3e, which is even stronger than the most frequently used antibiotic medications. 3f showed the best antifungal activity against Microsporum gypseum, which is stronger than standard antimycotic fluconazole, and is also an important result considering that Microsporum gypseum can cause dermatophytosis in both humans and animals. [ABSTRACT FROM AUTHOR]

Background: Biofilm formation is an essential virulence factor that creates a highly protected growth mode for Staphylococcus aureus (S. aureus) to survive in any hostile environment. Antibiotic sub-minimal inhibitory concentration (sub-MIC) may modulate the biofilm formation ability of bacterial pathogens, thereby affecting bacterial pathogenesis and infection outcomes. Intense antimicrobial therapy to treat biofilm-associated infections can control the pathogenic infection aggravation but cannot guarantee its complete eradication. Objective: This study aimed to assess the sub-MICs effect of 5 different antimicrobial classes on biofilm-forming capacity among Staphylococcus aureus clinical isolates using three different biofilm quantitation techniques. Methods: In this study, the effects of 5 different antimicrobial agents, namely, azithromycin, gentamicin, ciprofloxacin, doxycycline, and imipenem, at sub-MICs of 12.5%, 25%, and 50% were tested on 5 different clinical isolates of S. aureus. The biofilms formed in the absence and presence of different antimicrobial sub-MICs were then assessed using the following three different techniques: the crystal violet (CV) staining method, the quantitative PCR (qPCR) method, and the spread plate method (SPM). Results: Biofilm formation was significantly induced in 64% of the tested conditions using the CV technique. On the other hand, the qPCR quantifying the total bacterial count and the SPM quantifying the viable bacterial count showed significant induction only in 24% and 17.3%, respectively (Fig. 1). The difference between CV and the other techniques indicates an increase in biofilm biomass without an increase in bacterial growth. As expected, sub-MICs did not reduce the viable cell count, as shown by the SPM. The CV staining method revealed that sub-MICs of imipenem and ciprofloxacin had the highest significance rate (80%) showing an inductive effect on the biofilm development. On the other hand, doxycycline, azithromycin, and gentamicin displayed lower significance rates of 73%, 53%, and 47%, respectively. Conclusion: Exposure to sub-MIC doses of antimicrobial agents induces the biofilm-forming capacity of S. aureus via increasing the total biomass without significantly affecting the bacterial growth of viable count. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus spp. present challenges in clinical and veterinary settings because effective antimicrobial agents are limited. Phage-encoded peptidoglycan-degrading enzyme, endolysin, is expected to be a novel antimicrobial agent. The enzymatic activity has recently been shown to be influenced by the linker between functional domains in the enzyme. S6_ORF93 (ORF93) is one of the endolysins derived from previously isolated Staphylococcus giant phage S6. The ORF93 was speculated to have a catalytic and peptidoglycan-binding domain with a long linker. In this study, we examined the influence of linker shortening on the characteristics of ORF93. We produce wild-type ORF93 and the linker deletion mutants using an Escherichia coli expression system. These mutants were designated as ORF93-Δ05, ORF93-Δ10, ORF93-Δ15, and ORF93-Δ20, from which 5, 10, 15, and 20 amino acids were removed from the linker, respectively. Except for the ORF93-Δ20, ORF93 and its mutants were expressed as soluble proteins. Moreover, ORF93-Δ15 showed the highest yield and bacteriolytic activity, while the antimicrobial spectrum was homologous. The cold storage experiment showed a slight effect by the linker deletion. According to our results and other studies, linker investigations are crucial in endolysin development. [ABSTRACT FROM AUTHOR]

Sauerkraut‐derived lactic acid bacterial (LAB) strains have gained attention due to their potential health benefits. This study focuses on evaluating seven Sauerkraut‐derived RAMULAB strains isolated from sauerkraut, aiming to identify promising candidates for modulating α‐glucosidase (AG) and α‐amylase (AM) enzymatic functions. RAMULAB strains with remarkable probiotic potential can contribute to the digestive health and manage conditions like diabetes. Identifying robust candidates from sauerkraut, a fermented food, holds promise for natural and cost‐effective probiotic sources. The RAMULAB strains underwent extensive characterization, including identification through 16S ribosomal RNA (rRNA) sequencing. Their tolerance to harsh conditions, adherence properties, antimicrobial activity, antioxidant potential, and inhibition of AG and AM were assessed. In silico analyses explored their molecular interactions, particularly with hydroxycitric acid, a potential antidiabetic compound. Among the RAMULAB strains, RAMULAB48 emerged as a standout candidate. It displayed exceptional resilience to acidic bile (≥97%), and simulated gastrointestinal conditions (≥95%), highlighting its suitability for probiotic applications. RAMULAB48 exhibited robust adherence properties, including cell‐surface hydrophobicity (80%), autoaggregation (42%), coaggregation with pathogens (≥33%), and adhesion to epithelial cells. Additionally, all seven isolates demonstrated gamma‐hemolysis and resistance to antibiotics (Kanamycin, Methicillin, and Vancomycin), while displaying strong antibacterial properties against foodborne pathogens. These RAMULAB strains also exhibited varying degrees of antioxidant activity, with RAMULAB48 displaying the highest potential (≥41%). In terms of antidiabetic activity, cell‐free supernatant (CS) obtained from RAMULAB48 expressed the highest inhibition levels, notably inhibiting yeast AG by an impressive 59.55% and AM being by a remarkable 67.42%. RAMULAB48 produced organic acids, including hydroxycitric acid (28.024 mg/mL), which showed promising antidiabetic properties through in silico analyses, indicating favorable interactions with the target enzymes. This study identifies Lacticaseibacillus paracasei RAMULAB48, a Sauerkraut‐derived RAMULAB strain, as a promising probiotic candidate with exceptional tolerance, adherence properties, antimicrobial activity, antioxidant potential, and antidiabetic effects. The presence of hydroxycitric acid further underscores its potential in managing diabetes. [ABSTRACT FROM AUTHOR]

Antibacterial bone cements (ABCs), such as antibiotic-loaded bone cements (ALBCs), have been widely utilized in clinical treatments. Currently, bone cements loaded with vancomycin, gentamicin, tobramycin, or clindamycin are approved by the US Food and Drug Administration. However, traditional ALBCs exhibit drawbacks like burst release and bacterial resistance. Therefore, there is a demand for the development of antibacterial bone cements containing novel agents to address these defects. In this review, we provide an overview and prospect of the new antibacterial agents that can be used or have the potential to be applied in bone cement, including metallic antibacterial agents, pH-switchable antibacterial agents, cationic polymers, N-halamines, non-leaching acrylic monomers, antimicrobial peptides and enzymes. Additionally, we have conducted a preliminary assessment of the feasibility of bone cement containing N-halamine, which has demonstrated good antibacterial activities. The conclusion of this review is that the research and utilization of bone cement containing novel antibacterial agents contribute to addressing the limitations of ALBCs. Therefore, it is necessary to continue expanding the research and use of bone cement incorporating novel antibacterial agents. This review offers a novel perspectives for designing ABCs and treating bone infections. [ABSTRACT FROM AUTHOR]

Background: Effective endodontic treatment requires the use of a root canal sealer with optimal properties to ensure a hermetic seal, prevent reinfection, and promote healing. Despite the availability of various sealers, a standardized evaluation system still needs to be improved. Objectives: To develop a Clinical Utility Index (CUI) that systematically evaluates and ranks root canal sealers based on their sealing ability, antimicrobial efficacy, flow rate, and solubility. Methods: The CUI was developed through a structured process involving expert identification, panel discussions, and the establishment of scoring criteria. Five sealers were evaluated (Sealers A, B, C, D, and E). Mean values for the core properties were calculated, and sealers were ranked accordingly. The total CUI for each sealer was computed based on the assigned scores for each property. Results: Sealer B achieved the highest CUI at 95%, demonstrating superior performance across all core properties. Sealer C followed with a CUI of 80%, while Sealer A ranked third with 60%. Sealers D and E showed the lowest performance, with CUIs of 30% and 35%, respectively, highlighting deficiencies in multiple properties. Discussion: The CUI provides a comprehensive evaluation framework for root canal sealers, facilitating informed decision-making by practitioners. Sealer B's high CUI underscores the importance of balancing sealing ability, antimicrobial effect, flow rate, and solubility. The results align with existing literature emphasizing the critical role of these properties in endodontic success. Conclusion: The CUI offers a robust and balanced method for evaluating root canal sealers, aiding in selecting the most suitable sealer based on empirical data. Future research should refine the index and validate its applicability in diverse clinical scenarios to enhance endodontic treatment outcomes. [ABSTRACT FROM AUTHOR]

Mycobacterium marinum (M. marinum) is the most common causative bacteria of cutaneous non-tuberculous mycobacterial (NTM) infections, including fish tank granuloma. Treating M. marinum-caused infection takes longer than other NTM diseases because M. marinum is less susceptible to antimicrobial agents. A standard treatment regimen for M. marinum infection has not been established yet, and few in vivo experiments have been performed in mammals to evaluate the bactericidal effects of antimicrobials. In this study, we developed a noninvasive in vivo imaging method to assess the therapeutic efficacy of antimicrobials against M. marinum infection. The data obtained using fluorescent protein or bioluminescence from luciferase will offer valuable insights into bacteria visualization across various bacterial infections. Furthermore, through this imaging technique, we demonstrated that combining clarithromycin, rifampicin, ethambutol, and minocycline effectively cleared M. marinum from the footpad. Granulomas with necrotic abscesses formed on the footpad of M. marinum-infected mice, primarily due to neutrophils involved in the host's cell-mediated immune response. Inflammatory cytokine and chemokine levels significantly increased 7 days post-infection, aligning with the footpad swelling and granuloma formation observed in the untreated group. Interestingly, immune mediators and cells induced by M. marinum footpad infection were crucial factors associated with hypersensitivity and granuloma formation, as seen in pulmonary tuberculosis. This novel imaging analysis using a cutaneous NTM mouse model might be a powerful tool for the comprehensive analysis of mycobacterial infections. [ABSTRACT FROM AUTHOR]

The absence of novel antibiotic classes, coupled with the rising threat of antibiotic persistence and resistance, is pushing the world perilously close to a new pre-antibiotic era. Over 35 000 people die every year in the US as a consequence of antimicrobial-resistant infections. Bacterial biofilms further complicate this scenario, as they are inherently more resistant to antibiotic treatments. Currently, there are no approved single agent or adjuvant small molecules for treating biofilm-complicated infections. Herein, we report the synthesis and microbiological evaluation of a novel library of 25+ monomeric and dimeric pyrrolidine-2,3-dione scaffolds. These compounds have displayed improved aqueous solubility, potent anti-biofilm properties, a low MBEC-to-MIC ratio, and synergism with FDA-approved antimicrobials against biofilm infections, constituting a promising technology as antimicrobial adjuvants. [ABSTRACT FROM AUTHOR]

Infection of native tissues or implanted devices is common, but clinical diagnosis is frequently difficult and currently available noninvasive tests perform poorly. Immunocompromised individuals (for example transplant recipients, or those with cancer) are at increased risk. No imaging test in clinical use can specifically identify infection, or accurately differentiate bacterial from fungal infections. Commonly used [18F]fluorodeoxyglucose (18FDG) positron emission computed tomography (PET/CT) is sensitive for infection, but limited by poor specificity because increased glucose uptake may also indicate inflammation or malignancy. Furthermore, this tracer provides no indication of the type of infective agent (bacterial, fungal, or parasitic). Imaging tools that directly and specifically target microbial pathogens are highly desirable to improve noninvasive infection diagnosis and localization. A growing field of research is exploring the utility of radiometals and their chelators (siderophores), which are small molecules that bind radiometals and form a stable complex allowing sequestration by microbes. This radiometal-chelator complex can be directed to a specific microbial target in vivo, facilitating anatomical localization by PET or single photon emission computed tomography. Additionally, bifunctional chelators can further conjugate therapeutic molecules (e.g., peptides, antibiotics, antibodies) while still bound to desired radiometals, combining specific imaging with highly targeted antimicrobial therapy. These novel therapeutics may prove a useful complement to the armamentarium in the global fight against antimicrobial resistance. This review will highlight current state of infection imaging diagnostics and their limitations, strategies to develop infection-specific diagnostics, recent advances in radiometal-based chelators for microbial infection imaging, challenges, and future directions to improve targeted diagnostics and/or therapeutics. [ABSTRACT FROM AUTHOR]

Background: No clinical trials have evaluated the antimicrobial activity and substantivity of gel formulations containing chlorhexidine (CHX) and cymenol. Objective: To compare the in situ antimicrobial effect and substantivity of a new 0.20% CHX + cymenol gel (test) with the current 0.20% CHX gel formulation (control) on salivary flora and dental plaque biofilm up to seven hours after a single application. Methods: A randomised-crossover clinical trial was conducted with 29 orally healthy volunteers participating in the development of Experiments 1 (saliva) and 2 (dental plaque biofilm). All subjects participated in both experiments and were randomly assigned to receive either the test or control gels. Samples were collected at baseline and five minutes and one, three, five, and seven hours after a single application of the products. The specimens were processed using confocal laser scanning microscopy after staining with the LIVE/DEAD® BacLight™ solution. Bacterial viability (BV) was quantified in the saliva and biofilm samples. The BV was calculated using the DenTiUS Biofilm software. Results: In Experiment 1, the mean baseline BV was significantly reduced five minutes after application in the test group (87.00% vs. 26.50%; p < 0.01). This effect was maintained throughout all sampling times and continued up to seven hours (40.40%, p < 0.01). The CHX control followed the same pattern. In Experiment 2, the mean baseline BV was also significantly lower five minutes after applying the test gel for: (1) the total thickness of biofilm (91.00% vs. 5.80%; p < 0.01); (2) the upper layer (91.29% vs. 3.94%; p < 0.01); and (3) the lower layer (86.29% vs. 3.83%; p < 0.01). The reduction of BV from baseline was observed for the full-thickness and by layers at all sampling moments and continued seven hours after application (21.30%, 24.13%, and 22.06%, respectively; p < 0.01). Again, the control group showed similar results. No significant differences between test and control gels were observed in either saliva or dental plaque biofilm at any sampling time. Conclusions: A 0.20% CHX + cymenol gel application demonstrates potent and immediate antimicrobial activity on salivary flora and de novo biofilm. This effect is maintained seven hours after application. Similar effects are obtained with a 0.20% CHX-only gel. [ABSTRACT FROM AUTHOR]

The emergence of methicillin‐resistant Staphylococcus aureus (MRSA) several years ago highlighted the challenge of multidrug‐resistant infections, emphasizing the critical need for innovative treatment approaches. Myrtenol, known for its antibacterial and antibiofilm properties, holds promise as a potential treatment option. This study aimed to evaluate the effectiveness of myrtenol against MRSA. The collected MRSA isolates were assessed for antimicrobial susceptibility following the Clinical and Laboratory Standards Institute (CLSI) guidelines 2023. Biofilm formation by MRSA was evaluated using the tissue culture plate (TCP) technique. The minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), and minimal biofilm inhibitory concentration (MBIC) of myrtenol against MRSA were determined both individually and in combination with antibiotics. Real‐time PCR was employed to investigate the impact of myrtenol on the expression of virulence genes (sarA, agrA, and icaD) across the isolates. In this study, MRSA was identified in 90 out of 400 cases (22.5%) of hospital‐acquired pathogens. Among the collected MRSA isolates, 53 out of 90 (59%) were found to produce biofilms. The MIC of myrtenol was comparable to the MBC across all tested isolates, they were almost the same. Combinations of myrtenol with most tested antibiotics exhibited synergistic effects exceeding 60%. Among the 53 biofilm‐producing isolates, 45 isolates (85%) expressed the sarA gene, 49% expressed the agrA gene, and all biofilm‐producing MRSA isolates (100%) expressed the icaD gene. A notable reduction in the relative quantity (RQ) values of virulence gene expression was observed after treatment with the MBIC of myrtenol across all tested isolates. Myrtenol demonstrated strong antimicrobial activity against MRSA, notably reducing the expression of key virulence genes linked to biofilm formation. This suggests its potential as a therapeutic agent for treating biofilm‐associated MRSA infections. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing in incidence globally and challenging to manage. The 2020 multisociety treatment guideline and the 2022 consensus recommendations provide comprehensive evidence-based guides to manage pulmonary diseases caused by the most common NTM. However, with >190 different NTM species that may require different multidrug regimens for treatment, the breadth and complexity of NTM-PD remain daunting for both patients and clinicians. In this narrative review, we aim to distill this broad, complex field into principles applicable to most NTM species and highlight important nuances, specifically elaborating on the presentation, diagnosis, principles of patient-centered care, principles of pathogen-directed therapy, and prospects of NTM-PD. [ABSTRACT FROM AUTHOR]

Objectives Data supporting routine infectious diseases (ID) consultation in gram-negative bloodstream infection (GN-BSI) are limited. We evaluated the association between ID consultation and mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario using linked health administrative databases. Methods Hospitalized adult patients with GN-BSI between April 2017 and December 2021 were included. The primary outcome was time to all-cause mortality censored at 30 days, analyzed using a mixed effects Cox proportional hazards model with hospital as a random effect. ID consultation 1–10 days after the first positive blood culture was treated as a time-varying exposure. Results Of 30 159 patients with GN-BSI across 53 hospitals, 11 013 (36.5%) received ID consultation. Median prevalence of ID consultation for patients with GN-BSI across hospitals was 35.0% with wide variability (range 2.7%–76.1%, interquartile range 19.6%–41.1%). In total, 1041 (9.5%) patients who received ID consultation died within 30 days, compared to 1797 (9.4%) patients without ID consultation. In the fully adjusted multivariable model, ID consultation was associated with mortality benefit (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI].77–.88, P <.0001; translating to absolute risk reduction of −3.8% or number needed to treat [NNT] of 27). Exploratory subgroup analyses of the primary outcome showed that ID consultation could have greater benefit in patients with high-risk features (nosocomial infection, polymicrobial or non-Enterobacterales infection, antimicrobial resistance, or non-urinary tract source). Conclusions Early ID consultation was associated with reduced mortality in patients with GN-BSI. If resources permit, routine ID consultation for this patient population should be considered to improve patient outcomes. [ABSTRACT FROM AUTHOR]

The misuse of antibiotics leads to emergence of drug‐resistant bacteria. Developing artificial nanozymes with high stability and excellent catalytic performance is desirable to substitute for antibiotics, but still remains huge challenge. Herein, the study reports a new strategy for cascaded enhanced peroxidase (POD) reaction driving antibacterial therapy via constructing 2D conjugated metal‐organic frameworks (MOFs) with non coordination saturation as nanozyme. It is demonstrated that the non coordination saturation Cu atom promotes the adsorption of H2O2, followed by the Cu‐HHTP MOFs with high conjugated structure can enhance the photogenerated electron transfer for ·OH generation in POD reaction. The sequential enhancement of substrate adsorption and decomposition endows the as‐made Cu‐HHTP MOFs with outstanding antibacterial property of >99.9999% elimination with a concentration only 1/133 that of traditional nanozyme. In addition, the study also certifies its excellent in vivo antimicrobial activity and biocompatibility, indicating the therapeutic potential for infections by drug‐resistant bacteria. [ABSTRACT FROM AUTHOR]

Antimicrobial agents are safe preservatives having the ability to protect foods from microbial spoilage and extend their shelf life. Many factors, including antimicrobials' chemical features, storage environments, delivery methods, and diffusion in foods, can affect their antimicrobial activities. The physical-chemical characteristics of the food itself play an important role in determining the efficacy of antimicrobial agents in foods; however the mechanisms behind it have not been fully explored. This review provides new insights and comprehensive knowledge regarding the impacts of the food matrix, including the food components and food (micro)structures, on the activities of antimicrobial agents. Studies of the last 10 years regarding the influences of the food structure on the effects of antimicrobial agents against the microorganisms' growth were summarized. The mechanisms underpinning the loss of the antimicrobial agents' activity in foods are proposed. Finally, some strategies/technologies to improve the protection of antimicrobial agents in specific food categories are discussed. [ABSTRACT FROM AUTHOR]