How well do antimicrobial mouth rinses prevent dysbiosis in an in vitro periodontitis biofilm model?

BACKGROUND: Periodontal diseases are associated with dysbiosis in the oral microbial communities. Managing oral biofilms is therefore key for preventing these diseases. Management protocols often include over-the-counter antimicrobial mouth rinses, which lack data on their effects on the oral microbiome's ecology, bacterial composition, metabolic activity, and dysbiosis resilience. This study examined the efficacy of antimicrobial mouth rinses to halt dysbiosis in in vitro oral biofilms under periodontitis-simulating conditions. METHODS: Multispecies oral biofilms were grown on hydroxyapatite discs (HADs) and rinsed daily with one of six mouth rinses. Positive and negative controls were included. After three rinses, biofilms were analyzed with viability quantitative polymerase chain reaction and visualized using scanning electron microscopy. Supernatants of rinsed biofilms were used for metabolic activity analysis. In addition, human oral keratinocytes were exposed to rinsed biofilms to assess their inflammatory response. All outputs were analyzed for correlation using Spearman coefficient. RESULTS: Product-related changes were observed in the rinsed biofilms. Three of the six tested mouth rinses could significantly prevent dysbiosis with ≥30% reduction in pathobiont abundance relative to the control. These biofilms had lower metabolic activity, and the exposed human oral keratinocyte produced less interleukin-8. Interleukin-8 production correlated to both pathobiont quantity and the metabolic activity of the biofilms. CONCLUSION: Some mouth rinses could support biofilm resilience and stop dysbiosis evolution in the biofilm model, with a clear product-related effect. Such mouth rinses can be considered for patients under maintenance/supportive periodontal therapy to prevent/delay disease recurrence. Others are more useful for different periodontal therapy stages.

Applying Machine Learning for Antibiotic Development and Prediction of Microbial Resistance.

Antimicrobial resistance (AMR) poses a serious threat to human health worldwide. It is now more challenging than ever to introduce a potent antibiotic to the market considering rapid emergence of antimicrobial resistance, surpassing the rate of antibiotic drug discovery. Hence, new approaches need to be developed to accelerate the rate of drug discovery process and meet the demands for new antibiotics, while reducing the cost of their development. Machine learning holds immense promise of becoming a useful tool, especially since in the last two decades, exponential growth has occurred in computational power and biological big data analytics. Recent advancements in machine learning algorithms for drug discovery have provided significant clues for potential antibiotic classes. Apart from discovery of new scaffolds, machine learning protocols will significantly impact prediction of AMR patterns and drug metabolism. In this review, we outline power of machine learning in antibiotic drug discovery, metabolic fate, and AMR prediction to support researchers engaged and interested in this field.

Using the Zebrafish Larval Model of Infection to Investigate Antibiotic Efficacy and Combination Treatments Against Staphylococcus aureus.

There is an increasing need for new treatment regimens to combat antibiotic-resistant strains of bacteria. Staphylococcus aureus is a clinically important, opportunist pathogen that has developed resistance to a range of antibiotics. The zebrafish larval model of systemic disease has been increasingly utilized to elucidate S. aureus virulence mechanisms and host-pathogen interactions. Here, we outline how this model can be used to investigate the effects of different antibiotics alone and in combination against S. aureus.

Guideline-Concordant Therapy for Community-Acquired Pneumonia in the Hospitalized Population: A Systematic Review and Meta-analysis.

Background: A commonly used guideline for community-acquired pneumonia (CAP) is the joint American Thoracic Society and Infectious Diseases Society of America practice guideline. We aimed to investigate the effect of guideline-concordant therapy in the treatment of CAP. Methods: We systematically searched MEDLINE, Embase, CENTRAL, Web of Science, and Scopus from 2007 to December 2023. We screened citations, extracted data, and assessed risk of bias in duplicate. Primary outcomes were mortality rates, intensive care unit (ICU) admission, and length of stay. Secondary outcomes were guideline adherence, readmission, clinical cure rate, and adverse complications. We performed random-effect meta-analysis to estimate the overall effect size and assessed heterogeneity using the I2 statistics. Results: We included 17 observational studies and 82 240 patients, of which 10 studies were comparative and pooled in meta-analysis. Overall guideline adherence rate was 65.2%. Guideline-concordant therapy was associated with a statistically significant reduction in 30-day mortality rate (crude odds ratio [OR], 0.49 [95% confidence interval .34-.70; I2 = 60%]; adjusted OR, 0.49 [.37-.65; I2 = 52%]) and in-hospital mortality rate (crude OR, 0.63 [.43-.92]; I2 = 61%). Due to significant heterogeneity, we could not assess the effect of guideline-concordant therapy on length of stay, ICU admission, readmission, clinical cure rate, and adverse complications. Conclusions: In hospitalized patients with CAP, guideline-concordant therapy was associated with a significant reduction in mortality rate compared with nonconcordant therapy; however, there was limited evidence to support guideline-concordant therapy for other clinical outcomes. Future studies are needed to assess the clinical efficacy and safety of current guideline recommendations.

The interactive effects of medicinal dyes with conventional antimicrobials against skin pathogens.

AIMS: This study aimed to explore potential synergistic effects of medicinal dyes with antimicrobials against pathogens responsible for skin infections. METHODS AND RESULTS: Antimicrobial testing was conducted using minimum inhibitory concentrations and minimum bactericidal/fungicidal concentration assays. The fractional inhibitory index (ΣFIC) of combinations was calculated, and isobolograms were constructed on selected combinations. Toxicity studies were conducted using the brine-shrimp lethality assay. Combination (1:1 ratio) studies noted that 26% of dye-antibiotic combinations were synergistic against the Gram-positive strains, 15% against the Gram-negative strains, and 14% against the yeasts. The Mercurochrome: Betadine® combination noted synergy at ratios against all the Staphylococcus aureus strains with ΣFIC values ranging from 0.05 to 0.48. The combination of Gentian violet with Gentamycin noted a 15-fold decrease in toxicity, and a selectivity index of 977.50 against the Escherichia coli (DSM 22314) strain. Time-kill studies were conducted on the combinations with the highest safe selectivity index (SI) value and lowest safe SI value i.e. Gentian violet with Gentamycin and Malachite green with Neomycin. Both combinations demonstrated better antimicrobial activity in comparison to the independent values and the controls. CONCLUSION: This study highlights the potential for medicinal dye combinations as a treatment for skin infections.

Quantification of antimicrobial use on Irish dairy farms: A comparison of three recording methods.

Antimicrobial use (AMU) data are essential for monitoring usage over time, facilitating reduction strategies to combat the threat of antimicrobial resistance (AMR) to both human and animal health. The objective of this study was to measure and describe AMU over a 12-mo period in Irish dairy herds and compare 3 different recording methods to a reference method. A sample of 33 Irish dairy herds were randomly selected from 6 private veterinary practices across Ireland. The herds were followed for a 12-mo period and their AMU was monitored using 3 recording methods: 1. Veterinary prescription data (VET), 2. The inventory of medicine bins on the farms (BIN), and 3. Farmer treatment records from herd recording software (APP). Each recording method was compared with a previously developed reference method for AMU. The reference method used was based on pre- and poststudy medicine stock on the farms combined with veterinary prescription data. Antimicrobial use was analyzed using both mass- and dosed-based metrics, including mass (mg) of antimicrobial active ingredient per population correction unit (mg/PCU), defined daily doses for animals (DDDVET) and defined course doses for animals (DCDVET). Median AMU was 16.24, 10.47, 8.87 and 15.55 mg/PCU by mass, and 2.43, 1.55, 1.19 and 2.26 DDDVET by dose for VET, BIN, APP, and reference method data, respectively. Reliability of the agreement between each pair of methods was quantified using the concordance correlation coefficient (CCC). When compared with the reference method, VET data had excellent reliability [95% confidence interval (CI) of CCC: 0.992-0.998]. The BIN data had good to excellent reliability [95% CI of CCC: 0.776-0.936]. The APP data had poor reliability when compared with the reference method [95% CI of CCC: -0.167-0.156]. Our results highlight that a small number of herds were contributing most to overall use and farmers showed varying levels of consistency in recording AMU. Veterinary data were the most reliable approach for assessing AMU when compared with a reference method of AMU. This is an important finding for the future monitoring of AMU at a national level.

An updated description of bacterial pneumonia in adult horses and factors associated with death.

BACKGROUND: Available descriptive studies on equine pneumonia are outdated or focus on specific horse or bacterial populations. OBJECTIVES: To describe the clinical presentation and bacterial isolates of adult horses with bacterial pneumonia and identify factors associated with death. ANIMALS: One hundred sixteen horses >2 years old with bacterial pneumonia. METHODS: Retrospective case series. Data regarding history, physical examination, clinicopathologic features, treatment, bacterial culture and sensitivity, and outcome were collected and analyzed retrospectively. RESULTS: Historical risk factors were present for 60% of cases, whereas abnormal vital signs on intake were present for <50%. Most horses (58%) underwent at least 1 change of antimicrobial treatment, and 67% received the highest-priority critically important antimicrobials. Streptococcus zooepidemicus was the most isolated bacteria (44%), followed by Escherichia coli (19%), Klebsiella spp. (18%), other Streptococcus species (17%), and Bacillus spp. (13%). Fusobacterium spp. were the most common anaerobic isolates (11%). Antimicrobial susceptibility varied widely. Survival to discharge was 73%. Heart rate at presentation (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.008-1.17, P = .03) and higher creatinine (OR 14.1, 95% CI 1.56-127.6, P = .02) increased the risk of death. Higher lymphocyte count (OR 0.27, 95% CI 0.08-0.94, P = .04) reduced risk. CONCLUSIONS AND CLINICAL IMPORTANCE: Contrasting older literature, Fusobacterium spp. were the most common anaerobes. Streptococcus zooepidemicus remained the most common isolate and was predictably susceptible to penicillin. Antimicrobial susceptibility was otherwise variable and broad applicability is limited as this was a single-center study. Increased risk of death associated with tachycardia and abnormally high serum creatinine concentration is consistent with previous studies.

Surface-Charge Tuned Polymeric Nanoemulsions for Carvacrol Delivery in Interkingdom Biofilms.

Biofilms, intricate microbial communities entrenched in extracellular polymeric substance (EPS) matrices, pose formidable challenges in infectious disease treatment, especially in the context of interkingdom biofilms prevalent in the oral environment. This study investigates the potential of carvacrol-loaded biodegradable nanoemulsions (NEs) with systematically varied surface charges─cationic guanidinium (GMT-NE) and anionic carboxylate (CMT-NE). Zeta potentials of +25 mV (GMT-NE) and -33 mV (CMT-NE) underscore successful nanoemulsion fabrication (∼250 nm). Fluorescent labeling and dynamic tracking across three dimensions expose GMT-NE's superior diffusion into oral biofilms, yielding a robust antimicrobial effect with 99.99% killing for both streptococcal and Candida species and marked reductions in bacterial cell viability compared to CMT-NE (∼4-log reduction). Oral mucosa tissue cultures affirm the biocompatibility of both NEs with no morphological or structural changes, showcasing their potential for combating intractable biofilm infections in oral environment. This study advances our understanding of NE surface charges and their interactions within interkingdom biofilms, providing insights crucial for addressing complex infections involving bacteria and fungi in the demanding oral context.

Tailoring metal oxide nanozymes for biomedical applications: trends, limitations, and perceptions.

Nanomaterials with enzyme-like properties are known as 'nanozymes'. Nanozymes are preferred over natural enzymes due to their nanoscale characteristics and ease of tailoring of their physicochemical properties such as size, structure, composition, surface chemistry, crystal planes, oxygen vacancy, and surface valence state. Interestingly, nanozymes can be precisely controlled to improve their catalytic ability, stability, and specificity which is unattainable by natural enzymes. Therefore, tailor-made nanozymes are being favored over natural enzymes for a range of potential applications and better prospects. In this context, metal oxide nanoparticles with nanozyme-mimicking characteristics are exclusively being used in biomedical sectors and opening new avenues for future nanomedicine. Realising the importance of this emerging area, here, we discuss the mechanistic actions of metal oxide nanozymes along with their key characteristics which affect their enzymatic actions. Further, in this critical review, the recent progress towards the development of point-of-care (POC) diagnostic devices, cancer therapy, drug delivery, advanced antimicrobials/antibiofilm, dental caries, neurodegenerative diseases, and wound healing potential of metal oxide nanozymes is deliberated. The advantages of employing metal oxide nanozymes, their potential limitations in terms of nanotoxicity, and possible prospects for biomedical applications are also discussed with future recommendations.

Economic evaluations of therapeutic drug monitoring interventions in acute hospital-based settings: A systematic review.

AIMS: Therapeutic drug monitoring (TDM) aims to optimize drug therapy. As demand on health resources increases, and the technology underpinning TDM becomes more sophisticated, the economic benefits of TDM in hospitals is unclear. The aim of this systematic review was to summarize the economic evidence that could be used to support investment in TDM in hospital settings. In so doing, we sought to provide guidance for future economic evaluations. METHODS: Medline, Embase, CENTRAL, Econlit and NHS Economic Evaluation databases were searched (inception to December 2022) for economic evaluations of hospital-based TDM. Two authors reviewed the studies and extracted data. Overall quality of economic analysis reporting was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: Ten prospective studies (including six randomized studies) and nine retrospective studies were eligible. Overall study reporting was poor, publications meeting a median (range) of 61% (46-82%) of CHEERS checklist criteria. An antimicrobial TDM intervention for adult patients was the focus of most studies (n = 18). Variable clinical outcomes were reported, and length of stay was the primary economic outcome for most studies (n = 13). The majority of studies determined that TDM was economically and clinically favourable (n = 14), four studies reporting a cost-reduction in patient sub-populations. CONCLUSIONS: Significant improvements in both economic and clinical outcomes may be realized with TDM interventions, particularly when targeted to complex patient populations. Attainment of therapeutic target could serve as a feasible surrogate measure of benefit for hospital-based TDM interventions. However, systematic reporting of economic outcomes is needed to inform investment decisions.

Unveiling the mechanism of essential oil action against skin pathogens: from ancient wisdom to modern science.

Essential oils are among the most well-known phyto-compounds, and since ancient times, they have been utilized in medicine. Over 100 essential oils have been identified and utilized as therapies for various skin infections and related ailments. While numerous commercial medicines are available in different dosage forms to treat skin diseases, the persisting issues include their side effects, toxicity, and low efficacy. As a result, researchers are seeking novel classes of compounds as substitutes for synthetic drugs, aiming for minimal side effects, no toxicity, and high efficacy. Essential oils have shown promising antimicrobial activity against skin-associated pathogens. This review presents essential knowledge and scientific information regarding essential oil's antimicrobial capabilities against microorganisms that cause skin infections. Essential oils mechanisms against different pathogens have also been explored. Many essential oils exhibit promising activity against various microbes, which has been qualitatively assessed using the agar disc diffusion experiment, followed by determining the minimum inhibitory concentration for quantitative evaluation. It has been observed that Staphylococcus aureus and Candida albicans have been extensively researched in the context of skin-related infections and their antimicrobial activity, including established modes of action. In contrast, other skin pathogens such as Staphylococcus epidermidis, Streptococcus pyogens, Propionibacterium acnes, and Malassezia furfur have received less attention or neglected. This review report provides an updated understanding of the mechanisms of action of various essential oils with antimicrobial properties. This review explores the anti-infectious activity and mode of action of essential against distinct skin pathogens. Such knowledge can be valuable in treating skin infections and related ailments.

Subinhibitory concentrations of nisin enhance virulence gene expression in Staphylococcus aureus and increase mortality in Galleria mellonella.

Alternative strategies for controlling Staphylococcus aureus and other pathogens have been continuously investigated, with nisin, a bacteriocin widely used in the food industry as a biopreservative, gaining increasing attention. In addition to its antimicrobial properties, bacteriocins have significant effects on genome functionality even at inhibitory concentrations. This study investigated the impact of subinhibitory concentrations of nisin on S. aureus. Culturing in the presence of 0.625 µmol l-1 nisin, led to the increased relative expression of hla, saeR, and sarA, genes associated with virulence while expression of the sea gene, encoding staphylococcal enterotoxin A (SEA), decreased. In an in vivo experiment, Galleria mellonella larvae inoculated with S. aureus cultured in the presence of nisin exhibited 97% mortality at 72 h post-infection, compared to over 40% of larvae mortality in larvae infected with S. aureus. A comprehensive understanding of the effect of nisin on the transcriptional response of virulence genes and the impact of these changes on the virulence of S. aureus can contribute to assessing the application of this bacteriocin in food and medical contexts.

Etiological structure and antibiotic resistance pattern of burn wound infections in hospitalized patients - a one-center study in Varna, Bulgaria.

In the present retrospective study, we have evaluated bacterial pathogens isolated from patients admitted to the Burn Care Unit at the Military Medical Academy, Varna, Bulgaria over a three-year period (January 2019 - December 2021). We also tried to summarize the corresponding antibiotic resistance pattern of the isolated infectious agents. A total of 1030 isolates were obtained from 1912 burn wound samples investigated. There were 553 Gram-positive (53.7%) and 477 Gram-negative (46.3%) isolates. The most common isolates for the study period were coagulase-negative staphylococci (CoNS) (25%), Pseudomonas aeruginosa (17.7%), Staphylococcus aureus (16.6%), Acinetobacter baumannii (7.7%), Enterobacter spp. (7.1%), Escherichia coli (4.4%), Proteus spp. (3.4%), and Klebsiella spp. (2.9%). Glycopeptide antibiotics and linezolid were the most effective drugs against gram-positive isolates, followed by amikacin (for synergistic combinations), whereas colistin, imipenem, meropenem, cefoperazon/sulbactam, and piperacillin/tazobactam were the most active drugs against Gram-negative isolates, and colistin, ampicillin/sulbactam - against A. baumannii.

Moderate and serious adverse reactions to antimicrobials among hospitalized children: A systematic review.

AIMS: This systematic review aimed to investigate the occurrence of moderate and severe adverse drug reactions (ADRs) to antimicrobials among hospitalized children. METHODS: The PubMed/Medline, Cochrane Library, Embase, Web of Science, Scopus, Lilacs and CINAHL databases were searched in April 2023 to systematically review the published data describing the characteristics of moderate and severe ADRs to antimicrobials among hospitalized children. The search was carried out without date restrictions, up to the search date (April, 2023). RESULTS: At the end of the selection process, 30 articles met the inclusion criteria. Cutaneous reactions were the primary serious clinical manifestations in most articles (19/30), followed by erythema multiforme (71 cases), Stevens-Johnson syndrome (72 cases), and toxic epidermal necrolysis (22 cases). The main antimicrobials involved in moderate and severe ADRs were penicillins, cephalosporins and sulfonamides. Regarding the primary outcomes, 30% (9/30) of the articles reported deaths, and 46.7% (14/30) of studies reported increased lengths of hospital stay, need for intensive care, and transfer to another hospital. Regarding the main interventions, 10% (3/30) of the articles mentioned greater monitoring, suspension, medication substitution or prescription of specific medications for the symptomatology. CONCLUSIONS: The findings of this review could be used to identify areas for improvement and help health professionals and policymakers develop strategies. In addition, we emphasize the importance of knowing about ADRs so that there is adequate management to avoid undesirable consequences.

Genomic Characterization of Piscicolin CM22 Produced by Carnobacterium maltaromaticum CM22 Strain Isolated from Salmon (Salmo salar).

Carnobacterium maltaromaticum is a species of lactic acid bacteria (LAB) that has been isolated from various natural environments. It is well-known for producing a diverse spectrum of bacteriocins with potential biotechnological applications. In the present study, a new psychrotolerant strain of C. maltaromaticum CM22 is reported, isolated from a salmon gut sample and producing a variant of the bacteriocin piscicolin 126 that has been named piscicolin CM22. After identification by 16S rRNA gene, this strain has been genomically characterized by sequencing and assembling its complete genome. Moreover, its bacteriocin was purified and characterized. In vitro tests demonstrated that both the strain and its bacteriocin possess antimicrobial activity against several Gram-positive bacteria of interest in human and animal health, such as Listeria monocytogenes, Clostridium perfringens, or Enterococcus faecalis. However, this bacteriocin did not produce any antimicrobial effect on Gram-negative species. The study of its genome showed the genetic structure of the gene cluster that encodes the bacteriocin, showing a high degree of homology to the gene cluster of piscicolin 126 described in other C. maltaromaticum. Although more studies are necessary concerning its functional properties, this new psychrotolerant strain C. maltaromaticum CM22 and its bacteriocin could be considered an interesting candidate with potential application in agri-food industry.

Antibacterial activity of t-cinnamaldehyde: An approach to its mechanistic principle towards enterohemorrhagic Escherichia coli (EHEC).

BACKGROUND: Compounds of natural origin are potent source of drugs with unique mechanisms of action. Among phytochemicals, trans-cinnamaldehyde (t-CA) exhibits a wide range of biological activity, thus has been used for centuries to fight bacterial and fungal infections. However, the molecular basis of these properties has not been fully covered. Considering that difficult-to-control infections are becoming a rising global problem, there is a need to elucidate the molecular potential of t-CA. PURPOSE: To evaluate the antibacterial activity of t-CA against Shiga-toxigenic E. coli strains and elucidate its mechanism of action based on the inhibition of the virulence factor expression. METHODS: The antimicrobial potential of t-CA was assessed with two-fold microdilution and time-kill assays. Further evaluation included bioluminescence suppression assays, quantification of reactive oxygen species (ROS) and assessment of NAD+/NADH ratios. Morphological changes post t-CA exposure were examined using transmission electron microscopy. RNA sequencing and radiolabeling of nucleotides elucidated the metabolic alterations induced by t-CA. Toxin expression level was monitored through the application of fusion proteins, monitoring of bacteriophage development, and fluorescence microscopy studies. Lastly, the therapeutic efficacy in vivo was assessed using Galleria mellonella infection model. RESULTS: A comprehensive study of t-CA's bioactivity showed unique properties affecting bacterial metabolism and morphology, resulting in significant bacterial cell deformation and effective virulence inhibition. Elucidation of the underlying mechanisms indicated that t-CA activates the global regulatory system, the stringent response, manifested by its alarmone, (p)ppGpp, overproduction mediated by the RelA enzyme, thereby inhibiting bacterial proliferation. Intriguingly, t-CA effectively downregulates Shiga toxin gene expression via alarmone molecules, indicating its potential for therapeutic effect. In vivo validation demonstrated a significant improvement in larval survival rates post- t-CA treatment with 50 mg/kg (p < 0.05), akin to the efficacy observed with azithromycin, thus indicating its effectiveness against EHEC infections (p < 0.05). CONCLUSIONS: Collectively, these results reveal the robust antibacterial capabilities of t-CA, warranting its further exploration as a viable anti-infective agent.

Secondary metabolite profile of Streptomyces spp. changes when grown with the sub-lethal concentration of silver nanoparticles: possible implication in novel compound discovery.

The decline of new antibiotics and the emergence of multidrug resistance in pathogens necessitates a revisit of strategies used for lead compound discovery. This study proposes to induce the production of bioactive compounds with sub-lethal concentrations of silver nanoparticles (Ag-NPs). A total of Forty-two Actinobacteria isolates from four Saudi soil samples were grown with and without sub-lethal concentration of Ag-NPs (50 µg ml-1). The spent broth grown with Ag-NPs, or without Ag-NPs were screened for antimicrobial activity against four bacteria. Interestingly, out of 42 strains, broths of three strains grown with sub-lethal concentration of Ag-NPs exhibit antimicrobial activity against Staphylococcus aureus and Micrococcus luteus. Among these, two strains S4-4 and S4-21 identified as Streptomyces labedae and Streptomyces tirandamycinicus based on 16S rRNA gene sequence were selected for detailed study. The change in the secondary metabolites profile in the presence of Ag-NPs was evaluated using GC-MS and LC-MS analyses. Butanol extracts of spent broth grown with Ag-NPs exhibit strong antimicrobial activity against M. luteus and S. aureus. While the extracts of the controls with the same concentration of Ag-NPs do not show any activity. GC-analysis revealed a clear change in the secondary metabolite profile when grown with Ag-NPs. Similarly, the LC-MS patterns also differ significantly. Results of this study, strongly suggest that sub-lethal concentrations of Ag-NPs influence the production of secondary metabolites by Streptomyces. Besides, LC-MS results identified possible secondary metabolites, associated with oxidative stress and antimicrobial activities. This strategy can be used to possibly induce cryptic biosynthetic gene clusters for the discovery of new lead compounds.

Appropriateness of antimicrobial prescribing for oral and dental conditions in Australian hospitals: 2013 to 2022.

OBJECTIVES: Dentists manage a variety of oral infections in clinical practice. Inappropriate antimicrobial prescribing by dentists occurs frequently and antimicrobial stewardship strategies should include dentistry. The aim of this retrospective analysis of the Australian Hospital National Antimicrobial Prescribing Survey (Hospital NAPS) dataset, was to describe the types of oral and dental indications where antimicrobials were prescribed, and assess the guideline compliance and appropriateness of the antimicrobials in Australian hospitals. METHODS: Data from the Hospital NAPS was extracted for oral and dental indications from 2013 to 2022. The types of oral and dental indications presented, and the corresponding antimicrobials prescribed were assessed for compliance according to national prescribing guidelines and appropriateness according to the NAPS structured algorithm. RESULTS: A total of 8,001 prescriptions for 7,477 patients were identified, from 433 hospitals. Antifungal, antibiotic and antiviral agents accounted for 84.5%, 15.4% and 0.03% of prescriptions respectively. A greater proportion of antibiotics were prescribed in regional and rural areas compared to antifungals. The prescriptions assessed as compliant were 80.0% and 44.7% of antifungals and antibiotics respectively. Prescriptions assessed as appropriate were 84.4% of antifungals, and 65.3% of antibiotic prescriptions. CONCLUSIONS: A wide variety of antimicrobials were used with moderate levels of compliance and appropriateness. Future interventions should include targeted education, utilisation of prescribing guidelines and tools to diagnose and manage oral and dental conditions. Consideration can be given to adjustment of the Hospital NAPS tool to cater for oral conditions and include the provision of dental treatment in the management of these infections.

Multiple antimicrobial and immune-modulating activities of cysteamine in infectious diseases.

Infectious diseases are a major threat to global health and cause millions of deaths every year, particularly in developing countries. The emergence of multidrug resistance challenges current antimicrobial treatments, inducing uncertainty in therapeutic protocols. New compounds are therefore necessary. A drug repurposing approach could play a critical role in developing new treatments used either alone or in combination with standard therapy regimens. Herein, we focused on cysteamine, an aminothiol endogenously synthesized by human cells during the degradation of coenzyme-A, which is a drug approved for the treatment of nephropathic cystinosis. Cysteamine influences many biological processes due to the presence of the highly reactive thiol group. This review provides an overview of cysteamine-mediated effects on different viruses, bacteria and parasites, with a particular focus on infections caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Mycobacterium tuberculosis, non-tuberculous mycobacteria (NTM), and Pseudomonas aeruginosa. Evidences for a potential use of cysteamine as a direct antimicrobial agent and/or a host-directed therapy, either alone or in combination with other antimicrobial drugs, are described.

Metagenomic Analysis of Rhizospheric Bacterial Community of Citrus Trees Expressing Phloem-Directed Antimicrobials.

Huanglongbing, also known as citrus greening, is currently the most devastating citrus disease with limited success in prevention and mitigation. A promising strategy for Huanglongbing control is the use of antimicrobials fused to a carrier protein (phloem protein of 16 kDa or PP16) that targets vascular tissues. This study investigated the effects of genetically modified citrus trees expressing Citrus sinensis PP16 (CsPP16) fused to human lysozyme and ß-defensin-2 on the soil microbiome diversity using 16S amplicon analysis. The results indicated that there were no significant alterations in alpha diversity, beta diversity, phylogenetic diversity, differential abundance, or functional prediction between the antimicrobial phloem-overexpressing plants and the control group, suggesting minimal impact on microbial community structure. However, microbiota diversity analysis revealed distinct bacterial assemblages between the rhizosphere soil and root environments. This study helps to understand the ecological implications of crops expressing phloem-targeted antimicrobials for vascular disease management, with minimal impact on soil microbiota.