Myrtus communis leaves: source of bio - actives, traditional use, their biological properties, and prospects / Hojas de Myrtus communis: fuente de bioactivos, uso tradicional, sus propiedades biológicas y perspectivas

Myrtus communis L., commonly known as true myrtle, is a medicinal plant native to the Mediterranean area. Since ancient times, the inhabitant s of this area have been using it for its cultural and medicinal properties. Because of the vast diversity of biomolecules in its aerial parts, it exhibits several biological properties, including antioxidant, antimicrobial, and anticancer properties. This review retrospect the research on the source, biological activities with empirical evidence, chemical composition, applications, and cellular targets of extracts and essential oils obtained from M. communis leaves, which provides a perspective for further studies on the applications and formulations of extract and EO of M. communis leaves. The efficacy of constituents' individually, in association with other bioactive constituents, or in combination with available commercial drugs would provide insights in to the development of these bio - actives as future drugs and their evolving future potential applications in the pharmaceutical, food, and aroma industries.

Myrtus communis L., comúnmente conocido como arrayán verdadero, es una planta medicinal originaria de la zona mediterránea. Desde la antigüedad, los habitantes de esta zona lo utilizan por sus propiedades culturales y medicinales. Debido a la gran div ersidad de biomoléculas en sus partes aéreas, exhibe varias propiedades biológicas, incluidas propiedades antioxidantes, antimicrobianas y anticancerígenas. Esta revisión retrospectiva de la investigación sobre la fuente, las actividades biológicas con evi dencia empírica, la composición química, las aplicaciones y los objetivos celulares de los extractos y aceites esenciales obtenidos de las hojas de M. communis , lo que brinda una perspectiva para futuros estudios sobre las aplicaciones y formulaciones de l os extractos y EO de M. communis . La eficacia de los componentes individualmente, en asociación con otros componentes bioactivos o en combinación con medicamentos comerciales disponibles proporcionaría información sobre el desarrollo de estos bioactivos co mo medicamentos futuros y sus futuras aplicaciones potenciales en las industrias farmacéutica, alimentaria y aromática

The neutralizing effect of heparin on blood-derived antimicrobial compounds: impact on antibacterial activity and inflammatory response.

Acting through a combination of direct and indirect pathogen clearance mechanisms, blood-derived antimicrobial compounds (AMCs) play a pivotal role in innate immunity, safeguarding the host against invading microorganisms. Besides their antimicrobial activity, some AMCs can neutralize endotoxins, preventing their interaction with immune cells and avoiding an excessive inflammatory response. In this study, we aimed to investigate the influence of unfractionated heparin, a polyanionic drug clinically used as anticoagulant, on the endotoxin-neutralizing and antibacterial activity of blood-derived AMCs. Serum samples from healthy donors were pre-incubated with increasing concentrations of heparin for different time periods and tested against pathogenic bacteria (Acinetobacter baumannii, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus) and endotoxins from E. coli, K. pneumoniae, and P. aeruginosa. Heparin dose-dependently decreased the activity of blood-derived AMCs. Consequently, pre-incubation with heparin led to increased activity of LPS and higher values of the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6). Accordingly, higher concentrations of A. baumannii, E. coli, K. pneumoniae, and P. aeruginosa were observed as well. These findings underscore the neutralizing effect of unfractionated heparin on blood-derived AMCs in vitro and may lead to alternative affinity techniques for isolating and characterizing novel AMCs with the potential for clinical translation.

Multi-center study on mortality in children, and adults with sickle cell anemia-risk factors and causes of death.

Sickle cell disease (SCD) is a major public health burden worldwide with increasing morbidity and mortality. The study evaluates the risk factors associated with mortality in SCD patients, between the years 2006 and 2020 at three hospitals in Oman. The analysis includes clinical manifestations, haematological, biochemical, and radiological parameters, use of antibiotics, and blood and exchange transfusions. Our cohort included 123 patients (82 males, 41 females), with a median age of 27 (Interquartile Range 21-35 years). SCD related complications included acute chest syndrome (ACS) in 52.8%, splenic sequestration in 21.1%, right upper quadrant syndrome in 19.5%, more than > 6 VOC/year in 17.9%, and stroke in 13.8%. At the terminal admission, patients had cough, reduced O2 saturation, crepitation and fever in 24.4%, 49.6%, 53.6% and 68.3% respectively. Abnormal chest X-ray and chest CT scan were seen in 57.7%, and 76.4% respectively. Laboratory parameters showed a significant drop in hemoglobin (Hb) and platelet counts from baseline, with a significant rise in WBC, LDH and CRP from baseline (p < 0.05, Wilcoxon Signed Ranks test). All patients received antibiotics, whereas, 95.9% and 93.5% received simple blood transfusions, and exchange transfusions respectively, and 66.6% required non-invasive ventilation. Among the causes of death, ACS is seen in 32 (26%), sepsis in 49 (40%), and miscellaneous in 42 (34%). Sudden death was seen in 32 (26%) of patients. Male gender, with low HbF, rapid drop in Hb and platelet, and increased in WBC, LDH, ferritin, and CRP, correlated significantly with mortality in this cohort.

A role for the stringent response in ciprofloxacin resistance in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a major cause of nosocomial infections and the leading cause of chronic lung infections in cystic fibrosis and chronic obstructive pulmonary disease patients. Antibiotic treatment remains challenging because P. aeruginosa is resistant to high concentrations of antibiotics and has a remarkable ability to acquire mutations conferring resistance to multiple groups of antimicrobial agents. Here we report that when P. aeruginosa is plated on ciprofloxacin (cipro) plates, the majority of cipro-resistant (ciproR) colonies observed at and after 48 h of incubation carry mutations in genes related to the Stringent Response (SR). Mutations in one of the major SR components, spoT, were present in approximately 40% of the ciproR isolates. Compared to the wild-type strain, most of these isolates had decreased growth rate, longer lag phase and altered intracellular ppGpp content. Also, 75% of all sequenced mutations were insertions and deletions, with short deletions being the most frequently occurring mutation type. We present evidence that most of the observed mutations are induced on the selective plates in a subpopulation of cells that are not instantly killed by cipro. Our results suggests that the SR may be an important contributor to antibiotic resistance acquisition in P. aeruginosa.

Chondronecrosis of the cricoid treated with hyperbaric oxygen therapy: A case series.

We present two cases of cricoid chondronecrosis treated with hyperbaric oxygen (HBO2) therapy. Both patients presented with biphasic stridor and dyspnea several weeks after an intubation event. Tracheostomy was ultimately performed for airway protection, followed by antibiotic treatment and outpatient HBO2 therapy. Both patients were decannulated within six months of presentation and after at least 20 HBO2 therapy sessions. Despite a small sample size, our findings are consistent with data supporting HBO2 therapy's effects on tissue edema, neovascularization, and HBO2 potentiation of antibiotic treatment and leukocyte function. We suggest HBO2 therapy may have accelerated airway decannulation by way of infection resolution as well as the revitalization of upper airway tissues, ultimately renewing the structural integrity of the larynx. When presented with this rare but significant clinical challenge, physicians should be aware of the potential benefits of HBO2 therapy.

Drug delivery using reduction-responsive hydrogel based on carboxyethyl-succinoglycan with highly improved rheological, antibacterial, and antioxidant properties.

The development of exopolysaccharide-based polymers is gaining increasing attention in various industrial biotechnology fields for materials such as thickeners, texture modifiers, anti-freeze agents, antioxidants, and antibacterial agents. High-viscosity carboxyethyl-succinoglycan (CE-SG) was directly synthesized from succinoglycan (SG) isolated from Sinorhizobium meliloti Rm 1021, and its structural, rheological, and physiological properties were investigated. The viscosity of CE-SG gradually increased in proportion to the degree of carboxyethylation substitution. In particular, when the molar ratio of SG and 3-chloropropionic acid was 1:100, the viscosity was significantly improved by 21.18 times at a shear rate of 10 s-1. Increased carboxyethylation of SG also improved the thermal stability of CE-SG. Furthermore, the CE-SG solution showed 90.18 and 91.78 % antibacterial effects against Escherichia coli and Staphylococcus aureus and effective antioxidant activity against DPPH and hydroxyl radicals. In particular, CE-SG hydrogels coordinated with Fe3+ ions, which improved both viscosity and rheological properties, while also exhibiting reduction-responsive drug release through 1,4-dithiothreitol. The results of this study suggest that SG derivatives, such as CE-SG, can be used as functional biomaterials in various fields such as food, cosmetics, and pharmaceutical industries.

A structure-functionality insight into the bioactivity of microbial polysaccharides toward biomedical applications: A review.

Microbial polysaccharides (MPs) are biopolymers secreted by microorganisms such as bacteria and fungi during their metabolic processes. Compared to polysaccharides derived from plants and animals, MPs have advantages such as wide sources, high production efficiency, and less susceptibility to natural environmental influences. The most attractive feature of MPs lies in their diverse biological activities, such as antioxidative, anti-tumor, antibacterial, and immunomodulatory activities, which have demonstrated immense potential for applications in functional foods, cosmetics, and biomedicine. These bioactivities are precisely regulated by their sophisticated molecular structure. However, the mechanisms underlying this precise regulation are not yet fully understood and continue to evolve. This article presents a comprehensive review of the most representative species of MPs, including their fermentation and purification processes and their biomedical applications in recent years. In particular, this work presents an in-depth analysis into the structure-activity relationships of MPs across multiple molecular levels. Additionally, this review discusses the challenges and prospects of investigating the structure-activity relationships, providing valuable insights into the broad and high-value utilization of MPs.

Biofilm inhibition/eradication: exploring strategies and confronting challenges in combatting biofilm.

Biofilms are complex communities of microorganisms enclosed in a self-produced extracellular matrix, posing a significant threat to different sectors, including healthcare and industry. This review provides an overview of the challenges faced due to biofilm formation and different novel strategies that can combat biofilm formation. Bacteria inside the biofilm exhibit increased resistance against different antimicrobial agents, including conventional antibiotics, which can lead to severe problems in livestock and animals, including humans. In addition, biofilm formation also imposes heavy economic pressure on industries. Hence it becomes necessary to explore newer alternatives to eradicate biofilms effectively without applying selection pressure on the bacteria. Excessive usage of antibiotics may also lead to an increase in the number of resistant strains as bacteria employ an advanced antimicrobial resistance mechanism. This review provides insight into multifaceted technologies like quorum sensing inhibition, enzymes, antimicrobial peptides, bacteriophage, phytocompounds, and nanotechnology to neutralize biofilms without developing antimicrobial resistance (AMR). Furthermore, it will pave the way for developing newer therapeutic agents to deal with biofilms more efficiently.

Post-Transplant Fecal Carriage of Antibiotic Resistant and B-Lactamases-Producing Enterobacteriales among Renal Transplant Recipients.

BACKGROUND: The intestinal colonization and transmission of antibiotic-resistant Enterobacteriales to renal transplant recipients may pose a threat to them because they are profoundly immunocompromised and vulnerable to infection. Hence, it is crucial to identify these antibiotic-resistant fecal Enterobacteriales harboring high-risk populations. The objective of this study was to determine antibiotic resistance as well as ß-lactamases production in fecal Enterobacteriales among renal transplant recipients. METHODS: The stool samples, one collected from each transplant recipient, were processed for isolation and identification of Enterobacteriales and were tested for their antibiotic susceptibility, extended-spectrum ß-lactamase, and metallo-ß-lactamase production by standard methods. RESULTS: A total of 103 Enterobacteriales comprising of Escherichia coli (86.4%), Klebsiella species (11.7%), and Citrobacter species (1.9%) were isolated and more than 60% of the E. coli were found resistant to ceftazidime and ciprofloxacin and around half of the Klebsiella species were resistant to ceftazidime and fluroquinolones. The extended-spectrum ß-lactamase production was seen in 3.4% and 8.3% and metallo-ß-lactamase production in 24.7% and 33.3% of E. coli and Klebsiella species, respectively. The high proportion of ß-lactamase-producers were resistant to piperacillin-tazobactam, meropenem, gentamicin, and amikacin than ß-lactamases non-producers. CONCLUSION: Since the antibiotic resistance is higher in fecal Enterobacteriales, each renal transplant recipient should be screened for these highly resistant intestinal colonizers after transplantation in order to prevent infections and to reduce the rate of transplant failure due to infections.

Antibiotic Susceptibility of Staphylococcus Aureus with VanA and MecA Genes.

BACKGROUND: Staphylococcus aureus (S.aureus) is an emerging antibiotic resistant bacterium responsible for various infections in human. Resistance to methicillin and vancomycin are of prime concern in S. aureus. The study aims to determine the minimum inhibitory concentration (MIC) of Vancomycin and evaluate the existence of mecA and vanA genes, associated with antibiotic resistance. METHODS: Clinical specimens from three Kathmandu hospitals were processed and S. aureus was identified using conventional microbiological procedures. MRSA was phenotypically identified with cefoxitin (30µg) disc diffusion, while vancomycin susceptibility was assessed using the Ezy MICTM stripes. The mecA and vanA genes were detected by polymerase chain reaction (PCR). RESULTS: Out of 266 S. aureus samples from various clinical specimen subjected for analysis, 77 (28.9%) were found methicillin-resistant (MRSA) and 10 (3.8%) were observed vancomycin-resistant (VRSA). Vancomycin resistant isolates showed a significant correlation between resistance to ampicillin, chloramphenicol, and cefoxitin. The mecA gene was found in 39 of the MRSA isolates, having 50.64% of MRSA cases, while the vanA gene was detected in 4 of the VRSA cases, constituting 40% of VRSA occurrences. CONCLUSIONS: The strains with higher vancomycin minimum inhibitory concentration values (≥ 1.5 µg/ml) displayed increased resistance rates to various antibiotics compared to strains with lower minimum inhibitory concentration values (< 1.5 µg/ml). The presence of vanA genes was strongly associated (100%) with vancomycin resistance, while the 10.3% mecA gene was identified from MRSA having resistance towards vancomycin also.

Antibiotic Susceptibility and Biofilm Production among Coagulase Negative Staphylococci Isolated from Clinical Samples at Tertiary Care Hospital.

BACKGROUND: Coagulase Negative Staphylococci have been widely associated with medical device implant treatment and immune-compromised patients. Despite having increasing interest in Coagulase Negative Staphylococci, few studies from Nepal have reported the association of these organisms with urinary tract infections, conjunctivitis, high vaginal swabs, and cerebrospinal fluid. This study was carried out to determine antibiotic susceptibility pattern and biofilm production among Coagulase Negative Staphylococci isolated from clinical samples at tertiary care hospital. METHODS: This study was a hospital based cross-sectional study in which 3690 clinical samples were included. Isolation and identification of isolates was done following standard microbiological protocol. Coagulase Negative Staphylococci were identified phenotypically on the basis of gram staining, slide and tube coagulase test and by various sugar fermentation tests. Antibiotic susceptibility test was done following Kirby Bauer disk diffusion method (Clinical and Laboratory Standards Institute 2020). Biofilm production was determined by Tissue Culture Plate technique. RESULTS: A total of 113 isolates of Coagulase Negative Staphylococci were detected. Among them S. epidermidis (45.1%), S. saprophyticus (23.9%), S. haemolyticus (16.8%), S. hominis (5.3%), S. capitis (2.7%), -----S. cohini (1.8%), S. lugdunensis (1.8%) and S. sciuri (2.7%) were identified phenotypically. All isolates were found to be resistant against Ampicillin and 111 (98.2%) were sensitive against Linezolid.23.9% of CoNS were strong biofilm producers, 19.5% moderate and 56.6 % were non/weak biofilm producers. CONCLUSIONS: It requires susceptibility test for prescribing antibiotics against Coagulase Negative Staphylococci in hospital and the misuse of antibiotics should be prevented.

[Combating antimicrobial resistance: audits of practices to target actions]. / Lutte contre l'antibiorésistance : audits des pratiques pour cibler les actions.

Antibiotic resistance is a public health emergency requiring a concerted approach and motivating the implementation of antibiotic stewardship programmes. As part of an institutional project at the Centre hospitalier universitaire vaudois, we collected data on the appropriateness of antimicrobial prescriptions in various medical and surgical departments in order to identify areas for improvement. The results show that there is room for improvement and that there are differences between departments, particularly regarding surgical prophylaxis administered beyond the operating time, adaptation of the spectrum and duration. Prescribing appropriateness data is an essential complement to consumption data for adapting effective intervention strategies.

L'antibiorésistance constitue une urgence de santé publique justifiant une approche concertée et motivant la mise en place de programmes de gestion des antibiotiques (Antibiotic Stewardship). Dans le cadre d'un projet institutionnel conduit au Centre hospitalier universitaire vaudois, nous avons collecté dans différents services médico-chirurgicaux des données d'adéquation des prescriptions afin d'identifier les domaines d'amélioration. Les résultats obtenus montrent qu'il existe une marge d'amélioration et des différences interservices, en particulier concernant les prophylaxies chirurgicales administrées au-delà du temps opératoire, l'adaptation du spectre et la durée. Les données d'adéquation des prescriptions sont un complément essentiel aux données de consommation pour adapter des stratégies d'intervention efficaces.

Tetrahedral framework nucleic acids/hyaluronic acid-methacrylic anhydride hybrid hydrogel with antimicrobial and anti-inflammatory properties for infected wound healing.

Bacterial resistance and excessive inflammation are common issues that hinder wound healing. Antimicrobial peptides (AMPs) offer a promising and versatile antibacterial option compared to traditional antibiotics, with additional anti-inflammatory properties. However, the applications of AMPs are limited by their antimicrobial effects and stability against bacterial degradation. TFNAs are regarded as a promising drug delivery platform that could enhance the antibacterial properties and stability of nanodrugs. Therefore, in this study, a composite hydrogel (HAMA/t-GL13K) was prepared via the photocross-linking method, in which tFNAs carry GL13K. The hydrogel was injectable, biocompatible, and could be instantly photocured. It exhibited broad-spectrum antibacterial and anti-inflammatory properties by inhibiting the expression of inflammatory factors and scavenging ROS. Thereby, the hydrogel inhibited bacterial infection, shortened the wound healing time of skin defects in infected skin full-thickness defect wound models and reduced scarring. The constructed HAMA/tFNA-AMPs hydrogels exhibit the potential for clinical use in treating microbial infections and promoting wound healing.

Systematic culture of central catheters and infections related to catheters in a neonatal intensive care unit: an observational study.

Systematic culture of the tip of central lines is performed in many neonatal intensive care units (NICUs) to guide any subsequent antibiotic therapy. The clinical relevance of this procedure is debated, given the significant bacterial contamination during its removal. We aimed to describe infections related to catheters and assess the usefulness of central catheter systematic cultures for probabilistic antibiotic therapy in cases of suspicion of catheter-related infections in a NICU. A retrospective study in a NICU included all newborn patients hospitalized with a central catheter, between January 2018, and June 2019. The main outcome measures were bacterial catheter colonization, catheter-related infection rate, and simulation-based approach to antibiotic prescription. Three hundred and seventy-five newborns, with 634 central catheters were included. There were 273 (43%) catheters that were colonized by at least one microorganism. There were 183 cases of suspected sepsis, with 31 infections definitively related to the catheter. In our simulation antibiotic prescription approach, there was no significant difference in terms of the efficacy toward the microorganism(s) involved between the probabilistic antibiotic therapies proposed by the experts and those ultimately prescribed. Performing a catheter culture only if catheter-related infection is suspected could be an alternative to routine screening.

Decision support systems for antibiotic prescription in hospitals: a survey with hospital managers on factors for implementation.

BACKGROUND: Inappropriate antimicrobial use, such as antibiotic intake in viral infections, incorrect dosing and incorrect dosing cycles, has been shown to be an important determinant of the emergence of antimicrobial resistance. Artificial intelligence-based decision support systems represent a potential solution for improving antimicrobial prescribing and containing antimicrobial resistance by supporting clinical decision-making thus optimizing antibiotic use and improving patient outcomes. OBJECTIVE: The aim of this research was to examine implementation factors of artificial intelligence-based decision support systems for antibiotic prescription in hospitals from the perspective of the hospital managers, who have decision-making authority for the organization. METHODS: An online survey was conducted between December 2022 and May 2023 with managers of German hospitals on factors for decision support system implementation. Survey responses were analyzed from 118 respondents through descriptive statistics. RESULTS: Survey participants reported openness towards the use of artificial intelligence-based decision support systems for antibiotic prescription in hospitals but little self-perceived knowledge in this field. Artificial intelligence-based decision support systems appear to be a promising opportunity to improve quality of care and increase treatment safety. Along with the Human-Organization-Technology-fit model attitudes were presented. In particular, user-friendliness of the system and compatibility with existing technical structures are considered to be important for implementation. The uptake of decision support systems also depends on the ability of an organization to create a facilitating environment that helps to address the lack of user knowledge as well as trust in and skepticism towards these systems. This includes the training of user groups and support of the management level. Besides, it has been assessed to be important that potential users are open towards change and perceive an added value of the use of artificial intelligence-based decision support systems. CONCLUSION: The survey has revealed the perspective of hospital managers on different factors that may help to address implementation challenges for artificial intelligence-based decision support systems in antibiotic prescribing. By combining factors of user perceptions about the systems´ perceived benefits with external factors of system design requirements and contextual conditions, the findings highlight the need for a holistic implementation framework of artificial intelligence-based decision support systems.

Antimicrobial peptide thanatin fused endolysin PA90 (Tha-PA90) for the control of Acinetobacter baumannii infection in mouse model.

BACKGROUND: This study addresses the urgent need for infection control agents driven by the rise of drug-resistant pathogens such as Acinetobacter baumannii. Our primary aim was to develop and assess a novel endolysin, Tha-PA90, designed to combat these challenges. METHODS: Tha-PA90 incorporates an antimicrobial peptide (AMP) called thanatin at its N-terminus, enhancing bacterial outer membrane permeability and reducing host immune responses. PA90 was selected as the endolysin component. The antibacterial activity of the purified Tha-PA90 was evaluated using an in vitro colony-forming unit (CFU) reduction assay and a membrane permeability test. A549 cells were utilized to measure the penetration into the cytosol and the cytotoxicity of Tha-PA90. Finally, infection control was monitored in A. baumannii infected mice following the intraperitoneal administration of Tha-PA90. RESULTS: Tha-PA90 demonstrated remarkable in vitro efficacy, completely eradicating A. baumannii strains, even drug-resistant variants, at a low concentration of 0.5 µM. Notably, it outperformed thanatin, achieving only a < 3-log reduction at 4 µM. Tha-PA90 exhibited 2-3 times higher membrane permeability than a PA90 and thanatin mixture or PA90 alone. Tha-PA90 was found within A549 cells' cytosol with no discernible cytotoxic effects. Furthermore, Tha-PA90 administration extended the lifespan of A. baumannii-infected mice, reducing bacterial loads in major organs by up to 3 logs. Additionally, it decreased proinflammatory cytokine levels (TNF-α and IL-6), reducing the risk of sepsis from rapid bacterial lysis. Our findings indicate that Tha-PA90 is a promising solution for combating drug-resistant A. baumannii. Its enhanced efficacy, low cytotoxicity, and reduction of proinflammatory responses render it a potential candidate for infection control. CONCLUSIONS: This study underscores the significance of engineered endolysins in addressing the pressing challenge of drug-resistant pathogens and offers insights into improved infection management strategies.

Antimicrobial resistance prediction by clinical metagenomics in pediatric severe pneumonia patients.

BACKGROUND: Antimicrobial resistance (AMR) is a major threat to children's health, particularly in respiratory infections. Accurate identification of pathogens and AMR is crucial for targeted antibiotic treatment. Metagenomic next-generation sequencing (mNGS) shows promise in directly detecting microorganisms and resistance genes in clinical samples. However, the accuracy of AMR prediction through mNGS testing needs further investigation for practical clinical decision-making. METHODS: We aimed to evaluate the performance of mNGS in predicting AMR for severe pneumonia in pediatric patients. We conducted a retrospective analysis at a tertiary hospital from May 2022 to May 2023. Simultaneous mNGS and culture were performed on bronchoalveolar lavage fluid samples obtained from pediatric patients with severe pneumonia. By comparing the results of mNGS detection of microorganisms and antibiotic resistance genes with those of culture, sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: mNGS detected bacterial in 71.7% cases (86/120), significantly higher than culture (58/120, 48.3%). Compared to culture, mNGS demonstrated a sensitivity of 96.6% and a specificity of 51.6% in detecting pathogenic microorganisms. Phenotypic susceptibility testing (PST) of 19 antibiotics revealed significant variations in antibiotics resistance rates among different bacteria. Sensitivity prediction of mNGS for carbapenem resistance was higher than penicillins and cephalosporin (67.74% vs. 28.57%, 46.15%), while specificity showed no significant difference (85.71%, 75.00%, 75.00%). mNGS also showed a high sensitivity of 94.74% in predicting carbapenem resistance in Acinetobacter baumannii. CONCLUSIONS: mNGS exhibits variable predictive performance among different pathogens and antibiotics, indicating its potential as a supplementary tool to conventional PST. However, mNGS currently cannot replace conventional PST.

Improving Antibiotic Overuse in Primary Care: A Multimodal Quality Improvement Project.

PURPOSE: Antibiotic overuse has increased over time related to provider knowledge gaps about best practices, provider perception of patient expectations on receiving an antibiotic, possible pressure to see patients in a timely fashion, and concerns about decreased patient satisfaction when an antibiotic is not prescribed. The Centers for Disease Control and Prevention estimates that up to 30% of antibiotics are inappropriately prescribed in the outpatient setting. APPROACH: This quality improvement project consisted of a multimodal approach to decrease inappropriate antibiotic prescribing for viral upper respiratory infections (URIs) by using provider education, passive patient education, and clinical decision support tools based on Centers for Disease Control and Prevention recommendations and the Be Antibiotic Aware tool. OUTCOMES: Following implementation, there was an 11% decrease in viral URI antibiotic prescribing, from a rate of 29.33% to 18.33% following the multimodal implementation. CONCLUSION: The use of evidence-based education and treatment guidelines was found to decrease inappropriate antibiotic prescribing for patients diagnosed with viral URIs.

Comprehensive analysis of antimicrobial resistance in the Southwest Indian Ocean: focus on WHO critical and high priority pathogens.

The spread of antimicrobial resistance (AMR) is a major global concern, and the islands of the Southwest Indian Ocean (SWIO) are not exempt from this phenomenon. As strategic crossroads between Southern Africa and the Indian subcontinent, these islands are constantly threatened by the importation of multidrug-resistant bacteria from these regions. In this systematic review, our aim was to assess the epidemiological situation of AMR in humans in the SWIO islands, focusing on bacterial species listed as priority by the World Health Organization. Specifically, we examined Enterobacterales, Acinetobacter spp., Pseudomonas spp. resistant to carbapenems, and Enterococcus spp. resistant to vancomycin. Our main objectives were to map the distribution of these resistant bacteria in the SWIO islands and identify the genes involved in their resistance mechanisms. We conducted literature review focusing on Comoros, Madagascar, Maldives, Mauritius, Mayotte, Reunion Island, Seychelles, Sri Lanka, and Zanzibar. Our findings revealed a growing interest in the investigation of these pathogens and provided evidence of their active circulation in many of the territories investigated. However, we also identified disparities in terms of data availability between the targeted bacteria and among the different territories, emphasizing the need to strengthen collaborative efforts to establish an efficient regional surveillance network.

Klebsiella pneumoniae sequence type 147: a high-risk clone increasingly associated with plasmids carrying both resistance and virulence elements.

Introduction. The first hybrid resistance/virulence plasmid, combining elements from virulence plasmids described in hypervirulent types of Klebsiella pneumoniae with those from conjugative resistance plasmids, was described in an isolate of sequence type (ST) 147 from 2016. Subsequently, this type has been increasingly associated with these plasmids.Hypothesis or gap statement. The extent of carriage of hybrid virulence/resistance plasmids in nosocomial isolates of K. pneumoniae requires further investigation.Aim. To describe the occurrence of virulence/resistance plasmids among isolates of K. pneumoniae received by the UK reference laboratory, particularly among representatives of ST147, and to compare their sequences.Methodology. Isolates received by the laboratory during 2022 and the first half of 2023 (n=1278) were screened for virulence plasmids by PCR detection of rmpA/rmpA2 and typed by variable-number tandem repeat analysis. Twenty-nine representatives of ST147 (including a single-locus variant) from seven hospital laboratories were subjected to long-read nanopore sequencing using high-accuracy q20 chemistry to provide complete assemblies.Results. rmpA/rmpA2 were detected in 110 isolates, of which 59 belonged to hypervirulent K1-ST23, K2-ST86 and K2-ST65/375. Of the remainder, representatives of ST147 formed the largest group, with 22 rmpA/rmpA2-positive representatives (out of 47 isolates). Representatives were from 19 hospital laboratories, with rmpA/rmpA2-positive isolates from 10. Nanopore sequencing of 29 representatives of ST147 divided them into those with no virulence plasmid (n=12), those with non-New Delhi metallo-ß-lactamase (NDM) virulence plasmids (n=6) and those carrying bla NDM-5 (n=9) or bla NDM-1 (n=2) virulence plasmids. These plasmids were of IncFIB(pNDM-Mar)/IncHI1B(pNDM-MAR) replicon types. Most of the non-NDM virulence plasmids were highly similar to the originally described KpvST147L_NDM plasmid. Those carrying bla NDM-5 were highly similar to one another and to previously described plasmids in ST383 and carried an extensive array of resistance genes. Comparison of the fully assembled chromosomes indicated multiple introductions of ST147 in UK hospitals.Conclusion. This study highlights the high proportion of representatives of ST147 that carry IncFIB(pNDM-Mar)/IncHI1B(pNDM-MAR) hybrid resistance virulence plasmids. It is important to be aware of the high probability that representatives of this type carry these plasmids combining resistance and virulence determinants and of the consequent increased risk to patients.