[Molecular diagnosis of bacteriaemia: benefits of using the FilmArray® BCID2 sepsis panel in a third level hospital]. / Diagnóstico molecular de bacteriemias: beneficios del empleo del panel de sepsis BCID2 de Filmarray® en un hospital de tercer nivel.

INTRODUCTION: Delay in initiating appropriate antimicrobial therapy prolongs hospitalization, increases in-hospital mortality, and raises economic costs. Currently, the identification and susceptibility testing of bacteria in positive blood cultures require a considerable amount of time. The objective of this study was to assess the impact of the BCID2 FilmArray® (FA) panel on the timing of appropriate antimicrobial therapy and potential antimicrobial costs. METHODS: This is a retrospective observational study focused on positive blood cultures in hospitalized patients. FA processing was conducted concurrently with routine sample processing. Changes in antibiotic treatments based on FA results were evaluated, and the reduction in antimicrobial therapy duration and associated cost savings were calculated. RESULTS: Eighty-seven bacteremia episodes were analysed. In 42 (48%) of them antimicrobial therapy was de-escalated to narrower spectrum agents, while in 7 (8%) therapy was escalated to broader spectrum antimicrobials. Additionally, in 8 (9%) antimicrobials were switched without changing spectrum and in 30 (34%) no changes were made based on FA results. Antimicrobial changes were made 2.3 days faster than with routine sample processing resulting in calculated potential savings of US$ 7408. CONCLUSION: The implementation of FA facilitated a faster administration of appropriate antimicrobial therapy, leading to a reduction in the duration of broadspectrum empirical antimicrobial therapy and subsequent economic savings.

Introducción: Los retrasos en el tratamiento antimicrobiano adecuado de las bacteriemias prolongan la estadía hospitalaria, aumentan la mortalidad e incrementan los costos. Aún hoy en día se requiere un tiempo considerable para obtener la identificación y antibiograma de los microorganismos en los hemocultivos positivos. El objetivo fue evaluar el impacto de la implementación del panel BCID2 de FilmArray® (FA) sobre el tiempo de inicio de tratamientos antimicrobianos adecuados y sobre los costos potenciales de los mismos. Métodos: Estudio observacional retrospectivo de los hemocultivos positivos de pacientes hospitalizados, procesados por FA y por metodología tradicional. Se evaluaron los cambios de antimicrobianos en base a los resultados del FA. Se calcularon los días de reducción de tratamiento antimicrobiano y el ahorro potencial en el uso de los mismos, teniendo en cuenta también los costos del FA. Resultados: Se analizaron 87 episodios de bacteriemia. En 42 (48.3%) de ellos se desescaló el tratamiento a antimicrobianos de menor espectro, en 7 (8%) se escaló a antimicrobianos de mayor espectro, en 8 (9.2%) se cambió el antimicrobiano sin variar el espectro y en 30 (34.5%) no se realizaron cambios con los resultados del FA. Los cambios de antimicrobianos se realizaron en promedio 2.3 días más rápido que con los métodos convencionales. Se calculó un ahorro potencial de US$ 7408. Conclusión: La implementación del panel BCID2 de FilmArray® permitió adecuar los tratamientos antimicrobianos más rápidamente acortando la duración de los tratamientos empíricos de amplio espectro, lo cual resultó costo-efectivo.

Sex-dependent effects of antimicrobials and lipopolysaccharide on blood-brain-barrier permeability in pubertal male and female CD1 mice.

Exposure to stressors during puberty can disrupt normal development and possibly increase susceptibility to neurodegenerative disorders later in life. However, the mechanisms underlying the relationship between pubertal stress exposure and neurodegeneration remain unclear. As such, the current study was designed to examine the effects of pubertal antimicrobial (AMNS) and lipopolysaccharide (LPS) treatments on intestinal and blood-brain-barrier (BBB) permeability in male and female mice. Moreover, we also examined the sex-specific effects of pubertal AMNS and LPS treatments on gross motor activity, heart rate, and core body temperature. At four weeks of age, male and female CD1 mice were implanted with the G2 HR E-Mitter telemetry system. At five weeks of age, mice received 200 µL of broad-spectrum antimicrobial or water, through oral gavage, twice daily for seven days. Mice received an intraperitoneal injection of either saline or LPS at six weeks of age. BBB and intestinal permeability were examined 24 h, 72 h, and one week post-LPS/saline treatment. Telemetric data was collected for 48 h post-LPS/saline treatment. The results showed that pubertal AMNS and LPS treatments increased sickness behaviours and decreased body temperature and heart rate, in a sex-dependent manner. Furthermore, pubertal AMNS and LPS treatments resulted in sex-dependent regional increases in BBB permeability 24 h and 72 h post-LPS/saline treatment, while global increases in BBB permeability were only observed one week post-LPS/saline treatment. These results further our understanding of the combined effects of AMNS and LPS treatments on physiology and on the enduring negative changes observed following pubertal exposure to stressors.

Advances of antimicrobial dressings loaded with antimicrobial agents in infected wounds.

Wound healing is a complex process that is critical for maintaining the barrier function of the skin. However, when a large quantity of microorganisms invade damaged skin for an extended period, they can cause local and systemic inflammatory responses. If left untreated, this condition may lead to chronic infected wounds. Infected wounds significantly escalate wound management costs worldwide and impose a substantial burden on patients and healthcare systems. Recent clinical trial results suggest that the utilization of effective antimicrobial wound dressing could represent the simplest and most cost-effective strategy for treating infected wounds, but there has hitherto been no comprehensive evaluation reported on the efficacy of antimicrobial wound dressings in promoting wound healing. Therefore, this review aims to systematically summarize the various types of antimicrobial wound dressings and the current research on antimicrobial agents, thereby providing new insights for the innovative treatment of infected wounds.

The enduring effects of antimicrobials and lipopolysaccharide on the cellular mechanisms and behaviours associated with neurodegeneration in pubertal male and female CD1 mice.

Puberty is a sensitive developmental period during which stressors can cause lasting brain and behavioural deficits. While the acute effects of pubertal lipopolysaccharide (LPS) and antimicrobial (AMNS) treatments are known, their enduring impacts on neurodegeneration-related mechanisms and behaviours remain unclear. This study examined these effects in male and female mice. At five weeks old, mice received 200ul of either broad-spectrum antimicrobials or water through oral gavage twice daily for seven days. At six weeks of age, they received an intraperitoneal injection of either saline or LPS. Four weeks later, adult mice underwent neurodegeneration-related behavioural tests, including the rotarod, forepaw stride length, reversed grid hang, open field, and buried pellet tests. Two days after the final test, brain and ileal samples were collected. Results showed that female mice treated with both AMNS and LPS exhibited deficits in neuromuscular strength, while males treated with LPS alone showed increased anxiety-like behaviours. Males treated with AMNS alone had decreased sigma-1 receptor (S1R) expression in the cornu ammonis 1 (CA1) and dentate gyrus (DG), while females treated with both AMNS and LPS had decreased S1R expression. Additionally, males treated with either LPS or AMNS had lower glial-derived neurotrophic factor receptor alpha-1 (GFRA1) expression in the primary motor cortex (M1) than females. Mice treated with LPS alone had decreased GFRA1 expression in the DG and decreased S1R expression in the secondary motor cortex (M2). These findings suggest that pubertal AMNS and LPS treatments may lead to enduring changes in biomarkers and behaviours related to neurodegeneration.

A novel PCR-based genotyping method for Proteus mirabilis - Intergenic region polymorphism analysis.

Proteus mirabilis is a predominant species in cases of food poisoning associated with meat products and is also an opportunistic pathogen causing numerous infections in humans. This study aimed to differentiate P. mirabilis isolates using intergenic region polymorphism analysis (IRPA). The IRPA typing scheme was developed to amplify polymorphic fragments in intergenic regions (IGRs). The presence, absence, or size change of amplified products were identified and utilized as genetic markers for rapid differentiation of strains. A total of 75 P. mirabilis isolates were isolated from 63 fresh poultry and pork samples were subtyped using the IRPA and ERIC-PCR methods, and their antibiotic resistance profiles were tested. The majority of P. mirabilis isolates showed resistance to tetracycline (85.3%), doxycycline (93.3%), chloramphenicol (82.7%), streptomycin (92.0%), spectinomycin (80.0%), trimethoprim (97.3%); trimethoprim-sulfalleth (82.7%), and erythromycin (100.0%). In contrast, resistance rates to ceftriaxon, cefoxitin, cefepime, and cefotaxim were lower at only 17.3%, 5.3%, 6.7%, and 13.3%, respectively, among P. mirabilis isolates. Eleven loci were selected for analysis of the genetic diversity of 75 P. mirabilis isolates. A combination of 4 loci was determined as the optimal combination. The results compared to those obtained using ERIC-PCR for the same isolates. The Simpson's index of diversity was 0.999 for IRPA and 0.923 for ERIC-PCR, indicating that IRPA has a higher discriminatory power than ERIC-PCR. The concordance between IRPA and ERIC-PCR methods was low, primarily because IRPA classified isolates from the same ERIC cluster into separate clusters due to its high resolution. The IRPA method presented in this study offers a rapid, simple, reproducible, and economical approach for genotyping P. mirabilis.

Exploring antimicrobial interactions between metal ions and quaternary ammonium compounds toward synergistic metallo-antimicrobial formulations.

Multi-target antimicrobial agents are considered a viable alternative to target-specific antibiotics, resistance to which emerged as a global threat. Used centuries before the discovery of conventional antibiotics, metal(loid)-based antimicrobials (MBAs), which target multiple biomolecules within the bacterial cell, are regaining research interest. However, there is a significant limiting factor-the balance between cost and efficiency. In this article, we utilize a checkerboard assay approach to explore antimicrobial combinations of MBAs with commonly used quaternary ammonium compound (QAC) antiseptics in order to discover novel combinations with more pronounced antimicrobial properties than would be expected from a simple sum of antimicrobial effects of initial components. This phenomenon, called synergy, was herein demonstrated for several mixtures of Al3+with cetyltrimethylammonium bromide (CTAB) and TeO32- with benzalkonium chloride (BAC) and didecyldimethylammonium bromide (DDAB) against planktonic and biofilm growth of Pseudomonas aeruginosa ATCC27853. Biofilm growth of Escherichia coli ATCC25922 was synergistically inhibited by the Cu2 +and benzalkonium chloride (BAC) mixture. Multiple additive mixtures were identified for both organisms. The current study observed unexpected species and growth state specificities for the synergistic combinations. The benefit of synergistic mixtures will be captured in economy/efficiency optimization for antimicrobial applications in which MBAs and QACs are presently used. IMPORTANCE: We are entering the antimicrobial resistance era (AMR), where resistance to antibiotics is becoming more and more prevalent. In order to address this issue, various approaches are being explored. In this article, we explore for synergy between two very different antimicrobials, the antiseptic class of quaternary ammonium compounds and antimicrobial metals. These two antimicrobials have very different actions. Considering a OneHealth approach to the problem, finding synergistic mixtures allows for greater efficacy at lower concentrations, which would also address antimicrobial pollution issues.

Role of bacteriophages in shaping gut microbial community.

Phages are the most diversified and dominant members of the gut virobiota. They play a crucial role in shaping the structure and function of the gut microbial community and consequently the health of humans and animals. Phages are found mainly in the mucus, from where they can translocate to the intestinal organs and act as a modulator of gut microbiota. Understanding the vital role of phages in regulating the composition of intestinal microbiota and influencing human and animal health is an emerging area of research. The relevance of phages in the gut ecosystem is supported by substantial evidence, but the importance of phages in shaping the gut microbiota remains unclear. Although information regarding general phage ecology and development has accumulated, detailed knowledge on phage-gut microbe and phage-human interactions is lacking, and the information on the effects of phage therapy in humans remains ambiguous. In this review, we systematically assess the existing data on the structure and ecology of phages in the human and animal gut environments, their development, possible interaction, and subsequent impact on the gut ecosystem dynamics. We discuss the potential mechanisms of prophage activation and the subsequent modulation of gut bacteria. We also review the link between phages and the immune system to collect evidence on the effect of phages on shaping the gut microbial composition. Our review will improve understanding on the influence of phages in regulating the gut microbiota and the immune system and facilitate the development of phage-based therapies for maintaining a healthy and balanced gut microbiota.

Prevalence and antimicrobial resistance trends among vaginal bacteria isolates from pregnant bitches.

Many of the reproductive tract infections in the bitches are caused by bacteria that can normally be present on the vaginal mucosa. These bacteria also might have an important role as the cause responsible for pregnancy loss and fetal deaths. The choice of antibiotic therapy for the pregnant animal is narrow and represents a severe problem in veterinary practice, especially due to increased antimicrobial resistance. Due to incorrect antimicrobials use in breeding kennels, the aim of the present study was to assess the occurrence of the bacterial flora isolated from the pregnant bitches and their antibiotic sensitivity. The study was carried out at the private Veterinary clinic in Novi Sad, Serbia. The vaginal swabs were taken from 60 bitches diagnosed with pregnancy and were sent to be laboratory tested. Based on the results, the most common isolated pathogens were Staphylococcus pseudintermedius (20%) and beta-hemolytic streptococci (18.33%). Furthermore, significant resistance to antibiotics from beta-lactams group was detected. It is of particular importance that antimicrobial treatment be evidence based in order to reduce the overuse of antimicrobials due to increased concern regarding antimicrobial resistance.

Peri-anaesthetic complications in 1798 equids undergoing high-field elective orthopaedic MRI at a tertiary referral hospital.

BACKGROUND: Antimicrobial prophylaxis for elective orthopaedic magnetic resonance imaging (MRI) in equids is a topic of debate among practitioners and can have negative detrimental effects on patients if used unnecessarily. OBJECTIVES: To describe the complications with elective orthopaedic MRI of horses, mules, and donkeys under general anaesthesia without the use of peri-anaesthetic antimicrobial prophylaxis at a single large tertiary referral centre. We hypothesised that horses, mules, and donkeys undergoing general anaesthesia for elective orthopaedic MRI, without antimicrobial prophylaxis, will not be at increased risk of complications, including increased risk of infectious respiratory disease. STUDY DESIGN: Retrospective cross-sectional study. METHODS: This retrospective study of 1798 systemically healthy equids that underwent elective orthopaedic MRI under general anaesthesia without peri-anaesthetic antimicrobial prophylaxis between January 2009 and May 2020. RESULTS: A total of 1655 MRIs were included in the study, with 25 (1.5%) horses having complications. The most common complication was post-anaesthetic fever in 11 (0.7%) horses, of which 4 (0.2%) horses went on to develop pneumonia and one horse was diagnosed with equine herpesvirus (respiratory). Seven (0.4%) horses developed transient post-anaesthetic femoral neuropathy and 7 (0.4%) horses had mild post-anaesthetic colic that resolved with initial medical management. No horses were euthanised or died in this study. MAIN LIMITATIONS: The retrospective nature of the study led to non-randomised case selection, and some records were incomplete. CONCLUSIONS: These findings suggest that peri-anaesthetic antimicrobial prophylaxis may not be necessary for performance and sport horses undergoing general anaesthesia for elective orthopaedic MRI.

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity.

Antimicrobial resistance presents a substantial threat to global public health, demanding urgent attention and action. This study focuses on lanthipeptides, ribosomally encoded peptides that display significant structural diversity and hold promising potential as antibiotics. Genome mining was employed to locate biosynthetic gene clusters (BGCs) containing class II lanthipeptide synthetases encoded by lanM genes. A phylogenetic study analyzing homologous sequences of functional LanM sequences revealed a unique evolutionary clade of 17 LanM proteins associated with 12 Clostridium bacterial genomes. In silico exploration identified nine complete BGCs, including one super-cluster containing two co-localized operons from Clostridium cellulovorans 743B, that encode for two new peptides named clostrisin and cellulosin. Each operon was heterologously expressed in Escherichia coli. Molecular weights associated with the expected post-translational modifications of the purified lanthipeptide were confirmed by MS-MS/MS analysis for cellulosin, while clostrisin was not post-translationally modified. Both peptides demonstrated antimicrobial activity against multidrug-resistant bacteria, such as a clinical strain of Staphylococcus epidermidis MIQ43 and Pseudomonas aeruginosa PA14. This is the first report of lanthipeptides from the Clostridium genus produced with its native biosynthetic machinery, as well as chemically and biologically characterized. This study showcases the immense potential of genome mining in identifying new RiPP synthetases and associated bioactive peptides.

Endolysin CHAP domain-carbosilane metallodendrimer complexes with triple action on Gram-negative bacteria: Membrane destabilization, reactive oxygen species production and peptidoglycan degradation.

Bacterial resistance to antibiotics is a significant challenge that is associated with increased morbidity and mortality. Gram-negative bacteria are particularly problematic due to an outer membrane (OM). Current alternatives to antibiotics include antimicrobial peptides or proteins and multifunctional systems such as dendrimers. Antimicrobial proteins such as lysins can degrade the bacterial cell wall, whereas dendrimers can permeabilize the OM, enhancing the activity of endolysins against gram-negative bacteria. In this study, we present a three-stage action of endolysin combined with two different carbosilane (CBS) silver metallodendrimers, in which the periphery is modified with N-heterocyclic carbene (NHC) ligands coordinating a silver atom. The different NHC ligands contained hydrophobic methyl or N-donor pyridyl moieties. The effects of these endolysin/dendrimer combinations are based on OM permeabilization, peptidoglycan degradation, and reactive oxygen species production. The results showed that CBS possess a permeabilization effect (first action), significantly reduced bacterial growth at higher concentrations alone and in the presence of endolysin, increased ROS production (second action), and led to bacterial cell damage (third action). The complex formed between the CHAP domain of endolysin and a CBS silver metallodendrimer, with a triple mechanism of action, may represent an excellent alternative to other antimicrobials with only one resistance mechanism.

Identification of Ribonuclease Inhibitors for the Control of Pathogenic Bacteria.

Bacteria are known to be constantly adapting to become resistant to antibiotics. Currently, efficient antibacterial compounds are still available; however, it is only a matter of time until these compounds also become inefficient. Ribonucleases are the enzymes responsible for the maturation and degradation of RNA molecules, and many of them are essential for microbial survival. Members of the PNPase and RNase II families of exoribonucleases have been implicated in virulence in many pathogens and, as such, are valid targets for the development of new antibacterials. In this paper, we describe the use of virtual high-throughput screening (vHTS) to identify chemical compounds predicted to bind to the active sites within the known structures of RNase II and PNPase from Escherichia coli. The subsequent in vitro screening identified compounds that inhibited the activity of these exoribonucleases, with some also affecting cell viability, thereby providing proof of principle for utilizing the known structures of these enzymes in the pursuit of new antibacterials.

Implementing an Antimicrobial Stewardship Program in an Oncology Center in Lima, Peru: A Model for Low- and Middle-Income Countries.

Our center launched the first antimicrobial stewardship program in Peru. From 2016 to 2023, the proportion of antimicrobial prescriptions audited increased from 60% to 95%, and 65% to 95% of recommendations were accepted. Vancomycin and meropenem use dropped by 95% and 84%, respectively. The proportion of recommendations for surgical prophylaxis exceeded 90%.

Alginate composite films incorporated with Zn-based inorganic antimicrobials for food packaging: Effects of morphology.

Biopolymers-based food packaging materials have drawn attention as potential candidates for substitution of petroleum-based materials. In this study, composite alginate films were developed by incorporating Zn-based antimicrobials to overcome the intrinsic disadvantages of alginates that hinder their wide applications. Antimicrobials with different morphologies (nanoplatelets, nanorods, and nanospheres) were employed to investigate the effects of antimicrobials' morphology on antibacterial, thermal, mechanical, and barrier performance of composite alginate films. Meanwhile, morphological and structural characterizations were carried out to explore the interactions between antimicrobials and alginate matrix. Results indicated that films with nanospheres exhibited superior antibacterial property, while those with one-dimensional nanorods possessed better mechanical and barrier performance. Besides, preliminary test on fresh-cut potatoes and chicken breasts indicated that the composite films showed potential in extending shelf life of foods. By incorporating antimicrobials with three different morphologies, this study provides particular insights into improving properties of composite packaging materials.

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.

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.

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.

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.

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.

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.