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Early appropriate antimicrobial therapy plays a critical role for patients with Staphylococcus aureus bloodstream infection (SAB). We aim to determine the optimal time-window for appropriate antimicrobial therapy and evaluate the effects of delayed therapy on adverse clinical outcomes (in-hospital mortality, sepsis, and septic shock) in children with SAB by propensity score matching (PSM) analysis. Receiver-operating characteristic was used to determine the cut-off point of the time to appropriate therapy (TTAT), the patients were divided into timely and delayed appropriate antimicrobial therapy (delayed therapy) groups accordingly. The PSM was used to balance the characteristics between the two groups, controlling the effects of potential confounders. Kaplan-Meier methods and Cox proportional hazards regression were applied to the matched groups to analyze the association between delayed therapy and clinical outcomes. Inverse probability of treatment weighting and propensity score covariate adjustment were also performed to investigate the sensitivity of the results under different propensity score-based approaches. In total, 247 patients were included in this study. The optimal cut-off point of TTAT was identified as 6.4 h, with 85.0% sensitivity and 69.2% specificity (AUC 0.803, 95% confidence interval 0.702–0.904). Eighty-seven (35.22%) of the 247 patients who received delayed therapy (TTAT ≥ 6.4 h) had higher in-hospital mortality (19.54% vs 1.88%, p < 0.001), higher incidences of sepsis (44.83% vs 15.00%, p < 0.001) and septic shock (32.18% vs 6.25%, p < 0.001) when compared to timely therapy (TTAT < 6.4 h) patients. After PSM analysis, a total of 134 episodes (67 in each of the two matched groups) were further analyzed. No statistically significant difference was observed in in-hospital mortality between delayed and timely -therapy groups (log-rank test, P = 0.157). Patients with delayed therapy had a higher incidence of sepsis or septic shock than those with timely therapy (log-rank test, P = 0.009; P = 0.018, respectively). Compared to the timely-therapy group, the hazard ratio and 95% confidence interval in delayed-therapy group were 2.512 (1.227–5.144, P = 0.012) for sepsis, 3.109 (1.166–8.290, P = 0.023) for septic shock. Conclusion: Appropriate therapy delayed 6.4 h may increase the incidence of sepsis and septic shock, with similar in-hospital mortality in patients with SAB. What is Known: • Staphylococcus aureus (S. aureus) is a major cause of bloodstream infections in children. Undoubtedly, early antimicrobial application plays a critical role in the treatment of children with Staphylococcus aureus bloodstream infections (SAB). • However, rapid, and aggressive administration of antimicrobials may lead to the overuse of these drugs and the emergence of multidrug-resistant microorganisms. Therefore, it is crucial to determine the optimal time-window for appropriate antimicrobial administration in children with SAB. Unfortunately, the optimal time-window for appropriate antimicrobial administration in children with SAB remains unclear. What is New: • Determining the optimal time-window for appropriate antimicrobial administration in patients with matched data variables is particularly important. The Propensity score matching (PSM) analysis effectively controls for confounding factors to a considerable extent when assessing the impact of treatment, thereby approximating the effects observed in randomized controlled trials. • To our knowledge, this is the first study using PSM method to assess the effects of delayed appropriate antimicrobial therapy on adverse outcomes in children with SAB. In low-risk populations with SAB, a delay of 6.4 h in appropriate therapy might increase the occurrence rate for sepsis and septic shock; however, no correlation has been found between this delay and an increased risk for hospital mortality. [ABSTRACT FROM AUTHOR]

Background: Open fractures are challenging due to susceptibility to Staphylococcus aureus infections. This study examines the impact of Vancomycin-Loaded Calcium Sulfate (VLCS) and negative pressure wound therapy (NPWT) on macrophage behavior in enhancing healing and infection resistance. Both VLCS and NPWT were evaluated individually and in combination to determine their effects on macrophage polarization and infection resistance in open fractures. Methods: Through single-cell RNA sequencing, genomic expressions in macrophages from open fracture patients treated with VLCS and NPWT were compared to a control group. The analysis focused on MBD2 gene changes related to macrophage polarization. Results: Remarkable modifications in MBD2 expression in the treatment group indicate a shift towards M2 macrophage polarization. Additionally, the combined treatment group exhibited greater improvements in infection resistance and healing compared to the individual treatments. This shift suggests a healing-promoting atmosphere with improved infection resilience. Conclusions: VLCS and NPWT demonstrate the ability to alter macrophage behavior toward M2 polarization, which is crucial for infection prevention in open fractures. The synergistic effect of their combined use shows even greater promise in enhancing outcomes in orthopedic trauma care. [ABSTRACT FROM AUTHOR]

AbstractPurposeMaterials and MethodsResultsConclusionsRadiation cystitis (RC) is a complex and common complication after radiotherapy for pelvic cancer. Icariside II (ICAII) is a flavonoid compound extracted from Epimedium, a traditional Chinese medicine, with various pharmacological activities. The aim of the present study was to investigate the cysto-protective effects of ICAII in RC rats and its possible mechanisms.A rat model of induced radiation cystitis using pelvic X-ray irradiation was used, and bladder function was assessed by bladder volume and bladder leakage point pressure (LPP) after ICAII treatment. HE and Masson stains were used to assess the histopathological changes in the bladder. IL-6, TNF-α, IL-10, IL-4 and IL-1β were measured by ELISA to assess the level of inflammation. The gene-level changes in ICAII-treated RC were observed by transcriptome sequencing, and then the potential targets of action and biological mechanisms were explored by PPI, GO and KEGG enrichment analysis of the differentially expressed genes. Finally, the predicted targets of action were experimentally validated using immunohistochemistry, RT–qPCR, molecular docking and CETSA.ICAII significantly increased bladder volume and the LPP, ameliorated pathological damage to bladder tissues, decreased the levels of IL-6, TNF-α, and IL-1β, and increased the levels of IL-10 and IL-4 in radiation-injured rats. A total of 90 differentially expressed genes were obtained by transcriptome sequencing, and PPI analysis identified H3F3C, ISG15, SPP1, and LCN2 as possible potential targets of action. GO and KEGG analyses revealed that these differentially expressed genes were mainly enriched in the pathways metabolism of xenobiotics by cytochrome P450, arachidonic acid metabolism, Staphylococcus aureus infection and chemical carcinogenesis - reactive oxygen species. Experimental validation showed that ICAII could significantly increase the expression of H3F3C and ISG15 and inhibit the expression of SPP1 and LCN2. ICAII binds well to H3F3C, ISG15, SPP1 and LCN2, with the best binding ability to H3F3C. Furthermore, ICAII inhibited the protein degradation of H3F3C in bladder epithelial cells.ICAII may alleviate the bladder inflammatory response and inhibit the fibrosis process of bladder tissues through the regulation of H3F3C, ISG15, SPP1, and LCN2 targets and has a protective effect on the bladder of radioinjured rats. In particular, H3F3C may be one of the most promising therapeutic targets. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus infection and colonization in patients may be transmitted to healthcare providers and the environment and subsequently cause healthcare-associated infections in other patients. Pathogenic S. aureus strains produce virulence factors, such as Panton-Valentine Leukocidin (PVL), that contribute to the severity of infections and aid in their spread. The emergence of antimicrobial resistance (AMR) is additional concern with respect to S. aureus infection. In this study, the virulence genes and antibiotic resistance profiles of S. aureus were characterized from patients' clinical isolates, healthcare workers' (HCWs') nasal colonization screenings, and the environment at a tertiary healthcare hospital in Addis Ababa, Ethiopia. A total of 365 samples were collected from September 2021 to September 2022: 73 patients' clinical specimens, 202 colonization screenings from HCWs, and 90 hospital environment's swabs. Fifty-one (25.2%) HCW and 10/90 (11.1%) environment S. aureus isolates were identified. Among the 134 isolates, 10 (7.5%) were methicillin-resistant S. aureus (MRSA). Three (4.1%), five (9.8%), and two (20.0%) of the MRSA isolates were identified from the patients, HCWs, and the environment, respectively. Overall, 118 (88.1%) were ampicillin and penicillin resistant; 70 (52.2%) were trimethoprim sulfamethoxazole resistant; and 28 (20.9%) were erythromycin resistant. S. aureus isolates from patients were more resistant to antibiotics than isolates from HCWs or the hospital environment (p<0.05). A total of 92/134 (68.6%) isolates possessed the lukfF-PV gene, which was identified in 62 (85.0%), 26 (51.0%), and 4 (40.0%) of the patient, HCWs, and the environment, respectively. The proportion of lukfF-PV gene containing S. aureus isolated from patient samples was statistically significant. Four (40.0%) of the MRSA isolates also had the lukfF-PV gene. The identification of highly AMR and virulence factors from patients, HCWs and the environment is concerning. Further studies are needed to identify potential transmission links and improve infection prevention and control. [ABSTRACT FROM AUTHOR]

Introduction: Biofilm-associated infections persist as a therapeutic challenge in contemporary medicine. The efficacy of antibiotic therapies is ineffective in numerous instances, necessitating a heightened focus on exploring novel antibiofilm medical strategies. Among these, iminosugars emerge as a distinctive class of compounds displaying promising biofilm inhibition properties. Methods: This study employs an in vivo wound infection mouse model to evaluate the effectiveness of PDIA in treating biofilm-associated skin wound infections caused by Staphylococcus aureus and Pseudomonas aeruginosa. Dermic wounds in mice were infected with biofilm-forming strains, specifically S. aureus 48 and P. aeruginosa 5, which were isolated from patients with diabetic foot, and are well-known for their strong biofilm formation. The subsequent analysis included clinical, microbiological, and histopathological parameters. Furthermore, an exploration into the susceptibility of the infectious strains to hydrogen peroxide was conducted, acknowledging its potential presence during induced inflammation in mouse dermal wounds within an in vivo model. Results: The findings revealed the efficacy of PDIA iminosugar against the S. aureus strain, evidenced by a reduction in bacterial numbers within the wound and the inflammatory focus. Discussion: This study suggests that PDIA iminosugar emerges as an active and potentially effective antibiofilm agent, positioning it as a viable treatment option for staphylococcal infections. [ABSTRACT FROM AUTHOR]

The number of Methicillin-resistant Staphylococcus aureus (MRSA) cases in communities and hospitals is on the rise worldwide. In this work, a nonlinear deterministic model for the dynamics of MRSA infection in society was developed to visualize the significance of awareness in interventions that could be applied in the prevention of transmission with and without optimal control. Positivity and uniqueness were verified for the proposed corruption model to identify the level of resolution of infection factors in society. Furthermore, how various parameters affect the reproductive number R 0 and sensitivity analysis of the proposed model was explored through mathematical techniques and figures. The global stability of model equilibria analysis was established by using Lyapunov functions with the first derivative test. A total of seven years of data gathered from a private hospital consisting of inpatients and outpatients of MRSA were used in this model for numerical simulations and for observing the dynamics of infection by using a non-standard finite difference (NSFD) scheme. When optimal control was applied as a second model, it was determined that increasing awareness of hand hygiene and wearing a mask were the key controlling measures to prevent the spread of community-acquired MRSA (CA-MRSA) and hospital-acquired MRSA (HA-MRSA). Lastly, it was concluded that both CA-MRSA and HA-MRSA cases are on the rise in the community, and increasing awareness concerning transmission is extremely significant in preventing further spread. [ABSTRACT FROM AUTHOR]

Infections caused by Staphylococcus aureus pose a significant global public problem. Therefore, new antibiotics and therapeutic strategies are needed to combat this pathogen. This investigation delves into the effects of iclaprim, a newly discovered inhibitor of folic acid synthesis, on S. aureus virulence. The phenotypic and genotypic effects of iclaprim were thoroughly examined in relation to virulence factors, biofilm formation, and dispersal, as well as partial virulence-encoding genes associated with exoproteins, adherence, and regulation in S. aureus MW2, N315, and ATCC 25923. Then, the in vivo effectiveness of iclaprim on S. aureus pathogenicity was explored by a Galleria mellonella larvae infection model. The use of iclaprim at sub-inhibitory concentrations (sub-MICs) resulted in a reduction of α-hemolysin (Hla) production and a differential effect on the activity of coagulase in S. aureus strains. The results of biofilm formation and eradication assay showed that iclaprim was highly effective in depolymerizing the mature biofilm of S. aureus strains at concentrations of 1 MIC or greater, however, inhibited the biofilm-forming ability of only strains N315 and ATCC 25923 at sub-MICs. Interestingly, treatment of strains with sub-MICs of iclaprim resulted in significant stimulation or suppression of most virulence-encoding genes expression. Iclaprim did not affect the production of δ-hemolysin or staphylococcal protein A (SpA), nor did it impact the total activity of proteases, nucleases, and lipases. In vivo testing showed that sub-MICs of iclaprim significantly improves infected larvae survival. The present study offered valuable insights towards a better understating of the influence of iclaprim on different strains of S. aureus. The findings suggest that iclaprim may have potential as an anti-virulence and antibiofilm agent, thus potentially mitigating the pathogenicity of S. aureus and improving clinical outcomes associated with infections caused by this pathogen. Key points: • Iclaprim effectively inhibits α-hemolysin production and biofilm formation in a strain-dependent manner and was an excellent depolymerizing agent of mature biofilm • Iclaprim affected the mRNA expression of virulence-encoding genes associated with exoproteins, adherence, and regulation • In vivo study in G. mellonella larvae challenged with S. aureus exhibited that iclaprim improves larvae survival [ABSTRACT FROM AUTHOR]

Background and Objectives: Staphylococcal infections are one of the major infectious diseases affecting globally in spite of advances in development of antimicrobial agents. Knowledge and awareness about the local pattern and prevalence of MRSA infections plays a key role in treatment. The aim of this study was to identify MRSA strains by phenotypic and genotypic methods and to analyze the antibiotic susceptibility pattern of MRSA strains from patients attending a tertiary care hospital. Materials and Methods: This study was conducted over a period of 1 year, where 296 isolates of Staphylococcus aureus were isolated from various clinical specimens. The isolated strains were examined for antibiotic susceptibility by the modified Kirby Bauer disc diffusion method. Methicillin resistance was detected by cefoxitin disk diffusion test. Results: A total of 104 isolates were found to be MRSA and 192 were found to be MSSA. Among the 104 MRSA isolates, 10 strains that were multidrug resistant were subjected to 16S rRNA gene sequencing analysis. All the 10 strains had a 99% match with S. aureus strains that were responsible for causing some serious biofilm mediated clinical manifestations like cystic fibrosis and device mediated infections. The biofilms were quantified using crystal violet staining and their ability to produce biofilms was analyzed using scanning electron microscopy and matched with the Genbank. Conclusion: Hence these phylogenetic analysis aid in treating the patients and combating resistance to antibiotics. [ABSTRACT FROM AUTHOR]

Background: Daptomycin is a high‐use intravenous antimicrobial agent affording the convenience of once‐daily dosing. Prior studies suggest an opportunity to use a more operationally convenient fixed rather than weight‐based dosing but this approach has not been studied prospectively. Methods: This study quantified the probability of toxicity and efficacy end points by prospectively testing a fixed dose regimen of daptomycin (750 mg) in obese and non‐obese adults. At least, three daptomycin concentrations were measured at steady‐state for each patient. A population pharmacokinetic model was constructed to evaluate concentration‐time profiles and investigate covariates of daptomycin clearance. Simulations were performed to evaluate the probability of achieving efficacy (24‐h area under the curve (AUC0‐24) ≥ 666 mg∙h/L) and toxicity (minimum concentration (Cmin) ≥24.3 mg/L) targets for fixed (500–1000 mg) and weight‐based (6–12 mg/kg) daptomycin doses. Results: Thirty‐one patients (16 females, 15 males) with median (interquartile range (IQR)) age of 50 (30, 62) years and weight of 74 (54, 156) kg were included in the final analysis. Fixed dose daptomycin (750 mg) resulted in similar exposure across weights with a median (IQR) AUC0‐24 of 819 (499, 1501) mg∙h/L and 749 (606, 1265) mg∙h/L in patients weighing ≤74 kg and >74 kg, respectively. Overall, male sex and increased kidney function necessitate higher fixed and weight‐based doses to achieve efficacy. Creatine phosphokinase elevation was observed in two patients (6.5%) and predicted to be lower with fixed versus weight‐based regimens. Conclusions: Fixed daptomycin dosing adjusted for sex and kidney function is expected to improve the efficacy‐to‐toxicity ratio, transitions of care, and costs compared to weight‐based doses. However, no empiric dosing approach is predicted to achieve ≥90% efficacy while minimizing the risk of toxicity, so therapeutic drug monitoring should be considered on a patient‐specific basis. [ABSTRACT FROM AUTHOR]

Background/Objectives: Staphylococcus lugdunensis is a coagulase-negative staphylococcus (CoNS) commonly found on human skin. Unlike other CoNS, S. lugdunensis has a notable potential to cause severe infections comparable to Staphylococcus aureus. This study aimed to characterize the clinical and microbiological profile of patients with S. lugdunensis skin infections at a single center. Methods: We conducted a retrospective analysis of patient records from the Dermatology Department of the University Hospital of Heraklion, Greece, covering the period from January 2014 to January 2024. Patients' clinical presentations, demographics, infection sites, comorbidities, prior infections, antimicrobial treatments, and therapeutic responses were examined. Specimens were collected, transported, and processed according to standardized microbiological protocols. Bacterial identification and antibiotic susceptibility testing were performed using the Vitek 2 automated system and MALDI-TOF MS, with results interpreted according to Clinical and Laboratory Standards Institute (CLSI) criteria. Results: A total of 123 skin specimens positive for S. lugdunensis were analyzed. The cohort comprised 62 males (50.4%) and 61 females (49.6%), with a mean age of 40.24 ± 20.14 years. Most specimens were collected from pus (84%), primarily from below the waist (66.7%). Hidradenitis suppurativa (26%) was the most common condition associated with S. lugdunensis, followed by folliculitis, abscesses, ulcers, cellulitis, and acne. Co-infections with other bacteria were noted in 49.6% of cases, and 25.2% of infections were nosocomially acquired. The majority of patients (65%) received systemic antibiotics, predominantly amoxicillin/clavulanic acid, cefuroxime axetil, and doxycycline, with a cure rate of 100%. All isolates were susceptible to several antibiotics, though resistance to penicillin (28.5%) and clindamycin (36%) was observed. Conclusions: S. lugdunensis is a significant pathogen in skin infections, capable of causing severe disease. The high cure rate demonstrates the effectiveness of appropriate antibiotic therapy. Continued monitoring and antimicrobial stewardship are essential to manage resistance and ensure effective treatment. [ABSTRACT FROM AUTHOR]

Purpose: Staphylococcus aureus is the most common and impactful multi-drug resistant pathogen implicated in (periprosthetic) joint infections (PJI) and fracture-related infections (FRI). Therefore, the present proof-of-principle study was aimed at the rapid detection of S. aureus in synovial fluids and biofilms on extracted osteosynthesis materials through bacteria-targeted fluorescence imaging with the 'smart-activatable' DNA-based AttoPolyT probe. This fluorogenic oligonucleotide probe yields large fluorescence increases upon cleavage by micrococcal nuclease, an enzyme secreted by S. aureus. Methods: Synovial fluids from patients with suspected PJI and extracted osteosynthesis materials from trauma patients with suspected FRI were inspected for S. aureus nuclease activity with the AttoPolyT probe. Biofilms on osteosynthesis materials were imaged with the AttoPolyT probe and a vancomycin-IRDye800CW conjugate (vanco-800CW) specific for Gram-positive bacteria. Results: 38 synovial fluid samples were collected and analyzed. Significantly higher fluorescence levels were measured for S. aureus-positive samples compared to, respectively, other Gram-positive bacterial pathogens (p < 0.0001), Gram-negative bacterial pathogens (p = 0.0038) and non-infected samples (p = 0.0030), allowing a diagnosis of S. aureus-associated PJI within 2 h. Importantly, S. aureus-associated biofilms on extracted osteosynthesis materials from patients with FRI were accurately imaged with the AttoPolyT probe, allowing their correct distinction from biofilms formed by other Gram-positive bacteria detected with vanco-800CW within 15 min. Conclusion: The present study highlights the potential clinical value of the AttoPolyT probe for fast and accurate detection of S. aureus infection in synovial fluids and biofilms on extracted osteosynthesis materials. [ABSTRACT FROM AUTHOR]

Background Optimal antibiotic dosing for Staphylococcus aureus bloodstream infections (BSI) is still controversial. One reason is inter-individual variation in pharmacokinetics, which may be influenced by various patient-related factors, particularly in critically ill patients. Objectives To describe the population pharmacokinetics (PopPK) of the antibiotic flucloxacillin in patients with S. aureus BSI. Subsequently, we sought to translate the model into a user-friendly app for generating a priori and a posteriori time–concentration curves and dose recommendations to optimize dosing regimens. Methods Total and unbound flucloxacillin concentrations were included from 49 patients from a prospective cohort study conducted during clinical routine, including non-critically ill and critically ill individuals who received intermittent bolus applications. These data were analysed using non-linear mixed-effects modelling. Results Most patients (98%) were treated with 2 g of flucloxacillin every 4 h. We developed a joint model that simultaneously described total and unbound concentrations. The model included an allometric effect of glomerular filtration rate on clearance and albumin on the albumin dissociation constant. The latter was especially important, as in our population the unbound fraction was higher at 11.5% (16.7% for critically ill patients) compared with reported values of approximately 5%. Based on our joint model, we developed a web-based app for optimizing dosing regimens of flucloxacillin. Conclusions By utilizing data from clinical routine, we were able to create a predictive PopPK model of flucloxacillin and identify influential covariates. The web-based app is currently being validated in a clinical trial. [ABSTRACT FROM AUTHOR]

[Display omitted] • Interferon-induced protein 35 (IFP35) levels increased significantly after staphylococcus aureus (SA) infection. IFP35 deficiency protected against SA-induced lung damage in mice. • Ferroptosis occurred and led to lung injury after SA infection, which was ameliorated by IFP35 deletion. • IFP35 aggravated SA-induced ferroptosis and tissue injury by enhancing K48-linked ubiquitination and degradation of Nrf2. Serious Staphylococcus aureus (SA) infection is one of the most life-threatening diseases. Interferon-induced protein 35 (IFP35) is a pleiotropic factor that participates in multiple biological functions, however, its biological role in SA infection is not fully understood. Ferroptosis is a new type of regulated cell death driven by the accretion of free iron and toxic lipid peroxides and plays critical roles in tissue damage. Whether ferroptosis is involved in SA-induced immunopathology and its regulatory mechanisms remain unknown. We aimed to determine the role and underlying mechanisms of IFP35 in SA-induced lung infections. SA infection models were established using wild-type (WT) and IFP35 knockout (Ifp35−/−) mice or macrophages. Histological analysis was performed to assess lung injury. Quantitative real-time PCR, western blotting, flow cytometry, and confocal microscopy were performed to detect ferroptosis. Co-IP and immunofluorescence were used to elucidate the molecular regulatory mechanisms. We found that IFP35 levels increased in the macrophages and lung tissue of SA-infected mice. IFP35 deficiency protected against SA-induced lung damage in mice. Moreover, ferroptosis occurred and contributed to lung injury after SA infection, which was ameliorated by IFP35 deficiency. Mechanically, IFP35 facilitated the ubiquitination and degradation of nuclear factor E2-related factor 2 (Nrf2), aggravating SA-induced ferroptosis and lung injury. Our data demonstrate that IFP35 promotes ferroptosis by facilitating the ubiquitination and degradation of Nrf2 to exacerbate SA infection. Targeting IFP35 may be a promising approach for treating infectious diseases caused by SA. [ABSTRACT FROM AUTHOR]

Objective: To build and merge a diagnostic model called multi-input DenseNet fused with clinical features (MI-DenseCFNet) for discriminating between Staphylococcus aureus pneumonia (SAP) and Aspergillus pneumonia (ASP) and to evaluate the significant correlation of each clinical feature in determining these two types of pneumonia using a random forest dichotomous diagnosis model. This will enhance diagnostic accuracy and efficiency in distinguishing between SAP and ASP. Methods: In this study, 60 patients with clinically confirmed SAP and ASP, who were admitted to four large tertiary hospitals in Kunming, China, were included. Thoracic high-resolution CT lung windows of all patients were extracted from the picture archiving and communication system, and the corresponding clinical data of each patient were collected. Results: The MI-DenseCFNet diagnosis model demonstrates an internal validation set with an area under the curve (AUC) of 0.92. Its external validation set demonstrates an AUC of 0.83. The model requires only 10.24s to generate a categorical diagnosis and produce results from 20 cases of data. Compared with high-, mid-, and low-ranking radiologists, the model achieves accuracies of 78% vs. 75% vs. 60% vs. 40%. Eleven significant clinical features were screened by the random forest dichotomous diagnosis model. Conclusion: The MI-DenseCFNet multimodal diagnosis model can effectively diagnose SAP and ASP, and its diagnostic performance significantly exceeds that of junior radiologists. The 11 important clinical features were screened in the constructed random forest dichotomous diagnostic model, providing a reference for clinicians. Clinical relevance statement: MI-DenseCFNet could provide diagnostic assistance for primary hospitals that do not have advanced radiologists, enabling patients with suspected infections like Staphylococcus aureus pneumonia or Aspergillus pneumonia to receive a quicker diagnosis and cut down on the abuse of antibiotics. Key points: • MI-DenseCFNet combines deep learning neural networks with crucial clinical features to discern between Staphylococcus aureus pneumonia and Aspergillus pneumonia. • The comprehensive group had an area under the curve of 0.92, surpassing the proficiency of junior radiologists. • This model can enhance a primary radiologist's diagnostic capacity. [ABSTRACT FROM AUTHOR]

BACKGROUND: Insects mainly rely on innate immunity against pathogen infection. Plagiodera versicolora (Coleoptera: Chrysomelidae), is a worldwide leaf‐eating forest pest in salicaceous trees. However, the mechanisms behind the immunodeficiency pathway (IMD) remain poorly understood. RESULTS: In this study, we obtained a Relish gene from transcriptome analysis. Tissue and instar expression profiles were subsequently obtained using quantitative real‐time polymerase chain reaction analysis. The results showed that Relish has high expression levels in eggs, larvae and adults, and especially in fat bodies. Transcripts of the tested antimicrobial peptides (AMPs), defensin1, defensin2 and attacin2 were downregulated by dsRelish. Knockdown of Relish led to greater mortality in larvae after Staphylococcus aureus infection. In addition, we performed bacterial 16S ribosomal RNA‐based high‐throughput sequencing. The results showed that the relative abundance of some gut bacteria was significantly altered after dsRelish ingestion. CONCLUSION: This study provides a greater understanding of the IMD signaling pathway, facilitating functional studies of Relish in P. versicolora. Moreover, a genetic pest management technique might be developed using Relish as a lethal gene to control the pest P. versicolora. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Craniotomy is a common neurosurgery used to treat intracranial pathologies. Nearly 5% of the 14 million craniotomies performed worldwide each year become infected, most often with Staphylococcus aureus (S. aureus), which forms a biofilm on the surface of the resected bone segment to establish a chronic infection that is recalcitrant to antibiotics and immune-mediated clearance. Tumor necrosis factor (TNF), a prototypical proinflammatory cytokine, has been implicated in generating protective immunity to various infections. Although TNF is elevated during S. aureus craniotomy infection, its functional importance in regulating disease pathogenesis has not been explored. Methods: A mouse model of S. aureus craniotomy infection was used to investigate the functional importance of TNF signaling using TNF, TNFR1, and TNFR2 knockout (KO) mice by quantifying bacterial burden, immune infiltrates, inflammatory mediators, and transcriptional changes by RNA-seq. Complementary experiments examined neutrophil extracellular trap formation, leukocyte apoptosis, phagocytosis, and bactericidal activity. Results: TNF transiently regulated neutrophil and granulocytic myeloid-derived suppressor cell recruitment to the brain, subcutaneous galea, and bone flap as evident by significant reductions in both cell types between days 7 to 14 post-infection coinciding with significant decreases in several chemokines, which recovered to wild type levels by day 28. Despite these defects, bacterial burdens were similar in TNF KO and WT mice. RNA-seq revealed enhanced lymphotoxin-α (Lta) expression in TNF KO granulocytes. Since both TNF and LTα signal through TNFR1 and TNFR2, KO mice for each receptor were examined to assess potential redundancy; however, neither strain had any impact on S. aureus burden. In vitro studies revealed that TNF loss selectively altered macrophage responses to S. aureus since TNF KO macrophages displayed significant reductions in phagocytosis, apoptosis, IL-6 production, and bactericidal activity in response to live S. aureus, whereas granulocytes were not affected. Conclusion: These findings implicate TNF in modulating granulocyte recruitment during acute craniotomy infection via secondary effects on chemokine production and identify macrophages as a key cellular target of TNF action. However, the lack of changes in bacterial burden in TNF KO animals suggests the involvement of additional signals that dictate S. aureus pathogenesis during craniotomy infection. [ABSTRACT FROM AUTHOR]

Background: Neonatal sepsis is still a global health concern as it contributes to a high burden of neonatal morbidity and mortality especially in developing countries. The aim of the study is to give an insight into neonatal sepsis: risk factors, sepsis types, clinical features, pathogen burden with their antibiotic sensitivities, and outcome of admission in our facility. The study was a prospective hospital-based study conducted over 10 months, October 2018–July 2019. Result: Of the 248 term neonates with features of sepsis enrolled in the study 94 (37.9%) were confirmed to have sepsis. Late-onset sepsis LOS (68%) was found to be the most common, and most of the neonates were delivered elsewhere. Clinical features were non-specific for both early-onset (EOS) and LOS and include fever, jaundice, poor suck, and depressed primitive reflexes. Infections were mostly caused by gram-negative bacteria, and while Staphylococcus aureus was the single most common isolate for both EOS and LOS. Antibiotic sensitivity was highest with ciprofloxacin for both EOS and LOS. Mortality was high at 14.9% and was mostly contributed to by Staphylococcus aureus infection. Conclusion: Neonatal sepsis is still a burden with mostly non-specific clinical features. The local prevalent organisms were Staphylococcus aureus, Enterobacter agglomerans and Klebsiella pneumonia with good antibiotic susceptibility to ciprofloxacin. Most presented with late-onset sepsis and therefore infection is likely to be community-acquired which to a great extent can be prevented with robust public health interventions. [ABSTRACT FROM AUTHOR]

Background: No consensus in the literature has been found about the necessity of implementing a decolonization screening protocol for Staphylococcus aureus in patients who undergo prosthesis implantation of the knee (TKA) or of the hip (THA), with the aim of reducing periprosthetic infections (PJIs). Methods: A systematic literature search was conducted using PubMed, Web of Science, and Embase in April 2024. Studies conducted on patients who underwent a TKA or THA and who followed a screening and decolonization protocol from S. aureus were included. The benefits of implementing this protocol were evaluated through the number of infections overall caused by S. aureus and other pathogens. The risk of bias and quality of evidence were assessed using Cochrane guidelines. Results: A total of 922 articles were evaluated, and of these, 12 were included in the study for a total of 56,930 patients. The results of the meta-analysis showed a reduced risk of overall PJI (p = 0.002), PJI caused by S. aureus (p < 0.0001), and PJI caused by MRSA (p < 0.0001) and highlighted no differences between the two groups in the onset of a PJI caused by other bacteria (p = 0.50). Conclusions: This study showed that the screening and decolonization of S. aureus in patients undergoing THA or THA procedures reduced the risk of a PJI. The screening and decolonization protocol for this kind of patient represents an important procedure for the safety of the patient and in social-economic and medico-legal terms. [ABSTRACT FROM AUTHOR]

Although many clinical variants of Staphylococcus aureus infection are well‐recognized, atypical presentations may mimic other conditions. We describe two cases of atypical S. aureus infections in pediatric patients: a S. aureus infection presenting with a vesicopustular rash mimicking varicella zoster virus and a case of multifocal panniculitis. Both of these cases were specifically caused by methicillin‐resistant S. aureus (MRSA). Additional cases of atypical S. aureus infections and presenting features from the current literature are also discussed. [ABSTRACT FROM AUTHOR]

The growing incidence of bone injuries has elevated the demand for Titanium-based orthopedic implants, yet implant-associated infections and loosening remain significant contributors to implant failure in orthopedic surgeries. The present study addressed the issue of aseptic and septic loosening of Ti–6Al–4V orthopedic implants using a bidirectional strategy of developing extracellular matrix (ECM) mimicking electrospun nanofiber coating composed of polyvinyl alcohol (PVA)–Gelatin–Quercetin (PGQ) with concomitant antibacterial and osteoinductive property on Ti–6Al–4V surface. The polymeric nanofiber coating of PVA–Gelatin (PG) blend on the Ti–6Al–4V showed ECM mimicking morphology confirmed by SEM with desirable strong adhesion in accordance with ASTM D3359:3B over the implant surface. The physiochemical characterizations of the coated nanofibers performed by FTIR and contact angle measurement confirmed presence of hydrophilic PG coating on Ti–6Al–4V surface. Reinforcement of Quercetin, a natural polyphenol with promising antibacterial and osteogenic potential in PG nanofibers and coating on Ti–6Al–4V imparted antibacterial and osteogenic properties. Quercetin-loaded PGQ nanofibers showed a biphasic release pattern with initial burst release of Quercetin from the implant surface providing the required protection with early microbial infections from Staphylococcus aureus (S. aureus), whereas steady controlled release of Quercetin from Ti-PGQ implant supported alkaline phosphatase (ALP) activity and Ca–P mineral deposition by osteoblast. The Quercetin concentration of 0.1% (w/v) showed the overall optimum cellular response compared to 0.05 and 0.2% concentration. These findings reflect substantial progress in employing Quercetin-loaded nanofiber-coated Ti–6Al–4V to potentially lower aseptic and septic loosening risks in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Background: Phenome-Wide Association study (PheWAS) is a powerful tool designed to systematically screen clinical observations derived from medical records (phenotypes) for association with a variable of interest. Despite their usefulness, no systematic screening of phenotypes associated with Staphylococcusaureusinfections (SAIs) has been done leaving potential novel risk factors or complications undiscovered. Method and cohorts: We tailored the PheWAS approach into a two-stage screening procedure to identify novel phenotypes correlating with SAIs. The first stage screened for co-occurrence of SAIs with other phenotypes within medical records. In the second stage, significant findings were examined for the correlations between their age of onset with that of SAIs. The PheWAS was implemented using the medical records of 754,401 patients from the Marshfield Clinic Health System. Any novel associations discovered were subsequently validated using datasets from TriNetX and All of Us, encompassing 109,884,571 and 118,538 patients respectively. Results: Forty-one phenotypes met the significance criteria of a p-value < 3.64e-5 and odds ratios of > 5. Out of these, we classified 23 associations either as risk factors or as complications of SAIs. Three novel associations were discovered and classified either as a risk (long-term use of aspirin) or complications (iron deficiency anemia and anemia of chronic disease). All novel associations were replicated in the TriNetX cohort. In the All of Us cohort, anemia of chronic disease was replicated according to our significance criteria. Conclusions: The PheWAS of SAIs expands our understanding of SAIs interacting phenotypes. Additionally, the novel two-stage PheWAS approach developed in this study can be applied to examine other disease-disease interactions of interest. Due to the possibility of bias inherent in observational data, the findings of this study require further investigation. [ABSTRACT FROM AUTHOR]

Purpose: S. aureus bacteremia (SAB) is a common and severe infection with high mortality and morbidity. The clinical relevance of the finding of concurrent S. aureus bacteriuria (SABU) is debated. The goal of this study was to analyze whether a concurrent SABU is associated with complicated SAB, infective endocarditis (IE) and mortality. Methods: We conducted a retrospective cohort study, reviewing medical charts of all episodes of SAB in patients > 18 years in the region of Skåne, Sweden, between 1st of January and 31st of June 2020. Episodes where a concurrent urine culture was performed were included for analysis. An episode was considered as complicated SAB if there was either attributable mortality, recurrent infection, embolic stroke, or occurrence of a complicated focus of infection. Results: During the study period, there were 279 episodes of SAB. 154 episodes met the eligibility criteria, of whom 37 (24%) had concurrent SABU. In 78 episodes (51%), the patients had a complicated SAB. There was a significantly lower proportion of complicated SAB for episodes with concurrent SABU (32%), compared to episodes without concurrent SABU (56%), p-value 0.014. Moreover, in the cohort there were 11 episodes (7.1%) of IE and a 30 days mortality rate of 16%, with no difference between the groups with or without SABU. Conclusions: There is an association between concurrent SABU and a decreased risk for complicated SAB among patients with SAB. This study found no significant association between SABU and neither IE nor mortality for patients with SAB. [ABSTRACT FROM AUTHOR]

The effects of intestinal microflora on extraintestinal immune response by intestinal cytokines and metabolites have been documented, but whether intestinal microbes stimulate serum antibody generation is unknown. Here, serum antibodies against 69 outer membrane proteins of Escherichia coli, a dominant bacterium in the human intestine, are detected in 141 healthy individuals of varying ages. Antibodies against E. coli outer membrane proteins are determined in all serum samples tested, and frequencies of antibodies to five outer membrane proteins (OmpA, OmpX, TsX, HlpA, and FepA) are close to 100%. Serum antibodies against E. coli outer membrane proteins are further validated by Western blot and bacterial pull-down. Moreover, the present study shows that OstA, HlpA, Tsx, NlpB, OmpC, YfcU, and OmpA provide specific immune protection against pathogenic E. coli, while HlpA and OmpA also exhibit cross-protection against Staphylococcus aureus infection. These finding indicate that intestinal E. coli activate extraintestinal antibody responses and provide anti-infective immunity. [ABSTRACT FROM AUTHOR]

Background: Diabetic nephropathy (DN) is a major microvascular complication of diabetes and has become the leading cause of end-stage renal disease worldwide. A considerable number of DN patients have experienced irreversible end-stage renal disease progression due to the inability to diagnose the disease early. Therefore, reliable biomarkers that are helpful for early diagnosis and treatment are identified. The migration of immune cells to the kidney is considered to be a key step in the progression of DN-related vascular injury. Therefore, finding markers in this process may be more helpful for the early diagnosis and progression prediction of DN. Methods: The gene chip data were retrieved from the GEO database using the search term ' diabetic nephropathy '. The ' limma ' software package was used to identify differentially expressed genes (DEGs) between DN and control samples. Gene set enrichment analysis (GSEA) was performed on genes obtained from the molecular characteristic database (MSigDB. The R package 'WGCNA' was used to identify gene modules associated with tubulointerstitial injury in DN, and it was crossed with immune-related DEGs to identify target genes. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on differentially expressed genes using the 'ClusterProfiler' software package in R. Three methods, least absolute shrinkage and selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE) and random forest (RF), were used to select immune-related biomarkers for diagnosis. We retrieved the tubulointerstitial dataset from the Nephroseq database to construct an external validation dataset. Unsupervised clustering analysis of the expression levels of immune-related biomarkers was performed using the 'ConsensusClusterPlus 'R software package. The urine of patients who visited Dongzhimen Hospital of Beijing University of Chinese Medicine from September 2021 to March 2023 was collected, and Elisa was used to detect the mRNA expression level of immune-related biomarkers in urine. Pearson correlation analysis was used to detect the effect of immune-related biomarker expression on renal function in DN patients. Results: Four microarray datasets from the GEO database are included in the analysis : GSE30122, GSE47185, GSE99340 and GSE104954. These datasets included 63 DN patients and 55 healthy controls. A total of 9415 genes were detected in the data set. We found 153 differentially expressed immune-related genes, of which 112 genes were up-regulated, 41 genes were down-regulated, and 119 overlapping genes were identified. GO analysis showed that they were involved in various biological processes including leukocyte-mediated immunity. KEGG analysis showed that these target genes were mainly involved in the formation of phagosomes in Staphylococcus aureus infection. Among these 119 overlapping genes, machine learning results identified AGR2, CCR2, CEBPD, CISH, CX3CR1, DEFB1 and FSTL1 as potential tubulointerstitial immune-related biomarkers. External validation suggested that the above markers showed diagnostic efficacy in distinguishing DN patients from healthy controls. Clinical studies have shown that the expression of AGR2, CX3CR1 and FSTL1 in urine samples of DN patients is negatively correlated with GFR, the expression of CX3CR1 and FSTL1 in urine samples of DN is positively correlated with serum creatinine, while the expression of DEFB1 in urine samples of DN is negatively correlated with serum creatinine. In addition, the expression of CX3CR1 in DN urine samples was positively correlated with proteinuria, while the expression of DEFB1 in DN urine samples was negatively correlated with proteinuria. Finally, according to the level of proteinuria, DN patients were divided into nephrotic proteinuria group (n = 24) and subrenal proteinuria group. There were significant differences in urinary AGR2, CCR2 and DEFB1 between the two groups by unpaired t test (P < 0.05). Conclusions: Our study provides new insights into the role of immune-related biomarkers in DN tubulointerstitial injury and provides potential targets for early diagnosis and treatment of DN patients. Seven different genes (AGR2, CCR2, CEBPD, CISH, CX3CR1, DEFB1, FSTL1), as promising sensitive biomarkers, may affect the progression of DN by regulating immune inflammatory response. However, further comprehensive studies are needed to fully understand their exact molecular mechanisms and functional pathways in DN. [ABSTRACT FROM AUTHOR]

There is limited consensus regarding management of spinal epidural abscesses (SEAs), particularly in patients without neurologic deficits. Several models have been created to predict failure of medical management in patients with SEA. We evaluate the external validity of 5 predictive models in an independent cohort of patients with SEA. One hundred seventy-six patients with SEA between 2010 and 2019 at our institution were identified, and variables relevant to each predictive model were collected. Published prediction models were used to assign probability of medical management failure to each patient. Predicted probabilities of medical failure and actual patient outcomes were used to create receiver operating characteristic (ROC) curves, with the area under the receiver operating characteristic curve used to quantify a model's discriminative ability. Calibration curves were plotted using predicted probabilities and actual outcomes. The Spiegelhalter z-test was used to determine adequate model calibration. One model (Kim et al) demonstrated good discriminative ability and adequate model calibration in our cohort (ROC = 0.831, P value = 0.83). Parameters included in the model were age >65, diabetes, methicillin-resistant Staphylococcus aureus infection, and neurologic impairment. Four additional models did not perform well for discrimination or calibration metrics (Patel et al, ROC = 0.580, P ≤ 0.0001; Shah et al, ROC = 0.653, P ≤ 0.0001; Baum et al, ROC = 0.498, P ≤ 0.0001; Page et al, ROC = 0.534, P ≤ 0.0001). Only 1 published predictive model demonstrated acceptable discrimination and calibration in our cohort, suggesting limited generalizability of the evaluated models. Multi-institutional data may facilitate the development of widely applicable models to predict medical management failure in patients with SEA. [ABSTRACT FROM AUTHOR]

Injecting drug use is a risk factor for severe bacterial infection, but there is limited high-quality evidence to guide clinicians providing care to people who inject drugs. Management can be complicated by mistrust, stigma, and competing patient priorities. To review the management of severe infections in people who inject drugs, using an illustrative clinical scenario of complicated Staphylococcus aureus bloodstream infection. The discussion is based on recent literature searches of relevant topics. Very few randomized clinical trials have focussed specifically on the management of severe bacterial infections among people who inject drugs. Most recommendations are, therefore, based on observational studies, extrapolation from other patient groups, and the experience and opinions of the authors. We discuss evidence and options regarding the following management issues for severe bacterial infections among people who inject drugs: initial management of sepsis; indications for surgical management; assessment and management of substance dependence; approaches to antibiotic administration following clinical stability; opportunistic health promotion; and secondary prevention of bacterial infections. Throughout, we highlight the importance of harm reduction and strategies to optimize patient engagement in care through a patient-centred approach. We advocate for a multi-disciplinary trauma-informed approach to the management of severe bacterial infection among people who inject drugs. We emphasize the need for pragmatic trials to inform management guidelines, including those that are co-designed with the community. In particular, research is needed to establish the comparative effectiveness, safety, and cost-effectiveness of inpatient intravenous antibiotics vs. early oral antibiotic switch, outpatient parenteral therapy, and long-acting lipoglycopeptide antibiotics in this scenario. [ABSTRACT FROM AUTHOR]

Purpose: Bone and joint infections, complicated by the burgeoning challenge of antimicrobial resistance (AMR), pose significant public health threats by amplifying the disease burden globally. We leveraged results from the 2019 Global Burden of Disease Study (GBD) to explore the impact of AMR attributed to bone and joint infections in terms of disability-adjusted life years (DALYs), elucidating the contemporary status and temporal trends. Methods: Utilizing GBD 2019 data, we summarized the burden of bone and joint infections attributed to AMR across 195 countries and territories in the 30 years from 1990 to 2019. We review the epidemiology of AMR in terms of age-standardized rates, the estimated DALYs, comprising years of life lost (YLLs) and years lived with disability (YLDs), as well as associations between DALYs and socio-demographic indices. Results: The GBD revealed that DALYs attributed to bone and joint infections associated with AMR have risen discernibly between 1990 and 2019 globally. Significant geographical disparities and a positive correlation with socio-demographic indicators were observed. Staphylococcus aureus infections, Group A Streptococcus, Group B Streptococcus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter-related bone and joint infections were associated with the highest DALYs because of a high proportion of antimicrobial resistance. Countries with limited access to healthcare, suboptimal sanitary conditions, and inconsistent antibiotic stewardship were markedly impacted. Conclusions: The GBD underscores the escalating burden of bone and joint infections exacerbated by AMR, necessitating urgent, multi-faceted interventions. Strategies to mitigate the progression and impact of AMR should emphasize prudent antimicrobial usage and robust infection prevention and control measures, coupled with advancements in diagnostic and therapeutic modalities. [ABSTRACT FROM AUTHOR]

Bacterial infections continue to represent a significant healthcare burden worldwide, causing considerable mortality and morbidity every year. The emergence of multidrug-resistant bacterial strains continues to rise, posing serious risks to controlling global disease outbreaks. To develop novel and more effective treatment and vaccination programs, there is a need for clinically relevant small animal models. Since multiple bacterial species have human-specific tropism for numerous virulence factors and toxins, conventional mouse models do not fully represent human disease. Several human disease characteristic phenotypes, such as lung granulomas in the case of Mycobacterium tuberculosis infections, are absent in standard mouse models. Alternatively, certain pathogens, such as Salmonella enterica serovar typhi and Staphylococcus aureus, can be well tolerated in mice and cleared quickly. To address this, multiple groups have developed humanized mouse models and observed enhanced susceptibility to infection and a more faithful recapitulation of human disease. In the last two decades, multiple humanized mouse models have been developed to attempt to recapitulate the human immune system in a small animal model. In this review, we first discuss the history of immunodeficient mice that has enabled the engraftment of human tissue and the engraftment methods currently used in the field. We then highlight how humanized mouse models successfully uncovered critical human immune responses to various bacterial infections, including Salmonella enterica serovar Typhi, Mycobacterium tuberculosis, and Staphylococcus aureus. [ABSTRACT FROM AUTHOR]

Staphylococcus argenteus, identified in 2006, represents a challenging case of bacterial taxonomic identification because of its high similarity to Staphylococcus aureus. In this context, neither mass spectrometry (MS) nor 16S gene analysis cannot precisely reveal the difference between the two species. In our study, the sensitivity to antibiotics of S. argenteus isolated from blood culture was tested, and the investigation of the bacterial genome was performed by Multi-Locus Sequence Typing (MLST) and Whole-Genome Next-Generation Sequencing (WG-NGS). The pathogen was identified as ST2250 and presented perfectly matched resistance genes, namely aph(3′)-III, mgrA, and sepA, whereas the virulence gene detected was scn. Two plasmids were found: the pSAS plasmid, belonging to the family of Inc18, and plasmid pN315, belonging to the Rep3 group. The epidemiological distribution and the spread of S. argenteus infection are scarcely documented, particularly when associated with sepsis. Therefore, a correct taxonomy identification, antibiogram, and resistance gene analysis may help in acquiring knowledge about this bacterium and implement its detection and treatment. [ABSTRACT FROM AUTHOR]

Objective: Signs and symptoms of osteomyelitis or septic arthritis in neonates and infants are often nonspecific and early-stage bone infections in infants may often go unnoticed. The objective of this study was to analyze the clinical characteristics of newborns and infants with osteomyelitis and septic arthritis to improve understanding of the disorder and to assist clinicians with diagnosis. Methods: A retrospective multicenter study was conducted on neonates (0-28 days old, n = 94) and infants (1-12 months old, n = 415) with osteoarticular infections. Data consisting of clinical characteristics, complications, laboratory outcomes, and the pathogenic microorganisms causing osteomyelitis were tabulated. The statistics were further broken down into two regions and the significant differences between neonates and infants were evaluated and compared to the literature. Results: Compared to infants, neonates had significantly lower incidences of fever (p < 0.0001), higher incidences of localized swelling (p = 0.0021), higher rate of infection at the humerus (p = 0.0016), higher percentage of Escherichia coli (p < 0.0001) and Klebsiella pneumoniae (p = 0.0039) infections, lower percentage of Staphylococcus aureus infections (p < 0.0001) and were more likely to develop septic arthritis (p < 0.0001). Conclusion: Distinct differences were found between neonatal and infants with osteoarticular infections. Future studies should focus on improving diagnosis and subsequent treatment regimens for younger age groups. [ABSTRACT FROM AUTHOR]

Abstract Background Open fractures are challenging due to susceptibility to Staphylococcus aureus infections. This study examines the impact of Vancomycin-Loaded Calcium Sulfate (VLCS) and negative pressure wound therapy (NPWT) on macrophage behavior in enhancing healing and infection resistance. Both VLCS and NPWT were evaluated individually and in combination to determine their effects on macrophage polarization and infection resistance in open fractures. Methods Through single-cell RNA sequencing, genomic expressions in macrophages from open fracture patients treated with VLCS and NPWT were compared to a control group. The analysis focused on MBD2 gene changes related to macrophage polarization. Results Remarkable modifications in MBD2 expression in the treatment group indicate a shift towards M2 macrophage polarization. Additionally, the combined treatment group exhibited greater improvements in infection resistance and healing compared to the individual treatments. This shift suggests a healing-promoting atmosphere with improved infection resilience. Conclusions VLCS and NPWT demonstrate the ability to alter macrophage behavior toward M2 polarization, which is crucial for infection prevention in open fractures. The synergistic effect of their combined use shows even greater promise in enhancing outcomes in orthopedic trauma care.

Melt blending is considered a significant method to develop antibacterial textile materials. However, it is still challenging to the homogeneous dispersion and efficient antibacterial activity of inorganic nanoparticles in polymer fibers. In this work, ZnO/Ag@Si[O.sub.2] inorganic nanohybrid antibacterial agents were prepared by the direct precipitation method. The prepared antibacterial material had efficient antibacterial and thermal stability properties. Specifically, the decomposition temperature of the ZnO/Ag@Si[O.sub.2] was higher than 400[degrees]C, which was appropriate for melting polymers at high temperatures. Here, polyethylene terephthalate (PET) was used as a fiber matrix, and PET/ZnO/Ag@Si[O.sub.2] fibers were prepared by melt spinning technology. The results showed that the antibacterial material was well dispersed in the PET matrix, and the crystallization was promoted during the cooling process. The modified PET fibers presented better antibacterial properties against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), with a maximum antibacterial rate of 99.9%. Additionally, the modified PET fibers provide superior laundering durability, with an antibacterial rate of 95.7% for S. aureus and 94.8% for E. coli after 50 washes. This work offers a novel approach to preparing thermotolerant and efficient antibacterial agents and antibacterial-modified PET fibers. Highlights * ZnO/Ag@Si[O.sub.2] nanohybrid antibacterial agents were prepared. * High temperature resistant and highly antibacterial material. * The particles dispersed uniformly in PET matrix. * Excellent antibacterial and laundering properties of the fiber KEYWORDS highly effective antibacterial, high-temperature, polyethylene terephthalate fiber, uniform dispersion, ZnO/Ag@Si[O.sub.2] nanohybrid, 1 | INTRODUCTION The United Nations Environment Programme stated that up to 10 million people worldwide could die each year from antimicrobial drug resistance problems by 2050, which would be [...]

Background: Tuberculosis (TB), one of the leading causes of death worldwide, has a higher incidence among indigenous people. Albeit uncommon, autoimmune hemolytic anemia (AIHA) has been deemed a risk condition to develop mycobacterial infection, as a result of the immunosuppressive treatments. TB, in turn, can be a predisposing factor for secondary infections. Case presentation: Here we present a case of a 28-year-old indigenous woman from Colombia, previously diagnosed with AIHA and pulmonary TB. Despite various treatments, therapies and medical interventions, the patient died after severe medullary aplasia of multiple causes, including secondary myelotoxicity by immunosuppressive therapy and secondary disseminated infections, underlining infection by Staphylococcus aureus, Klebsiella pneumoniae and Candida glabrata, which were identified as drug-resistant microorganisms. Together, this led to significant clinical complications. Invasive aspergillosis was diagnosed at autopsy. Conclusions: This report presents a rarely finding of AIHA followed by TB, and highlights the great challenges of dealing with co-infections, particularly by drug resistant pathogens. It also aims to spur governments and public health authorities to focus attention in the prevention, screening and management of TB, especially among vulnerable communities, such as indigenous people. [ABSTRACT FROM AUTHOR]

Antibacterial photocatalytic therapy (APCT) is one of the most promising non‐antibiotic treatment strategies for biofilm‐infected wounds and inflammation caused by drug‐resistant bacteria. However, it still faces issues such as inadequate single antibacterial capacity and lack of antioxidant capacity. In this study, a Z‐scheme heterojunction (Bi2S3‐X@PDA) is designed using a polydopamine (PDA) shell firmly anchored to the surface of sulfur vacancy‐rich bismuth sulfide nanorods (Bi2S3‐X NRs). Under near‐infrared light and hydrogen peroxide, Bi2S3‐X@PDA significantly improves the photocatalytic efficiency of reactive oxygen species generation and shows a nearly 100% broad‐spectrum antibacterial effect against multiple bacterial strains and bacterial biofilms in vitro. Interestingly, the antioxidant activity of the PDA shell in Bi2S3‐X@PDA remarkably downregulates the expression of pro‐inflammatory factors and promotes macrophage reprogramming toward the proregenerative M2 phenotype. In a mouse wound model of methicillin‐resistant Staphylococcus aureus biofilm infection, Bi2S3‐X@PDA effectively eliminates drug‐resistant bacterial biofilms through APCT/mild photothermal therapy, while reducing inflammation in normal tissues and regulating the immune microenvironment, thereby promoting rapid wound healing. Overall, this light‐controlled treatment strategy, which provides both antibacterial and anti‐inflammatory functions, is a reliable tool for combating biofilm infection and inflammation caused by drug‐resistant bacteria. [ABSTRACT FROM AUTHOR]

A cationic aggregation-induced emission photosensitizer (AIE-PS) MNNPyBB has been reported to have antibacterial effects against both Gram-positive and Gram-negative bacteria. The bacterial kill mechanism has been investigated and elucidated. In a methicillin-resistant Staphylococcus aureus subcutaneous infection model, wound closure has been achieved with normal re-epithelialization and preserved skin morphology [ABSTRACT FROM AUTHOR]

Background The optimal duration and choice of antibiotic for fracture-related infection (FRI) is not well defined. This study aimed to determine whether antibiotic duration (≤6 vs >6 weeks) is associated with infection- and surgery-free survival. The secondary aim was to ascertain risk factors associated with surgery- and infection-free survival. Methods We performed a multicenter retrospective study of patients diagnosed with FRI between 2013 and 2022. The association between antibiotic duration and surgery- and infection-free survival was assessed by Cox proportional hazard models. Models were weighted by the inverse of the propensity score, calculated with a priori variables of hardware removal; infection due to Staphylococcus aureus , Staphylococcus lugdunensis , Pseudomonas or Candida species; and flap coverage. Multivariable Cox proportional hazard models were run with additional covariates including initial pathogen, need for flap, and hardware removal. Results Of 96 patients, 54 (56.3%) received ≤6 weeks of antibiotics and 42 (43.7%) received >6 weeks. There was no association between longer antibiotic duration and surgery-free survival (hazard ratio [HR], 0.95; 95% CI,.65–1.38; P =.78) or infection-free survival (HR, 0.77; 95% CI,.30–1.96; P =.58). Negative culture was associated with increased hazard of reoperation or death (HR, 3.52; 95% CI, 1.99–6.20; P <.001) and reinfection or death (HR, 3.71; 95% CI, 1.24–11.09; P <.001). Need for flap coverage had an increased hazard of reoperation or death (HR, 3.24; 95% CI, 1.61–6.54; P =.001). Conclusions The ideal duration of antibiotics to treat FRI is unclear. In this multicenter study, there was no association between antibiotic treatment duration and surgery- or infection-free survival. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a common cause of skin and soft-tissue infections (SSTIs) and has become the most common cause of bloodstream infections (BSIs) in recent years, but whether the strains causing these two clinical syndromes overlap has not been studied adequately. USA300/500 (clonal complex [CC] 8–sequence type [ST] 8) and USA100 (CC5-ST5) have dominated among methicillin-resistant S aureus (MRSA) strains in the United States since the early 2000s. We compared the genomes of unselected MRSA isolates from 131 SSTIs with those from 145 BSIs at a single US center in overlapping periods in 2018–2021. CC8 MRSA was more common among SSTIs, and CC5 was more common among BSIs, consistent with prior literature. Based on clustering genomes with a threshold of 15 single-nucleotide polymorphisms, we identified clusters limited to patients with SSTI and separate clusters exclusively comprising patients with BSIs. However, we also identified eight clusters that included at least one SSTI and one BSI isolate. This suggests that virulent MRSA strains are transmitted from person to person locally in the healthcare setting or the community and that single lineages are often capable of causing both SSTIs and BSIs. [ABSTRACT FROM AUTHOR]

Simple Summary: The gut microbiome, a complex microbial community, is intricately linked to the host's genetic background. The regulatory role of host genes on the microbiome has garnered considerable attention due to its impact not only on physiological and immune responses but also on the composition and functionality of intestinal microbes and the overall immune system. Nitric oxide synthase (NOS), through the production of nitric oxide (NO), participates in host defense, immune regulation, inflammatory responses, and autoimmune diseases. However, the effects of NOS on the composition and function of the zebrafish gut microbiota and the regulation of its homeostasis remain unclear. Genomic editing technologies have enabled the creation of zebrafish with specific genetic defects, making them a recognized model for studying host–microbiome–immune interactions. In this study, we characterized the impact of inducible nitric oxide synthase (iNOS) deficiency on the gut microbiota of zebrafish through 16S rRNA amplicon sequencing. Results revealed significant alterations in the microbial diversity and abundance in iNOS-deficient zebrafish, notably a reduction in Vibrio and an increase in Aeromonas. Transcriptomic sequencing of the gut confirmed functional changes, showing significant alterations in pathways related to the complement and coagulation cascades, PPAR signaling, cell adhesion molecules, Staphylococcus aureus infection, steroid synthesis, and bile acid synthesis. These pathways are crucial in pathogen clearance, inflammatory responses, and immune regulation, highlighting the significant role of the iNOS gene not only in microbial composition but also in gut immune and metabolic functions. The gut microbiota constitutes a complex ecosystem that has an important impact on host health. In this study, genetically engineered zebrafish with inducible nitric oxide synthase (iNOS or NOS2) knockout were used as a model to investigate the effects of nos2a/nos2b gene single knockout and nos2 gene double knockout on intestinal microbiome composition and function. Extensive 16S rRNA sequencing revealed substantial changes in microbial diversity and specific taxonomic abundances, yet it did not affect the functional structure of the intestinal tissues. Notably, iNOS-deficient zebrafish demonstrated a decrease in Vibrio species and an increase in Aeromonas species, with more pronounced effects observed in double knockouts. Further transcriptomic analysis of the gut in double iNOS knockout zebrafish indicated significant alterations in immune-related and metabolic pathways, including the complement and PPAR signaling pathways. These findings underscore the crucial interplay between host genetics and gut microbiota, indicating that iNOS plays a key role in modulating the gut microbial ecology, host immune system, and metabolic responses. [ABSTRACT FROM AUTHOR]

Diabetics are susceptible to severe trophic problems and wounds, which are frequently referred to as "unhealable wounds". Untreated diabetic wounds provide an ideal habitat for the growth of bacteria, which can eventually develop resistance to standard treatments and need amputation. This study aimed to assess the in vitro antibacterial activity of ethanolic and aqueous extracts of Eriosema robustum leaves on the same bacterium, as well as the resistance profile of bacteria isolated from diabetic wounds to conventional antibiotics. Thirty samples from diabetic wounds were collected at the Baleveng Hospital, subjected to bacteria isolation and antibiotics resistance tests using the disk diffusion method. On the other hands, leaves of Eriosema robustum were collected, hydroethanolic extraction were performed. The extract obtained was used for the antibacterial (by determination of the MIC) and antioxidant (DPPH and FRAP tests) activities as well as phytochemicals composition (using HPLC methods) assessment. Amon the 30 samples analyzed, 19 (63.33 %) showed bacterial infections and Staphylococcus aureus was the most common pathogen (48 %), followed by Pseudomonas aeruginosa (24 %), Klebsiella pneumoniae (19 %), and Streptococcus agalactiae (9 %). Fifty percent (50 %) of S. aureus isolates were MRSA (methicillin-resistant S. aureus). The MIC value obtained 64 µg/mL against S. aureus, Streptococcus agalactiae and Pseudomonas aeruginosa. Phytochemicals analysis of fractions from the 70 ° hydroethanolic leaves of Eriosema robustum revealed the presence of coumarin, gallic acid, quinoline, vanillin, ascorbic acid, caffeic acid, kaempferol, and cinnamic acid. The antibacterial and antioxidant potential of the extracts highlighted in this study could make this plant a good avenue for the discovery of new molecules effective against infected diabetic wounds. [ABSTRACT FROM AUTHOR]

Introduction: Persistent nasal carriage has been associated with Staphylococcus aureus infection. Previous S. aureus studies in Asia have primarily focused on clinical patients, providing limited information on persistent nasal carriage among the general adult population. Methods: This study examined 143 healthy adults in a community in Jiangsu, China. Nasal swab samples were collected 10 times. The colonization status was identified using SPA typing. We also determined antimicrobial susceptibility, genotype, and genomic characteristics of S. aureus. Results: The prevalence of S. aureus nasal carriage among the community individuals was on average 16.78%. The carriage rates of methicillin-resistant S. aureus and multidrug-resistant S. aureus were 6.29% and 7.69%, respectively. We identified 8.39% persistent carriers, 39.16% intermittent carriers, and 52.45% noncarriers. Furthermore, family members displayed concordance in terms of genotype and genomic characteristics. Conclusion: Persistent nasal sampling captured intermittent carriers that were missed during short-term sampling, thus highlighting the necessity for regular community testing. SPA typing can serve as a rapid method for determining S. aureus colonization. The potential for intrafamilial transmission of S. aureus is evident, with persistent carriers being the most probable source of infection. [ABSTRACT FROM AUTHOR]

Prosthetic joint infections (PJIs) are dreaded arthroplasty complications often caused by Staphylococcus aureus. Due to methicillin-resistant S. aureus (MRSA) strains or biofilm formation, successful treatment remains difficult. Currently, two-stage revision surgery constitutes the gold standard therapy of PJIs, sometimes replaced or supplemented by debridement, antibiotics, and implant retention (DAIR). Given the dire consequences of therapeutic failure, bacteriophage therapy might be another treatment option. Here we provide a comprehensive literature review addressing the efficacy of phages applied against S. aureus as causative agent of PJIs. The included 17 publications had in common that the applied phages proved to be effective against various S. aureus isolates including MRSA even in biofilms. Experiments with mice, rats, rabbits, and moth larvae confirmed favorable features of phage preparations in PJI treatment in vivo ; including its synergistic with antibiotics. Case reports of PJI patients unanimously described the bacterial eradication following, alongside other measures, intravenous and intra-articular phage administration. Generally, no major side effects occurred, but in some cases elevated liver transaminases were observed. To conclude, our review compiled promising evidence suggesting the safety and suitability of phage therapy as an adjuvant to DAIR in S. aureus PJIs, and thus, underscores the significance of further research. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (S. aureus) is a major human pathogen and can cause a wide range of diseases, including pneumonia, osteomyelitis, skin and soft tissue infections (SSTIs), endocarditis, mastitis, bacteremia, and so forth. Rats have been widely used in the field of infectious diseases due to their unique advantages, and the models of S. aureus infections have played a pivotal role in elucidating their pathogenic mechanisms and the effectiveness of therapeutic agents. This review outlined the current application of rat models in S. aureus infections and future prospects for rat models in infectious diseases caused by S. aureus. [ABSTRACT FROM AUTHOR]

BACKGROUND: The repair process of skin trauma is complex and susceptible to infection, easy to lead to poor healing, is the current difficulty and hot spot in wound repair research, and has received extensive attention in the fields of traditional Chinese medicine and tissue engineering. OBJECTIVE: To investigate the effect of moxibustion and reduced graphene oxide/cerium oxide nanocomposite on promoting the healing of infectious wounds. METHODS: (1) Reduced graphene oxide/cerium dioxide nanocomposites with mass ratios of 2:1, 1:1 and 1:2 were synthesized by hydrothermal method. The resulting composites were recorded as G2C1, G1C1and G1C2, respectively. The photothermal properties, cytotoxicity and antibacterial properties of the three kinds of materials were tested. After taking moxa sticks, three kinds of moxibustion distances were set (3.0-3.5 cm, recorded as moxibustion 1; 2.5-3.0 cm, recorded as moxibustion 2; 2.0-2.5 cm, recorded as moxibustion 3). Moxibustion was applied to the surface of human skin for 10 minutes to detect the photothermal properties. The antibacterial properties of moxibustion were tested at three different distance intervals. Simultaneously, the back body surface infrared imaging of rats with different mass concentrations of G1C1material, moxibustion (three kinds of moxibustion distances) and moxibustion 2+G1C1material was detected. (2) Sixty male Sprague-Dawley rats were selected to model the wound of Staphylococcus aureus infection. 48 hours later, they were randomly divided into 10 groups with 6 rats in each group: control group (did not receive any treatment), mupirocin group, moxibustion 2+G1C1group, moxibustion 1 group, moxibustion 2 group, moxibustion 3 group and 60, 80, 100, and 120 μg/mL G1C1groups (The G1C1group was given 808 nm near-infrared laser irradiation for 10 min/time, and the G1C1suspension was loaded on the wound surface before each treatment. Each group of moxibustion underwent insitu suspension moxibustion, and the intervention time was 10 min/time. Moxibustion 2+G1C1group was loaded with G1C1suspension on the wound surface before each treatment, and moxibustion was suspended in situ with moxa strips, and the intervention time was 10 min/time). The frequency of treatment was 2 days once. Wound healing, wound colony count and repair were detected after 7 days of intervention. RESULTS AND CONCLUSION: (1) The three kinds of reduced graphene oxide/cerium dioxide nanocomposites had good photothermal properties, and the higher the mass concentration of the composites, the better the photothermal properties. The temperature of the moxibustion 2 group reached 47.6 °C for 10 minutes without causing thermal damage, which was more suitable for animal experiments. The results of co-culture with NIH-3T3 cells exhibited that 60, 80, and 100 μg/mL G1C1had good biocompatibility. The results of a co-culture experiment with Staphylococcus aureus suspension displayed that G2C1, G1C1and G1C2 had good antibacterial activity, among which G1C1group demonstrated excellent antibacterial performance, and the antibacterial rate reached 100% when its mass concentration was 80 μg/mL. 60-120 μg/mL G1C1could effectively remove Staphylococcus aureus biofilm, and the higher the material mass concentration, the better the removal effect. Moxibustion could also effectively remove Staphylococcus aureus biofilm, and the closer the moxibustion was, the better the removal effect. (2) Compared with the control group, the wound area of the mupirocin group, moxibustion 2 group, moxibustion 2+G1C1group and 80, 100 μg/mL G1C1groups was significantly reduced on day 7 of treatment, and the quality of wound repair was better. Mupirocin, G1C1, moxibustion and moxibustion 2+G1C1could effectively remove the residual bacteria on the wound surface, and the higher the mass concentration of G1C1, the lower the residual bacteria. Among them, the wound repair efficiency and bacterial residue of 80 μg/mL G1C1group and moxibustion 2 group were very similar, and the wound repair efficiency of both was better than that of mupirocin group. In addition, it was also observed that the combination of materials and moxibustion had a better ability to clear wound bacteria than that used alone. (3) The results confirm that moxibustion, reduced graphene oxide/cerium dioxide nanocomposites and their combination have good anti-infection and wound healing effects. [ABSTRACT FROM AUTHOR]

Multidrug-resistant bacterial infections are a major global health challenge, especially the emergence and rapid spread of methicillin-resistant Staphylococcus aureus (MRSA) urgently require alternative treatment options. Our study has identified that a magnolol derivative 6i as a promising agent with significant antibacterial activity against S. aureus and clinical MRSA isolates (MIC = 2-8 µg/mL), showing high membrane selectivity. Unlike traditional antibiotics, 6i demonstrated rapid bactericidal efficiency and a lower propensity for inducing bacterial resistance. Compound 6i also could inhibit biofilm formation and eradicate bacteria within biofilms. Mechanistic studies further revealed that 6i could target bacterial cell membranes, disrupting the integrity of the cell membrane and leading to increased DNA leakage, resulting in potent antibacterial effects. Meanwhile, 6i also showed good plasma stability and excellent biosafety. Notably, 6i displayed good in vivo antibacterial activity in a mouse skin abscess model of MRSA-16 infection, which was comparable to the positive control vancomycin. These findings indicated that the magnolol derivative 6i possessed the potential to be a novel anti-MRSA infection agent. [ABSTRACT FROM AUTHOR]

Recently, OTULIN haploinsufficiency was linked to enhanced susceptibility to Staphylococcus aureus infections accompanied by local necrosis and systemic inflammation. The pathogenesis observed in haploinsufficient patients differs from the hyperinflammation seen in classical OTULIN-related autoinflammatory syndrome (ORAS) patients and is characterized by increased susceptibility of dermal fibroblasts to S. aureus alpha toxin-inflicted cytotoxic damage. Immunological abnormalities were not observed in OTULIN haploinsufficient patients, suggesting a non-hematopoietic basis. In this research report, we investigated an Otulin+/- mouse model after in vivo provocation with lipopolysaccharide (LPS) to explore the potential role of hematopoietic-driven inflammation in OTULIN haploinsufficiency. We observed a hyperinflammatory signature in LPS-provoked Otulin+/- mice, which was driven by CD64+ monocytes and macrophages. Bone marrow-derived macrophages (BMDMs) of Otulin+/- mice demonstrated higher proinflammatory cytokine secretion after in vitro stimulation with LPS or polyinosinic:polycytidylic acid (Poly(I:C)). Our experiments in full and mixed bone marrow chimeric mice suggest that, in contrast to humans, the observed inflammation was mainly driven by the hematopoietic compartment with cell-extrinsic effects likely contributing to inflammatory outcomes. Using an OTULIN haploinsufficient mouse model, we validated the role of OTULIN in the regulation of environmentally directed inflammation. [ABSTRACT FROM AUTHOR]

Insect host defense comprises two complementary dimensions, microbial killing-mediated resistance and microbial toxin neutralization-mediated resilience, both jointly providing protection against pathogen infections. Insect defensins are a class of effectors of innate immunity primarily responsible for resistance to Gram-positive bacteria. Here, we report a newly originated gene from an ancestral defensin via genetic deletion following gene duplication in Drosophila virilis, which confers an enhanced resilience to Gram-positive bacterial infection. This gene encodes an 18-mer arginine-rich peptide (termed DvirARP) with differences from its parent gene in its pattern of expression, structure and function. DvirARP specifically expresses in D. virilis female adults with a constitutive manner. It adopts a novel fold with a 310 helix and a two CXC motif-containing loop stabilized by two disulfide bridges. DvirARP exhibits no activity on the majority of microorganisms tested and only a weak activity against two Gram-positive bacteria. DvirARP knockout flies are viable and have no obvious defect in reproductivity but they are more susceptible to the DvirARP-resistant Staphylococcus aureus infection than the wild type files, which can be attributable to its ability in neutralization of the S. aureus secreted toxins. Phylogenetic distribution analysis reveals that DvirARP is restrictedly present in the Drosophila subgenus, but independent deletion variations also occur in defensins from the Sophophora subgenus, in support of the evolvability of this class of immune effectors. Our work illustrates for the first time how a duplicate resistance-mediated gene evolves an ability to increase the resilience of a subset of Drosophila species against bacterial infection. [ABSTRACT FROM AUTHOR]

Daptomycin is gaining prominence for the treatment of methicillin-resistant Staphylococcus aureus infections. However, the dosage selection for daptomycin in critically ill patients remains uncertain, especially in Chinese patients. This study aimed to establish the population pharmacokinetics of daptomycin in critically ill patients, optimize clinical administration plans, and recommend appropriate dosage for critically ill patients in China. The study included 64 critically ill patients. Blood samples were collected at the designated times. The blood daptomycin concentration was determined using validated liquid chromatography-tandem mass spectrometry. A nonlinear mixedeffects model was applied for the population pharmacokinetic analysis and Monte Carlo simulations of daptomycin. The results showed a twocompartment population pharmacokinetic model of daptomycin in critically ill adult Han Chinese patients. Monte Carlo simulations revealed that a daily dose of 400 mg of daptomycin was insufficient for the majority of critically ill adult patients to achieve the anti-infective target. For critically ill adult patients with normal renal function (creatinine clearance rate >90 mL/min), the probability of achieving the target only reached 90% when the daily dose was increased to 700 mg. For patients undergoing continuous renal replacement therapy (CRRT), 24 h administration of 500 mg met the pharmacodynamic goals and did not exceed the safety threshold in most patients. Therefore, considering its efficacy and safety, intravenous daptomycin doses are best scaled according to creatinine clearance, and an increased dose is recommended for critically ill patients with hyperrenalism. For patients receiving CRRT, medication is recommended at 24 h intervals. [ABSTRACT FROM AUTHOR]

Aim. The increasing antibiotic resistance and the ability to form biofilms in medical devices have become the leading cause of severe infections associated with Staphylococcus aureus (S. aureus). Since the bacteria living in biofilms can exhibit 10- to 1,000-fold increase in antibiotic resistance and implicate chronic infectious diseases, the detection of S. aureus ability to form biofilms is of great importance for managing, minimizing, and effectively treating infections caused by it. This study aimed to compare the tube and tissue culture methods to detect biofilm production and antibiotic susceptibility in MRSA and MSSA. Materials and Methods. The S. aureus isolates were identified by the examination of the colony morphology, Gram staining, and various biochemical tests. Antimicrobial susceptibility testing of all isolates was performed by the modified Kirby–Bauer disc diffusion method as recommended by CLSI guidelines. MRSA screening was performed phenotypically using a cefoxitin disc (30 µg). Isolates were tested for inducible resistance using the D-test, and two phenotypic methods detected biofilm formation. Results. Among 982 nonrepeated clinical specimens, S. aureus was isolated from 103 (10.48%). Among 103 clinical isolates of S. aureus, 54 (52.42%) isolates were MRSA, and 49 (47.57%) were MSSA. Among 54 MRSA isolates, the inducible MLSB phenotype was observed in 23/54 (42.59%) with a positive D-test. By TCP method, 26 (48.1%) MRSA isolates were strong biofilm producers, whereas, among all MSSA isolates, only 6 (12.2%) were strong biofilm producers. Conclusion. MRSA showed strong biofilm production in comparison with MSSA. The TCP method is a recommended reliable method to detect the biofilm among S. aureus isolates, and the TM method could be useful for the screening of biofilm production in S. aureus in the routine clinical laboratory. [ABSTRACT FROM AUTHOR]

Background Fracture-related infection is a serious complication after trauma. CERAMENT® G combines dead-space management with local release of gentamicin in a single-stage procedure. Bacterial resistance against antibiotics is increasing. The local effect of CERAMENT® G on bacteria resistant to systemically administered gentamicin is unknown. Questions/purposes (1) What is the in vitro elution pattern of gentamicin from CERAMENT® G using a full washout model? (2) What is the in vitro antimicrobial activity (zone of inhibition) of CERAMENT® G against bacterial isolates found in fracture-related infection with different susceptibility levels toward gentamicin? Methods Elution of gentamicin from CERAMENT®Gwas determined in vitro over a period of 2 months. Elution experiments were performed in fivefold, with gentamicin being sampled in threefold at 19 different timepointswithin 2 months. Antimicrobial activity was determined using the four most-frequently cultured bacterial species found in fracture-related infection: Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Enterobacter cloacae. For each of the species, four different isolates with a different susceptibility to gentamicin were used. According to the European Committee on Antimicrobial Susceptibility Testing, the susceptibility of each isolate was classified into four different groups: fully susceptible (minimum inhibitory concentration 0.064 to 4 mg/L), minimally resistant (minimum inhibitory concentration 4 to 16 mg/L), moderately resistant (minimum inhibitory concentration 8 to 96 mg/L), and highly resistant (minimum inhibitory concentration 24 to 1024 mg/L), depending on each organism. The antimicrobial activity of CERAMENT® Gwas determined according to the European Committee on Antimicrobial Susceptibility Testing disk protocol. The experiment was performed in fivefold for each isolate. The zone of inhibition was compared between each bacterial isolate and within each of the four separate species. Nonlinear regression statistics were calculated between the zone of interest and logarithmic minimum inhibitory concentration for each bacterial species. Results After 24 hours, 95% of all available gentamicin was eluted, and gentamicin was still detectable after 2 months. CERAMENT® G showed antimicrobial activity against all bacterial species; only Staphylococcus aureus (with a minimum inhibitory concentration > 1024 mg/L) was not susceptible. The zone of interest of the different bacterial isolates was correlated with the logarithmic minimum inhibitory concentration. Conclusion CERAMENT® G offers a bone substitute capable of releasing high levels of gentamicin within a short period of time. This study shows that CERAMENT® G has antimicrobial activity against bacterial isolates that are resistant to gentamicin when systemically administered. This finding raises the question of whether European Committee on Antimicrobial Susceptibility Testing cutoff points for systemic application are useful for the use of local CERAMENT® G. Standardized experiments to determine local antibiotic antimicrobial activity in fracture-related infection treatment are needed to form guidelines for the use of local antibiotics and ultimately improve fracture-related infection treatment. Clinical Relevance Local concentrations of gentamicin with CERAMENT® G are much higher than when systemically administered. It seems effective against certain bacterial strains that are not affected by systemically reachable concentrations of gentamicin. CERAMENT® G might still be effective when bacteria that are resistant to systemically administered concentrations of gentamicin are occulated from patients with fracture-related infection. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (S. aureus) is an opportunistic pathogen causing diseases ranging from mild skin infections to life threatening conditions, including endocarditis, pneumonia, and sepsis. To identify host genes modulating this host-pathogen interaction, we infected 25 Collaborative Cross (CC) mouse strains with methicillin-resistant S. aureus (MRSA) and monitored disease progression for seven days using a surgically implanted telemetry system. CC strains varied widely in their response to intravenous MRSA infection. We identified eight 'susceptible' CC strains with high bacterial load, tissue damage, and reduced survival. Among the surviving strains, six with minimal colonization were classified as 'resistant', while the remaining six tolerated higher organ colonization ('tolerant'). The kidney was the most heavily colonized organ, but liver, spleen and lung colonization were better correlated with reduced survival. Resistant strains had higher pre-infection circulating neutrophils and lower post-infection tissue damage compared to susceptible and tolerant strains. We identified four CC strains with sexual dimorphism: all females survived the study period while all males met our euthanasia criteria earlier. In these CC strains, males had more baseline circulating monocytes and red blood cells. We identified several CC strains that may be useful as new models for endocarditis, myocarditis, pneumonia, and resistance to MRSA infection. Quantitative Trait Locus (QTL) analysis identified two significant loci, on Chromosomes 18 and 3, involved in early susceptibility and late survival after infection. We prioritized Npc1 and Ifi44l genes as the strongest candidates influencing survival using variant analysis and mRNA expression data from kidneys within these intervals. Author summary: Methicillin-resistant Staphylococcus aureus is a human opportunistic pathogen that can cause life-threatening diseases. To study the influence of host genetics on the outcome of MRSA infection, we infected a collection of genetically diverse mice. We identified different phenotypes for survival, organ colonization, and tissue damage, and classified CC strains into MRSA susceptible, tolerant, and resistant categories. We identified several parameters that correlated with these phenotypes. Four CC strains exhibited strong sexual dimorphism in infection outcome: females lived longer, and males had higher baseline circulating monocytes and red blood cells. Several of the CC strains we characterize may represent better animal models for diseases caused by MRSA. QTL analysis identified two genes, Npc1 and Ifi44l, as strong candidates for involvement in early susceptibility and late survival after MRSA infection. Our data suggests a strong involvement of host genetics in MRSA infection outcome. [ABSTRACT FROM AUTHOR]