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Copper selenide nanosheets with photothermal therapy-related properties and multienzyme activity for highly effective eradication of drug resistance. [Display omitted] • CuSe NSs showed excellent GSH consumption-, PTT- and PDT-related properties. • CuSe NSs are a promising and potentially safe antibacterial agents for treatment of infected wounds. • The multifunctional CuSe NSs could enable more effective bacterial infections therapy and enhanced PDT. Bacterial infections are among the most significant causes of death in humans. Chronic misuse or uncontrolled use of antibiotics promotes the emergence of multidrug-resistant superbugs that threaten public health through the food chain and cause environmental pollution. Based on the above considerations, copper selenide nanosheets (CuSe NSs) with photothermal therapy (PTT)- and photodynamic therapy (PDT)-related properties have been fabricated. These CuSe NSs possess enhanced PDT-related properties and can convert O 2 into highly toxic reactive oxygen species (ROS), which can cause significant oxidative stress and damage to bacteria. In addition, CuSe NSs can efficiently consume glutathione (GSH) at bacterial infection sites, thus further enhancing their sterilization efficacy. In vitro antibacterial experiments with near-infrared (NIR) irradiation have shown that CuSe NSs have excellent photothermal bactericidal properties. These experiments also showed that CuSe NSs exerted excellent bactericidal effects on wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) and significantly promoted the healing of infected wounds. Because of their superior biological safety, CuSe NSs are novel copper-based antimicrobial agents that are expected to enter clinical trials, serving as a modern approach to the major problem of treating bacterially infected wounds. [ABSTRACT FROM AUTHOR]

Background Equitable representation of members from historically marginalized groups is important in clinical trials, which inform standards of care. The goal of this study was to characterize the demographics and proportional subgroup reporting and representation of participants enrolled in randomized controlled trials (RCTs) of antibacterials used to treat Staphylococcus aureus infections. Methods We examined randomized controlled registrational and strategy trials published from 2000 to 2021 to determine the sex, race, and ethnicity of participants. Participant to incidence ratios (PIRs) were calculated by dividing the percentage of study participants in each demographic group by the percentage of the disease population in each group. Underrepresentation was defined as a PIR < 0.8. Results Of the 87 included studies, 82 (94.2%) reported participant sex, 69 (79.3%) reported participant race, and 20 (23.0%) included ethnicity data. Only 17 (19.5%) studies enrolled American Indian/Alaskan Native participants. Median PIRs indicated that Asian and Black participants were underrepresented in RCTs compared with the incidence of methicillin-resistant S. aureus infections in these subgroups. Underrepresentation of Black participants was associated with a larger study size, international sites, industry sponsorship, and phase 2/3 trials compared with phase 4 trials (P <.05 for each). Black participants had more than 4 times the odds of being underrepresented in phase 2/3 trials compared with phase 4 trials (odds ratio, 4.57; 95% confidence interval: 1.14–18.3). Conclusions Standardized reporting methods for race and ethnicity and efforts to increase recruitment of marginalized groups would help ensure equity, rigor, and generalizability in RCTs of antibacterial agents and reduce health inequities. [ABSTRACT FROM AUTHOR]

Staphylococcal cassette chromosome mec (SCC mec) typing is crucial for investigating methicillin-resistant Staphylococcus aureus (MRSA), relying primarily on the combination of ccr and mec gene complexes. To date, 19 ccr genes and 10 ccr gene complexes have been identified, forming 15 SCC mec types. With the vast release of bacterial genome sequences, mining the database for novel ccr gene complexes and SCC/SCC mec elements could enhance MRSA epidemiological studies. In this study, we identified 12 novel ccr genes (6 ccrA , 3 ccrB, and 3 ccrC) through mining of the National Center for Biotechnology Information (NCBI) database, forming 12 novel ccr gene complexes and 10 novel SCC elements. Overexpression of 5 groups of novel Ccr recombinases (CcrA9B3, CcrA10B1, CcrC3, CcrC4, and CcrC5) in a mutant MRSA strain lacking the ccr gene and extrachromosomal circular intermediate (ciSCC) production significantly promoted ciSCC production, demonstrating their biological activity. This discovery provides an opportunity to advance MRSA epidemiological research and develop database-based bacterial typing methods. [ABSTRACT FROM AUTHOR]

Background Cytochrome bd complexes are respiratory oxidases found exclusively in prokaryotes that are important during infection for numerous bacterial pathogens. Methods In silico docking was employed to screen approved drugs for their ability to bind to the quinol site of Escherichia coli cytochrome bd -I. Respiratory inhibition was assessed with oxygen electrodes using membranes isolated from E. coli and methicillin-resistant Staphylococcus aureus strains expressing single respiratory oxidases (ie, cytochromes bd , bo ′, or aa 3). Growth/viability assays were used to measure bacteriostatic and bactericidal effects. Results The steroid drugs ethinylestradiol and quinestrol inhibited E. coli bd -I activity with median inhibitory concentration (IC50) values of 47 ± 28.9 µg/mL (158 ± 97.2 µM) and 0.2 ± 0.04 µg/mL (0.5 ± 0.1 µM), respectively. Quinestrol inhibited growth of an E. coli " bd -I only" strain with an IC50 of 0.06 ± 0.02 µg/mL (0.2 ± 0.07 µM). Growth of an S. aureus " bd only" strain was inhibited by quinestrol with an IC50 of 2.2 ± 0.43 µg/mL (6.0 ± 1.2 µM). Quinestrol exhibited potent bactericidal effects against S. aureus but not E. coli. Conclusions Quinestrol inhibits cytochrome bd in E. coli and S. aureus membranes and inhibits the growth of both species, yet is only bactericidal toward S. aureus. [ABSTRACT FROM AUTHOR]

In response to the escalating global threat of antimicrobial resistance, our laboratory has established a phagemid packaging system for the generation of CRISPR-Cas13a-antimicrobial capsids targeting methicillin-resistant Staphylococcus aureus (MRSA). However, a significant challenge arose during the packaging process: the unintentional production of wild-type phages alongside the antimicrobial capsids. To address this issue, the phagemid packaging system was optimized by strategically incorporated silent mutations. This approach effectively minimized contamination risks without compromising packaging efficiency. The study identified the indispensable role of phage packaging genes, particularly terL-terS, in efficient phagemid packaging. Additionally, the elimination of homologous sequences between the phagemid and wild-type phage genome was crucial in preventing wild-type phage contamination. The optimized phagemid-LSAB(mosaic) demonstrated sequence-specific killing, efficiently eliminating MRSA strains carrying target antibiotic-resistant genes. While acknowledging the need for further exploration across bacterial species and in vivo validation, this refined phagemid packaging system offers a valuable advancement in the development of CRISPR-Cas13a-based antimicrobials, shedding light on potential solutions in the ongoing battle against bacterial infections. [ABSTRACT FROM AUTHOR]

Background: A parotid abscess (PA) is a complication of an acute bacterial parotitis with a potentially life-threatening course. To date, data on the diagnosis and therapy of PA is sparse and mostly consists of case reports or case series. Therefore, this study aimed at comprehensively analyzing the microbiological spectrum and the therapeutic management in a bi-institutional setting. Methods: A retrospective clinical chart review was performed to identify all patients surgically treated for PA at two tertiary care centers in Germany. Data on demographics, clinical management and microbiological data including species identification, pathogenicity, type of antibiotic therapy, adjustment of antibiotics, antibiotic sensitivity testing, and smear test results were extracted. Intervention-related variables and etiology were analyzed for their statistical association with outcome variables. Results: Overall, 85 patients were included. Most patients (92.9%) underwent surgical incision. Around half of the patients (45.9%) were treated under local anesthesia. No facial nerve palsy was observed. The most frequently detected pathogens were Streptococci (n = 23), followed by Staphylococcus aureus (n = 6) including one case of methicillin-resistant Staphylococcus aureus. Most patients (68.2%) received an aminopenicillin ± beta-lactamase inhibitor as empiric antibiotic therapy. In 6 cases the antibiotic therapy was modified after receiving the antibiogram. Four patients (5.2%) presented with recurrent PA. Etiology was idiopathic (42.4%), followed by tumorous (12.9%), obstructive, and immunosuppressive (each 11.8%). Patients with a dental focus (p = 0.007) had a longer duration of hospitalization. Conclusion: The results show that the surgical therapy of PA under local anesthesia is safe. A dental examination should routinely be performed to rule out a dental focus. Obtaining a microbiological specimen in order to modify antibiotic therapy if necessary and a histopathological specimen to rule out a tumorous etiology is obligate. [ABSTRACT FROM AUTHOR]

Treating bacteremia caused by antibiotic-resistant bacteria is a global concern. Antibacterial photodynamic inactivation is a promising strategy to combat it. However, it's challenging to achieve the inactivation of antibiotic-resistant bacteria in whole blood because of its opacity and complexity. We investigated a riboflavin photodynamic method to effectively inactivate antibiotic-resistant bacteria in whole blood. Four strains of antibiotic-resistant bacteria were isolated, identified, and cultured in this research: methicillin-resistant Staphylococcus aureus (MRSA), pan-drug-resistant Acinetobacter baumannii (PDRAB), ESBLs-producing Escherichia coli (EPEC) and pan-drug-resistant Klebsiella pneumoniae (PDRKP). To simulate bacteremia, antibiotic-resistant bacteria was added into whole blood. Whole blood was treated using riboflavin photodynamic method with ultraviolet irradiation (308 nm and 365 nm). The ultraviolet irradiation dose was divided into 18 J/cm², 36 J/cm², and 54 J/cm². Microbial count of antibiotic-resistant bacteria in whole blood was used for evaluating inactivation effectiveness. The roles of red blood cells, lymphocytes, coagulation factors, and platelets in whole blood were assessed. In results, inactivation effectiveness increased as the ultraviolet dose increased from 18 J/cm² to 54 J/cm². At the dose of 18 J/cm², inactivation effectiveness of four antibiotic-resistant bacteria were more than 80%, while only 67% of MRSA. The antibacterial effect was enhanced by the combination of riboflavin photodynamic treatment and antibiotic. The red blood cell function was susceptible to ultraviolet dose. At the dose of 18 J/cm², hemolysis rate was less than 0.8% and there was no change in levels of ATP and 2,3-DPG. At the same dose, the proliferation, cell killing, and cytokine secretion activities of lymphocytes decreased 20--70%; Factor V and Factor VIII activities decreased 50%; Fibrinogen and platelet function loss significantly but reparable. Consequently, we speculated that riboflavin photodynamic method with a ultraviolet dose of 18 J/cm² was effective in inactivating four antibiotic- resistant bacteria in whole blood while whole blood function was preserved. We also provided a novel extracorporeal circulation phototherapy mode for treating bacteremia caused by antibiotic-resistant bacteria. [ABSTRACT FROM AUTHOR]

The Pelargonium genus encompasses around 280 species, most of which are used for medicinal purposes. While P. graveolens, P. odoratissimum, and P. zonale are known to exhibit antimicrobial activity, there is an evident absence of studies evaluating all three species to understand their chemical differences and biological effects. Through the analysis of the hydroalcoholic extracts of P. graveolens, P. odoratissimum, and P. zonale, using HPLC-DAD-MS/MS, quercetin and kaempferol derivatives were identified in these three species. Conversely, gallotannins and anthocyanins were uniquely detected in P. zonale. P. graveolens stood out due to the various types of myricetin derivatives that were not detected in P. odoratissimum and P. zonale extracts. Evaluation of their biological activities revealed that P. zonale displayed superior antibacterial and antibiofilm activities in comparison to the other two species. The antibacterial efficacy of P. zonale was observed towards the clinically relevant strains of Staphylococcus aureus ATCC 25923, Methicillin-resistant Staphylococcus aureus (MRSA) 333, Enterococcus faecalis ATCC 29212, and the Vancomycin-resistant E. faecalis INSPI 032. Fractionation analysis of P. zonale suggested that the antibacterial activity attributed to this plant is due to the presence of quercetin derivatives and kaempferol and its derivatives, alongside their synergistic interaction with gallotannins and anthocyanins. Lastly, the three Pelargonium species exhibited notable antioxidant activity, which may be attributed to their high content of total phenolic compounds. [ABSTRACT FROM AUTHOR]

Healthcare associated infections (HAIs) are costly but preventable. A limited understanding of the effects of environmental cleaning on the riskiest HAI associated pathogens is a current challenge in HAI prevention. This project aimed to quantify the effects of terminal hospital cleaning practices on HAI pathogens via environmental sampling in three hospitals located throughout the United States. Surfaces were swabbed from 36 occupied patient rooms with a laboratory-confirmed, hospital- or community-acquired infection of at least one of the four pathogens of interest (i.e., Acinetobacter baumannii (A. baumannii), methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus faecalis/faecium (VRE), and Clostridioides difficile (C. difficile)). Six nonporous, high touch surfaces (i.e., chair handrail, bed handrail, nurse call button, desk surface, bathroom counter near the sink, and a grab bar near the toilet) were sampled in each room for Adenosine Triphosphate (ATP) and the four pathogens of interest before and after terminal cleaning. The four pathogens of interest were detected on surfaces before and after terminal cleaning, but their levels were generally reduced. Overall, C. difficile was confirmed on the desk (n = 2), while MRSA (n = 24) and VRE (n = 25) were confirmed on all surface types before terminal cleaning. After cleaning, only MRSA (n = 6) on bed handrail, chair handrail, and nurse call button and VRE (n = 5) on bathroom sink, bed handrail, nurse call button, toilet grab bar, and C. difficile (n = 1) were confirmed. At 2 of the 3 hospitals, pathogens were generally reduced by >99% during terminal cleaning. One hospital showed that VRE increased after terminal cleaning, MRSA was reduced by 73% on the nurse call button, and VRE was reduced by only 50% on the bathroom sink. ATP detections did not correlate with any pathogen concentration. This study highlights the importance of terminal cleaning and indicates room for improvement in cleaning practices to reduce surface contamination throughout hospital rooms. [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]

Background: Understanding the biology of methicillin resistant Staphylococcus aureus (MRSA) is crucial to unlocking insights for new targets in our fight against this antimicrobial resistant priority pathogen. Although proteomics and metabolomic profiling offer the potential to elucidating such biological markers, reports of methodological approaches for carrying this out in S. aureus isolates remain limited. We describe the use of a dual-functionality methanol extraction method for the concurrent extraction of protein and metabolites from S. aureus and report on the comparative analysis of the proteomic and metabolomic profiles of MRSA versus methicillin sensitive S. aureus (MSSA). Methods: Bacterial reference strains MRSA ATCC43300 and MSSA ATCC25923 were used. The conventional urea methodology was used for protein extraction and a methanol based method was used for concurrent proteins and metabolites extraction. Proteomic and metabolomic profiling was carried out using TimsTOF mass spectrometry. Data processing was carried out using the MaxQuant version 2.1.4.0. Results: This study represents the first report on the utilization of the methanol extraction method for concurrent protein and metabolite extraction in Gram positive bacteria. Our findings demonstrate good performance of the method for the dual extraction of proteins and metabolites from S. aureus with demonstration of reproducibility. Comparison of MRSA and MSSA strains revealed 407 proteins with significantly different expression levels. Enrichment analysis of those proteins revealed distinct pathways involved in fatty acid degradation, metabolism and beta-lactam resistance. Penicillin-binding protein PBP2a, the key determinant of MRSA resistance, exhibited distinct expression patterns in MRSA isolates. Metabolomic analysis identified 146 metabolites with only one exclusive to the MRSA. The enriched pathways identified were related to arginine metabolism and biosynthesis. Conclusion: Our findings demonstrate the effectiveness of the methanol-based dual-extraction method, providing simultaneous insights into the proteomic and metabolomic landscapes of S. aureus strains. These findings demonstrate the utility of proteomic and metabolomic profiling for elucidating the biological basis of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Despite the improved outcomes in patients with hematological malignancies, infections caused by multidrug-resistant organisms (MDROs) pose a new threat to these patients. We retrospectively reviewed the patients with hematological cancer and bacterial bloodstream infections (BSIs) at a tertiary hospital between 2003 and 2022 to assess the impact of MDROs on outcomes. Among 328 BSIs, 81 (24.7%) were caused by MDROs. MDRO rates increased from 10.3% (2003–2007) to 39.7% (2018–2022) (P < 0.001). The 30-day mortality rate was 25.0%, which was significantly higher in MDRO-infected patients than in non-MDRO-infected patients (48.1 vs. 17.4%; P < 0.001). The observed trend was more pronounced in patients with newly diagnosed diseases and relapsed/refractory disease but less prominent in patients in complete remission. Among MDROs, carbapenem-resistant Gram-negative bacteria exhibited the highest mortality, followed by vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and extended-spectrum β-lactamase-producing Enterobacteriaceae. Multivariate analysis identified independent risk factors for 30-day mortality as age ≥ 65 years, newly diagnosed disease, relapsed/refractory disease, MDROs, polymicrobial infection, CRP ≥ 20 mg/L, and inappropriate initial antibiotic therapy. In conclusion, MDROs contribute to adverse outcomes in patients with hematological cancer and bacterial BSIs, with effects varying based on the underlying disease status and causative pathogens. Appropriate initial antibiotic therapy may improve patient outcomes. [ABSTRACT FROM AUTHOR]

This study explores a sustainable approach for synthesizing silver nanocomposites (AgNCs) with enhanced antimicrobial and bioactivity using safe Lactobacillus strains and a whey-based medium (WBM). WBM effectively supported the growth of Lactobacillus delbrueckii and Lactobacillus acidophilus, triggering a stress response that led to AgNCs formation. The synthesized AgNCs were characterized using advanced spectroscopic and imaging techniques such as UV‒visible, Fourier transform infrared (FT-IR) spectroscopy, transmission electron (TEM), and scanning electron microscopy with energy dispersive X-ray analysis (SEM–Edx). Lb acidophilus-synthesized AgNCs in WBM (had DLS size average 817.2–974.3 ± PDI = 0.441 nm with an average of metal core size 13.32 ± 3.55 nm) exhibited significant antimicrobial activity against a broad spectrum of pathogens, including bacteria such as Escherichia coli (16.47 ± 2.19 nm), Bacillus cereus (15.31 ± 0.43 nm), Clostridium perfringens (25.95 ± 0.03 mm), Enterococcus faecalis (32.34 ± 0.07 mm), Listeria monocytogenes (23.33 ± 0.05 mm), methicillin-resistant Staphylococcus aureus (MRSA) (13.20 ± 1.76 mm), and filamentous fungi such as Aspergillus brasiliensis (33.46 ± 0.01 mm). In addition, Lb acidophilus-synthesized AgNCs in WBM exhibit remarkable free radical scavenging abilities, suggesting their potential as bioavailable antioxidants. These findings highlight the dual functionality of these biogenic AgNCs, making them promising candidates for applications in both medicine and nutrition. [ABSTRACT FROM AUTHOR]

The threat of methicillin-resistant Staphylococcus aureus (MRSA) is increasing worldwide, making it significantly necessary to discover a novel way of dealing with related infections. The quick spread of MRSA isolates among infected individuals has heightened public health concerns and significantly limited treatment options. Vancomycin (VAN) can be applied to treat severe MRSA infections, and the indiscriminate administration of this antimicrobial agent has caused several concerns in medical settings. Owing to several advantageous characteristics, a niosomal drug delivery system may increase the potential of loaded antimicrobial agents. This work aims to examine the antibacterial and anti-biofilm properties of VAN-niosome against MRSA clinical isolates with emphasis on cytotoxicity and stability studies. Furthermore, we aim to suggest an effective approach against MRSA infections by investigating the inhibitory effect of formulated niosome on the expression of the biofilm-associated gene (icaR). The thin-film hydration approach was used to prepare the niosome (Tween 60, Span 60, and cholesterol), and field emission scanning electron microscopy (FE-SEM), an in vitro drug release, dynamic light scattering (DLS), and entrapment efficiency (EE%) were used to investigate the physicochemical properties. The physical stability of VAN-niosome, including hydrodynamic size, polydispersity index (PDI), and EE%, was analyzed for a 30-day storage time at 4 °C and 25 °C. In addition, the human foreskin fibroblast (HFF) cell line was used to evaluate the cytotoxic effect of synthesized niosome. Moreover, minimum inhibitory and bactericidal concentrations (MICs/MBCs) were applied to assess the antibacterial properties of niosomal VAN formulation. Also, the antibiofilm potential of VAN-niosome was investigated by microtiter plate (MTP) and real-time PCR methods. The FE-SEM result revealed that synthesized VAN-niosome had a spherical morphology. The hydrodynamic size and PDI of VAN-niosome reported by the DLS method were 201.2 nm and 0.301, respectively. Also, the surface zeta charge of the prepared niosome was − 35.4 mV, and the EE% ranged between 58.9 and 62.5%. Moreover, in vitro release study revealed a sustained-release profile for synthesized niosomal formulation. Our study showed that VAN-niosome had acceptable stability during a 30-day storage time. Additionally, the VAN-niosome had stronger antibacterial and anti-biofilm properties against MRSA clinical isolates compared with free VAN. In conclusion, the result of our study demonstrated that niosomal VAN could be promising as a successful drug delivery system due to sustained drug release, negligible toxicity, and high encapsulation capacity. Also, the antibacterial and anti-biofilm studies showed the high capacity of VAN-niosome against MRSA clinical isolates. Furthermore, the results of real-time PCR exhibited that VAN-niosome could be proposed as a powerful strategy against MRSA biofilm via down-regulation of icaR gene expression. [ABSTRACT FROM AUTHOR]

Previous studies have shown that antimicrobial photodynamic inactivation (aPDI) can be strongly potentiated by the addition of the non-toxic inorganic salt, potassium iodide (KI). This approach was shown to apply to many different photosensitizers, including the xanthene dye Rose Bengal (RB) excited by green light (540 nm). Rose Bengal diacetate (RBDA) is a lipophilic RB derivative that is easily taken up by cells and hydrolyzed to produce an active photosensitizer. Because KI is not taken up by microbial cells, it was of interest to see if aPDI mediated by RBDA could also be potentiated by KI. The addition of 100 mM KI strongly potentiated the killing of Gram-positive methicillin-resistant Staphylocccus aureus, Gram-negative Eschericia coli, and fungal yeast Candida albicans when treated with RBDA (up to 15 µM) for 2 hours followed by green light (540 nm, 10 J/cm2). Both RBDA aPDI regimens (400 µM RBDA with or without 400 mM KI followed by 20 J/cm2 green light) accelerated the healing of MRSA-infected excisional wounds in diabetic mice, without damaging the host tissue. [ABSTRACT FROM AUTHOR]

Background Methicillin-resistant Staphylococcus aureus (MRSA) nares screening has been shown to be a powerful antibiotic stewardship tool for MRSA infections within 7 days of screening across a variety of anatomical locations given the high negative predictive value (NPV). However, the utility outside of 7 days and among transplant recipients and patients with neutropenia is less clear. Methods This was a retrospective cohort study across Veterans Affairs medical centers in the United States from 1 January 2007 to 1 January 2023 of patients tested for MRSA colonization and who had a subsequent positive bacterial culture within 28 days of MRSA sc---reening. Sensitivity, specificity, positive predictive value, and NPV were calculated across different time points and anatomical culture locations. Results The cohort consisted of 686 174 patients, 6 277 437 MRSA nares tests, and 2 446 766 positive bacterial cultures within 28 days of MRSA testing. The NPV of MRSA nares screening for ruling out a MRSA infection within 28 days was 95.8% across all anatomical culture sites. The NPV was 97.9% among patients with neutropenia and 97.5% in solid organ and hemopoietic stem cell transplant recipients. Conclusions MRSA nares screening can reliably be used for de-escalation of anti-MRSA therapy within 28 days of bacterial culture for all patients, including solid organ and hematopoietic transplant recipients and patients with neutropenia. [ABSTRACT FROM AUTHOR]

Background: Although vancomycin is typically employed against methicillin-resistant Staphylococcus aureus (MRSA) infections, the optimal ratio of 24-h area under the concentration–time curve to minimum inhibitory concentration (AUC24/MIC) for severe or complicated infections lacks clear guideline recommendations. This study aimed to determine the target AUC24/MIC ratio associated with treatment outcomes of infections treated with vancomycin. Methods: This retrospective multicenter cohort study included adult patients receiving ≥ 5 days of vancomycin for severe/complicated MRSA infections (e.g., osteoarticular, pulmonary, endocarditis, etc.) between January 2018 and December 2023. The primary outcome was 30-day mortality, with secondary outcomes including clinical success, microbiological eradication, and nephrotoxicity. Receiver operating characteristic (ROC) curve analysis was used to identify the AUC24/MIC cutoff for 30-day mortality. Multivariate regression analysis was used to determine association between AUC24/MIC and outcomes. Results: This study included 82 patients. ROC identified a target AUC24/MIC of ≥ 505 for 30-day mortality. The overall 30-day mortality rate (22.0%) was significantly higher for below average AUC24/MIC cutoff (34.1%) than for above AUC24/MIC cutoff group (9.8%). Multivariate analysis confirmed AUC24/MIC of < 505 as an independent predictor (adjusted odds ratio, 5.001; 95% confidence interval, 1.335–18.75). The clinical success rate differed significantly between below- and above-cutoff groups, whereas microbiological eradication tended to favor the above-cutoff group. The nephrotoxicity rates were comparable between groups. Conclusions: In treating severe/complicated MRSA infections, vancomycin AUC24/MIC ratio ≥ 505 was independently associated with favorable 30-day mortality. Given the retrospective nature of this study, further prospective studies are essential to confirm the reliability of the target AUC24/MIC ratios. [ABSTRACT FROM AUTHOR]

The aim was to investigate methicillin‐resistant Staphylococcus aureus (MRSA) incidence, conversion and outcomes in diabetic foot infections (DFIs). This is a pooled patient‐level analysis of combined data sets from two randomised clinical trials including 219 patients admitted to the hospital with moderate or severe DFIs. Intraoperative bone and tissue cultures identified bacterial pathogens. We identified pathogens at index infections and subsequent re‐infections. We identified MRSA conversion (MSSA to MRSA) in re‐infections. MRSA incidence in index infections was 10.5%, with no difference between soft tissue infections (STIs) and osteomyelitis (OM). MRSA conversion occurred in 7.7% of the re‐infections in patients who initially had MSSA in their cultures. Patients with re‐infection were 2.2 times more likely to have MRSA compared to the first infection (10.5% vs. 25.8%, relative risk [RR] = 2.2, p = 0.001). Patients with MRSA had longer antibiotic treatment during the 1‐year follow‐up, compared to other pathogens (other 49.8 ± 34.7 days, MRSA 65.3 ± 41.5 days, p = 0.04). Furthermore, there were no differences in healing, time to heal, length of stay, re‐infection, amputation, re‐ulceration, re‐admission, surgery after discharge and amputation after discharge compared to other pathogens. The incidence of MRSA at the index was 10.5% with no difference in STI and OM. MRSA incidence was 25.8% in re‐infections. The RR of having MRSA was 2.2 times higher in re‐infections. Patients with MRSA used more antibiotics during the 1‐year follow‐up. Furthermore, there were no differences in clinical outcomes compared to other bacterial pathogens. [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]

The article offers information on the increasing incidence of sinogenic and otogenic intracranial empyemas following the COVID-19 pandemic, reviewing their presentation, imaging, and treatment. Topics include the severe complications of bacterial rhinosinusitis or otomastoiditis leading to cerebritis and brain abscesses, the polymicrobial nature involving gram-positive, gram-negative, and anaerobic bacteria, with a focus on Streptococcus anginosus group infections.

Introduction: Garlic (Allium sativum) is a popular food spice worldwide with many health benefits. Garlic and its products have been used to treat various infections in traditional medicine in India, the Middle East, and Southeast Asia. Garlic and its organosulphur compounds have antibacterial properties against methicillin-resistant Staphylococcus aureus (MRSA), but the antibiofilm property and interaction with methicillin have been relatively unexplored. Biofilm formation is crucial in MRSA infections, one of the most common nosocomial infections. Method: The antibacterial activity fresh garlic extract (FGE) against MRSA was evaluated by determining the minimum inhibitory concentration (MIC) and zone of inhibition using microdilution and well diffusion assays respectively. Microtiter plate crystal violet assay and scanning electron microscopy was use to evaluate the antibiofilm activity of FGE against MRSA. Results: Sub-MIC concentrations of FGE significantly reduce methicillin-susceptible S. aureus (MSSA) and MRSA biofilm formation. Scanning electron microscopy analysis suggests that FGE reduces the attachment of MSSA and MRSA. Diallyl sulphide, one of the organosulphur compounds of garlic, inhibited the biofilm formation of MSSA and MRSA. Sub-MIC concentration of FGE also sensitized MRSA to methicillin, completely inhibiting MRSA growth when used in combination. Similar effects were noticed when FGE was combined with other β-lactam antibiotics to which MRSA was resistant. Conclusions: The study validates garlic as an antibacterial agent in ethnomedicine through scientific evidence. Garlic and its organosulphur compounds are potential antibiofilm agents against MRSA. Moreover, garlic could be potentially used as a complementary or alternative medicine to treat infections caused by drug-resistant bacteria such as MRSA. [ABSTRACT FROM AUTHOR]

Background and aim. Infections caused by pathogenic bacteria increase patient morbidity and mortality and significantly raise treatment costs. The use of silver nanoparticles as an alternative treatment for S aureus, E coli, MRSA, E faecalis, K pneumoniae and P aeruginosa indicates their antibacterial effect and prompts medical research to consider the next generation of antibacterial drugs that could change antibiotic therapy. By combining silver nanoparticles with different classes of antibiotics, the antibacterial effect is evidenced by increased values of the inhibition zone compared to the values obtained for some antibiotics commonly used in the treatment of bacterial infections. This study focuses on comparing the antibacterial activity of antibiotics versus antibiotics combined with silver nanoparticles against various bacteria, by comparing inhibition zones obtained for both. We aim to prove that the size of the inhibition zone for antibiotics combined with silver nanoparticles is greater, thus confirming the improved antibacterial effect. Metods. In this study we tested the antibacterial activity of solutions of silver nanoparticles alone or in combination with different antibiotics. We used standard bacterial strains, ATCC, both Gram positive bacteria Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, as well as Gram negative bacteria Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, but also on clinical isolates: a strain MRSA (Methicillin Resistant Staphylococcus aureus) and a PDR strain (pan drug resistant) of Klebsiella pneumoniae. Bacterial identification was performed using Vitek MS analyzer (bioMerieux). Antibiotic susceptibility determination was performed with VITEK2 COMPACT SYSTEM (bio Merieux, Inc Durham NC) with ready to use VITEK AST cards. The interpretation of the results was done in compliance with EUCAST 2023-2024 standards. Testing was performed for several classes of antibiotics, silver nanoparticle solutions in 2 concentrations (10 μg/mL and 100 μg/mL) and for combinations of antibiotics with silver nanoparticle solutions. The diameter of the inhibition zone (ZOI) for silver nanoparticles, antibiotics and silver nanoparticles combined with antibiotic against each bacterium was expressed in millimeters. The Kirby-Bauer diskdiffusion method, in accordance with current EUCAST standards, was used to analyze the antibacterial effect of antibiotics, silver nanoparticles, and antibiotics combined with silver nanoparticles at biocompatible doses of 10 and 100 μg/mL. The experiments were conducted in triplicate, and the results were almost identical. Results. The results of this study show that the silver nanoparticles displayed antibacterial activity, proven by the appearance of the inhibition zone, in various sizes, for all bacteria studied. The antibiotic classes tested were beta-lactamins, first, second, third and fourth generation cephalosporins, macrolides, fluoroquinolones, lincosamides, aminoglycosides, glycopeptides, tetracyclines, oxazolidinones, sulfonamides, rifamycins, amphenicols. Testing S aureus ATCC 29213, the highest zone of inhibition was demonstrated for cephalosporins (32.6667 ± 0.701 mm), macrolides (31.6667 ± 0.701 mm, and lincosamides (29.6667 ± 0.701 mm). Testing MRSA (internal code GR0333), the highest zone of inhibition for combination of silver nanoparticles and antibiotics was demonstrated for fluoroquinolones (36.3333 ± 0.701 mm), lincosamides (32.3333 ± 0.701 mm), Fusid acid (32.3333 ± 0.701 mm) and aminoglicosides (31.3333 ± 0.701 mm). Testing E coli ATCC 25922 the highest zone of inhibition was for Fosfomycine, 39 mm and for E faecalis ATCC 29212 for aminoglicosides was 19 mm. For K pneumoniae (internal code GQ8575) the inhibition zone for silver nanoparticles 100 µg/mL was 12.3333 ± 0.701 mm and for P aeruginosa ATCC 27253 was 16 ± 1.214 mm. Conclusions. The use of metallic nanoparticles, especially silver ones, as antimicrobial agents with definite bactericidal activity has led medical specialists to consider this new treatment which may change antibacterial therapy. Studies of in vitro combinations between silver nanoparticles and different classes of antibiotics represent a highly efficient and effective new antibacterial treatment against multidrug-resistant bacteria. To avoid the problem of antimicrobial resistance associated with conventional antibiotics, it is necessary to understand the adaptive mechanisms of bacteria under the action of metal nanoparticles, which could be exploited in future studies. Further in vitro and in vivo studies that would assess specify the biocompatibility and toxicity of silver nanoparticles will make these super nanomaterials the medicines of the future. [ABSTRACT FROM AUTHOR]

Seagrass serves as a quintessential reservoir for obligate marine Lulworthiaceae fungi. Our current knowledge of the mycological diversity associated with seagrass in Hong Kong remains poor. We analyzed the diversity of fungi associated with the most widely distributed seagrass species in Hong Kong Halophila ovalis (Hydrocharitaceae), using a combination of culture-based methods and high-throughput amplicon sequencing. Halophilomyces hongkongensis, a novel fungal species in a newly proposed genus within the Lulworthiaceae family, was isolated from H. ovalis roots and rhizomes. The novel fungus showed distinct morphological characteristics, while both combined 18S-28S and internal transcribed spacer (ITS) phylogenetic trees based on maximum likelihood and Bayesian methods supported its discrimination from other existing Lulworthiaceae members. The ITS2 region in the Illumina sequencing results of multiple H. ovalis compartments, water, and adjacent non-seagrass sediments revealed continuous recruitment of H. hongkongensis by H. ovalis throughout the year despite dramatically fluctuating environmental conditions, with remarkably high proportions of this taxon found in root and rhizome internal tissues, possibly indicating a strong and specialized relationship established between the Lulworthiaceae fungal partner and its seagrass host. The inhibitory abilities exhibited by H. hongkongensis against Staphylococcus aureus SA29213 and ATCC 43300 (methicillin-resistant) may imply its capacity in producing (novel) antibacterial compounds. The discovery of H. hongkongensis as the first novel Lulworthiaceae taxon in Hong Kong, along with its distributional pattern in the seagrass meadow, provides valuable insights into the systematics and ecology of this strictly marine fungal family. [ABSTRACT FROM AUTHOR]

This document summarizes a study on endogenous Staphylococcus aureus endophthalmitis (ESaE), a rare but serious complication that can lead to vision loss. The study focused on cases in Taiwan and examined the source of infection, risk factors, treatments, and visual outcomes. The most common predisposing factor for ESaE was diabetes mellitus, and septic arthritis was the most frequently identified source of infection. Poor initial visual acuity and retinal detachment were predictors for worse visual outcomes. All MRSA and MSSA strains were susceptible to vancomycin. The study did not find a statistically significant difference in visual acuity outcomes between the MRSA and MSSA groups. [Extracted from the article]

Objectives MRSA is a major cause of hospital-acquired and community-acquired infections. Treatment options for MRSA are limited because of the rapid development of β-lactam resistance. Combining antibiotics offers an affordable, time-saving, viable and efficient approach for developing novel antimicrobial therapies. Both amoxicillin and cefdinir are oral β-lactams with indications for a wide range of bacterial infections and mild side effects. This study aimed to investigate the in vitro and in vivo efficacy of combining these two β-lactams against MRSA strains. Methods Fourteen representative prevalent MRSA strains with diverse sequence types (STs) were tested with a combination of amoxicillin and cefdinir, using chequerboard and time–kill assays. The Galleria mellonella larvae infection model was used to evaluate the in vivo efficacy of this dual combination against the community-acquired MRSA (CA-MRSA) strain USA300 and the hospital-acquired MRSA (HA-MRSA) strain COL. Results The chequerboard assay revealed a synergistic activity of the dual amoxicillin/cefdinir combination against all tested MRSA strains, with fractional inhibitory concentration index (FICI) values below 0.5 and at least a 4-fold reduction in the MICs of both antibiotics. Time–kill assays demonstrated synergistic bactericidal activity of this dual combination against the MRSA strain USA300 and strain COL. Moreover, in vivo studies showed that the administration of amoxicillin/cefdinir combination to G. mellonella larvae infected with MRSA strains significantly improved the survival rate up to 82%, which was comparable to the efficacy of vancomycin. Conclusions In vitro and in vivo studies indicate that the dual combination of amoxicillin/cefdinir demonstrates a synergistic bactericidal efficacy against MRSA strains of various STs. Further research is needed to explore its potential as a treatment option for MRSA infections. [ABSTRACT FROM AUTHOR]

Antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using the national surveillance data, comprising 793 bacterial strains from eight clinically relevant species. Data were collected for the fourth national surveillance project from July 2020 to December 2021 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was supervised with the cooperation of 43 medical institutions throughout Japan. Fluoroquinolone required a minimum inhibitory concentration (MIC) of 2–64 mg/L to inhibit the 330 tested Escherichia coli strains. The proportion of levofloxacin-resistant E. coli strains increased from 28.6% in 2008 to 29.6% in 2011, 38.5% in 2015, and 44.5% in 2021. The proportion of levofloxacin-resistant strains of Pseudomonas aeruginosa also increased from previous survey results, showing a continuing downward trend. Conversely, the proportion of levofloxacin-resistant strains of Enterococcus faecalis decreased relative to previous reports. Neither multidrug-resistant P. aeruginosa nor carbapenem-resistant Enterobacteriaceae were detected. For methicillin-resistant Staphylococcus aureus (MRSA), the proportion of vancomycin-susceptible strains (MIC of 2 μg/mL) decreased from 14.7% to 7.7%. Bacterial strains that produced extended-spectrum β-lactamase included E. coli (82/330 strains, 24.8%), Klebsiella pneumoniae (11/68 strains, 16.2%), and Proteus mirabilis (4/26 strains, 15.4%). As compared to previous surveillance reports, these strains showed an increase in proportion over the years. [ABSTRACT FROM AUTHOR]

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a global concern, primarily as a cause of skin and soft tissue infections, particularly in young people. Here, we describe a case of unilateral multiple lymphadenitis caused by the CA-MRSA sequence type (ST) 834 strain. A previously healthy 15-year-old girl was referred to our hospital with fever and swollen lymph nodes in the right axillary, cubital, and groin regions. Imaging examinations revealed enlargement of the lymph nodes in these areas but no swelling in any other lymph nodes. The patient had self-destructive lymph nodes in her groin. MRSA was detected in all swollen lymph node samples. Antimicrobial susceptibility tests showed that MRSA was susceptible to clindamycin and levofloxacin, leading to the suspicion of CA-MRSA. Genetic analysis revealed that all strains were ST834 and carried the staphylococcal cassette chromosome mec IV and the toxic shock syndrome toxin-1 gene but not the Panton–Valentine leukocidin gene. The patient was treated with linezolid followed by oral clindamycin. This was a rare case of unilateral multiple lymphadenitis caused by ST834 CA-MRSA. Although ST834 strains are rarely reported, lymphadenitis has been frequently reported and is considered more likely to cause lymphadenitis than other CA-MRSA strains. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus, a commensal bacterium, colonizes the skin and mucous membranes of approximately 30% of the human population. Apart from conventional resistance mechanisms, one of the pathogenic features of S. aureus is its ability to survive in a biofilm state on both biotic and abiotic surfaces. Due to this characteristic, S. aureus is a major cause of human infections, with Methicillin-Resistant Staphylococcus aureus (MRSA) being a significant contributor to both community-acquired and hospital-acquired infections. Results: Analyzing non-repetitive clinical isolates of MRSA collected from seven provinces and cities in China between 2014 and 2020, it was observed that 53.2% of the MRSA isolates exhibited varying degrees of ability to produce biofilm. The biofilm positivity rate was notably high in MRSA isolates from Guangdong, Jiangxi, and Hubei. The predominant MRSA strains collected in this study were of sequence types ST59, ST5, and ST239, with the biofilm-producing capability mainly distributed among moderate and weak biofilm producers within these ST types. Notably, certain sequence types, such as ST88, exhibited a high prevalence of strong biofilm-producing strains. The study found that SCCmec IV was the predominant type among biofilm-positive MRSA, followed by SCCmec II. Comparing strains with weak and strong biofilm production capabilities, the positive rates of the sdrD and sdrE were higher in strong biofilm producers. The genetic determinants ebp, icaA, icaB, icaC, icaD, icaR, and sdrE were associated with strong biofilm production in MRSA. Additionally, biofilm-negative MRSA isolates showed higher sensitivity rates to cefalotin (94.8%), daptomycin (94.5%), mupirocin (86.5%), teicoplanin (94.5%), fusidic acid (81.0%), and dalbavancin (94.5%) compared to biofilm-positive MRSA isolates. The biofilm positivity rate was consistently above 50% in all collected specimen types. Conclusions: MRSA strains with biofilm production capability warrant increased vigilance. [ABSTRACT FROM AUTHOR]

The improvement of photodynamic inactivation (PDI) significantly depends on the development of new families of photosensitizers (PSs). In this sense, three BOPHY derivatives (BP, BP‐Br and BP‐I) were synthetized, studied, and compared to assess their antimicrobial photodynamic properties. BP is an interesting fluorescent probe for cell imaging, while the halogenated analogs (BP‐Br and BP‐I) are excellent oxygen photosensitizing agents. BP compound presented a fluorescence quantum yield close unity and showed no reactive oxygen species (ROS) production. In contrast, BP‐I did not show emission properties but exhibited a high production of ROS through both photodynamic mechanisms, generating singlet oxygen (type II) and superoxide radical anion (type I) under aerobic light irradiation. BP‐Br presented an adequate balance between ROS production and emission properties. The photokilling action and the binding to bacterial cells of these macrocycles were evaluated in vitro against methicillin‐resistant Staphylococcus aureus (MRSA) and Escherichia coli bacteria. Our results demonstrated that the halogenated BOPHY derivatives were effective PSs in inactivating MRSA using shorter irradiation periods. In addition, the antimicrobial action sensitized by these BOPHYs was potentiated by adding KI. The combination of halogenated BOPHY and KI led to a complete elimination of both Gram‐positive and Gram‐negative bacteria. Hence, BP‐Br and BP‐I prove to be potent broad‐spectrum antimicrobial PSs. To the best of our knowledge, this is the first time that BOPHY derivatives have been applied to photokill pathogenic microorganisms. [ABSTRACT FROM AUTHOR]

Objective Late-onset sepsis (LOS) is a substantial contributor to morbidity and mortality among neonates. The use of nonculture-based tools for early diagnosis is an area of active investigation. Therefore, we aimed to evaluate the diagnostic value of serum interleukin-27 (IL-27) and mean platelet volume (MPV) in full-term neonates with LOS. Study Design In this single-center, cross-sectional study, 90 full-term newborns were assigned to two equal-matched groups as follows: (1) culture-proven sepsis and (2) control groups. Clinical data and laboratory findings as complete blood pictures, including MPV, highly sensitive C-reactive protein, and blood culture results, were recorded. Moreover, IL-27 levels were measured using enzyme-linked immunosorbent assay. Results IL-27 levels (median = 4,364 pg/mL) and MPV (mean = 12.02 ± 1.54 FL) were significantly higher in the culture-proven sepsis group than in the control group (p < 0.001). For IL-27, the optimum cut-off value for the diagnosis of LOS was 283.8 pg/mL with sensitivity and specificity of 97.8 and 100%, respectively. For MPV, the optimum cut-off value was 11.6 FL, with diagnostic sensitivity and specificity of 77.8 and 97.8%, respectively. Conclusion IL-27 and MPV are promising markers for the diagnosis of LOS in full-term neonates. The diagnostic performance of IL-27 was superior to MPV. Key Points Late-onset neonatal sepsis diagnosis is time consuming. Nonculture-based rapid diagnostic tests are much needed. IL-27 is superior in LOS diagnosis to MPV. [ABSTRACT FROM AUTHOR]

Scant data are available on the link between armed conflicts and the development and spread of antimicrobial resistance. We performed a systematic review with the aim to summarize the available data on the prevalence and features of antibiotic resistance and the causes of antibiotic resistance development during armed conflicts in the 21st century. Data sources: PubMed and SCOPUS databases were searched from 1 January 2000 to 30 November 2023. Study eligibility criteria: Original articles reporting data on armed conflicts and antimicrobial resistance were included in this systematic review. No attempt was made to obtain information from unpublished studies. No language restriction was applied. Methods of data synthesis: Both quantitative and qualitative information were summarized by means of textual descriptions. Participants: Patients or soldiers deployed in armed conflict zones. Tests: culture-dependent antibiotic sensitivity testing or molecular detection of the genetic determinants of antibiotic resistance after a confirmed diagnosis of bacterial infection. Assessment of risk of bias: To evaluate the quality of the included studies, we adapted the tool recommended by the Joanna Briggs Institute. Thirty-four studies were identified, published between November 2004 and November 2023. The quality of included studies was high and medium in 47% and 53% of the studies, respectively. The included studies reported high infection and colonization rates of multidrug-resistant bacteria. Studies performed during the Eastern Ukraine conflict reported high rates of New Delhi metallo-β-lactamase producers. Our findings confirm that wars lead to a large pool of multidrug-resistant infections that could potentially spread. Infection control in healthcare facilities in conflict zones and proper antimicrobial stewardship are crucial. [ABSTRACT FROM AUTHOR]

To improve the hydrophobic character of silk and impart iodine complex ion adsorption, the surface of woven silk fabric is enriched by different functional groups through the grafting of N‐vinylpyrrolidone (NVP), ethylene glycol dimethacrylate (EGDMA), and their mixtures (NVP–EGDMA). The dominant fibrous texture of silk enables an efficient graft copolymerization in terms of high grafting yield (>30%) after applying a mild degumming process. The structural and morphological alterations in the silk surface are evidenced with attenuated total reflectance‐fourier transform infrared spectroscopy (ATR‐FTIR), X‐ray diffraction (XRD), and scanning electron microscopy (SEM) techniques. The imparted hydrophilicity property of the samples is revealed by contact angle–wetting time measurements. The usability of the graft‐modified samples as an iodophor polymeric substrate is then examined by treatment with I2/KI solutions, and the results are monitored using UV–vis spectroscopy. It is obtained that the NVP–EGDMA mixture‐grafted sample exhibits satisfactorily high iodine adsorption compared to untreated and NVP‐grafted silk samples, such as 0.05 g per 1 g fabric with high antibacterial activity against various pathogens, including methicillin‐resistant Staphylococcus aureus (MRSA) responsible for hospital‐acquired infections. This finding evidences its potential as an alternative antiseptic tissue for biomedical applications. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a pathogenic bacterium‐contaminating milk and milk products causing food poisoning primarily due to its enterotoxins. A cross‐sectional study was conducted from November 2021 to June 2022 in Wolaita Sodo Town, to detect Methicillin‐resistant Staphylococcus aureus (MRSA) in raw cow's milk and assess their resistance levels to different antimicrobials. Purposive sampling was used to select 34 dairy farms. Accordingly, 419 raw milk samples from the farm and collection centers were collected. Isolates of S. aureus showing resistance to Cefoxitin were classified as MRSA. From the total 419 samples, 22.19% (93/419) were contaminated with S. aureus in dairy cows. The prevalence of S. aureus in raw milk, bulk milk from the farm, and bulk tank milk from the collection centers was 16.9%, 2.1%, and 3.1%, respectively. The risk of S. aureus contamination in dairy farm owners and milkers who do not take food safety training was 5.303 times higher than the risk of S. aureus contamination in dairy farm owners and milkers who take food safety training. The risk of S. aureus contamination in dairy farms kept under poor management system was 7.34 times more than that of dairy farms kept under good management. The cefoxitin disk diffusion method was used to detect MRSA, 57.14% being resistant to Cefoxitin in total while approximately 87.5% were sensitive to Sulfamethoxazole‐trimethoprim and Gentamycin, while Erythromycin registered 75%, Ciprofloxacin 62.5%, Chloramphenicol 62.5%, and Tetracycline 25%. This study revealed that MRSA exhibited a notable multidrug resistance pattern, encompassing resistance to multiple drugs, with a prevalence of 75%. Significantly, the hands of milkers and the milking containers emerged as pivotal sources of contamination. This underscores the crucial importance of maintaining stringent hygienic practices during the milking process, with particular emphasis on thorough cleaning and decontamination of utensils. [ABSTRACT FROM AUTHOR]

Background: Infections caused by multidrug-resistant organisms (MDROs) have been increasingly reported from healthcare facilities. The spread of MDROs in hospitals further increases the financial burden on healthcare facility due to prolonged hospital stays and the need for more expensive investigations and treatment. Methicillin Resistant Staphylococcus aureus (MRSA) is known to be widely distributed in the healthcare facilities and accounts for a substantial proportion of the infectious disease burden. Hence, active surveillance for MRSA is carried out to identify colonized patients or Healthcare workers (HCWs) in a facility. This prospective study was conducted to study and compare the carriage of MRSA among doctors, nurses, General Duty Attendants (GDA) and Houseman/ House woman (HM/HW) working in cardiac unit of a tertiary care hospital. Screening was done by collecting swabs from hands and anterior nares. These specimens were processed by standard procedures for the isolation of Staphylococcus aureus and resistance to methicillin was determined using cefoxitin, 30µg disks as per Clinical and Laboratory Standards Institute (CLSI) guidelines. The carriage rate of MRSA was found to be highest among HM/HW (13%) followed by nurses (8%) and GDA (7%). Out of 11 doctors screened, none was found to carry MRSA. A higher percentage carriage in HM/HW can probably be accounted to their close and prolonged contact with infected patients and involvement in activities like emptying urinary bags, floor mopping and other activities of environmental cleaning. Management of MRSA carriers include applying stringent hand hygiene, contact precautions and core strategies including isolating and cohorting patients, increased environmental cleaning, dedicated patient equipment and decolonization. Active surveillance including screening of HCWs can help in decreased risk of spread to their close contacts and further reduction of MRSA prevalence among patients. [ABSTRACT FROM AUTHOR]

Background: The emergence of the multidrug-resistant bacteria strain has become a global world crisis. This study was designed to evaluate the antibiofilm and synergistic effects of Lippia multiflora leaf extracts on the activity of cefotaxime against the methicillin-resistant Staphylococcus aureus (S. aureus). Methods: The synergistic effect of methanol and dichloromethane extracts on the bactericidal activity of cefotaxime was determined by using the antibiotic susceptibility test on agar medium. The antibiofilm activity of the extracts was measured by using the crystal violet method. The antioxidant potential of the extracts was assessed by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric Reduction Activity Potential (FRAP) methods. The main secondary metabolites groups were analyzed by using different standard analytical tests. The total phenolics and total flavonoids were quantified spectrophotometrically. Results: The methanol extract (final concentration of 100 µg/ml) inhibited the formation of bacterial biofilm more than salicylic acid (p<0.05). All extracts combined with cefotaxime (20 µg and 200 µg) showed good synergistic bactericidal effect on S. aureus with inhibitory diameters of up to 40 mm. The methanol extract showed higher total phenolics (462.20±10.90 mg EAG/g) and total flavonoids (26.20±0.20 mg EQ/g) contents than the dichloromethane extract (96.70±1.70 mg EAG/g and 8.00±1.20 mg EQ/g). Moreover, the methanol extract showed a higher FRAP reducing power (353.6± 4.17 mmol EQ/g) than the dichloromethane extract (385.3±7.01 mmol EQ/g). Qualitative phytochemical analysis showed the presence of tannins, flavonoids, terpenes and sterols in both extracts. Conclusion: These data showed that L. multiflora leaves contain effective antibacterial phytomolecules for combating bacterial resistance. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus has the ability to develop many efficient mechanisms to neutralize them and it has become difficult to control the virulent strains of S. aureus from causing staphylococcal diseases in animals and humans. Mostly Staphylococcal strains have become resistant to methicillin, β-lactamase and ESBL activity and sometime to vancomycin also. The present study investigated the phenotypic and genotypic characteristics of all the 62 S. aureus isolates for sensitivity towards methicillin, β-lactamase, ESBL production and vancomycin. Methods: The isolates were obtained by conventional microbiological methods, confirmed genotypically by 23S rRNA ribotyping and Maldi-Tof MS. Methicillin resistance activity among S. aureus isolates was detected by culturing them on MeReSa Agar. Extendedspectrum β-lactamase activity among S. aureus isolates was detected by the combined disc method. Result: On MeReSa agar, 53(85.48%) isolates were detected as methicillin resistant S. aureus (MRSA), but none of the isolates from any source or place of sampling was detected positive by the methicillin disk method. Extended-spectrum β-lactamase (ESBL) activity was exhibited by 51 (82.25%) isolates with 100% (maximum) isolates from human pus showing activity and 66.66% (least activity) was seen in isolates from unprocessed meat. All the isolates were susceptible to vancomycin. [ABSTRACT FROM AUTHOR]

A previously healthy woman, 5 weeks pregnant, was admitted to the intensive care unit in critical condition for septic shock and acute respiratory distress syndrome due to methicillin‐resistant Staphylococcus aureus (MRSA) after being infected with Influenza for 3 days. The patient in this case suffered from severe sequelae due to necrotizing pneumonia and later died on the 20th day after admission. We would like to remind clinicians to be aware of this rare but serious diagnosis. The key is to begin appropriate treatment immediately because MRSA necrotizing pneumonia is mediated by toxins and once the toxins are released they cannot be limited by antibiotic treatments. Necrotizing pneumonia related to MRSA should be considered in young patients with pneumonia, sepsis, and neutropenia following seasonal influenza infection with rapidly progressive symptoms. [ABSTRACT FROM AUTHOR]

Bacterial infections pose a global concern due to high fatality rates, particularly with the rise of drug-resistant bacteria and biofilm formation. There is an urgent need for innovative strategies to combat this issue. A study on chemodynamic therapy (CDT) using nanozymes in conjunction with photothermal therapy (PTT) has displayed potential in addressing drug-resistant bacterial infections. However, the effectiveness of this combined approach is limited by inadequate light absorption. This work suggests the NiOx nanoparticles enriched with oxygen vacancies enhance CDT and PTT to overcome this challenge. The presence of oxygen vacancies in NiOx can reduce the energy gap between its valence band and conduction band, facilitating oxygen adsorption. NiOx has exhibited notable antibacterial properties and complete eradication of biofilms in both laboratory and animal trials. In animal abscess models, NiOx demonstrated antibacterial and anti-inflammatory effects in the initial stages, while also promoting wound healing and tissue regeneration by influencing immune factors and encouraging collagen deposition and neovascularization. With positive biosafety and biocompatibility profiles, the oxygen vacancy-enhanced CDT and PTT therapy proposed in this article hold promise for effective sterilization, deep biofilm removal, and treatment of infections caused by drug-resistant bacteria. This study constructs oxygen vacancies NiOx nanoparticles (NiOx NPs) to improve the efficacy of photothermal therapy and chemodynamic therapy. The presence of oxygen vacancies in NiOx NPs helps bridge the energy gap between its valence band and conduction band, facilitating oxygen adsorption and improving catalytic efficiency. In both in vivo and in vitro antibacterial experiments, NiOx NPs demonstrate effective antibacterial and anti-inflammatory properties. Furthermore, it aids in wound healing and tissue regeneration by modulating immune factors, collagen deposition, and angiogenesis. This approach presents a promising collaborative strategy for utilizing nickel-based defective nanomaterials in combating deep drug-resistant bacterial infections. [Display omitted] [ABSTRACT FROM AUTHOR]

The present study aimed to isolate and identify Methicillin-Resistant DOIStaphylococcus aureus MRSA from the nasal cavity of healthy cows and buffaloes and their breeders in Nineveh Governorate and detect some virulence factors by using molecular methods. A total of 150 samples of cotton swabs were collected randomly from different areas of Nineveh governorate. The samples were cotton swabs from the nasal passages of healthy cattle, buffaloes, and their breeders (50 swabs of each type). All the samples were subjected to culture and molecular testing. The results showed the highest isolation percentage of S. aureus from cattle followed by breeders, then buffaloes, at 54%, 40%, and 32%, respectively. The total isolation percentage of MRSA was 65.1%. The highest percentage was in buffaloes, followed by breeders and cattle, at 93.75%, 70%, and 44.44%, respectively. Out of 41 isolates from cattle, buffaloes, and their breeders, the virulence genes clfA, clfB, and coa were detected in MRSA at rates of 100%, 80.49%, and 65.85%, respectively. The current study concluded that cattle and buffalo are considered carriers and potential transmitters of MRSA, which makes them risk factors for infection in humans, especially those who are in direct contact with animals. Together, these findings also highlight the need to prevent the transmission of zoonotic pathogens to humans via occupational exposure or consumption of contaminated animal products. [ABSTRACT FROM AUTHOR]

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Immune activation is essential for lung control of viral and bacterial infection, but an overwhelming inflammatory response often leads to the onset of acute respiratory distress syndrome. IL-10 plays a crucial role in regulating the balance between antimicrobial immunity and immunopathology. In the present study, we investigated the role of IL-10 in acute lung injury induced by influenza A virus and methicillin-resistant Staphylococcus aureus coinfection. This unique coinfection model resembles patients with acute pneumonia undergoing appropriate antibiotic therapies. Using global IL-10 and IL-10 receptor gene-deficient mice, as well as in vivo neutralizing antibodies, we show that IL-10 deficiency promotes IFN-γ–dominant cytokine responses and triggers acute animal death. Interestingly, this extreme susceptibility is fully preventable by IFN-γ neutralization during coinfection. Further studies using mice with Il10ra deletion in selective myeloid subsets reveal that IL-10 primarily acts on mononuclear phagocytes to prevent IFN-γ/TNF-α hyperproduction and acute mortality. Importantly, this antiinflammatory IL-10 signaling is independent of its inhibitory effect on antiviral and antibacterial defense. Collectively, our results demonstrate a key mechanism of IL-10 in preventing hypercytokinemia and acute respiratory distress syndrome pathogenesis by counteracting the IFN-γ response. [ABSTRACT FROM AUTHOR]

Heteropyxis natalensis is a South African medicinal tree that has been utilized by Venda and Zulu communities to treat several health ailments. The aim of this study was to elucidate the secondary metabolites in leaf extracts as well as to investigate the chemical profile and antibacterial efficacy of the methanolic leaf extract of H. natalensis. Qualitative phytochemical screening confirmed the presence of carbohydrates, alkaloids, phenolics, saponins, sterols, terpenes and fixed fats and oils in leaf extracts. Gas chromatographymass spectrometry identified 119 bioactive chemical compounds in the methanolic leaf extract of which 14 compounds had a peak area greater than 1%. In addition, methanolic extract was subjected to antibacterial screening using the well diffusion method. Heteropyxis natalensis exhibited antibacterial efficacy against 5 strains of pathogenic bacteria: Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis. The results obtained in this study indicate the presence of naturally occurring bioactive compounds in H. natalensis leaves. [ABSTRACT FROM AUTHOR]

There have been few reports regarding the long-term trends in the genotypes of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream isolates. Therefore, this study was performed to investigate the longitudinal trends in the genotypes of MRSA bloodstream isolates obtained from hospitalized patients during a 12-year study period from 2010 to 2021 at a tertiary care university hospital. Over the 12-year period from 2010 to 2021, we conducted a genetic investigation focusing on 245 MRSA strains isolated from the blood of hospitalized patients. The genotypes of the MRSA bloodstream isolates were determined by Staphylococcal Cassette Chromosome mec (SCCmec) typing, accessory gene regulator (agr) typing, PCR-based ORF typing (POT), and multilocus sequence typing (MLST). Strains with the same POT type detected in two or more isolates were designated as epidemic clones, while strains without a common POT type were classified as sporadic clones. Until 2015, isolates with SCCmec II/agr II were prevalent, but isolates with SCCmec IV/agr III increased from 2016. A total of 128 strains (52%) were identified as epidemic clones, while 117 strains (48%) were classified as sporadic clones. The detection rate of sporadic clones increased significantly since 2016 (p < 0.05). The epidemic clones were classified into three clusters, with MRSA of clonal complex (CC) 1 being prominent after 2016. This study showed that the genotypes of MRSA bloodstream isolates underwent a shift from SCCmec II/agr II type to SCCmec IV/agr III type, with a notable increase in MRSA of CC1, after 2016. There was a significant increase in the proportion of sporadic strains among the isolates, suggesting the diversification of genotypes. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is one of humanity's main health problems today. Despite all the breakthroughs and research over the past few years, the number of microbial illnesses that are resistant to the available antibiotics is increasing at an alarming rate. In this article, we estimated the biomedical potential of Portuguese propolis harvested from the Gerês apiary over five years, evaluating the in vitro antimicrobial effect of five hydroalcoholic extracts prepared from five single propolis samples and of a hydroalcoholic extract obtained from the mixture of all samples. The antimicrobial potential was firstly assessed by determining the minimum inhibitory concentration (MIC) of these extracts against a panel of three Gram-positive (Bacillus subtilis, methicillin-sensitive Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus) and one Gram-negative bacteria (Escherichia coli), as well as two yeasts (Candida albicans and Saccharomyces cerevisiae). As MIC values against each bacterium were consistent across all the evaluated propolis extracts, we decided to further conduct a disk diffusion assay, which included three commercial antibiotics—erythromycin, vancomycin, and amoxicillin/clavulanic acid—for comparison purposes. In addition to displaying a concentration-dependent antibacterial effect, the hydroalcoholic extracts prepared with 70% ethanol exhibited stronger antimicrobial capacity than vancomycin against B. subtilis (% of increase ranged between 26 and 59%) and methicillin-sensitive S. aureus (% of increase ranged between 63 and 77%). Moreover, methicillin-resistant S. aureus (MRSA) showed susceptibility to the activity of the same extracts and resistance to all tested antibiotics. These findings support that propolis from Gerês is a promising natural product with promising antimicrobial activity, representing a very stimulating result considering the actual problem with AMR. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is a global public health threat caused by the misuse and overuse of antibiotics. It leads to infections becoming difficult to treat, causing serious illness, disability, and death. Current antibiotic development is slow, with only 25% of current antibiotics exhibiting novel mechanisms against critical pathogens. Traditional medicinal plants' secondary metabolites offer potential for developing novel antibacterial compounds. These compounds, often with strong antimicrobial activity, can be used to develop safe and effective antibacterial chemotherapies. This study investigated the antibacterial activity of Phyllanthus niruri Linn. extracts against a panel of bacterial pathogens using disc diffusion and microdilution assays and quantified by calculation of minimum inhibition concentration (MIC). Additionally, the effects of combinations of the extracts and selected conventional antibiotics were examined by sum of fractional inhibition concentration (ƩFIC) calculation and isobologram analysis. Liquid chromatography–mass spectrometry (LC-MS) phytochemistry analysis was used to identify noteworthy compounds in the active extracts and the Artemia nauplii bioassay was used to evaluate toxicity. The aqueous and methanolic extracts exhibited notable antibacterial activity in the broth microdilution assay against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) (MIC = 669 µg/mL and 738 µg/mL, respectively). The methanolic extract also showed noteworthy antibacterial action in the broth assay against Klebsiella pneumoniae (MIC = 738 µg/mL). The aqueous extract had noteworthy growth inhibitory activity against Bacillus cereus (MIC = 669 µg/mL), whilst the methanolic extract demonstrated good antibacterial activity against that bacterium (MIC = 184 µg/mL). The aqueous and methanol extracts showed minimal antibacterial action against Shigella flexneri and Shigella sonnei. The extracts were subjected to LC-MS analysis, which revealed several interesting phytochemicals, including a variety of flavonoids and tannins. The antibacterial activity and lack of toxicity of the P. niruri extracts indicates that they may be worthwhile targets for antibiotic development and further mechanistic and phytochemistry studies are required. [ABSTRACT FROM AUTHOR]

High-level delafloxacin-resistant (H-L DLX-R) Staphylococcus aureus isolates (minimum inhibitory concentration ≥1 mg/L) associated with mutations affecting position 84 of ParC have emerged. We aimed to elucidate the role of these mutations as a mechanism of H-L DLX resistance in methicillin-resistant S. aureus (MRSA) isolates recovered from blood cultures. Susceptibility to DLX was determined in 75 MRSA isolates by E-test, and an rt-PCR was developed to detect mutations affecting position 84 of ParC to screen a further 185 MRSA isolates. The genomes of 48 isolates, including all DLX-R isolates or with alterations at position 84, and also a subset of DLX-susceptible isolates were analyzed. Among the 75 isolates studied, 77.34% were DLX-susceptible and only 4 H-L DLX-R isolates were found. Seven (3.8%) isolates with alterations at position 84 of ParC were detected by rt-PCR. Genomic analysis showed that 89.9% (8/9) of isolates with the substitution E84K/G in ParC, together with other mutations in gyrA and parC, were H-L DLX-R. However, the E84K substitution in ParC alone or with other alterations was found in two isolates without H-L DLX-R. Alterations at position 84 of ParC are rare but play a key role in H-L DLX resistance in MRSA but only when other alterations in GyrA are present. [ABSTRACT FROM AUTHOR]

S. aureus, particularly methicillin-resistant S. aureus, has been recognized as a main cause of bovine mastitis and food poisoning. This study investigated the prevalence, antibiotic resistance, and phage-based biocontrol of S. aureus and methicillin-resistant S. aureus isolated from raw milk of cows with subclinical mastitis. The results showed that the prevalence of S. aureus and methicillin-resistant S. aureus was 12% (48/400) and 1.5% (6/400), respectively. The S. aureus isolates were highly resistant to penicillin (72.92%), erythromycin (43.75%), and tetracycline (39.58%). Out of 48 S. aureus isolates, 6 were identified as methicillin-resistant strains. Among them, one isolate was found to harbor the sea gene. A total of 5 phages were recovered from 50 pork and 50 chicken meat samples, 1 from pork and 4 from chicken meat samples. Phage PSA2 capable of lysing all 6 methicillin-resistant isolates was selected for characterization. The use of phage PSA2 completely inactivated methicillin-resistant S. aureus SA33 in raw milk at both 24 °C and 4 °C, indicating its potential as a promising antibacterial agent in controlling methicillin-resistant S. aureus in raw milk and treating bovine mastitis. [ABSTRACT FROM AUTHOR]

In order to contribute to an assessment of the role of food in the risks of transmission of methicillin-resistant Staphylococcus aureus (MRSA), a review was undertaken of research on this microorganism in milk and dairy products published from January 2001 to February 2024. A total of 186 publications were selected, 125 for dairy products and 61 for bulk-tank milk (BTM). MRSA was detected in 68.8% of the research into dairy products and 73.8% of investigations relating to BTM, although in most studies the prevalence was less than 5%. Of the set of S. aureus strains isolated, approximately 30% corresponded to MRSA. The foods most extensively contaminated with this microorganism were raw milk and some types of soft cheese. Determination of the mecA gene on its own is known not to suffice for the detection of all MRSA strains. The great diversity of techniques used to study MRSA in milk and dairy products made it difficult to draw comparisons between studies. It would thus be advisable to develop a standardized protocol for the study of this microorganism in foods. [ABSTRACT FROM AUTHOR]

The emergence of antimicrobial resistance (AMR) in pathogens and their spillover into the environment have become a global public health menace. Insects can acquire these pathogens from the environment and would serve as mechanical and biological vectors. The current study assessed the ability of Culex quinquefasciatus mosquitoes to acquire methicillin-resistant Staphylococcus aureus (MRSA) through the exposure of the mosquitoes to the pathogen via rearing water, blood feed, or a feeding membrane under laboratory conditions. In addition, mosquito immatures collected from their habitat in the vicinity of hospitals, veterinary dispensaries, and butcher shops at 15 study sites in Puducherry were screened for MRSA infection. All samples were subjected to the culture-based isolation of S. aureus from the surface and homogenate. The presence of the S. aureus-specific nuc gene and the genes that confer resistance to methicillin (mecA and mecC) were screened using PCR tests. MRSA was not evident either on the external surface or in the homogenate of the mosquitoes emerging from the larvae reared in the MRSA-spiked water or those fed with MRSA through blood or smeared membranes. Furthermore, the presence of MRSA was not evident in any of the field-caught mosquitoes. Hence, we conclude that C. quinquefasciatus mosquitoes are impervious to MRSA colonization. [ABSTRACT FROM AUTHOR]