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PloS One 2024Implant-associated osteomyelitis remains a major orthopaedic problem. As neutrophil swarming to the surgical site is a critical host response to prevent infection,...
Implant-associated osteomyelitis remains a major orthopaedic problem. As neutrophil swarming to the surgical site is a critical host response to prevent infection, visualization and quantification of this dynamic behavior at the native microenvironment of infection will elucidate previously unrecognized mechanisms central to understanding the host response. We recently developed longitudinal intravital imaging of the bone marrow (LIMB) to visualize host cells and fluorescent S. aureus on a contaminated transfemoral implant in live mice, which allows for direct visualization of bacteria colonization of the implant and host cellular responses using two-photon laser scanning microscopy. To the end of rigorous and reproducible quantitative outcomes of neutrophil swarming kinetics in this model, we developed a protocol for robust segmentation, tracking, and quantifications of neutrophil dynamics adapted from Trainable Weka Segmentation and TrackMate, two readily available Fiji/ImageJ plugins. In this work, Catchup mice with tdTomato expressing neutrophils received a transfemoral pin with or without ECFP/EGFP-expressing USA300 methicillin-resistant Staphylococcus aureus (MRSA) to obtain 30-minute LIMB videos at 2-, 4-, and 6-hours post-implantation. The developed semi-automated neutrophil tracking protocol was executed independently by two users to quantify the distance, displacement, speed, velocity, and directionality of the target cells. The results revealed high inter-user reliability for all outcomes (ICC > 0.96; p > 0.05). Consistent with the established paradigm on increased neutrophil swarming during active infection, the results also demonstrated increased neutrophil speed and velocity at all measured time points, and increased displacement at later time points (6 hours) in infected versus uninfected mice (p < 0.05). Neutrophils and bacteria also exhibit directionality during migration in the infected mice. The semi-automated cell tracking protocol provides a streamlined approach to robustly identify and track individual cells across diverse experimental settings and eliminates inter-observer variability.
Topics: Animals; Neutrophils; Mice; Femur; Cell Tracking; Staphylococcal Infections; Disease Models, Animal; Osteomyelitis; Methicillin-Resistant Staphylococcus aureus; Prosthesis-Related Infections; Prostheses and Implants; Staphylococcus aureus; Female
PubMed: 38900759
DOI: 10.1371/journal.pone.0296140 -
Antimicrobial Agents and Chemotherapy Jun 2024Delafloxacin, a fluoroquinolone antibiotic to treat skin infections, exhibits a broad-spectrum antimicrobial activity. The first randomized, open-label phase I clinical...
Delafloxacin, a fluoroquinolone antibiotic to treat skin infections, exhibits a broad-spectrum antimicrobial activity. The first randomized, open-label phase I clinical trial was conducted to assess the safety and pharmacokinetics (PK) of intravenous delafloxacin in the Chinese population. A population pharmacokinetic (PopPK) model based on the clinical trial was conducted by NONMEM software. Monte Carlo simulation was performed to evaluate the antibacterial effects of delafloxacin at different doses in different Chinese populations. The PK characteristics of delafloxacin were best described by a three-compartment model with mixed linear and nonlinear clearance. Body weight was included as a covariate in the model. We simulated the AUC in a steady state at five doses in patient groups of various weights. The results indicated that for patients weighing 70 kg and treated with methicillin-resistant (MRSA) infections, a minimum dose of 300 mg achieved a PTA > 90% at MIC of 0.25 µg/mL, suggesting an ideal bactericidal effect. For patients weighing less than 60 kg, a dose of 200 mg achieved a PTA > 90% at MIC of 0.25 µg/mL, also suggesting an ideal bactericidal effect. Additionally, this trial demonstrated the high safety of delafloxacin in single-dose and multiple-dose groups of Chinese. Delafloxacin (300 mg, q12h, iv) was recommended for achieving optimal efficacy in Chinese bacterial skin infections patients. To ensure optimal efficacy, an individualized dose of 200 mg (q12h, iv) could be advised for patients weighing less than 60 kg, and 300 mg (q12h, iv) for those weighing more than 60 kg.
PubMed: 38899925
DOI: 10.1128/aac.00428-24 -
BioMed Research International 2024In a research experiment, 48 male Wistar rats were anesthetized and second-degree burns were induced on their backs. The rats' wounds were then uniformly inoculated with...
MATERIALS AND METHODS
In a research experiment, 48 male Wistar rats were anesthetized and second-degree burns were induced on their backs. The rats' wounds were then uniformly inoculated with MRSA. Various treatments were applied to the burn wounds daily, including Myrtus ointment, silver nanoparticles, silver nanoparticles-Myrtus ointment, silver sulfadiazine-Myrtus ointment, silver sulfadiazine 1%, mupirocin ointment, and a positive control. The study measured the antimicrobial effects, wound area, percentage of wound healing, antioxidant capacities, malondialdehyde, and nitric oxide concentrations in the serum of the rats. Data analysis was performed using GraphPad software, with one-way ANOVA and Tukey's tests used to determine the statistical significance of the results.
RESULTS
Rats treated with Myrtus ointment, silver nanoparticles-Myrtus ointment, and mupirocin had reduced bacterial growth compared to the positive control group, nanoparticle ointment, and silver sulfadiazine ( < 0.05). The wound area of the Myrtus ointment group decreased significantly on the seventh and fourteenth days, as well as the level of MDA and nitric oxide, compared to the other groups. In Myrtus and silver sulfadiazine-Myrtus ointment increased the thickness of the epidermis and dermis compared to the other groups.
CONCLUSION
Based on the anti-inflammatory, antimicrobial, and wound healing properties of Myrtus, with further studies, an ointment of this plant may be used as a main or complementary treatment for burn wound infections caused by MRSA.
Topics: Animals; Wound Healing; Methicillin-Resistant Staphylococcus aureus; Burns; Plant Extracts; Male; Ointments; Rats; Rats, Wistar; Anti-Inflammatory Agents; Plant Leaves; Myrtus; Anti-Infective Agents; Wound Infection; Staphylococcal Infections; Metal Nanoparticles; Silver Sulfadiazine
PubMed: 38899039
DOI: 10.1155/2024/6758817 -
Clinical Microbiology and Infection :... Jun 2024This review aims to explore the characteristics of outbreaks of community-acquired community-onset methicillin-resistant Staphylococcus aureus (CO-MRSA) in low... (Review)
Review
OBJECTIVES
This review aims to explore the characteristics of outbreaks of community-acquired community-onset methicillin-resistant Staphylococcus aureus (CO-MRSA) in low prevalence areas, to understand the factors involved in its rise, and to translate this knowledge into public health policy and further research needs.
SOURCES
PubMed, EMBASE and Google Scholar were searched using combinations of the terms "transmission", "acquisition", "CA-MRSA" "MRSA", "community-acquired", "low prevalence", "genomic", "outbreak", "colonisation" and "carriage". Wherever evidence was limited, additional articles were sought specifically, via PubMed searches. Papers where materials were not available in English were excluded.
CONTENT
Community-acquired, community onset MRSA infection presents a significant public health challenge, even in low prevalence areas; where MRSA rates are historically lower. Despite successes in reducing hospital-onset MRSA (HO-MRSA), CO-MRSA rates are increasing globally, with a need to understand this trend, and the potential risk factors for re-emergence. Challenges in defining low prevalence areas and the significance of exposure to various risk factors for community acquisition, such as healthcare settings, travel, livestock, and environmental factors, are discussed. The importance of genomic surveillance in identifying outbreak strains and understanding the transmission dynamics is highlighted, along with the need for robust public health policies and control measures.
IMPLICATIONS
The findings emphasise the complexity of CO-MRSA transmission and the necessity of a multifaceted approach in low prevalence areas. This includes integrated and systematic surveillance of HO-, CO-, and livestock-associated MRSA (LA-MRSA), as has been effective in some Northern European countries. The evolution of CO-MRSA underscores the need for global collaboration, routine genomic surveillance, and comprehensive antimicrobial stewardship to mitigate the rise of CO-MRSA and address the broader challenge of antimicrobial resistance. These efforts are crucial for maintaining low MRSA prevalence and managing the increasing burden of CO-MRSA in both low and higher prevalence regions.
PubMed: 38897351
DOI: 10.1016/j.cmi.2024.06.006 -
Acta Biomaterialia Jun 2024Antimicrobial phototherapy has gained recognition as a promising approach for addressing bacterial biofilms, however, its effectiveness is often impeded by the robust...
Antimicrobial phototherapy has gained recognition as a promising approach for addressing bacterial biofilms, however, its effectiveness is often impeded by the robust physical and chemical defenses of the biofilms. Traditional antibacterial nanoplatforms face challenges in breaching the extracellular polymeric substances (EPS) barrier to efficiently deliver photosensitizers deep into biofilms. Moreover, the prevalent hypoxia within biofilms restricts the success of oxygen-reliant phototherapy. In this study, we engineered a soft mesoporous organosilica nanoplatform (SMONs) by incorporating polyethylene glycol (PEG), catalase (CAT), and indocyanine green (ICG), forming SMONs-PEG-CAT-ICG (SPCI). We compared the antimicrobial efficacy of SPCI with more rigid nanoplatforms. Our results demonstrate that SPCI's unique flexible mechanical properties enable it to navigate through biofilm barriers, markedly enhancing ICG penetration in methicillin-resistant Staphylococcus aureus (MRSA) biofilms. Notably, in a murine subcutaneous MRSA biofilm infection model, SPCI showed superior biofilm penetration and pharmacokinetic benefits over its rigid counterparts. The embedded catalase in SPCI effectively converts excess HO present in infected tissues into O, alleviating hypoxia and significantly boosting the antibacterial performance of phototherapy. Both in vitro and in vivo experiments confirm that SPCI surpasses traditional rigid nanoplatforms in overcoming biofilm barriers, offering improved treatment outcomes for infections associated with bacterial biofilms. This study presents a viable strategy for managing bacterial biofilm-induced diseases by leveraging the unique attributes of a soft mesoporous organosilica-based nanoplatform. STATEMENT OF SIGNIFICANCE: This research introduces an innovative antimicrobial phototherapy soft nanoplatform that overcomes the inherent limitations posed by the protective barriers of bacterial biofilms. By soft nanoplatform with flexible mechanical properties, we enhance the penetration and delivery of photosensitizers into biofilms. The inclusion of catalase within this soft nanoplatform addresses the hypoxia in biofilms by converting hydrogen peroxide into oxygen in infected tissues, thereby amplifying the antibacterial effectiveness of phototherapy. Compared to traditional rigid nanoplatforms, this flexible nanoplatform not only promotes the delivery of therapeutic agents but also sets a new direction for treating bacterial biofilm infections, offering significant implications for future antimicrobial therapies.
PubMed: 38897337
DOI: 10.1016/j.actbio.2024.06.018 -
Frontiers in Pediatrics 2024infections are a significant cause of morbidity and mortality in pediatric populations worldwide. The Staphylo Research Network conducted an extensive study on...
BACKGROUND
infections are a significant cause of morbidity and mortality in pediatric populations worldwide. The Staphylo Research Network conducted an extensive study on pediatric patients across Colombia from 2018 to 2021. The aim of this study was to describe the epidemiological and microbiological characteristics of in this patient group.
METHODS
We analyzed isolates from WHONET-reporting centers. An "event" was a positive culture isolation in a previously negative individual after 2 weeks. We studied center characteristics, age distribution, infection type, and antibiotic susceptibilities, comparing methicillin sensitive (MSSA) and resistant (MRSA) isolates.
RESULTS
Isolates from 20 centers across 7 Colombian cities were included. Most centers (80%) served both adults and children, with 55% offering oncology services and 85% having a PICU. We registered 8,157 culture isolations from 5,384 events (3,345 MSSA and 1,961 MRSA) in 4,821 patients, with a median age of 5 years. Blood (26.2%) and skin/soft tissue (18.6%) were the most common infection sources. Most isolates per event remained susceptible to oxacillin (63.2%), clindamycin (94.3%), and TMP-SMX (98.3%). MRSA prevalence varied by city (<0.001), with slightly higher rates observed in exclusively pediatric hospitals. In contrast, the MRSA rate was somewhat lower in centers with Antimicrobial Stewardship Program (ASP). MRSA was predominantly isolated from osteoarticular infections and multiple foci, while MSSA was more frequently associated with recurrent infections compared to MRSA.
CONCLUSIONS
This is the largest study of pediatric infections in Colombia. We found MSSA predominance, but resistance have important regional variations. remains susceptible to other commonly used antibiotics such as TMP-SMX and clindamycin. Ongoing monitoring of infections is vital for understanding their behavior in children. Prospective studies within the Staphylored LATAM are underway for a more comprehensive clinical and genetic characterization.
PubMed: 38895192
DOI: 10.3389/fped.2024.1386310 -
Molecules (Basel, Switzerland) May 2024Isoflavones are a class of natural products that exhibit a wide range of interesting biological properties, including antioxidant, hepatoprotective, antimicrobial, and...
Isoflavones are a class of natural products that exhibit a wide range of interesting biological properties, including antioxidant, hepatoprotective, antimicrobial, and anti-inflammatory activities. Scandenone (), osajin (), and 6,8-diprenylgenistein () are natural prenylated isoflavones that share the same polyphenol framework. In this research, the key intermediate was used for the synthesis of the natural isoflavones -, establishing a stereoselective synthetic method for both linear and angular pyran isoflavones. The antibacterial activities of - were also evaluated, and all of them displayed good antibacterial activity against Gram-positive bacteria. Among them, was the most potent one against MRSA, with a MIC value of 2 μg/mL, and the SEM assay indicated that the bacterial cell membranes of both MRSA and could be disrupted by . These findings suggest that this type of isoflavone could serve as a lead for the development of novel antibacterial agents for the treatment of Gram-positive bacterial infections.
Topics: Anti-Bacterial Agents; Isoflavones; Microbial Sensitivity Tests; Molecular Structure; Methicillin-Resistant Staphylococcus aureus; Gram-Positive Bacteria; Biological Products; Enterococcus faecalis
PubMed: 38893450
DOI: 10.3390/molecules29112574 -
Nutrients May 2024Propolis has potential anti-inflammatory properties, but little is known about its efficacy against inflammatory reactions caused by drug-resistant bacteria, and the...
Propolis has potential anti-inflammatory properties, but little is known about its efficacy against inflammatory reactions caused by drug-resistant bacteria, and the difference in efficacy between propolis and tree gum is also unclear. Here, an in vivo study was performed to study the effects of ethanol extract from poplar propolis (EEP) and poplar tree gum (EEG) against heat-inactivated methicillin-resistant (MRSA)-induced acute lung injury (ALI) in mice. Pre-treatment with EEP and EEG (100 mg/kg, ) resulted in significant protective effects on ALI in mice, and EEP exerted stronger activity to alleviate lung tissue lesions and ALI scores compared with that of EEG. Furthermore, EEP significantly suppressed the levels of pro-inflammatory mediators in the lung, including , , , and . Gut microbiota analysis revealed that both EEP and EEG could modulate the composition of the gut microbiota, enhance the abundance of beneficial microbiota and reduce the harmful ones, and partly restore the levels of short-chain fatty acids. EEP could modulate more serum metabolites and showed a more robust correlation between serum metabolites and gut microbiota. Overall, these results support the anti-inflammatory effects of propolis in the treatment of ALI, and the necessity of the quality control of propolis.
Topics: Propolis; Animals; Methicillin-Resistant Staphylococcus aureus; Acute Lung Injury; Gastrointestinal Microbiome; Mice; Male; Inflammation Mediators; Anti-Inflammatory Agents; Staphylococcal Infections; Cytokines; Hot Temperature; Disease Models, Animal
PubMed: 38892531
DOI: 10.3390/nu16111598 -
International Journal of Molecular... May 2024Flavonoids are an abundant class of naturally occurring compounds with broad biological activities, but their limited abundance in nature restricts their use in...
Flavonoids are an abundant class of naturally occurring compounds with broad biological activities, but their limited abundance in nature restricts their use in medicines and food additives. Here we present the synthesis and determination of the antibacterial and antioxidant activities of twenty-two structurally related flavonoids (five of which are new) by scientifically validated methods. Flavanones (-) had low inhibitory activity against the bacterial growth of MRSA 97-7. However, (C5,7,3',4' = OH) and (C5,7 = OH; C4' = SCH) had excellent bacterial growth inhibitory activity against Gram-negative (MIC = 25 µg/mL for both), while Chloramphenicol (MIC = 25 µg/mL) and (C5,7,3' = OCH; 4' = OH) showed inhibitory activity against Gram-positive (MIC = 25 µg/mL). From the flavone series (-), (C5,7,3',4' = OH), (C5,7,4' = OH; 3' = OCH) and (C5,7,4' = OH) showed good inhibitory activity against Gram-positive MRSA 97-7 (MIC = 50, 12, and 50 µg/mL, respectively), with being more active than the positive control Vancomycin (MIC = 25 µg/mL). (C5,7= OH; 4' = OCH) showed high inhibitory activity against and (MIC = 25 and 15 µg/mL, respectively). These data add significantly to our knowledge of the structural requirements to combat these human pathogens. The positions and number of hydroxyl groups were key to the antibacterial and antioxidant activities.
Topics: Anti-Bacterial Agents; Antioxidants; Flavonoids; Microbial Sensitivity Tests; Escherichia coli; Listeria monocytogenes; Flavanones; Methicillin-Resistant Staphylococcus aureus
PubMed: 38892186
DOI: 10.3390/ijms25115999 -
JAC-antimicrobial Resistance Jun 2024There are limited data describing outcomes of patients treated with ceftaroline for infections with CNS or ocular involvement.
BACKGROUND
There are limited data describing outcomes of patients treated with ceftaroline for infections with CNS or ocular involvement.
OBJECTIVES
To describe outcomes of patients treated with ceftaroline for methicillin-resistant staphylococcal infections involving the CNS or eye.
PATIENTS AND METHODS
This was a retrospective review of 10 patients at an academic medical centre who received ceftaroline for CNS or ocular infections.
RESULTS
All patients were treated with ceftaroline as part of a combination for salvage therapy. Four patients died, whereas six patients experienced clinical cure. Only one experienced microbiological recurrence.
CONCLUSIONS
These preliminary data suggest that ceftaroline may be an option for salvage therapy of severe staphylococcal infections when used in combination.
PubMed: 38887612
DOI: 10.1093/jacamr/dlae095