Rapid and sensitive detection of methicillin-resistant Staphylococcus aureus through the RPA-PfAgo system.

Introduction: Both the incidence and mortality rates associated with methicillin-resistant Staphylococcus aureus (MRSA) have progressively increased worldwide. A nucleic acid testing system was developed in response, enabling swift and precise detection of Staphylococcus aureus (S. aureus) and its MRSA infection status. This facilitates improved prevention and control of MRSA infections. Methods: In this work, we introduce a novel assay platform developed by integrating Pyrococcus furiosus Argonaute (PfAgo) with recombinase polymerase amplification (RPA), which was designed for the simultaneous detection of the nuc and mecA genes in MRSA. Results: This innovative approach enables visual MRSA detection within 55 mins, boasting a detection limit of 102 copies/µL. Characterized by its high specificity, the platform accurately identifies MRSA infections without cross-reactivity to other clinical pathogens, highlighting its unique capability for S. aureus infection diagnostics amidst bacterial diversity. Validation of this method was performed on 40 clinical isolates, demonstrating a 95.0% accuracy rate in comparison to the established Vitek2-COMPACT system. Discussion: The RPA-PfAgo platform has emerged as a superior diagnostic tool, offering enhanced sensitivity, specificity, and identification efficacy for MRSA detection. Our findings underscore the potential of this platform to significantly improve the diagnosis and management of MRSA infection.

Phenotypic and genotypic characterization of methicillin resistant Staphylococcus aureus associated with pyogenic infections.

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

Pharmacokinetics of vancomycin in sputum of intubated patients: Optimized intravenous delivery vs. inhaled therapy.

AIMS: Intubated patients with methicillin-resistant Staphylococcus aureus pneumonia, fail optimized treatment with intravenous (IV) vancomycin (serum trough 15-20 µg/mL) in 38-79% of cases. Airway blood flow is diminished compared to alveoli and we hypothesized that vancomycin concentrations achieved in airway secretions are suboptimal and nonbactericidal. Targeted therapy by inhalation may overcome this deficit. METHODS: Airway pharmacokinetics of optimized IV and inhaled vancomycin in infected clinically stable prolonged mechanically ventilated patients were measured. First, IV vancomycin was given until optimized concentrations were achieved (15-20 µg/mL), and, at the same time point, sputum vancomycin concentrations were measured. Then, sputum concentrations were re-assessed after 4 treatments of inhaled vancomycin (120 mg/2 mL) via a previously characterized nebulizing system that deposited 18 ± 2 mg in the lungs. Vancomycin post-distribution phase serum peak and trough concentrations were also obtained. Serum albumin was measured to assess binding to vancomycin. RESULTS: Mean serum trough concentration was 18.4 ± 6.5 µg/mL. Sputum concentrations were affected by serum albumin. Only patients with severe hypoalbuminaemia had penetration of drug leading to therapeutic (15.7-17 µg/mL) sputum concentrations. Following inhaled vancomycin, sputum concentrations increased significantly to 199 ± 37.0 µg/mL (P = .002) exceeding minimum inhibitory concentration by 2 orders of magnitude. CONCLUSION: Despite optimized serum concentrations, patients with albumin near normal had suboptimal concentrations of vancomycin in their sputum. Inhaled therapy may be clinically important for successful treatment of ventilator-associated methicillin-resistant Staphylococcus aureus infection. Further studies of inhaled therapy are needed to define their role as adjunctive therapy in ventilator-associated pneumonia and as single therapy in tracheobronchitis.

Antibacterial Activity and Multi-Targeted Mechanism of Action of Suberanilic Acid Isolated from Pestalotiopsis trachycarpicola DCL44: An Endophytic Fungi from Ageratina adenophora.

Methicillin-resistant Staphylococcus aureus (MRSA) is a highly threatening foodborne pathogen capable of causing severe organ and life-threatening diseases. Over the past years, various commercial antibiotics have been used to treat MRSA infections. However, these commercial antibiotics have not yielded efficient results and also cause other side effects; therefore, there is a need for the development of effective alternatives to replace these commercial antibiotics. Suberanilic acid, an amide alkaloid obtained from the endophytic fungus Pestalotiopsis trachycarpicola DCL44, has been identified as a significant antimicrobial agent. However, its antibiotic properties on multi-drug-resistant bacteria such as MRSA have not been fully explored. Therefore, to investigate the potential antimicrobial mechanism of suberanilic acid against MRSA, a quantitative proteomics approach using tandem mass tagging (TMT) was used. The results obtained in the study revealed that suberanilic acid targets multiple pathways in MRSA, including disruption of ribosome synthesis, inhibition of membrane translocation for nutrient uptake (ABC transporter system), and causing dysregulation of carbohydrate and amino acid energy metabolism. These results provide new insights into the mechanism of action of suberanilic acid against MRSA and offer technical support and a theoretical basis for the development of novel food antimicrobial agents derived from endophytic fungal origin.

Discovery of membrane-targeting amphiphilic honokiol derivatives containing an oxazolethione moiety to combat methicillin-resistant Staphylococcus aureus (MRSA) infections.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major pathogen causing infections in hospitals and the community, and there is an urgent need for the development of novel antibacterials to combat MRSA infections. Herein, a series of amphiphilic honokiol derivatives containing an oxazolethione moiety were prepared and evaluated for their in vitro antibacterial and hemolytic activities. The screened optimal derivative, I3, exhibited potent in vitro antibacterial activity against S. aureus and clinical MRSA isolates with MIC values of 2-4 µg/mL, which was superior to vancomycin in terms of its rapid bactericidal properties and was less susceptible to the development of resistance. The SARs analysis indicated that amphiphilic honokiol derivatives with fluorine substituents had better antibacterial activity than those with chlorine and bromine substituents. In vitro and in vivo toxicity studies revealed that I3 has relatively low toxicity. In a MRSA-infected mouse skin abscess model, I3 (5 mg/kg) effectively killed MRSA at the infected site and attenuated the inflammation effects, comparable to vancomycin. In a MRSA-infected mouse sepsis model, I3 (12 mg/kg) was found to significantly reduce the bacterial load in infected mice and increase survival of infected mice. Mechanistic studies indicated that I3 has membrane targeting properties and can interact with phosphatidylglycerol (PG) and cardiolipin (CL) of MRSA cell membranes, thereby disrupting MRSA cell membranes, further inducing the increase of reactive oxygen species (ROS), protein and DNA leakage to achieve rapid bactericidal effects. Finally, we hope that I3 is a potential candidate molecule for the development of antibiotics to conquer superbacteria-related infections.

Unveiling the Potential of Bergenia Phenolics: Vitexin's Role in Allosteric Modulation of PBP2a as a Strategy against MRSA Resistance.

BACKGROUND: For cell wall biosynthesis, drug-resistant S. aureus uses a special protein called PBP2a, even when antibiotics are present and stop its natural processes from working. To combat this, novel therapies are required to specifically target PBP2a with greater efficacy. METHODS: Using computational approaches, we screened nine phenolic compounds from other Bergenia species, including Bergenia ciliata, Begenia ligulata, Bergenia purpurascens, and Ber-genia stracheyi, against the PBP2a allosteric site to explore the potential interaction between phe-nolic compounds and a specific region of PBP2a known as the allosteric site. RESULTS: Based on interaction patterns and estimated affinity, vitexin has been found to be the most prominent phenolic compound. We performed MD simulations on vitexin and ceftazidime as control molecules based on the docking results. The binding free energy estimates of vitexin (-94.48 +/- 17.92 kJ/mol) using MM/PBSA were lower than those of the control (-67.61 +/- 12.29 kJ/mol), which suggests that vitexin may be able to inhibit PBP2a activity in MRSA. CONCLUSION: It has been intriguing to observe a correlation between the affinity of the lead com-pounds at the allosteric site and the modification of Tyr446, the active site gatekeeper residue in PBP2a. Our findings have implied that lead compounds can either directly or indirectly decrease PBP2a activity by inducing allosteric site change in conventional medicine.

Chemical optimization and derivatization of micrococcin p2 to target multiple bacterial infections: new antibiotics from thiopeptides.

Antimicrobial resistance poses a significant threat to humanity, and the development of new antibiotics is urgently needed. Our research has focused on thiopeptide antibiotics such as micrococcin P2 (MP2) and derivatives thereof as new anti-infective agents. Thiopeptides are sulfur-rich, structurally complex substances that exhibit potent activity against Gram-positive pathogens and Mycobacteria species, including clinically resistant strains. The clinical development of thiopeptides has been hampered by the lack of efficient synthetic platforms to conduct detailed structure-activity relationship studies of these natural products. The present contribution touches upon efficient synthetic routes to MP2 that laid the groundwork for clinical translation. The medicinal chemistry campaign on MP2 has been guided by computational molecular dynamic simulations and parallel investigations to improve drug-like properties, such as enhancing the aqueous solubility and optimizing antibacterial activity. Such endeavors have enabled identification of promising lead compounds, AJ-037 and AJ-206, against Mycobacterium avium complex (MAC). Extensive in vitro studies revealed that these compounds exert potent activity against MAC species, a subspecies of non-tuberculous mycobacteria (NTM) that proliferate inside macrophages. Two additional pre-clinical candidates have been identified: AJ-024, for the treatment of Clostridioides difficile infections, and AJ-147, for methicillin-resistant Staphylococcus aureus impetigo. Both compounds compare quite favorably with current first-line treatments. In particular, the ability of AJ-147 to downregulate pro-inflammatory cytokines adds a valuable dimension to its clinical use. In light of above, these new thiopeptide derivatives are well-poised for further clinical development.

Phenotypic and genomic analysis of the hypervirulent methicillin-resistant Staphylococcus aureus ST630 clone in China.

Methicillin-resistant Staphylococcus aureus (MRSA) sequence type 630 (ST630) is a rarely reported lineage worldwide. This study aimed to trace the dissemination of the emerging MRSA ST630 clones in China and investigate their virulence potential. We collected 22 ST630-MRSA isolates from across China and performed whole-genome sequencing analysis and virulence characterization on these isolates. Epidemiological results showed that MRSA ST630 isolates were primarily isolated from pus/wound secretions, mainly originating from Jiangxi province, and carried diverse virulence and drug resistance genes. Staphylococcal cassette chromosome mec type V (SCCmec V) predominated (11/22, 50.0%) among the MRSA ST630 isolates. Interestingly, nearly half (45.5%) of the 22 ST630-MRSA isolates tested lacked intact SCCmec elements. Phylogenetic analysis demonstrated that ST630-MRSA could be divided into two distinct clades, with widespread dissemination mainly in Chinese regions. Five representative isolates were selected for phenotypic assays, including hemolysin activity, real-time fluorescence quantitative PCR, western blot analysis, hydrogen peroxide killing assay, blood killing assay, cell adhesion and invasion assay, and mouse skin abscess model. The results showed that, compared to the USA300-LAC strain, ST630 isolates exhibited particularly strong invasiveness and virulence in the aforementioned phenotypic assays. This study described the emergence of a highly virulent ST630-MRSA lineage and improved our insight into the molecular epidemiology of ST630 clones in China.IMPORTANCEMethicillin-resistant Staphylococcus aureus (MRSA) sequence type 630 (ST630) is an emerging clone with an increasing isolation rate in China. This study raises awareness of the hypervirulent MRSA ST630 clones in China and alerts people to their widespread dissemination. ST630-staphylococcal cassette chromosome mec V is a noteworthy clone in China, and we present the first comprehensive genetic and phenotypic analysis of this lineage. Our findings provide valuable insights for the prevention and control of infections caused by this emerging MRSA clone.

A novel chlorin derivative Shengtaibufen (STBF) mediated photodynamic therapy combined with iodophor for the treatment of chronic superficial leg wounds infected with methicillin-resistant Staphylococcus aureus: A retrospective clinical study.

OBJECTIVE: Chronic wounds are costly and difficult to treat, resulting in morbidity and even mortality in some cases due to a high methicillin-resistant Staphylococcus aureus (MRSA) burden contributing to chronicity. We aimed to observe the antimicrobial activity and healing-promoting effect of a novel photosensitizer Shengtaibufen (STBF)-mediated antibacterial photodynamic therapy (PDT) on MRSA-infected chronic leg ulcers. PATIENTS AND METHODS: This was a retrospective, comparative, single-center clinical study. A total of 32 patients with chronic lower limb wounds infected with MRSA from January 2022 to December 2023 were finally included in this study by searching the electronic medical records of the dermatology department of Huadong Hospital, including a group of red light combined with iodophor (control+iodophor, n=16, receiving red light once a week for 8 weeks and routine dressing change with iodophor once a day) and a group of STBF-mediated PDT (STBF-PDT) combined with iodophor (STBF-PDT+iodophor, n=16, receiving STBF-PDT and routine dressing change with iodophor once a day). STBF-PDT was performed once a week (1 mg/ml STBF, 1 h incubation, 630 nm red light, 80 J/cm2) for 8 weeks. The primary endpoints included wound clinical signs, wound size, wound-related pain, re-epithelialization score, MRSA load and wound-related quality of life (wound-QoL). Any adverse events were also recorded. RESULTS: We found that STBF-PDT+iodophor could effectively alleviate clinical infection symptoms, accelerate wound closure, reduce average biological burden and improve wound-QoL without severe adverse events in comparison to the control+iodophor group. The STBF-PDT+iodophor group obtained a mean percentage reduction of 65.22% in wound size (from 18.96±11.18 cm2 to 6.59±7.94 cm2) and excellent re-epithelialization scores, as compared with a decrease of 30.17% (from 19.23±9.80 cm2 to 13.43±9.32 cm2) for the control+iodophor group. Significant differences in wound area were observed at week 6 (p=0.028*) and week 8 (p=0.002**). The bacterial load decreased by 99.86% (from 6.45 × 107±2.69 × 107 to 8.94 × 104±1.92 × 105 CFU/cm2, p<0.0001) in the STBF-PDT+iodophor group and 1.82% (from 6.61 × 107±2.13 × 107 to 6.49 × 107±2.01 × 107 CFU/cm2, p=0.029) in the control+iodophor group. The wound-QoL in STBF-PDT+iodophor group had a 51.62% decrease in overall score (from 29.65±9.33 at the initial to 14.34±5.17 at week 8, p<0.0001) compared to those receiving red light and routine wound care (from 30.73±17.16 to 29.32±15.89 at week 8, p=0.003). Moreover, patients undergoing STBF-PDT+iodophor exhibited great improvements in all domains of wound-QoL (physical, psychological and everyday-life), whereas the control+iodophor group ameliorated in only one field (everyday-life). CONCLUSION: Our data confirmed that a novel photosensitizer, STBF-mediated PDT, when combined with iodophor, served as a potential modality for MRSA infection and a possible therapy for other drug-resistant microorganisms, and as a promising alternative for chronic cutaneous infectious diseases.

Synthesis of Graphene@C3N4-Cu Beads Nanocomposites and their Antimicrobial Efficacy Against Drug-Resistant Bacteria and Fungi.

BACKGROUND: Increased intake of drugs worldwide and the subsequent advent of resistance to existing antibiotics have globally threatened health organizations. To combat the problem of these drug-resistant infections, as an alternative approach, graphene (GN)-related nanomaterials have attracted significant interest because of their effective anti-microbial potential. The present study shows the synthesis and characterization of nanocomposite of GN with carbon nitride viz. g- C3N4, g-C3N4-Cu, and GN@g-C3N4-Cu. Further, we investigated the anti-microbial potential of these nanocomposites against strains of Gram-negative and Gram-positive bacteria, viz., a multidrug- resistant strain of Pseudomonas aeruginosa (MDRPA), a methicillin-resistant strain of Staphylococcus aureus ATCC33593 (MRSA), and an azole-sensitive fungal strain (Candida albicans ATCC14053). METHODS: The morphological characterization of GN@g-C3N4-Cu nanocomposite was executed by scanning electron microscopy, whereas the elemental analysis and their distribution were studied by energy-dispersive X-ray spectroscopy and elemental mapping methods. Furthermore, the anti-microbial and antibiofilm efficacies of g-C3N4, g-C3N4-Cu, and GN@g-C3N4-Cu nanocomposites were evaluated by disc diffusion, two-fold serial micro broth dilution, and 96 well microtiter plate methods. RESULTS: The ternary g-C3N4-Cu@GN, apart from the structures of g-C3N4-Cu, showed big sheets of GN. The observance of C, N, O, and Cu in the elemental analysis, as well as their uniform distribution in the mapping, indicated the successful fabrication of g-C3N4-Cu@GN. GN@g-C3N4-Cu followed by g-C3N4-Cu and (g-C3N4) exhibited significantly higher antimicrobial activity (zone of inhibition from 14.33 to 49.33 mm) against both the drug-resistant bacterial strains and azole-sensitive C. albicans. MICs of nanocomposites ranged from 32 -256 µg/ml against the tested strains. Whereas all three nanocomposites at sub-MICs (0.25 A- and 0.5 A- MICs) showed concentration- dependent inhibition of biofilm formation in MDRPA, MRSA, and C. albicans by allowing 11.35% to 32.59% biofilm formation. CONCLUSION: Our study highlights the enhanced efficiency of GN@g-C3N4-Cu nanocomposites as potential anti-microbial and antibiofilm agents to overcome the challenges of multi-drug-resistant bacteria and azole-sensitive fungi. Such kind of nanocomposites could be used to prevent nosocomial infections if coated on medical devices and food manufacturing instruments.

The crucial relationship between vancomycin minimum inhibitory concentration and therapeutic efficacy against methicillin-resistant coagulase-negative staphylococci.

The area under the curve (AUC)/minimum inhibitory concentration (MIC) ratio was used as an indicator of the clinical efficacy of vancomycin. However, the target AUC/MIC has not been set for methicillin-resistant coagulase-negative staphylococci (MR-CNS), and the effectiveness of vancomycin in strains with high MIC is unknown. Therefore, we aimed to investigate the relationship between the vancomycin MIC and therapeutic efficacy in patients with MR-CNS bacteremia. The primary outcome was the difference in treatment failure rate when the MR-CNS vancomycin MIC was 1 or 2 µg/mL. The treatment failure rate did not significantly differ between the two groups (MIC 1 vs. MIC 2: 27.0% vs. 31.0%; p = 0.779). As a result of multivariate analysis, AUC/MIC0-24 h ≤230 was extracted as risk factor for treatment failure, suggesting the importance of a sufficient initial loading dose and early blood concentration monitoring to increase AUC/MIC0-24 h for successful treatment.

Emergence of methicillin-resistant Staphylococcus aureus (MRSA) RdJ clone (CC5-ST105-SCCmecII-t002) in Santa Catarina, Brazil.

The emergence of highly successful genetic lineages of methicillin-resistant Staphylococcus aureus (MRSA) poses a challenge in human healthcare due to increased morbidity and mortality rates. The RdJ clone (CC5-ST105-SCCmecII-t002 lineage), previously identified in Rio de Janeiro, Brazil, was linked to bloodstream infections and features a mutation in the aur gene (encoding aureolysin). Additionally, clinical isolates derived from this clone were more effective at evading monocytic immune responses. This study aimed to detect the RdJ clone among clinical MRSA isolated in Santa Catarina (SC) and examine its antimicrobial resistance and phagocytosis evasion capabilities. Our findings revealed the RdJ clone in 20 % of MRSA isolates, all exhibiting multiresistance. RdJ clone isolates from SC did not demonstrate a decreased rate of phagocytosis compared to CC5 non-RdJ isolates. Structural analysis suggests that the aur mutation is unlikely to significantly impact aureolysin activity. Genomic analysis of one isolate unveiled a genetic variant of the RdJ clone, sharing lineage and gene distribution but lacking the aur mutation. This study enhances the understanding of the clinical and epidemiologic risks associated with the RdJ clone and the biological mechanisms underlying its spreading in SC.

Therapeutic drug monitoring of antibiotics for methicillin-resistant Staphylococcus aureus infections: an updated narrative review for clinicians.

BACKGROUND: Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are associated with high mortality rates. Optimal antibiotic dosage plays a crucial role in reducing MRSA burden; thus, the use of therapeutic drug monitoring (TDM) in the clinical practice, especially of new drugs such as ceftobiprole, ceftaroline, dalbavancin and oritavancin, should be implemented. OBJECTIVES: We aim to examine and summarize the available evidence about TDM of anti-MRSA molecules, with a focus on pneumonia, endocarditis and vascular infections, and bone and joint infections. SOURCES: We applied "therapeutic drug monitoring" and "Staphylococcus aureus" as search terms in PubMed, considering a time frame of 24 years (2001-2024). Articles in English language, non-duplicated, evaluating antibiotic therapeutic target and role of TDM were included in the study. CONTENT: In this review, available data for therapeutic target and TDM were critically analyzed and summarized and suggestions about the use of old and new anti-MRSA antibiotics were provided, focusing on optimal dosages, tissue penetration according to infection types and toxicity. Limitations to the widespread use of TDM in the clinical practice were discussed. IMPLICATIONS: The use of TDM may play an important role for the optimal management of patients with MRSA infections and may impact on patient outcomes by increasing efficacy and reducing the risk of adverse events. TDM may be implemented in clinical practice, however several limitations such as the wide variability in the methodology and the need for skilled personnel need to be considered.

Multiplex fluorescence loop-mediated isothermal amplification with lateral flow assay for rapid simultaneous detection of mecA and nuc genes in methicillin-resistant Staphylococcus aureus.

BACKGROUND: Antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), pose a significant threat to public health. Existing detection methods, like cultivation-based techniques, demand significant time and labor, while molecular diagnostic techniques, such as PCR, necessitate sophisticated instrumentation and skilled personnel. Although previous multiplex loop-mediated isothermal amplification assays based on fluorescent dyes (mfLAMP) offer simplicity and cost-effectiveness, they are prone to false-positive results. Therefore, developing a rapid and efficient multiplex assay for high-sensitivity MRSA is imperative to create a practical diagnostic tool for point-of-care testing. RESULTS: Here, we developed a mfLAMP combined with a lateral flow assay (mfLAMP-LFA) for the visual and simultaneous detection of the mecA (PBP2a-specific marker) and nuc (S. aureus-specific marker) genes in MRSA. We optimized mfLAMP-LFA using graphene oxide (GO)-based purification and specific DNA probes and evaluated its sensitivity, specificity, and stability. Utilizing GO to mitigate false-positive results by acting as a trap for free DNA probes, the mfLAMP-LFA method successfully identified mecAf and nucf-probes, exhibiting distinct red, green, and yellow fluorescence signals. The detection sensitivity of the developed mfLAMP-LFA method (1 CFU mL-1 in phosphate-buffered saline (PBS)) was comparable to other highly sensitive MRSA detection methods (1 CFU mL-1 in PBS). Furthermore, the method demonstrated specificity for MRSA, detecting it in irrigation water samples within the desired range and achieving reliable recovery rates from spiked samples. SIGNIFICANCE: This novel strategy is the first to incorporate GO into mfLAMP-LFA, enabling specific and sensitive MRSA detection and advancing rapid bacterial detection. This assay facilitates MRSA diagnostics, contributing to improved public health and food safety by delivering rapid, cost-effective point-of-care results. It enables the simultaneous detection of multiple bacteria, even in irrigation water samples artificially inoculated with MRSA, which contain aerobic bacteria at 2.7 × 102 CFU mL-1.

A case of acute purulent pericarditis due to MRSA treated with daily pericardial lavage for one month followed by pericardial fenestration.

Acute purulent pericarditis is a rare infection in developed countries. We herein report a case with diabetic nephropathy under maintenance hemodialysis who suffered from acute purulent pericarditis caused by methicillin-resistant Staphylococcus aureus (MRSA). The treatment of purulent pericarditis mainly involves rapid administration of appropriate antibiotics and drainage. However, in this case, the patient was unresponsive to vancomycin and performing early surgical intervention was challenging due to highly pathogenic MRSA. Therefore, we performed pericardial fenestration in the chronic phase to suppress the risk of fatal secondary infections after daily irrigation for one month to reduce bacterial load mechanically. Learning objective: In a case of purulent pericarditis caused by highly pathogenic methicillin-resistant Staphylococcus aureus resistant to antibiotics and resulting in constrictive pericarditis, it was possible to perform pericardial fenestration in the chronic phase, while mitigating the risk of fatal secondary infections, by controlling the inflammation through daily irrigation for a long time to reduce the bacterial load mechanically.

Isolated Acromioclavicular Joint Septic Arthritis: A Case Report and Review of Literature.

A 60-year-old diabetic patient presented with acute pain and swelling localized to the left acromioclavicular joint. Laboratory and radiological investigations revealed the presence of pus in the left acromioclavicular joint along with bony erosion of the lateral end of the left clavicle. She was treated with open arthrotomy, debridement, and appropriate antibiotics for the causative methicillin-resistant Staphylococcus aureus (MRSA) infection. Prompt diagnosis and timely intervention can reduce the morbidity and mortality due to septic arthritis. We conducted a review of the literature on patients treated for isolated septic arthritis of the acromioclavicular joint.

Outcome of extracorporeal membrane oxygenation support among children with methicillin-resistant Staphylococcus aureus infection: A single-center experience.

Introduction: The use of extracorporeal membrane oxygenation (ECMO) in children continues to increase nationally, including patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. Survival of pediatric patients with MRSA sepsis has not improved over the last 20 years. We sought to review our institutional experience and outcomes of ECMO support among children with MRSA infection.Methods: Children aged 0-19 years who received ECMO support from October 2014 to June 2021 were reviewed retrospectively. Patients with laboratory confirmed MRSA infections were identified.Results: Out of 88 unique pediatric patients requiring ECMO support, eight patients had documented MRSA infections. The duration of mechanical ventilation prior to ECMO initiation was an average of seven days (range 0.7 to 21.8 days). The median ECMO duration was 648.1 h (range 15.5 to 1580.5 h). Five patients were successfully decannulated; however, only two patients survived to discharge. The two surviving patients were both cannulated via VV-ECMO. Mechanical ventilation prior to ECMO was 4.5 and 21.8 days in these cases with run durations of 18.9 and 29.9 days, respectively.Conclusions: Our institutional survival of patients with MRSA on ECMO is lower than what has been reported in recent database studies, but notably, 62.5% were successfully decannulated. While both surviving patients were supported with VV-ECMO, there was no other clear trend in factors that contributed to survival. MRSA continues to be a source of significant morbidity and mortality among pediatric patients. On-going investigation of outcomes and factors contributing to survival in patients with MRSA infection on ECMO is warranted.

Antibacterial efficacy of antimicrobial peptide-functionalized hydrogel particles combined with vancomycin and oxacillin antibiotics.

The rise of antibiotic resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), requires novel approaches to combat infections. Medical devices like implants and wound dressings are frequently used in conjunction with antibiotics, motivating the development of antibacterial biomaterials capable of exhibiting combined antibacterial effects with conventional antibiotics. This study explores the synergistic antibacterial effects of combining antimicrobial peptide (AMP) functionalized hydrogel particles with conventional antibiotics, vancomycin (VCM) and oxacillin (OXA), against Staphylococcus aureus and MRSA. The AMP employed, RRPRPRPRPWWWW-NH2, has previously demonstrated broad-spectrum activity and enhanced stability when attached to hydrogel substrates. Here, checkerboard assays revealed additive and synergistic interactions between the free AMP and both VCM and OXA against Staphylococcus aureus and MRSA. Notably, the AMP-OXA combination displayed a significant synergistic effect against MRSA, with a 512-fold reduction in OXA's minimum inhibitory concentration (MIC) when combined with free AMP. The observed synergism against MRSA was retained upon covalent AMP immobilization onto the hydrogel particles; however, at a lower rate with a 64-fold reduction in OXA MIC. Despite this, the OXA-AMP hydrogel particle combinations retained considerable synergistic potential against MRSA, a strain resistant to OXA, highlighting the potential of AMP-functionalized materials for enhancing antibiotic efficacy. These findings underscore the importance of developing antimicrobial biomaterials for future medical devices to fight biomaterial-associated infections and reverse antimicrobial resistance.

Detection of foodborne methicillin-resistant Staphylococcus aureus via fluorescence-encoded microsphere and Argonaute-mediated decoding.

Molecular diagnosis of foodborne methicillin-resistant Staphylococcus aureus (MRSA) is crucial for controlling its dissemination and ensuring food safety. However, existing genetic methods are limited by susceptibility to aerosol contamination and restricted to single-gene detection. Herein, a fluorescent biosensor employing fluorescence-encoded microspheres and Argonaute-mediated decoding is developed, enabling ultrasensitive, accurate, and duplex detection of MRSA genes. This assay utilizes a target-triggered polymerization/nicking reaction to cyclically produce specific guide DNA, guiding Argonaute protein to site-specifically cleave the molecular beacon on the microsphere, thereby decoding a fluorescent signal. Notably, the fluorescence-encoded microsphere, designed via on-tetrahedron rolling circle amplification, achieves high fluorescence loadings in a unit area. This biosensor demonstrates simultaneous detection of two unamplified MRSA genes, mecA and femA, at concentrations as low as 0.63 fM and 0.48 fM, respectively. Moreover, the method exhibited excellent recoveries in milk, egg, and pork samples ranging from 73% to 112%, highlighting its practicability in real scenarios.

An Unusual Presentation of Monofocal Methicillin-Resistant Staphylococcus aureus Hepatic Abscess in an Otherwise Healthy Man.

A hepatic abscess is the collection of suppurative matter within the parenchyma of the liver. While most pyogenic liver abscesses (PLAs) are polymicrobial in nature, some rare cases are caused by methicillin-resistant Staphylococcus aureus (MRSA). We present a case of a 43 year-old male without evident exposures who presented with abdominal pain and via CT imaging was found to have monofocal MRSA hepatic abscess. An ultrasonography (US)-guided abscess drainage along with a pigtail catheter placement was performed along with antibiotic initiation. This article emphasizes the clinical manifestations of hepatic abscesses and employs literature reviews to offer a comprehensive approach to managing these patient populations.