Methicillin-resistant Strains Research Articles

Jellyfish protein hydrolysates: Multifunctional bioactivities unveiled in the battle against diabetes, inflammation, and bacterial pathogenesis

This study investigates the multifunctional bioactivities of pepsin-hydrolyzed jellyfish by-products (Rhopilema hispidum and Lobonema smithii), focusing on their anti-α-glucosidase activity, anti-inflammatory effects, anti-bacterial properties, and ability to inhibit biofilm formation of Staphylococcus aureus. Our findings revealed that jellyfish protein hydrolysates, particularly from Rhopilema hispidum, exhibit significant anti-α-glucosidase activity, surpassing the well-known α-glucosidase inhibitor Acarbose. Furthermore, we demonstrated the anti-inflammatory capabilities of these hydrolysates in suppressing lipopolysaccharide (LPS)-induced nitric oxide production in murine macrophage cells. This effect was dose-dependent and non-cytotoxic, highlighting the hydrolysate potential in treating inflammation-related conditions. Regarding anti-bacterial activity, pepsin-hydrolyzed jellyfish selectively exhibited a potent effect against S. aureus, including Methicillin-susceptible and Methicillin-resistant strains. This activity was evident at minimum inhibitory concentrations (MIC) of 25 μg/mL for S. aureus ATCC10832, while a modest effect was observed against other Gram-positive strains. The hydrolysates effectively delayed bacterial growth dose-dependently, suggesting their use as alternative agents against bacterial infections. Most notably, pepsin-hydrolyzed jellyfish showed significant anti-biofilm activity against S. aureus. The umbrella section hydrolysate of Rhopilema hispidum was particularly effective, reducing biofilm formation through downregulating the icaA gene, crucial for biofilm development. Furthermore, the hydrolysates modulated the expression of the agrA gene, a key regulator in the pathogenesis of S. aureus. In conclusion, pepsin-hydrolyzed jellyfish protein hydrolysates exhibit promising multifunctional bioactivities, including anti-diabetic, anti-inflammatory, antibacterial, and anti-biofilm properties. These findings suggest their potential application in pharmaceutical and nutraceutical fields, particularly in managing diabetic risks, inflammation, bacterial infections, and combating the biofilm-associated pathogenicity of S. aureus.

Occurrence, antimicrobial susceptibility, and resistance genes of Staphylococcus aureus in milk and milk products in the Arsi highlands of Ethiopia.

In Ethiopia, milk production and handling practices often lack proper hygiene measures, leading to the potential contamination of milk and milk products with Staphylococcus aureus (S. aureus), including methicillin-resistant strains,posing significant public health concerns. This study aimed to investigate the occurrence, antimicrobial susceptibility profiles and presence of resistance genes in S. aureus strains isolated from milk and milk products. A cross-sectional study was conducted in the Arsi highlands, Oromia, Ethiopia from March 2022 to February 2023. A total of 503 milk and milk product samples were collected, comprising 259 raw milk, 219 cottage cheese, and 25 traditional yogurt samples. S. aureus isolation and coagulase-positive staphylococci enumeration were performed using Baird-Parker agar supplemented with tellurite and egg yolk. S. aureus was further characterized based on colony morphology, Gram stain, mannitol fermentation, catalase test, and coagulase test. Phenotypic antimicrobial resistance was assessed using the Kirby-Bauer disc diffusion method, while the polymerase chain reaction (PCR) was employed for confirming the presence of S. aureus and detecting antimicrobial resistance genes. S. aureus was detected in 24.9% of the milk and milk products, with the highest occurrence in raw milk (40.9%), followed by yogurt (20%), and cottage cheese (6.4%). The geometric mean for coagulase-positive staphylococci counts in raw milk, yogurt, and cottage cheese was 4.6, 3.8, and 3.2 log10 CFU/mL, respectively. Antimicrobial resistance analysis revealed high levels of resistance to ampicillin (89.7%) and penicillin G (87.2%), with 71.8% of the isolates demonstrating multidrug resistance. Of the 16 S. aureus isolates analyzed using PCR, all were found to carry the nuc gene, with the mecA and blaZ genes detected in 50% of these isolates each. This study revealed the widespread distribution of S. aureus in milk and milk products in the Arsi highlands of Ethiopia. The isolates displayed high resistance to ampicillin and penicillin, with a concerning level of multidrug resistance. The detection of the mecA and blaZ genes in selected isolates is of particular concern, highlighting a potential public health hazard and posing a challenge to effective antimicrobial treatment. These findings highlight the urgent need to enhance hygiene standards in milk and milk product handling and promote the rational use of antimicrobial drugs. Provision of adequate training for all individuals involved in the dairy sector can help minimize contamination. These measures are crucial in addressing the threats posed by S. aureus, including methicillin-resistant strains, and ensuring the safety of milk and its products for consumers.

Novel 4-nitroimidazole analogues: synthesis, invitro biological evaluation, in silico studies, and molecular dynamics simulation.

A new series of 4-nitroimidazole bearing aryl piperazines 7-16, tetrazole 17 and 1,3,4-thiadiazole 18 derivatives was synthesized. All derivatives were screened for their anticancer activity against eight diverse human cancer cell lines (Capan-1, HCT-116, LN229, NCI-H460, DND-41, HL-60, K562, and Z138). Compound 17 proved the most potent compound of the series inhibiting proliferation of most of the selected human cancer cell lines with IC50 values in the low micromolar range. In addition, compound 11 exhibited IC50 values ranging 8.60-64.0 μM against a selection of cancer cell lines. These findings suggest that derivative 17 can potentially be a new lead compound for further development of novel antiproliferative agents. Additionally, 17-18 were assessed for their antibacterial andantituberculosis activity. Derivatives 17 and 18 were the most potent compounds of this series against both Staphylococcus aureus strain Wichita and a methicillin resistant strain of S.aureus (MRSA), as well as against Mycobacterium tuberculosis strain mc26230. The antiviral activity of 7-18 was also evaluated against diverse viruses, but no activity was detected. The docking study of compound 17 with putative protein targets in acute myeloid leukemia had beenstudied. Furthermore, the molecular dynamics simulation of 17 and 18 had been investigated.

Impact of PVC microplastics in photodynamic inactivation of Staphylococcus aureus and MRSA.

Photodynamic processes have found widespread application in therapies. These processes involve photosensitizers (PSs) that, when excited by specific light wavelengths and in the presence of molecular oxygen, generate reactive oxygen species (ROS), that target cells leading to inactivation. Photodynamic action has gained notable attention in environmental applications, particularly against pathogens and antibiotic-resistant bacteria (ARB) that pose a significant challenge to public health. However, environmental matrices frequently encompass additional contaminants and interferents, including microplastics (MPs), which are pollutants of current concern. Their presence in water and effluents has been extensively documented, highlighting their impact on conventional treatment methods, but this information remains scarce in the context of photodynamic inactivation (PDI) setups. Here, we described the effects of polyvinyl chloride (PVC) microparticles in PDI targeting Staphylococcus aureus and its methicillin-resistant strain (MRSA), using curcumin as a PS under blue light. The presence of PVC microparticles does not hinder ROS formation; however, depending on its concentration, it can impact bacterial inactivation. Our results underscore that PDI remains a potent method for reducing bacterial concentrations in water and wastewater containing ARB, even in highly contaminated scenarios with MPs.

A decade of neonatal sepsis in Stockholm, Sweden: Gram-positive pathogens were four times as common as Gram-negatives.

To assess Gram-positive bacterial (GPB) bloodstream infection (BSI) in neonates, covering incidence, morbidity, mortality, antimicrobial resistance patterns and biomarkers in Region Stockholm, Sweden between 2006 and 2016. A population-based retrospective epidemiological study including infants with GPB-BSI, admitted to the neonatal units at Karolinska University Hospital (KUH). Data were collected from patient records, the Swedish Neonatal Quality Register, the microbiological laboratory at KUH and the Swedish Public Health Agency. We identified 357 infants with GPB-BSI, representing an incidence of 1.47/1000 live births (LB). Group B streptococcus (GBS) was the most common pathogen causing BSI in full-term infants and early-onset sepsis (EOS) (0.20/1000 LB), while coagulase-negative staphylococci (CoNS) were predominant in infants born very preterm and in late-onset sepsis (LOS) (0.79/1000 LB). There were no fatal GBS BSI cases, but 10.2% developed meningitis. The GPB case fatality rate was 9.5% and the sepsis fatality rate 2.8%. In GPB-BSI, 1/10 did not have an elevated C-reactive protein level. Staphylococcus aureus (S. aureus) BSI increased during the study period, but no methicillin or vancomycin resistant strains were found. The antimicrobial resistance (AMR) rate was highest in CoNS isolates. GPB-BSI was four times more common than Gram-negative BSI in neonates but resulted in lower mortality rate. GBS was the most common pathogen in full-term infants and in EOS. CoNS was the most common pathogen in LOS and infants born very preterm, and the AMR rate was high in these isolates. The increasing trend of S. aureus BSI indicates a need of further investigation.

Outcome and microbiological findings of patients with cardiac implantable electronic device infection.

Infections associated with cardiac implantable electronic devices (CIEDs) are a multifactorial disease that leads to increased morbidity and mortality. The aim was to analyze patient-, disease- and treatment-related characteristics including microbiological and bacterial spectrum according to survival status and to identify risk factors for 1- and 3-year mortality in patients with local and systemic CIED infection. In a retrospective cohort study, we analyzed data from patients with CIED-related local or systemic infection undergoing successful transvenous lead extraction (TLE). Survival status as well as incidence and cause of rehospitalization were recorded. Microbiology and antibiotics used as first-line therapy were compared according to mortality. Independent risk factors for 1- and 3-year mortality were determined. Data from 243 Patients were analyzed. In-hospital mortality was 2.5%. Mortality rates at 30days, 1- and 3years were 4.1%, 18.1% and 30%, respectively. Seventy-four (30.5%) patients had systemic bacterial infection. Independent risk factors for 1-year mortality included age (OR 1.05 [1.01-1.10], p = 0.014), NT-proBNP at admission (OR 4.18 [1.81-9.65], p = 0.001), new onset or worsened tricuspid regurgitation after TLE (OR 6.04 [1.58-23.02], p = 0.009), and systemic infection (OR 2.76 [1.08-7.03], p = 0.034), whereas systemic infection was no longer an independent risk factor for 3-year mortality. Staphylococcus aureus was found in 18.1% of patients who survived and in 25% of those who died, p = 0.092. There was a high proportion of methicillin-resistant strains among coagulase-negative staphylococci (16.5%) compared to Staphylococcus aureus (1.2%). Staphylococci are the most common causative germs of CIED-infection with coagulase-negative staphylococci showing higher resistance rates to antibiotics. The independent risk factors for increased long-term mortality could contribute to individual risk stratification and well-founded treatment decisions in clinical routine. Especially the role of tricuspid regurgitation as a complication after TLE should be investigated in future studies.

Этические и юридические аспекты назначения антибактериальных препаратов резерва

The article explains what an antibacterial reserve preparation means. It has been shown that the drug belonging to the group is determined by its pharmacological properties only such as a clinically significant (sufficient for empirical application) activity in relation to Pseudomonas aeruginosa or nosocomial (methicillin-resistant) strains of Staphylococcus aureus. It allows to differentiate between two categories of reserve antibiotics, which exert an anti-Gram-negative and anti-Gram-positive activity. There is an exhaustive list of preparations included into each group and available in the Russian market. Meanwhile, no drugs that correspond to inclusion requirements for both groups are available. Possible conflicts that occur during clinical application of antibacterial reserve drugs are comprehensively analyzed. It is based on divergence of interests of a patient and the patient’s representatives, treating physician, management of the clinic, hospital epidemiologists and manufacturers of reserve generics. Economic and general biological (selection of drug-resistant strains in extensively wide application) arguments commonly contradict the legal (compliance with clinical recommendations), moral and ethical (independence of aid quality from the patient’s prognosis) standards. The Legislator’s position in relation to the issue has been reviewed. Imperfect regularity framework and insufficient legal safety of a doctor make it possible to resolve conflicts through concessions and agreements including reserve antibiotics prescribed as per conditionally social indications.

Antimicrobial Resistance and the Prevalence of the Panton-Valentine Leukocidin Gene among Clinical Isolates of Staphylococcus aureus in Lithuania.

This study aimed to determine resistance to antimicrobials of Staphylococcus aureus strains isolated from clinical specimens in Lithuanian hospitals and to identify the genes conferring resistance and virulence. The study was carried out from June 2019 to September 2021. S. aureus strains were isolated from skin, soft tissues, blood, lower respiratory tract, urine and other specimens. Antibiotic susceptibility testing was performed using the disc diffusion method according to EUCAST guidelines. All isolates were analyzed for detection of the ermA, ermC, mecA, mecC, tetK, tetM, and lukF-PV genes by multiplex real-time PCR. The 16S rRNA coding sequence was applied as an internal PCR control. Altogether, 745 S. aureus strains were analyzed. Antimicrobial susceptibility testing revealed that all isolates were susceptible to rifampin and vancomycin. Of the 745 strains, 94.8% were susceptible to tetracycline, 94.5% to clindamycin, and 88.3% to erythromycin. The lowest susceptibility rate was found for penicillin (25.8%). Six percent of the tested strains were methicillin-resistant S. aureus (MRSA). The majority of methicillin-resistant strains were isolated from skin and soft tissues (73.3%), with a smaller portion isolated from blood (17.8%) and respiratory tract (8.9%). The ermC gene was detected in 41.1% of erythromycin-resistant S. aureus strains, whereas ermA was detected in 32.2% of erythromycin-resistant S. aureus strains. 69.2% of tetracycline-resistant S. aureus strains had tetK gene, and 28.2% had tetM gene. 7.3% of S. aureus isolates harbored lukF-PV gene. The frequency of the pvl gene detection was significantly higher in MRSA isolates than in methicillin-susceptible S. aureus isolates (p < 0.0001).

Increased production of aureolysin and staphopain A is a primary determinant of the reduced virulence of Staphylococcus aureus sarA mutants in osteomyelitis.

We previously demonstrated that mutation of sarA in Staphylococcus aureus limits biofilm formation, cytotoxicity for osteoblasts and osteoclasts, and virulence in osteomyelitis, and that all of these phenotypes can be attributed to the increased production of extracellular proteases. Here we extend these studies to assess the individual importance of these proteases alone and in combination with each other using the methicillin-resistant USA300 strain LAC, the methicillin-susceptible USA200 strain UAMS-1, and isogenic sarA mutants that were also unable to produce aureolysin (Aur), staphopain A (ScpA), staphylococcal serine protease A (subsp.), staphopain B (SspB), and the staphylococcal serine protease-like proteins A-F (SplA-F). Biofilm formation was restored in LAC and UAMS-1 sarA mutants by subsequent mutation of aur and scpA, while mutation of aur had the greatest impact on cytotoxicity to mammalian cells, particularly with conditioned medium (CM) from the more cytotoxic strain LAC. However, SDS-PAGE and western blot analysis of CM confirmed that mutation of sspAB was also required to mimic the phenotype of sarA mutants unable to produce any extracellular proteases. Nevertheless, in a murine model of post-traumatic osteomyelitis, mutation of aur and scpA had the greatest impact on restoring the virulence of LAC and UAMS-1 sarA mutants, with concurrent mutation of sspAB and the spl operon having relatively little effect. These results demonstrate that the increased production of Aur and ScpA in combination with each other is a primary determinant of the reduced virulence of S. aureus sarA mutants in diverse clinical isolates including both methicillin-resistant and methicillin-susceptible strains.IMPORTANCEPrevious work established that SarA plays a primary role in limiting the production of extracellular proteases to prevent them from limiting the abundance of S. aureus virulence factors. Eliminating the production of all 10 extracellular proteases in the methicillin-resistant strain LAC has also been shown to enhance virulence in a murine sepsis model, and this has been attributed to the specific proteases Aur and ScpA. The importance of this work lies in our demonstration that the increased production of these same proteases largely accounts for the decreased virulence of sarA mutants in a murine model of post-traumatic osteomyelitis not only in LAC but also in the methicillin-susceptible human osteomyelitis isolate UAMS-1. This confirms that sarA-mediated repression of Aur and ScpA production plays a critical role in the posttranslational regulation of S. aureus virulence factors in diverse clinical isolates and diverse forms of S. aureus infection.

Prevalence of inducible clindamycin resistance amongst methicillin resistant and sensitive strains of Staphylococcus aureus from a tertiary care hospital, West Bengal, India.

Background: Staphylococcus aureus is a prevalent pathogen causing both nosocomial and community-acquired infections worldwide. The emergence of methicillin-resistant Staphylococcus aureus (MRSA) due to the acquisition of mecA and mecC genes poses a significant clinical challenge. The injudicious use of clindamycin for treating MRSA has led to the development of clindamycin resistance. This study aimed to determine the prevalence of inducible clindamycin resistance (iMLSB resistance phenotype) in Staphylococcus aureus isolates, employing the D test according to CLSI guidelines, particularly focusing on erythromycin-resistant strains. Methodology: A total of 147 Staphylococcus aureus isolates were subjected to antibiotic susceptibility testing using the Kirby Bauer disc diffusion method. The D test was employed to identify inducible clindamycin resistance. Results: The study revealed that 34% of isolates exhibited inducible clindamycin resistance, 40% demonstrated constitutive resistance, and the remaining 26% exhibited the MS phenotype. Notably, inducible clindamycin resistance was more prevalent in MRSA (40%) compared to MSSA (22%). Conclusion: The findings underscore the importance of incorporating the D test as a mandatory procedure in standard disc diffusion testing to accurately identify inducible clindamycin resistance. This knowledge is crucial for guiding appropriate antibiotic therapy in the face of increasing resistance patterns.

Coagulase-negative staphylococci are the main causes of bacterial meningitis in duck

Since September 2018, serious meningitis has been found on some breeding-duck farms in Shandong Province, China. A large number of ducks exhibit severe neurological symptoms. The ducks were randomly selected for laboratory testing. Duck brain samples were collected using standard sterile techniques, and the staphylococci isolates were detected in 404 (70.14%) out of 576 brain samples. A total of 525 coagulase-negative staphylococci (CoNS) strains were isolated, including 6 species: Staphylococcus sciuri (S. sciuri) (67.24%, 353/525), Staphylococcus epidermidis (S. epidermidis) (9.71%, 51/525), Staphylococcus saprophyticus (S. saprophyticus) (8.38%, 44/525), Staphylococcus lentus (S. lentus) (7.62%, 40/525), Staphylococcus haemolyticus (S. haemolyticus) (2.48%, 13/525), and Staphylococcus xylosus (S. xylosus) (4.57%, 24/525). Mixed strain infections were detected in 121 (29.95%) infected presentations. The antimicrobial susceptibility testing indicated that 40.38% of the isolates exhibited multi-drug resistance, and 53.90% of the strains were methicillin-resistant strains by amplification of the methicillin resistance gene (mecA) gene. Through experimental reproduction of the disease, we determined that the CoNS strains were the leading pathogens causing bacterial meningitis in ducks. Although these CoNS strains does not directly cause the death of sick ducks, they still cause large economic losses due to the retarded growth and development of the sick ducks, lower feed returns, and lower grades of processed duck products. The results of this study will contribute to our understanding of the epidemiology and pathogenesis of CoNS and be helpful in the prevention and treatment of the infection.

New Frontier on Antimicrobial Therapy: Long-Acting Lipoglycopeptides.

Long-acting lipoglycopeptides (LGPs), such as dalbavancin and oritavancin, are semisynthetic antibiotics known for their strong effectiveness against a wide array of Gram-positive bacteria. This includes Staphylococcus aureus, both methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) strains, coagulase-negative Staphylococci (CoNS), streptococci, and vancomycin-sensitive Enterococcus faecalis. A literature search was conducted on PubMed and on ClinicalTrials.gov to identify articles published until July 2023 investigating the use of oritavancin and dalbavancin in clinical practice. The review included case reports, case series, observational studies, and clinical studies. Although more consistent data are needed, LGPs seem to be a good alternative that may provide a quicker hospital discharge and reduce long-term intravenous access and therapy. This is attributed to their unique pharmacologic and pharmacokinetic characteristics. More quality data (i.e., number of patients treated with clinical success) are needed before clinicians may use these therapies more widely.

Novel sulfonamide derivatives as a tool to combat methicillin-resistant Staphylococcus aureus.

Increasing resistance in Staphylococcus aureus has created a critical need for new drugs, especially those effective against methicillin-resistant strains (methicillin-resistant Staphylococcus aureus [MRSA]). Sulfonamides are a privileged scaffold for the development of novel antistaphylococcal agents. This review covers recent advances in sulfonamides active against MRSA. Based on thesubstitution patterns of sulfonamide moieties, its derivatives can be tuned for desired properties and biological activity. Contrary to the traditional view, not only N-monosubstituted 4-aminobenzenesulfonamides are effective. Novel sulfonamides have various mechanisms of action, not only 'classical'inhibition of the folate biosynthetic pathway. Some of them can overcome resistance to classicalsulfa drugs and cotrimoxazole, are bactericidal andactive in vivo. Hybrid compounds with distinct bioactive scaffolds are particularly advantageous.

Synthesis and invitro evaluation of antibacterial and antibiofilm activities of novel triphenylphosphonium-functionalized substituted pyrimidines.

The increase in the prevalence of antibiotic-resistant pathogens leads to a decrease in the number of antimicrobial agents for the treatment of infections and prompts researchers to search for new effective antimicrobial drugs. This study reports the synthesis of novel triphenylphosphonium-functionalized substituted pyrimidines and invitro evaluation of their antibacterial and antibiofilm activity. Most of the synthesized derivatives showed high antibacterial activity (MIC = 0.39-1.56 μg/mL) against the methicillin-resistant strain of S. aureus 222. Compounds 2a and 11 exhibited a high level of antibiofilm activity against S. aureus 222 and E. coli 311. The triphenylphosphonium-containing pyrimidines 11 and 2a reduced S. aureus 222 biofilm formation by 99.1% and 95.8%, respectively. In addition, compound 2a was the most active against E. coli 311 biofilm formation (the biomass decreased by 98.4%).

The Purine Biosynthesis Repressor, PurR, Contributes to Vancomycin Susceptibility of Methicillin-resistant Staphylococcus aureus in Experimental Endocarditis.

Staphylococcus aureus is the most common cause of life-threatening endovascular infections, including infective endocarditis (IE). These infections, especially when caused by methicillin-resistant strains (MRSA), feature limited therapeutic options and high morbidity and mortality rates. Herein, we investigated the role of the purine biosynthesis repressor, PurR, in virulence factor expression and vancomycin (VAN) treatment outcomes in experimental IE due to MRSA. The PurR-mediated repression of purine biosynthesis was confirmed by enhanced purF expression and production of an intermediate purine metabolite in purR mutant strain. In addition, enhanced expression of the transcriptional regulators, sigB and sarA, and their key downstream virulence genes (eg, fnbA, and hla) was demonstrated in the purR mutant in vitro and within infected cardiac vegetations. Furthermore, purR deficiency enhanced fnbA/fnbB transcription, translating to increased fibronectin adhesion versus the wild type and purR-complemented strains. Notably, the purR mutant was refractory to significant reduction in target tissues MRSA burden following VAN treatment in the IE model. These findings suggest that the purine biosynthetic pathway intersects the coordination of virulence factor expression and in vivo persistence during VAN treatment, and may represent an avenue for novel antimicrobial development targeting MRSA.

Augmenting Neutrophil Extracellular Traps with Carbonized Polymer Dots: A Potential Treatment for Bacterial Sepsis.

Sepsis is a life-threatening condition that can progress to septic shock as the body's extreme response to pathogenesis damages its own vital organs. Staphylococcus aureus (S. aureus) accounts for 50% of nosocomial infections, which are clinically treated with antibiotics. However, methicillin-resistant strains (MRSA) have emerged and can withstand harsh antibiotic treatment. To address this problem, curcumin (CCM) is employed to prepare carbonized polymer dots (CPDs) through mild pyrolysis. Contrary to curcumin, the as-formed CCM-CPDs are highly biocompatible and soluble in aqueous solution. Most importantly, the CCM-CPDs induce the release of neutrophil extracellular traps (NETs) from the neutrophils, which entrap and eliminate microbes. In an MRSA-induced septic mouse model, it is observed that CCM-CPDs efficiently suppress bacterial colonization. Moreover, the intrinsic antioxidative, anti-inflammatory, and anticoagulation activities resulting from the preserved functional groups of the precursor molecule on the CCM-CPDs prevent progression to severe sepsis. As a result, infected mice treated with CCM-CPDs show a significant decrease in mortality even through oral administration. Histological staining indicates negligible organ damage in the MRSA-infected mice treated with CCM-CPDs. It is believed that the in vivo studies presented herein demonstrate that multifunctional therapeutic CPDs hold great potential against life-threatening infectious diseases.

Surgical Site Infections with MRSA in young Patients

Introduction: Surgical site infections (SSIs) pose a global health concern. While various pathogenic microorganisms can cause SSIs, a predominant causative agent is Staphylococcus aureus, particularly its methicillin-resistant strain (MRSA). MRSA, known for its resistance to multiple antibiotics, significantly complicates treatment options, leading to increased morbidity. In some cases, particularly among patients with pre-existing comorbidities, MRSA infections can prove fatal. Moreover, eradicating MRSA from hospital settings presents a formidable challenge.&#x0D; This study aims to report on two young, otherwise healthy patients who developed MRSA infections in their surgical wounds during hospitalization.&#x0D; Case Descriptions: A 22-year-old female patient developed an MRSA infection following an appendectomy and a 12-year-old male patient exhibited similar complications post-orchiopexy. In both cases, MRSA presence was confirmed through microbiological cultures a few days post-surgery. Repeated cultures indicated successful MRSA eradication after isolation and initiation of targeted antibiotic therapy based on antibiograms. Once their general health stabilized, the patients were discharged and continued outpatient antibiotic treatment for a prescribed duration.&#x0D; Conclusion: These cases emphasize that MRSA infections, typically associated with elderly patients or those with underlying health conditions, can also occur in younger, healthier individuals. Eradicating these infections remains a significant challenge for healthcare facilities encountering MRSA.&#x0D; Keywords: Staphylococcus aureus, Methicillin-resistant, young patients, Surgical site infections.

The effect of Locally Applied Bacillus safensis Strain 440-1 from Antarctic Soil on the Course of Experimental Wound Staphylococcal Infection

Relevance. Infections caused by methicillin-resistant strains of Staphylococcus aureus are an urgent problem of hospital epidemiology, and control measures involve the development of new antimicrobials. Probiotics based on bacterial strains isolated fro natural habitats are considered promising means of combating MRSA.Aims. To test the possibility of using the Bacillus safensis 440-1 strain isolated from Antarctic soil. as an antibacterial agent for the treatment of experimental staphylococcal infection.Purpose of the study – check the possibility of using the Bacillus safensis 440-1 strain, isolated from Antarctic soil, as a topical antibacterial agent for the treatment of experimental staphylococcal infection.Material and methods. The potential virulence of Bacillus safensis strain 440-1 was studied on a mouse peritonitis model, and its activity against the methicillin-resistant Staphylococcus aureus SA776 test strain was studied on a localized wound infection model.Results and discussion. Our study demonstrated the safety of the tested strain due intraperitoneal use. We found that the use of the studied strain reduces the staphylococci amount in wounds from the third day from the start of the study to the end of the observation period, without aggravating the course of the infection.Conclusion. Bacillus safensis strain is a promising potential probiotic and it can be used as a part of complex antiseptic or disinfectant after additional studies aimed at developing an optimal mode of its use.

Novel small-molecule compound YH7 inhibits the biofilm formation of Staphylococcus aureus in a sarX-dependent manner.

The emergence of antibiotic-resistant and biofilm-producing Staphylococcus aureus isolates presents major challenges for treating staphylococcal infections. Biofilm inhibition is an important anti-virulence strategy. In this study, a novel maleimide-diselenide hybrid compound (YH7) was synthesized and demonstrated remarkable antimicrobial activity against methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) in both planktonic cultures and biofilms. The minimum inhibitory concentration (MIC) of YH7 for S. aureus isolates was 16 µg/mL. Quantification of biofilms demonstrated that the sub-MIC (4 µg/mL) of YH7 significantly inhibits biofilm formation in both MSSA and MRSA. Confocal laser scanning microscopy analysis further confirmed the biofilm inhibitory potential of YH7. YH7 also significantly suppressed bacterial adherence to A549 cells. Moreover, YH7 treatment significantly inhibited S. aureus colonization in nasal tissue of mice. Preliminary mechanistic studies revealed that YH7 exerted potent biofilm-suppressing effects by inhibiting polysaccharide intercellular adhesin (PIA) synthesis, rather than suppressing bacterial autolysis. Real-time quantitative PCR data indicated that YH7 downregulated biofilm formation-related genes (clfA, fnbA, icaA, and icaD) and the global regulatory gene sarX, which promotes PIA synthesis. The sarX-dependent antibiofilm potential of YH7 was validated by constructing S. aureus NCTC8325 sarX knockout and complementation strains. Importantly, YH7 demonstrated a low potential to induce drug resistance in S. aureus and exhibited non-toxic to rabbit erythrocytes, A549, and BEAS-2B cells at antibacterial concentrations. In vivo toxicity assays conducted on Galleria mellonella further confirmed that YH7 is biocompatible. Overall, YH7 demonstrated potent antibiofilm activity supports its potential as an antimicrobial agent against S. aureus biofilm-related infections. IMPORTANCE Biofilm-associated infections, characterized by antibiotic resistance and persistence, present a formidable challenge in healthcare. Traditional antibacterial agents prove inadequate against biofilms. In this study, the novel compound YH7 demonstrates potent antibiofilm properties by impeding the adhesion and the polysaccharide intercellular adhesin production of Staphylococcus aureus. Notably, its exceptional efficacy against both methicillin-resistant and methicillin-susceptible strains highlights its broad applicability. This study highlights the potential of YH7 as a novel therapeutic agent to address the pressing issue of biofilm-driven infections.

Chemical composition, antimicrobial and antiproliferative activity of the essential oil from Ambrosia artemisiifolia L

ABSTRACT The aim of our study was to characterize the composition and certain bioactivities of the essential oil of Ambrosia artemisiifolia. Eighty organic compounds were identified in the essential oils obtained by hydrodistillation and microwave-assisted isolation. Germacrene D was the main component in both oils. The essential oil obtained by hydrodistillation exerted antibacterial activity against two S. aureus strains, with MIC values of 0.015% for the methicillin-susceptible strain and 0.25% for the methicillin-resistant strain. In the biofilm formation assay, a dose-dependent inhibition was observed in case of the K. pneumoniae ATCC 600,703. In the ethidium bromide accumulation assay, a dose-dependent inhibition activity was observed against the bacterial efflux pump of the Gram-negative bacteria E. coli ATCC 25,922. The essential oil displayed strong in vitro cytotoxicity against the multidrug-resistant (MDR) Colo 320 cancer cell line with an IC50 value of 0.0103%. The essential oil showed strong inhibition on the proliferation of the doxorubicin-sensitive Colo 205 cells (IC50 values of 0.054%) and in the case of MDR Colo 320 colonic adenocarcinoma cells (IC50 values of 0.008%). This is the first report of the cytotoxic and antiproliferative activities of the essential oil from these species.