Methicillin-resistant Staphylococcus Aureus Skin Research Articles

Three Common Skin Infections in a Student Athlete and a Subsequent Outbreak of Methicillin-resistant Staphylococcus aureus Skin Infections in a Single Gym: a Case Report

Individuals with frequent physical contact, such as wrestlers, are at an increased risk of developing infectious diseases, including bacterial, viral, and fungal infections. Herein, we report the case of a student wrestler who developed three common skin infections and a subsequent outbreak of methicillin-resistant Staphylococcus aureus (MRSA) skin infections in a single gym. A 14-year-old male presented with a 2-week history of an edematous, painful skin lesion on the left outer ear. He responded poorly to empirical antimicrobial therapy. Examination revealed multiple crusts and oozing on the left ear helix. A solitary, erythematous firm nodule was also observed on the left posterior neck. Bacterial culture confirmed MRSA resistance to clindamycin and tetracycline. Further assessment confirmed the diagnosis of herpes labialis and tinea faciei. Within 3 weeks, six additional cases of MRSA skin infections were reported, all linked to the same wrestling gym. Most patients were effectively treated with oral cephalosporins combined with topical fluoroquinolones and occlusive dressing.

Vancomycin and nisin-modified magnetic Fe3O4@SiO2 nanostructures coated with chitosan to enhance antibacterial efficiency against methicillin resistant Staphylococcus aureus (MRSA) infection in a murine superficial wound model

BackgroundThe objective of this research was to prepare some Fe3O4@SiO2@Chitosan (CS) magnetic nanocomposites coupled with nisin, and vancomycin to evaluate their antibacterial efficacy under both in vitro and in vivo against the methicillin-resistant Staphylococcus. aureus (MRSA).MethodsIn this survey, the Fe3O4@SiO2 magnetic nanoparticles (MNPs) were constructed as a core and covered the surface of MNPs via crosslinking CS by glutaraldehyde as a shell, then functionalized with vancomycin and nisin to enhance the inhibitory effects of nanoparticles (NPs). X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), field emission scanning electron microscope (FE-SEM), vibrating sample magnetometer (VSM), and dynamic light scattering (DLS) techniques were then used to describe the nanostructures.ResultsBased on the XRD, and FE-SEM findings, the average size of the modified magnetic nanomaterials were estimated to be around 22–35 nm, and 34–47 nm, respectively. The vancomycin was conjugated in three polymer-drug ratios; 1:1, 2:1 and 3:1, with the percentages of 45.52%, 35.68%, and 24.4%, respectively. The polymer/drug ratio of 1:1 exhibited the slowest release rate of vancomycin from the Fe3O4@SiO2@CS-VANCO nanocomposites during 24 h, which was selected to examine their antimicrobial effects under in vivo conditions. The nisin was grafted onto the nanocomposites at around 73.2–87.2%. All the compounds resulted in a marked reduction in the bacterial burden (P-value < 0.05).ConclusionThe vancomycin-functionalized nanocomposites exhibited to be more efficient in eradicating the bacterial cells both in vitro and in vivo. These findings introduce a novel bacteriocin–metallic nanocomposite that can suppress the normal bacterial function on demand for the treatment of MRSA skin infections.

Descriptive evaluation of patients receiving one-time intravenous vancomycin doses at a large academic medical center emergency department

BackgroundIntravenous (IV) vancomycin is commonly used to treat a variety of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). The practice of administering a single dose of IV vancomycin prior to emergency department (ED) discharge may be clinically ineffective and foster antimicrobial resistance. Furthermore, this practice introduces an unnecessary infection risk along with preventable adverse effects while potentially increasing ED length of stay (LOS). There is a paucity of literature identifying patient characteristics and objective findings in this patient population, which may foster future antimicrobial stewardship initiatives in the ED. MethodsThis was a single-center, retrospective, descriptive analysis of adult patients seen in the ED between January 2020 and January 2023 who received a single dose of IV vancomycin and were subsequently discharged from the ED without hospital admission. Information was collected on patient demographics and select comorbidities, vancomycin indication and dosing, ED LOS, initial vitals and labs, concomitant antibiotics administered, culture results, 30-day return ED visits and admissions, and antibiotics prescribed at ED discharge. ResultsA total of 295 patients met inclusion criteria. A total of 32.1% of patients met SIRS criteria. The most commonly selected order indication for IV vancomycin was “skin and skin structure infection” (41%). A total of 86.1% of patients received concomitant antibiotics in the ED and only 54.6% of patients were prescribed oral antibiotics at ED discharge. A total of 80% of patients had at least one culture obtained during the ED visit. In those who had at least one culture obtained, 78.4% of patients had negative cultures and 4.2% of patients had MRSA positive cultures, with MRSA skin cultures being the most common (3.1%). Return ED visits and admissions within 30 days were not statistically significantly different between patients who did and did not receive oral antibiotics at ED discharge. ConclusionsDespite a lack of clinical efficacy reported in prior literature and the potential risks, administration of a one-time dose of IV vancomycin prior to ED discharge is commonly encountered in clinical practice. There are opportunities for enhanced antimicrobial stewardship related to IV vancomycin use in the ED. Areas of future focus include the utilization of oral antimicrobials when clinically appropriate, particularly for skin and soft tissue infections, and clarification of antibiotic allergies.

Peptide Supramolecular Hydrogels with Sustained Release Ability for Combating Multidrug-Resistant Bacteria.

Chronic wound infection caused by multidrug-resistant bacteria is a major threat globally, leading to high mortality rates and a considerable economic burden. To address it, an innovative supramolecular nanofiber hydrogel (Hydrogel-RL) harboring antimicrobial peptides was developed based on the novel arginine end-tagging peptide (Pep 6) from our recent study, triggering cross-linking. In vitro results demonstrated that Hydrogel-RL can sustain the release of Pep 6 up to 120 h profiles, which is biocompatible and exhibits superior activity for methicillin-resistant Staphylococcus aureus (MRSA) biofilm inhibition and elimination. A single treatment of supramolecular Hydrogel-RL on an MRSA skin infection model revealed formidable antimicrobial activity and therapeutic effects in vivo. In the chronic wound infection model, Hydrogel-RL promoted mouse skin cell proliferation, reduced inflammation, accelerated re-epithelialization, and regulated muscle and collagen fiber formation, rapidly healing full-thickness skin wounds. To show its vehicle property for wound infection combined therapy, etamsylate, an antihemorrhagic drug, was loaded into the porous network of Hydrogel-RL, which demonstrated improved hemostatic activity. Collectively, Hydrogel-RL is a promising clinical candidate agent for functional supramolecular biomaterials designed for combating multidrug-resistant bacteria and rescuing stalled healing in chronic wound infections.

Prevalence and clinical characteristics of methicillin-resistant Staphylococcus aureus infections among dermatology inpatients: A 7-year retrospective study at a tertiary care center in southwest China.

Increased rates of methicillin-resistant Staphylococcus aureus (MRSA) antibiotic resistance and the associated morbidity have increased dermatologists' attention to skin and soft tissue MRSA infections. However, the clinical characterization of MRSA skin and soft tissue infections (SSTIs) in Southwest China is lacking, which precludes optimal prevention and treatment of these infections. This study was conducted to characterize the prevalence, clinical comorbidities and antibiotic susceptibility of MRSA isolates from SSTIs, including community-associated (CA) and healthcare-associated (HA) isolates. In the Dermatology Inpatient Department of the First Affiliated Hospital of Guangxi Medical University, a retrospective study was conducted on data, including patient demographics and clinical information, from culture-confirmed S. aureus isolated from skin and soft tissue between January 1, 2015, and December 31, 2021. Isolate susceptibility to 13 antibiotics was determined using the Vitek 2 system. From among 864 S. aureus strains, we identified 283 MRSA (32.75%) isolates comprising 203 CA-MRSA and 80 HA-MRSA isolates. The average rate of CA-MRSA isolation for MRSA SSTIs was 71.73%. The HA-MRSA isolation rate for MRSA SSTIs increased significantly. HA-MRSA-infected patients were older. The most common dermatological presentation of CA-MRSA infection was staphylococcal scalded skin syndrome, while the comorbidity severe drug eruption was significantly associated with HA-MRSA infection. One CA-MRSA strain was resistant to linezolid, and one HA-MRSA strain had an intermediate phenotype for vancomycin; both strains had low sensitivity to clindamycin and erythromycin (3.70%~19.40%). However, HA-MRSA isolates were more susceptible to trimethoprim/sulfamethoxazole. CA-MRSA is a predominant pathogen causing SSTIs, and HA-MRSA infection incidence is increasing gradually. Both strains showed increasing antibiotic resistance. Our data on MRSA susceptibility may guide dermatologist antibiotic treatment decisions. Dermatologists should consider these identified comorbidities of MRSA SSTIs when patients are admitted and initiate early prevention and treatment of MRSA.

Antimicrobial photodynamic therapy with Ligularia fischeri against methicillin-resistant Staphylococcus aureus infection in Caenorhabditis elegans model

The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection threatens the effectiveness of current clinical settings. Antimicrobial photodynamic therapy (APDT) is a promising alternative to antibiotics for treating infections due to its low resistance. This study aimed to evaluate the antibacterial properties of APDT with L. fischeri extract (LFE) against MRSA and various skin and oral pathogens in vitro and its photopharmaceutical actions in Caenorhabditis elegans. The antimicrobial activities of APDT with LFE against pathogens were evaluated using plate counting method. The chemical profile was characterized using high-performance liquid chromatography and spectrophotometry. The growth rate assay, lifespan assay, and bacterial attachment on worms were performed to assess the therapeutics effects in C. elegans. The swab method was used for the detection of pathogens on the micropig skin surface. The APDT treatment with L. fischeri extract (LFE, 20 µg/mL) and red light (intensity of 120 W/m2) reduced 4.3–4.9 log (colony forming unit/mL) of Staphylococcus aureus, MRSA, Cutibacterium acnes, Streptococcus mutans; and 2.4 log (CFU/mL) of Candida albicans. Chemical analysis revealed that LFE enriched three active photosensitizers. APDT reduced bacterial populations on worms, recovered growth retardation, and improved lifespan in MRSA-infected C. elegans without causing severe side effects. The surface eradication of MRSA after exposure to LFE with red light was demonstrated on micropig skin. These findings highlight the significance of L. fischeri as a natural resource for the safe phototreatment of MRSA infection in the biomedical and cosmeceutical industries.

Streptomyces spp. Isolated from Rosa davurica Rhizome for Potential Cosmetic Application

Streptomyces species are widely studied and used in different fields, including antibiotics and pesticides, and are spread in several places as soil-derived microorganisms. However, research on anti-aging, including antioxidants obtained from Streptomyces, has not been performed as much. Skin aging due to bacterial infection, especially methicillin-resistant Staphylococcus aureus (MRSA), is challenging to recover, so it is essential to prevent aging by preventing or inhibiting infection. Therefore, this study was conducted to isolate Streptomyces species from Rosa davurica rhizome soil and to determine the effect of the ethyl acetate extract of the isolated strain Streptomyces chattanoogensis THA-663 (THA-663S) on the inhibition of MRSA and UVB-irradiated human skin keratinocytes, to determine whether it could be a treatment for skin aging. The MRSA inhibition and antioxidant activities were evaluated using disc diffusion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2’-azino-bis-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS), and a reactive oxygen species (ROS) assay. The expression of aging-related markers, including mitogen-activated protein kinases/activator protein 1 (MAPK)/AP-1) and transforming growth factor-β/suppressor of mothers against decapentaplegic (TGF-β/Smad) was assessed using Western blotting. The antibacterial effect on four MRSA strains, CCARM 0204, CCARM 0205, CCARM 3855, and CCARM 3089, showed that THA-663S could greatly inhibit MRSA growth. Moreover, the findings showed that THA-663S is efficient in scavenging free radicals and dose-dependently reducing ROS generation. Furthermore, THA-663S notably reduced UVB-induced matrix metalloproteinase-1 (MMP-1) expression by inhibiting the MAPK/AP-1 signaling pathways and blocking extracellular matrix (ECM) degradation in UVB-irradiated HaCaT cells. Additionally, THA-663S improved and enhanced transforming growth factor-beta (TGF-β) signaling activation to promote procollagen type I synthesis, relieving UVB-induced skin cell damage. In conclusion, THA-663S has a high potential to protect skin cells from aging, and, simultaneously, it can prevent or treat aging caused by infection due to pathogen inhibition.

Validation of a Clinical Decision Rule for Ultrasound Identification of MRSA Skin Abscesses in Children.

The aim of this study was to validate an adult-derived clinical decision rule for ultrasound identification of methicillin-resistant Staphylococcus aureus (MRSA) skin abscesses in a pediatric cohort. We conducted a retrospective study of skin and soft tissue infections in patients <21 years presenting to the emergency department who had radiology performed ultrasounds completed and wound cultures obtained. Ultrasound scans were reviewed for edge definition, volume, and shape by 2 pediatric emergency physicians with expertise in point-of-care ultrasound, with approximately 25% of scans reviewed by both experts to evaluate interrater reliability. A third, blinded expert weighed in for discrepancies before analysis. Test performance characteristics were calculated for the clinical decision rule in children. Two hundred nine patients were enrolled, with mean age of 9.8 (±6.7) years; 87 (42%) were male. Sixty-nine (33%) patients had a wound culture positive for MRSA. The clinical decision rule had a sensitivity of 86% (95% confidence interval [CI], 75%-93%), specificity of 32% (95% CI, 25%-41%), positive predictive value of 38% (95% CI, 35%-42%), negative predictive value of 82% (95% CI, 71%-89%), positive likelihood ratio of 1.26 (95% CI, 1.08-1.46), negative likelihood ratio of 0.45 (95% CI, 0.24-0.84), and an odds ratio of 2.8 (95% CI, 1.31-5.97). This clinical decision rule for ultrasound identification of MRSA abscesses had moderately high sensitivity and negative predictive value in pediatric patients, with similar sensitivity compared with the original adult validation group. Ultrasound may help identify MRSA abscesses, allowing for improved antibiotic choices and outcomes for children with MRSA abscesses.

A PEGylated Nanostructured Lipid Carrier for Enhanced Oral Delivery of Antibiotics.

Antimicrobial resistance is a major concern for public health throughout the world that severely restricts available treatments. In this context, methicillin-resistant Staphylococcus aureus (MRSA) is responsible for a high percentage of S. aureus infections and mortality. To overcome this challenge, nanoparticles are appropriate tools as drug carriers to improve the therapeutic efficacy and decrease the toxicity of drugs. In this study, a polyethylene glycol (PEG)ylated nanostructured lipid carrier (PEG-NLC) was synthesized to improve the oral delivery of trimethoprim/sulfamethoxazole (TMP/SMZ) for the treatment of MRSA skin infection in vitro and in vivo. The nanoformulation (PEG-TMP/SMZ-NLC) was synthesized with size and drug encapsulation efficiencies of 187 ± 9 nm and 93.3%, respectively, which could release the drugs in a controlled manner at intestinal pH. PEG-TMP/SMZ-NLC was found efficient in decreasing the drugs’ toxicity by 2.4-fold in vitro. In addition, the intestinal permeability of TMP/SMZ was enhanced by 54%, and the antibacterial effects of the drugs were enhanced by 8-fold in vitro. The results of the stability study demonstrated that PEG-TMP/SMZ-NLC was stable for three months. In addition, the results demonstrated that PEG-TMP/SMZ-NLC after oral administration could decrease the drugs’ side-effects such as renal and hepatic toxicity by ~5-fold in MRSA skin infection in Balb/c mice, while it could improve the antibacterial effects of TMP/SMZ by 3 orders of magnitude. Overall, the results of this study suggest that the application of PEGylated NLC nanoparticles is a promising approach to improving the oral delivery of TMP/SMZ for the treatment of MRSA skin infection.

A Perfect Pair: Stabilized Black Phosphorous Nanosheets Engineering with Antimicrobial Peptides for Robust Multidrug Resistant Bacteria Eradication.

Black phosphorus (BP) nanosheets emerged as promising 2D nanomaterial that have been applied to eradicate antibiotic-resistant bacteria. However, their applications are limited by intrinsic ambient instability. Here, the ε-poly-l-lysine (ε-PL)-engineered BP nanosheets are constructed via simple electrostatic interaction to cater the demand for passivating BP with amplified antibacterial activity. The dual drug-delivery complex named BP@ε-PL can closely anchor onto the surface of bacteria, leading to membrane disintegration. Subsequently, in situ hyperthermia generated by BP under near-infrared (NIR) irradiation can precisely eradicate pathogenic bacteria. In vitro antibacterial studies verify the rapid disinfection ability of BP@ε-PL against Methicillin-resistant Staphylococcus aureus (MRSA) within 15min. Moreover, ε-PL can serve as an effective protector to avoid chemical degradation of bare BP. The in vivo antibacterial study shows that a 99.4% antibacterial rate in a MRSA skin infection model is achieved, which is accompanied by negligible toxicity. In conclusion, this work not merely provides a new conjecture for protecting the BP, but also opens a novel window for synergistic antibiotic-resistant bacteria therapy based on antimicrobial peptides and 2D photothermal nanomaterial.

Investigational agents for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia: progress in clinical trials

ABSTRACT Introduction Bacteremia caused by Staphylococcus aureus is common. Cases caused by methicillin-resistant S. aureus (MRSA) are particularly formidable and often lethal. The mortality associated with MRSA bacteremia has not significantly decreased over the past couple of decades and concerns regarding efficacy and toxicity of standard therapy highlight the need for novel agents and new therapeutic approaches. Areas covered This paper explores clinical trials investigating novel therapeutic approaches to S. aureus bacteremia. There is a special focus on MRSA bacteremia. Monotherapy and combination therapies and novel antimicrobials and adjunctive therapies that are only recently being established for therapeutic use are discussed. Expert opinion The unfavorable safety profile of combination antimicrobial therapy in clinical trials has outweighed its benefits. Therefore, future investigation should focus on optimizing duration and de-escalation protocols. Antibody and bacteriophage lysin-based candidates have mostly been limited to safety trials, but progress with these agents is demonstrated through a lysin-based agent receiving a phase III trial. Antibiotics indicated for use in treating MRSA skin infections see continued investigation as treatments for MRSA bacteremia despite the difficulty of completing trials in this patient population. Promising agents include dalbavancin, ceftobiprole, ceftaroline, and exebacase.

Chemerin-Derived Peptide Val66-Pro85 Is Effective in Limiting Methicillin-Resistant S. aureus Skin Infection.

Chemerin-derived peptide Val66-Pro85 (p4) restricts the growth of a variety of skin-associated bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). To better understand the antimicrobial potential of chemerin peptide, we compared p4 activity against MRSA in vitro to cathelicidin LL-37, one of the key endogenous peptides implicated in controlling the growth of S. aureus. The efficacy of p4 was also validated in relevant experimental models of skin pathology, such as topical skin infection with community-acquired MRSA, and in the context of skin inflammatory diseases commonly associated with colonization with S. aureus, such as atopic dermatitis (AD). We showed that p4 collaborates additively with LL-37 in inhibiting the growth of S. aureus, including MRSA, and that p4 was effective in vivo in reducing MRSA burden. p4 was also effective in reducing levels of skin-infiltrating leukocytes in S. aureus-infected AD-like skin. Taken together, our data suggest that p4 is effective in limiting S. aureus and, in particular, MRSA skin infection.

Open study of photodynamic therapy for skin ulcers infected with MRSA and Pseudomonas aeruginosa

Background: Drug-resistant bacterial infections are a global problem. Novel treatment methods that simultaneously control infection and promote wound healing without leading to new resistant bacteria are needed. Photodynamic therapy (PDT) is a useful antibiotic-free treatment approach. Our previous studies have shown that PDT for skin ulcers infected with methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA) can achieve infection control and promoting wound healing in vitro and in vivo murine model. Here, we investigated the safety and effectiveness of PDT with 5-aminolevulinic acid (ALA-PDT) for human skin ulcers infected with MRSA and PA.Methods: ALA-PDT with macrogol ointment containing 0.5% ALA-HCl and 0.005% EDTA-2Na (wavelength 410 nm, 10 J/cm2) was performed on consecutive days in patients aged ≥20 years who had skin ulcers infected with MRSA and PA.Results: Six of our seven patients showed a clear tendency for ulcer area reduction to ≤60% of that measured at baseline. ALA-PDT was judged to be completely safe in all patients; only one patient had an increase in bacterial count.Conclusions: ALA-PDT is safe and effective for MRSA and PA infected skin ulcers to control and heal wound.

Castaneroxy A keeps MRSA at bay

Extracts made from the leaves of the European chestnut tree Castanea sativa have been used in traditional medicine for over 100 years. Researchers have shown that these extracts can prevent methicillin-resistant Staphylococcus aureus (MRSA) from producing a variety of dangerous toxins and can halt skin infections in mice, but they didn’t know which molecule or molecules were responsible for keeping the bacterium at bay until now. Researchers led by Emory University’s Cassandra L. Quave have identified a new compound, which they named castaneroxy A, as the key antibacterial compound. They also found that, like the leaf extract, castaneroxy A blocks MRSA skin infections from progressing in mice ( Front. Pharmacol. 2021, DOI: 10.3389/fphar.2021.640179 ). While all antibiotic drugs approved by the US Food and Drug Administration work by killing bacteria or preventing bacterial growth, Quave and colleagues found that castaneroxy A has a different mechanism: it disrupts quorum sensing —chemical

Bioguided Isolation of Antibiofilm and Antibacterial Pregnane Glycosides from Caralluma quadrangula: Disarming Multidrug-Resistant Pathogens.

Methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Acinetobacter baumannii (MDRAB) present a serious challenge because of their capability to cause biofilm resistance to commonly used antibiotics producing chronic infections and hindering the process of wound healing. In the current study, we investigated the antibacterial activity of Caralluma quadrangula extracts (MeOH, and its fractions CH2Cl2 and n-butanol) against multidrug-resistant MRSA USA300 and A. baumannii AB5057. In vitro, the MeOH extract and both fractions of C. quadrangula significantly inhibited biofilm formation and disrupted previously established biofilm by MRSA and MDRAB at all the tested concentrations (0.625, 0.313, and 0.156 mg/mL). In vivo, C. quadrangula extracts successfully decreased bacterial loads in MRSA-infected skin lesions in mice. Four pregnane glycosides and one flavone glycoside were isolated from the bioactive n-butanol fraction. The isolated compounds (Rus A–E) were tested for their biofilm inhibition and biofilm detachment activities. The results revealed that Rus C was the most active compound (IC50 = 0.139 mmole), while Rus E was the least active (IC50 = 0.818 mmole). These results support the potential use of C. quadrangula extracts or their isolated compounds for hindering the biofilm attachment and the virulence of MRSA and MDRAB and their application as a topical antimicrobial preparation for MRSA skin infections.

In Vitro and In Vivo Activity of 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] Mutilin against Methicillin-Resistant Staphylococcus aureus.

Staphylococcus aureus (S. aureus) is a major human pathogen that requires new antibiotics with unique mechanism. A new pleuromutilin derivative, 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] mutilin (DPTM), has been synthesized and proved as a potent antibacterial agent using in vitro and in vivo assays. In the present study, DPTM was further in vitro evaluated against methicillin-resistant Staphylococcus aureus (MRSA) isolated from dairy farms and outperformed tiamulin fumarate, a pleuromutilin drug used for veterinary. Moreover, a murine skin wound model caused by MRSA infection was established, and the healing effect of DPTM was investigated. The results showed that DPTM could promote the healing of MRSA skin infection, reduce the bacterial burden of infected skin MRSA and decrease the secretion of IL-6 and TNF-α inflammatory cytokines in plasma. These results provided the basis for further in-depth drug targeted studies of DPTM as a novel antibacterial agent.

Topical Application of Ozonated Oils for the Treatment of MRSA Skin Infection in an Animal Model of Infected Ulcer.

Simple SummaryMethicillin-resistant Staphylococcus aureus is often found in skin lesions infected in particular in diabetic foot ulcers, in which the prevalence can reach 40%. Clinical methicillin-resistant Staphylococcus aureus is generally resistant to most classes of antibiotics and therefore it is necessary to develop new antimicrobial agents. Ozone has a recognized bactericidal activity and has been widely used as a clinical therapeutic agent for chronic wounds, such as ulcers and other injuries, due to its ability to heal wounds. This is a preliminary study that reports the effectiveness of ozonated oils on the eradication of skin infection in vivo. The study provides further insights into the antibacterial effect of ozone in infected skin ulcers in diabetic rats and also, the potential wound healing effect of ozonated oils. Furthermore, this is the first study investigating the efficacy of ozone in the eradication of diabetic foot ulcers infected by methicillin-resistant Staphylococcus aureus. Our results indicate that topical application of ozonated oils infected skin in rats have significant antimicrobial activity as well as wound healing capacity. Achieving the healing of infected diabetic foot wounds has become a challenge and ozonated oils may be used to treat these infections.Diabetic foot ulcers are a common cause of morbidity in diabetic patients. One of the main pathogens found in these ulcers is methicillin-resistant Staphylococcus aureus (MRSA). MRSA often carries resistance to several classes of antibiotics and their infections are becoming harder to treat. Therefore, new alternatives are urgently needed. Thus, this study aimed to investigate the capacity of topical ozonated oil application on the treatment of early-stage skin infected with MRSA in an animal model. Ozonated oil was prepared from a mixture of oils subjected to a gas stream of O2/O3 mixture. Sixteen Wistar rats were inoculated by an intradermic injection of MRSA suspension, producing an abscess lesion. After 3 days, the skin epidermis was removed to open the wound. Group 1 received an application of oil mixture without ozone treatment and Group 2 received an application of ozonated oil. After the treatment period, skin was collected, colony-forming units (CFU) of bacteria were quantified and the histological analysis of the skin was carried out. Skin samples from the control 1 and 2 had a bacterial load was of 1.1 × 105 and 5.7 × 103 CFU/mL, respectively. Group 2 showed better wound healing from mild to moderate epidermal regeneration. Topical application of ozonated vegetable oil in MRSA-infected skin in rats showed a small reduction of the bacterial load and better wound healing.

SOCS-1 inhibition of type I interferon restrains Staphylococcus aureus skin host defense.

The skin innate immune response to methicillin-resistant Staphylococcus aureus (MRSA) culminates in the formation of an abscess to prevent bacterial spread and tissue damage. Pathogen recognition receptors (PRRs) dictate the balance between microbial control and injury. Therefore, intracellular brakes are of fundamental importance to tune the appropriate host defense while inducing resolution. The intracellular inhibitor suppressor of cytokine signaling 1 (SOCS-1), a known JAK/STAT inhibitor, prevents the expression and actions of PRR adaptors and downstream effectors. Whether SOCS-1 is a molecular component of skin host defense remains to be determined. We hypothesized that SOCS-1 decreases type I interferon production and IFNAR-mediated antimicrobial effector functions, limiting the inflammatory response during skin infection. Our data show that MRSA skin infection enhances SOCS-1 expression, and both SOCS-1 inhibitor peptide-treated and myeloid-specific SOCS-1 deficient mice display decreased lesion size, bacterial loads, and increased abscess thickness when compared to wild-type mice treated with the scrambled peptide control. SOCS-1 deletion/inhibition increases phagocytosis and bacterial killing, dependent on nitric oxide release. SOCS-1 inhibition also increases the levels of type I and type II interferon levels in vivo. IFNAR deletion and antibody blockage abolished the beneficial effects of SOCS-1 inhibition in vivo. Notably, we unveiled that hyperglycemia triggers aberrant SOCS-1 expression that correlates with decreased overall IFN signatures in the infected skin. SOCS-1 inhibition restores skin host defense in the highly susceptible hyperglycemic mice. Overall, these data demonstrate a role for SOCS-1-mediated type I interferon actions in host defense and inflammation during MRSA skin infection.

Successful Development of Bacteriocins into Therapeutic Formulation for Treatment of MRSA Skin Infection in a Murine Model.

The emergence of antibiotic-resistant pathogens has caused a serious worldwide problem in infection treatment in recent years. One of the pathogens is methicillin-resistant Staphylococcus aureus (MRSA), which is a major cause of skin and soft tissue infections. Alternative strategies and novel sources of antimicrobials to solve antibiotic resistance problems are urgently needed. In this study, we explored the potential of two broad-spectrum bacteriocins, garvicin KS and micrococcin P1, in skin infection treatments. The two bacteriocins acted synergistically with each other and with penicillin G in killing MRSA in vitro The MICs of the antimicrobials in the three-component mixture were 40 ng/ml for micrococcin P1 and 2 μg/ml for garvicin KS and penicillin G, which were 62, 16, and at least 1,250 times lower than their MICs when assessed individually. To assess its therapeutic potential further, we challenged the three-component formulation in a murine skin infection model with the multidrug-resistant luciferase-tagged MRSA Xen31, a strain derived from the clinical isolate S. aureus ATCC 33591. Using the tagged-luciferase activity as a reporter for the presence of Xen31 in wounds, we demonstrated that the three-component formulation was efficient in eradicating the pathogen from treated wounds. Furthermore, compared to Fucidin cream, which is an antibiotic commonly used in skin infection treatments, our formulation was also superior in terms of preventing resistance development.

Electrospun vancomycin-loaded nanofibers for management of methicillin-resistant Staphylococcus aureus-induced skin infections.

Skin damage exposes the underlying layers to bacterial invasion, leading to skin and soft tissue infections. Several pathogens have developed resistance against conventional topical antimicrobial treatments and rendered them less effective. Recently, several nanomedical strategies have emerged as a potential approach to improve therapeutic outcomes of treating bacterial skin infections. In the current study, nanofibers were utilized for topical delivery of the antimicrobial drug vancomycin and evaluated as a promising tool for treatment of topical skin infections. Vancomycin-loaded nanofibers were prepared via electrospinning technique, and vancomycin-loaded nanofibers of the optimal composition exhibited nanosized uniform smooth fibers (ca. 200nm diameter), high drug entrapment efficiency and sustained drug release patterns over 48h. In vitro cytotoxicity assays, using several cell lines, revealed the biocompatibility of the drug-loaded nanofibers. In vitro antibacterial studies showed sustained antibacterial activity of the vancomycin-loaded nanofibers against methicillin-resistant Staphylococcus aureus (MRSA), in comparison to the free drug. The nanofibers were then tested in animal model of superficial MRSA skin infection and demonstrated a superior antibacterial efficiency, as compared to animals treated with the free vancomycin solution. Hence, nanofibers might provide an efficient nanodevice to overcome MRSA-induced skin infections and a promising topical delivery vehicle for antimicrobial drugs.