Methicillin-resistant Staphylococcus Aureus Skin Infections 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.

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.

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.

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.

Antibiotic Susceptibility Pattern and Associated Factors of Methicillin-Resistant Staphylococcus aureus among Dermatological Patients at the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia: a Prospective Cross-Sectional Study.

Determination of the distribution pattern and associated factors of skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA) is a fundamental step to set up an effective control program to improve the health status. The purpose of this study was to assess the antibiotic susceptibility pattern and associated factors of MRSA among dermatological patients. In this hospital-based, prospective, cross-sectional study, 189 pus and skin swabs were collected from dermatological patients through a convenient sampling method in 2019. A structured questionnaire was employed for data collection of associated factors. Pus and skin swabs were collected using a sterile cotton swab and needle aspiration, then inoculated on mannitol salt agar. We followed a standard bacteriological procedure for identification of MRSA. Logistic regression models at a 95% confidence interval and p-value < 0.05 was considered for significance. A total of 127/189 (67.2%) of Staphylococcus aureus isolates were recovered and 80/127 (63.0%) were MRSA. Over 97% of Staphylococcus aureus isolates showed resistance to penicillin. MRSA was sensitive to gentamicin (78.75%), ciprofloxacin (83.75%), and clindamycin (86.25%). Frequency of washing body, method of hand washing, and recent hospitalization had a significant association with MRSA skin infection. The study revealed a high prevalence of MRSA among dermatological patients. Staphylococcus aureus showed a very high degree of resistance to different antimicrobials and most of Staphylococcus aureus isolates also showed multidrug-resistance patterns.

PLGA microsphere-based composite hydrogel for dual delivery of ciprofloxacin and ginsenoside Rh2 to treat Staphylococcus aureus-induced skin infections

When antibiotic-resistant pathogenic bacteria pose a high threat to human health, bacterial multidrug efflux pumps become major contributors to the high-level antibiotic resistance in most microorganisms. Since traditional antibiotics are still indispensable currently, we report a dual drug delivery system to maximize the antibacterial efficacy of antibiotics by inhibiting efflux pumps in bacteria before their exposure to antibiotics. In this research, a microsphere/hydrogel composite was constructed from ciprofloxacin (Cip)-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres and ginsenoside Rh2 (G-Rh2) dispersed thermo-sensitive hydrogel to treat skin infections. In vitro drug release studies indicated that while G-Rh2 in hydrogel presented a faster and short-term release manner to rapidly inhibit the NorA efflux pumps, Cip showed a sustained and long-term release behavior to provide a local high concentration gradient for facilitating drug percutaneous penetration. The combination of Cip and G-Rh2 demonstrated a high degree of synergism against both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), hence significantly improving their in vitro antibacterial activity and efficiency. Moreover, the antibacterial performance of the microsphere/hydrogel composite with a sequential release profile is superior to that of other formulations in mouse model of MRSA skin infections, indicating its great potential to treat antibiotic-resistant skin infections.

The bactericidal effect of liposomal vancomycin as a topical combating system against Methicillin-resistant Staphylococcus aureus skin wound infection in mice.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common causes of skin infections and treatment is difficult due to its resistance to the most of antibiotics. Although vancomycin is often considered as an antibacterial agent of choice for the treatment of MRSA, its use is limited because of the high side effects. One solution is using liposomal formulation for local drug delivery. The aim of this study was to determine in vitro and in vivo efficacies of liposomal vancomycin as topical use. Methods: To prepare liposomal vancomycin, the ammonium sulfate gradient using remote loading and freeze-thaw methods was applied. Then, synthesized nanoliposomes were evaluated in terms of particle size, morphology, stability, and encapsulation efficiency. Minimum inhibitory concentration (MIC) of synthesized nanoliposome against MRSA was detected. The cytotoxicity of synthesized nanoliposome was evaluated using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Finally, the topical antibacterial activity of each formulation was tested against MRSA-infected skin wound model in mice. Results: High encapsulation efficiency was achieved for all synthesized nanoliposomes. The results of in vitro and in vivo showed that liposomal vancomycin was more effective than free vancomycin. Also, synthesized nanoliposome showed no cytotoxicity on human epidermoid cell line. Conclusion: The results showed that synthesized nanoliposome could be applied as a great topical antimicrobial construct for treatment of MRSA skin infections.

Homelessness, Personal Hygiene, and MRSA Nasal Colonization among Persons Who Inject Drugs.

Methicillin-resistant Staphylococcus aureus (MRSA) infection is a leading cause of hospitalization and medical visits among individuals experiencing homelessness and also among persons who inject drugs (PWID), populations with significant overlap in urban centers in the USA. While injection drug use is a risk factor for MRSA skin infections, MRSA is also known to transmit easily in crowded, public locations in which individuals have reduced personal hygiene. Individuals in urban centers who experience homelessness or drug addiction may spend significant amounts of time in environments where MRSA can be easily transmitted, and may also experience reduced access to facilities to maintain personal hygiene. We assessed the relationship between homelessness, personal hygiene, and MRSA nasal colonization, a proxy for MRSA infection risk, in a study of PWID in Boston, MA (n = 78). Sleeping in a homeless shelter for at least one night in the last 3months was significantly associated with MRSA nasal colonization (OR 3.0; p = 0.02; 95% CI 1.2, 7.6). Sleeping at more than one place during the last week (considered a metric of elevated housing instability) was also associated with a threefold increase in odds of MRSA nasal colonization (OR 3.1; p = 0.01; 95% CI 1.3, 7.6). MRSA nasal colonization was strongly associated with use of public showers (OR 13.7; p = 0.02; 95% CI 1.4, 132.8), although few people in this study (4 of 78) reported using these public facilities. Sharing bedding with other people was also associated with increased risk of MRSA colonization (OR 2.2; p = 0.05; 95% CI 1.0-4.7). No associations between hand hygiene, frequency of bathing or clothes laundering, or street sleeping were observed. Use of public facilities supporting persons experiencing homelessness and housing instability, including shelters and public showers, is associated with an increased risk of MRSA nasal colonization in this study. Personal hygiene behaviors appear less associated with MRSA nasal colonization. Environmental assessments of MRSA contamination in homeless shelters and public sanitation facilities are warranted so as to inform appropriate intervention activities.

Antibacterial Amino Acid-Based Poly(ionic liquid) Membranes: Effects of Chirality, Chemical Bonding Type, and Application for MRSA Skin Infections.

Bacteria induced infection remains a serious medical hazard to humans. Antibacterial polymeric materials, which can kill or inhibit bacteria by disrupting cell membranes, inhibiting certain enzymes, or interfering with the transcription or synthesis of DNA or RNA, have been applied to reduce or inhibit microbial drug resistance. Herein, amino acid-based ionic liquids (ILs) and poly(ionic liquid) (PIL) membranes were synthesized and used as antibacterial materials to treat skin wounds infected by methicillin-resistant Staphylococcus aureus (MRSA). The effects of chirality (D- orL-enantiomers) and chemical bonding (ionic or covalent) of the amino acid groups attached to the IL (or PIL) on antibacterial properties were investigated. Both the ILs and PIL membranes containingD-enantiomeric amino acid groups exhibited higher antibacterial activities compared with those containingL-enantiomeric amino acids. In addition, the ionically-bonded PIL membranes showed higher antibacterial activities than the corresponding covalently-bonded polymeric membranes. These results indicate that both the chirality and chemical bonding type of amino acid groups affect the antimicrobial activity of the PIL membranes. Additionally, the amino acid-based PIL membranes accelerated the wound-healing process, alleviated local tissue inflammation, and reduced the influence of bacteria on vital organs (liver and spleen) in MRSA-infected mouse models, demonstrating the potential applications for antimicrobial wound dressing.