Methicillin-resistant Staphylococcus Aureus Skin Infections Research Articles

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.

Natural Flavones from Morus alba against Methicillin-Resistant Staphylococcus aureus via Targeting the Proton Motive Force and Membrane Permeability.

The emergence and rapid spread of methicillin-resistant Staphylococcus aureus (MRSA) critically requires alternative therapeutic options. New antibacterial drugs and strategies are urgently needed to combat MRSA-associated infections. Here, we investigated the antibacterial activity of flavones from Morus alba and the potential mode of action against MRSA. Kuwanon G, kuwanon H, mulberrin, and morusin displayed high efficiency in killing diverse MRSA isolates. On the basis of structure-activity analysis, the cyclohexene-phenyl ketones and isopentenyl groups were critical to increase the membrane permeability and to dissipate the proton motive force. Meanwhile, mechanistic studies further showed that kuwanon G displayed rapid bactericidal activity in vitrowith difficulty in developing drug resistance. Kuwanon G targeted phosphatidylglycerol and cardiolipin in the cytoplasmic membrane through the formation of hydrogen bonds and electrostatic interactions. Additionally, kuwanon G promoted wound healing in a mouse model of MRSA skin infection. In summary, these results indicate that flavones are promising lead compounds to treat MRSA-associated infections through disrupting the proton motive force and membrane permeability.

The bactericidal effect of lysostaphin coupled with liposomal vancomycin as a dual combating system applied directly on methicillin-resistant Staphylococcus aureus infected skin wounds in mice.

Background and aimMethicillin-resistant Staphylococcus aureus (MRSA) is one of the most common causes of surgical infection, and its resistance to numerous conventional antibiotics makes treatment difficult. Although vancomycin is often an effective agent for the initial therapy of MRSA, clinical failure sometimes occurs. Therefore, there is an urgent need to develop better therapies. Here, we prepared some vancomycin-loaded nanoliposomes coupled with anti-staphylococcal protein (lysostaphin) and evaluated their in vitro and in vivo efficacy as a topical MRSA therapy.MethodsVancomycin was encapsulated in liposomes, and the coupling of lysostaphin with the surface of liposomes was carried out through cyanuric functional groups. The bactericidal efficacies and a full characterization were evaluated. To define different nanoliposomal–bacterium interactions and their bactericidal effect, flow cytometry was employed. Finally, in vivo, the topical antibacterial activity of each formulation was measured against surgical wound MRSA infection in a mouse model.ResultsHigh encapsulation and conjugation efficiency were achieved for all formulations. All the formulations showed a significant reduction in bacterial counts (p<0.05). The targeted liposomes more effectively suppress bacterial infection in vitro and in vivo relative to equivalent doses of untargeted vancomycin liposome. The flow cytometry results confirmed liposome–bacterium interactions, which increased during the incubation time. The maximum binding rate and the bactericidal effect were significantly higher in targeted liposomes (p<0.05) compared with control liposomes.ConclusionOur data suggest a novel nano-vehicle (lysostaphin-conjugated coupled liposomal vancomycin) which could be used as a great topical antimicrobial construct for treatment of MRSA skin infections.

An aryl isonitrile compound with an improved physicochemical profile that is effective in two mouse models of multidrug-resistant Staphylococcus aureus infection.

The aim of this study was to investigate the antibacterial activity of a synthetic aryl isonitrile compound (35) that was developed as part of a compound library to identify new antibacterial agents effective against methicillin-resistant Staphylococcus aureus (MRSA). Compound 35 was evaluated against MRSA isolates by the broth microdilution assay and for toxicity to mammalian keratinocytes using the MTS assay. A multistep resistance selection assay was conducted to investigate MRSA resistance development to 35. A Caco-2 bidirectional permeability assay was employed to evaluate the ability of 35 to permeate across the gastrointestinal tract, and compound 35 was incubated with human liver microsomes to determine susceptibility to hepatic metabolism. Finally, compound 35 was evaluated in an uncomplicated MRSA skin infection mouse model and an MRSA neutropenic thigh infection mouse model. Compound 35 inhibited the growth of MRSA clinical isolates at 2-4μM and was non-toxic to human keratinocytes. No resistance formation was observed with MRSA against compound 35 after 10 serial passages. In a murine skin wound model, compound 35 significantly reduced the burden of MRSA, similar to the antibiotic fusidic acid. Compound 35 exhibited a marked improvement both in permeability and stability to hepatic metabolism (half-life >11h) relative to the first-generation lead compound. In a neutropenic thigh infection mouse model, compound 35 successfully reduced the burden of MRSA in immunocompromised mice. In summary, compound 35 was identified as a new lead aryl isonitrile compound that warrants further investigation as a novel antibacterial agent.

Increase in the prevalence of Panton–Valentine leukocidin and clonal shift in community-onset methicillin-resistant Staphylococcus aureus causing skin and soft-tissue infections in the Rhine-Neckar Region, Germany, 2012–2016

Methicillin-resistant Staphylococcus aureus (MRSA) remains a major challenge for patient care. Community-associated (CA)-MRSA often have a fitness and virulence advantage compared with their nosocomial counterparts. Increased mobility, travel activities and migration accelerate the intercontinental spread of virulent CA-MRSA strains. Outpatient clinics are the most important route of entry for CA-MRSA into hospitals. However, systematic data on CA-MRSA in Germany are limited. In this study, community-onset (CO)-MRSA skin and soft-tissue infection (SSTI) isolates in the Rhine-Neckar Region from 2012-2016 were characterised to gain an insight into their molecular epidemiology and to monitor potential introduction of virulent and dominant MRSA strains into our hospital. A total of 2475 patients with S. aureus SSTI were identified in the outpatient departments of our hospital, of which 94 (3.8%) were MRSA. In addition, 40.4% of the CO-MRSA harboured the virulence factor Panton-Valentine leukocidin (PVL). ST8-t008-MRSA-IVa/c (23.7%; 9/39) and ST80-t044-MRSA-IVc (15.8%; 6/38) were the predominant PVL-positive MRSA. Molecular typing and epidemiological data revealed that 42.6% (40/94) of strains could be traced back to a local origin and 44.7% (42/94) were endemic outside of Europe. Resistance to quinolones, clindamycin and macrolides was common, whilst resistance to trimethoprim/sulfamethoxazole, tetracycline, mupirocin, chlorhexidine and fusidic acid was low. No resistance to rifampicin, fosfomycin or linezolid was observed. This study provides insight into the clonal composition of CO-MRSA in the Rhine-Neckar Region. The increase of PVL-positive MRSA and the introduction of imported strains may affect the local MRSA landscape in the near future and should be monitored closely.

Methicillin-Resistant Staphylococcus aureus: The Effects Are More Than Skin Deep

To assess the psychosocial effects of a methicillin-resistant Staphylococcus aureus (MRSA) diagnosis on the households of children with MRSA skin and soft tissue infection (SSTI). We constructed and administered an interview to the primary caregiver within the home of a child with a history of MRSA SSTI. Seventy-six households were enrolled. Survey responses were analyzed and grouped into 4 themes: health behavior changes, disclosure, social interactions, and knowledge/awareness. The most common theme was disclosure; 91% of participants reported sharing their child's MRSA diagnosis with someone outside of the household. Forty-two percent of respondents reported a change in the manner in which household contacts interacted as a result of the index patient's MRSA diagnosis, including isolating the index patient from other children in the household. Many households reported adopting enhanced personal hygiene behaviors and environmental cleaning routines. Thirty-eight percent of participating households reported altering how they interact with people outside of their home, largely to avoid spreading MRSA to vulnerable individuals. In addition, many participants perceived that others regarded them with caution, especially at daycare, whereas other affected households were excluded from family gatherings. Primary caregivers of children with MRSA SSTI reported changing their health behaviors, altering their interactions with people outside of their home, and feeling isolated by others in response to their child's MRSA diagnosis. The findings of our study highlight a need for community interventions and education to prevent the negative psychosocial repercussions associated with MRSA.

Prevalence and Risk Factors for Methicillin-Resistant Staphylococcus aureus (MRSA) Infections in Custodial Populations: A Systematic Review.

early identification, isolation, and treatment of skin infections at admission; education on maintaining skin integrity and presenting early with skin infections; increasing hygiene by not sharing items and encouraging handwashing; improved handling and disinfection of communal laundering; influenza vaccination for all prisoners and staff; and population-based longitudinal studies including younger detainees.

The antibacterial effect of topical ozone on the treatment of MRSA skin infection.

Skin can be infected by many types of microorganisms, most commonly by gram-positive strains of Staphylococcus and Streptococcus spp. Treatment of Staphylococcus aureus (S. aureus) infections, particularly that of methicillin resistant Staphylococcus aureus (MRSA), is a challenge in clinical practice. Ozone therapy has proven to be one of the strongest antiseptics against the majority of microorganisms involved in skin infections. The purpose of the present study was to evaluate the microbicidal effects of topical ozone therapy on S. aureus and MRSA, and determine the clinical efficacy of ozone therapy on patients with MRSA skin infection. Microbicidal effects of ozonated oil and ozonated water were determined by plating and Kirby Bauer methods. Clinical efficacy and safety of topical ozone were evaluated in two cases with skin MRSA infection. The killing rates of ozonated oil for S. aureus and MRSA were greater when compared with the control oil group. Almost 100% of S. aureus were eliminated by ozonated oil following 5 min. Almost 100% MRSA were eliminated by ozonated oil following 15 min. In addition, 100% S. aureus and 100% MRSA were eliminated by ozonated water in 1 min. The inhibition zone diameters of ozonated oil for S. aureus and MRSA were 17 and 13 mm, respectively, which were significantly larger than the control group. Both cases of skin MRSA infection were completely healed with ozone therapy. In conclusion, ozone therapy is a potential treatment for S. aureus and MRSA skin infection as it has great efficacy, few side effects and low-costs.

Experience with High Dose Once-daily Vancomycin for Patients with Skin and Soft-tissue infections in an Ambulatory Setting

BackgroundIntravenous (IV) vancomycin is commonly used to treat MRSA (methicillin-resistant Staphylococcus aureus) infections and is typically dosed at 15 mg/kg every 12 hours. Pharmacokinetic studies, animal models, and limited human study suggest that once-daily high dose (30 mg/kg) vancomycin is similar in efficacy for certain types of infection in the hospital setting, but there is little evidence for its use in outpatient antibiotic therapy (OPAT).We have used a high dose vancomycin regimen for MRSA skin and soft-tissue infections (SSTI) since 2011. We describe our experience with this regimen in an ambulatory setting supervised by Infectious Diseases (ID) physicians and evaluate its efficacy and safety.MethodsThis retrospective observational study included patients treated with vancomycin for SSTI from Jan 1, 2014 to July 31, 2015. Exclusion criteria included noncompliance with treatment. Patients with initial renal impairment were also excluded as they would be given 15 mg/kg vancomycin daily. Patient demographics, response to vancomycin, duration of therapy, readmission to emergency department (ER), and side effects experienced by patients were collected. A successful outcome was defined as no further requirement for IV vancomycin on the last day of therapy with either oral step down therapy or no further antibiotic.Results407 charts were reviewed and 208 patients qualified for inclusion. The mean age of included patients was 38 years. Of the 208 patients, 31% were people who inject drugs, 39% had preceding SSTI in the 12 months prior, and 48% had been on antibiotics in the previous 8 weeks. Incision and drainage was done in 50% of the patients. There were 135 positive wound cultures, of which 58% grew MRSA. The average duration of treatment was 4.7 days.A successful outcome was achieved in 162 patients (79%). Side effects including red man syndrome and phlebitis were seen in 19 patients (9.3%). 42 patients (20.5%) were readmitted to ER within 30 days of initial referral, and 18 of those were related to the original infections.ConclusionHigh dose (30 mg/kg) once-daily vancomycin for SSTI was effective and safe when used for select patients under the supervision of ID physicians in an ambulatory setting.Disclosures All authors: No reported disclosures.

Synthetic Antibacterial Peptide Exhibits Synergy with Oxacillin against MRSA.

One proposed solution to the crisis of antimicrobial resistant (AMR) infections is the development of molecules that potentiate the activity of antibiotics for AMR bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). Rather than develop broad spectrum compounds, we developed a peptide that could potentiate the activity of a narrow spectrum antibiotic, oxacillin. In this way, the combination treatment could narrowly target the resistant pathogen and limit impact on host flora. We developed a peptide, ASU014, composed of a S. aureus binding peptide and a S. aureus inhibitory peptide conjugated to a branched peptide scaffold, which has modest activity against S. aureus but exhibits synergy with oxacillin for MRSA both in vitro and in a MRSA skin infection model. The low concentration of ASU014 and sub-MIC concentration of oxacillin necessary for activity suggest that this molecule is a candidate for future medicinal chemistry optimization.

Factors associated with persistent colonisation with methicillin-resistant Staphylococcus aureus.

We conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38-17·40), prior MRSA infection (OR 3·59; 95% CI 1·05-12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7-159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08-0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated.

Comparative in vitro activity of oritavancin and other agents against methicillin-susceptible and methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) infections constitute a threat to the public health due to their prevalence and associated mortality and morbidity. Several agents have been recently approved to treat MRSA skin infections including lipoglycopeptides (dalbavancin, oritavancin, and telavancin), ceftaroline, and tedizolid. This study compared the MIC, minimum bactericidal concentration (MBC), and time-kill of these agents alongside daptomycin, linezolid, and vancomycin against MRSA (n=15); meropenem, cefazolin, and nafcillin were also included against methicillin-susceptible S. aureus (MSSA [n=12]). MIC and MBC testing was conducted in accordance with Clinical and Laboratory Standards Institute guidelines, and time-kills were evaluated at multiples of the MIC and the free-drug maximum plasma concentration (fCmax) at both standard and high inoculum densities for a subset of MRSA (n=2) and MSSA (n=2). MRSA and MSSA were highly susceptible to all agents, with the lipoglycopeptides having the most potent activity by MIC50/90. All agents excluding tedizolid and linezolid were bactericidal by MBC for MRSA and MSSA, though dalbavancin and telavancin exhibited strain-specific bactericidal activity for MRSA. All agents excluding tedizolid and linezolid were bactericidal by time-kill at their respective fCmax against MRSA and MSSA at standard inoculum density, though oritavancin exhibited the most rapid bactericidal activity. Oritavancin and daptomycin at their respective fCmax maintained similar kill curves at high inoculum density. In contrast, the killing observed with other agents was typically reduced or slowed at high inoculum density. These data demonstrate the rapid bactericidal activity of oritavancin and daptomycin against S. aureus relative to other MRSA agents regardless of bacterial burden.

The Effect of Total Household Decolonization on Clearance of Colonization With Methicillin-Resistant Staphylococcus aureus.

OBJECTIVE To determine the impact of total household decolonization with intranasal mupirocin and chlorhexidine gluconate body wash on recurrent methicillin-resistant Staphylococcus aureus (MRSA) infection among subjects with MRSA skin and soft-tissue infection. DESIGN Three-arm nonmasked randomized controlled trial. SETTING Five academic medical centers in Southeastern Pennsylvania. PARTICIPANTS Adults and children presenting to ambulatory care settings with community-onset MRSA skin and soft-tissue infection (ie, index cases) and their household members. INTERVENTION Enrolled households were randomized to 1 of 3 intervention groups: (1) education on routine hygiene measures, (2) education plus decolonization without reminders (intranasal mupirocin ointment twice daily for 7 days and chlorhexidine gluconate on the first and last day), or (3) education plus decolonization with reminders, where subjects received daily telephone call or text message reminders. MAIN OUTCOME MEASURES Owing to small numbers of recurrent infections, this analysis focused on time to clearance of colonization in the index case. RESULTS Of 223 households, 73 were randomized to education-only, 76 to decolonization without reminders, 74 to decolonization with reminders. There was no significant difference in time to clearance of colonization between the education-only and decolonization groups (log-rank P=.768). In secondary analyses, compliance with decolonization was associated with decreased time to clearance (P=.018). CONCLUSIONS Total household decolonization did not result in decreased time to clearance of MRSA colonization among adults and children with MRSA skin and soft-tissue infection. However, subjects who were compliant with the protocol had more rapid clearance Trial registration. ClinicalTrials.gov identifier: NCT00966446 Infect Control Hosp Epidemiol 2016;1-8.

Antivirulence and wound healing effects of royal jelly and garlic extract for the control of MRSA skin infections

Abstract Methicillin Resistant Staphylococcus aureus (MRSA) has become increasingly a major problem and responsible for most of the hospital acquired infections in Egypt. Thus, there is an urgent need for agents with new therapeutic targets particularly those targeting bacterial virulence. MRSA isolates were investigated for biofilm formation, adhesion and invasion assays. Thereafter, the effect of garlic extract and royal jelly on those virulence factors was tested. These two agents were tested in vitro and in vivo using an animal model of MRSA skin infection. The garlic extract caused significant reduction in biofilm formation (60% median reduction) however, it had no significant effect on bacterial adhesion. Royal jelly reduced biofilm formation and bacterial adhesion significantly (≥50% median reduction). Animal study revealed that royal jelly could eradicate MRSA completely and promote wound healing even in the uninfected groups. However, the wound in case of garlic treated groups was dry and no exudates or pus was observed indicating its antiseptic effect. Conclusion The results implied the significant role of royal jelly not only in eradication of MRSA infection, but also in promoting the healing process in the wounds.

Aberrant localized LTB4 production exacerbates methicillin-resistant Staphylococcus aureus skin infection in diabetic mice.

Abstract A major cause of severe skin infections is methicillin-resistant Staphylococcus aureus (MRSA). Immunotherapeutic strategies are needed to treat infections. Neutrophils and macrophages control MRSA skin infection but undue inflammation causes injury. The bioactive eicosanoid leukotriene B4 is a potent chemoattractant and enhances phagocyte effector functions in naïve mice. However we have shown that diabetic mice produce chronic LTB4 which promotes susceptibility to sepsis but the role of LTB4 in localized infections is unknown. We hypothesize that aberrant LTB4 drive excessive inflammation during MRSA skin infection in diabetics. Diabetic mice at day 1 post infection had larger infected areas, bacterial and apoptotic cell burdens than nondiabetic controls. By intravital microscopy we observed more neutrophil recruitment in diabetic mice. These effects correlated with high levels of LTB4 and its receptor BLT1. At day 9 post infection nondiabetic mice were nearly healed but diabetic mice still had cell infiltration, high bacterial and apoptotic burdens, which associated with high levels of inflammatory mediators. To test whether chronic LTB4 causes uncontrolled infection, diabetic mice were treated daily with a topical ointment containing BLT1 antagonist. The treatment reduced infection area, bacterial burden and neutrophil recruitment. We also detected fewer apoptotic cells and lower expression of inflammatory mediators. These findings reveal that LTB4 is detrimental for diabetics by chronically inducing a damaging inflammatory response. We observe that topical BLT1 antagonist treatment improves host defense in diabetic mice and promises to be an effective therapeutic to treat MRSA infections in diabetic patients.

Colonization With Methicillin-resistant Staphylococcus aureus and Risk for Infection Among Asymptomatic Athletes: A Systematic Review and Metaanalysis.

Athletes are a vulnerable population for methicillin-resistant Staphylococcus aureus (MRSA) infection. Our aim was to determine MRSA colonization in asymptomatic athletes and estimate the risk for subsequent MRSA infection. We searched the PubMed and EMBASE (through 29 October 2015) for studies on MRSA colonization among asymptomatic athletes. The pooled prevalence of MRSA colonization among athletes was 6% (95% confidence interval [CI], 1,13), and it was higher in the United States (8%; 95% CI, 2,17). USA300 was the most common strain detected (22%), and 62% and 36% of isolates were resistant to clindamycin and trimethoprim/sulfamethoxazole, respectively. The prevalence of MRSA colonization among collegiate athletes reached 13% (95% CI, 4,25). Sports with the highest prevalence among collegiate athletes were wrestling (22%; 95% CI, 0,85), football (8%; 95% CI, 3,15) and basketball (8%; 95% CI, 0,28). The risk for MRSA skin and soft tissue infection within 3 months after documented colonization among MRSA-colonized athletes was significantly higher than for noncolonized athletes (relative risk = 7.37, 95% CI, [2.47,21.94]). Decolonization treatment among colonized athletes decreased significantly the risk for infection (relative risk reduction = 0.33; 95% CI, .03,4.28). The prevalence of MRSA colonization among asymptomatic athletes is comparable to that among individuals with chronic illness, it is higher among collegiate athletes and can be twice that for patients in intensive care units. Importantly, colonization is associated with a >7-fold increase in the incidence of subsequent MRSA infection. Infection control and decontamination protocols for this population need to be studied and implemented with urgency.

Nanoparticle-Based Antivirulence Vaccine for the Management of Methicillin-Resistant Staphylococcus aureus Skin Infection.

With the rising threat of antibiotic-resistant bacteria, vaccination is becoming an increasingly important strategy to prevent and manage bacterial infections. Made from deactivated bacterial toxins, toxoid vaccines are widely used in the clinic as they help to combat the virulence mechanisms employed by different pathogens. Herein, the efficacy of a biomimetic nanoparticle-based anti-virulence vaccine is examined in a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) skin infection. Vaccination with nanoparticle-detained staphylococcal α-hemolysin (Hla) effectively triggers the formation of germinal centers and induces high anti-Hla titers. Compared to mice vaccinated with control samples, those vaccinated with the nanoparticle toxoid show superior protective immunity against MRSA skin infection. The vaccination not only inhibits lesion formation at the site of bacterial challenge, but also reduces the invasiveness of MRSA, preventing dissemination into other organs. Overall, this biomimetic nanoparticle-based toxin detainment strategy is a promising method for the design of potent anti-virulence vaccines for managing bacterial infections.

Exploring simvastatin, an antihyperlipidemic drug, as a potential topical antibacterial agent.

The rapid rise of bacterial resistance to traditional antibiotics combined with the decline in discovery of novel antibacterial agents has created a global public health crisis. Repurposing existing drugs presents an alternative strategy to potentially expedite the discovery of new antimicrobial drugs. The present study demonstrates that simvastatin, an antihyperlipidemic drug exhibited broad-spectrum antibacterial activity against important Gram-positive (including methicillin-resistant Staphylococcus aureus (MRSA)) and Gram-negative pathogens (once the barrier imposed by the outer membrane was permeabilized). Proteomics and macromolecular synthesis analyses revealed that simvastatin inhibits multiple biosynthetic pathways and cellular processes in bacteria, including selective interference of bacterial protein synthesis. This property appears to assist in simvastatin’s ability to suppress production of key MRSA toxins (α-hemolysin and Panton-Valentine leucocidin) that impair healing of infected skin wounds. A murine MRSA skin infection experiment confirmed that simvastatin significantly reduces the bacterial burden and inflammatory cytokines in the infected wounds. Additionally, simvastatin exhibits excellent anti-biofilm activity against established staphylococcal biofilms and demonstrates the ability to be combined with topical antimicrobials currently used to treat MRSA skin infections. Collectively the present study lays the foundation for further investigation of repurposing simvastatin as a topical antibacterial agent to treat skin infections.

Antibacterial Evaluation of Synthetic Thiazole Compounds In Vitro and In Vivo in a Methicillin-Resistant Staphylococcus aureus (MRSA) Skin Infection Mouse Model.

The emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA), including strains resistant to current antibiotics, has contributed to an increase in the number of skin infections reported in humans in recent years. New therapeutic options are needed to counter this public health challenge. The aim of the present study was to examine the potential of thiazole compounds synthesized by our research group to be used topically to treat MRSA skin and wound infections. The broth microdilution method confirmed that the lead thiazole compound and four analogues are capable of inhibiting MRSA growth at concentrations as low as 1.3 μg/mL. Additionally, three compounds exhibited a synergistic relationship when combined with the topical antibiotic mupirocin against MRSA in vitro via the checkerboard assay. Thus the thiazole compounds have potential to be used alone or in combination with mupirocin against MRSA. When tested against human keratinocytes, four derivatives of the lead compound demonstrated an improved toxicity profile (were found to be non-toxic up to a concentration of 20 μg/mL). Utilizing a murine skin infection model, we confirmed that the lead compound and three analogues exhibited potent antimicrobial activity in vivo, with similar capability as the antibiotic mupirocin, as they reduced the burden of MRSA present in skin wounds by more than 90%. Taken altogether, the present study provides important evidence that these thiazole compounds warrant further investigation for development as novel topical antimicrobials to treat MRSA skin infections.