Methicillin-resistant Staphylococcus Aureus Burden Research Articles

The Effect of Retinoic Acid on Neutrophil Innate Immune Interactions With Cutaneous Bacterial Pathogens.

Vitamin A and its biologically active derivative, retinoic acid (RA), are important for many immune processes. RA, in particular, is essential for the development of immune cells, including neutrophils, which serve as a front-line defense against infection. While vitamin A deficiency has been linked to higher susceptibility to infections, the precise role of vitamin A/RA in host-pathogen interactions remains poorly understood. Here, we provided evidence that RA boosts neutrophil killing of methicillin-resistant Staphylococcus aureus (MRSA). RA treatment stimulated primary human neutrophils to produce reactive oxygen species, neutrophil extracellular traps, and the antimicrobial peptide cathelicidin (LL-37). Because RA treatment was insufficient to reduce MRSA burden in an in vivo murine model of skin infection, we expanded our analysis to other infectious agents. RA did not affect the growth of a number of common bacterial pathogens, including MRSA, Escherichia coli K1 and Pseudomonas aeruginosa; however, RA directly inhibited the growth of group A Streptococcus (GAS). This antimicrobial effect, likely in combination with RA-mediated neutrophil boosting, resulted in substantial GAS killing in neutrophil killing assays conducted in the presence of RA. Furthermore, in a murine model of GAS skin infection, topical RA treatment showed therapeutic potential by reducing both skin lesion size and bacterial burden. These findings suggest that RA may hold promise as a therapeutic agent against GAS and perhaps other clinically significant human pathogens.

Neutrophil-targeted combinatorial nanosystems for suppressing bacteremia-associated hyperinflammation and MRSA infection to improve survival rates

There is currently no specific and effective treatment for bacteremia-mediated sepsis. Hence, this study engineered a combinatorial nanosystem containing neutrophil-targeted roflumilast-loaded nanocarriers and non-targeted fusidic acid-loaded nanoparticles to enable the dual mitigation of bacteremia-associated inflammation and methicillin-resistant Staphylococcus aureus (MRSA) infection. The targeted nanoparticles were developed by conjugating anti-lymphocyte antigen 6 complex locus G6D (Ly6G) antibody fragment on the nanoparticulate surface. The particle size and zeta potential of the as-prepared nanosystem were about 200 nm and −25 mV, respectively. The antibody-conjugated nanoparticles showed a three-fold increase in neutrophil internalization compared to the unfunctionalized nanoparticles. As a selective phosphodiesterase (PDE) 4 inhibitor, the roflumilast in the nanocarriers largely inhibited cytokine/chemokine release from the activated neutrophils. The fusidic acid-loaded nanocarriers were vital to eliminate biofilm MRSA colony by 3 log units. The nanoparticles drastically decreased the intracellular bacterial count compared to the free antibiotic. The in vivo mouse bioimaging demonstrated prolonged retention of the nanosystem in the circulation with limited organ distribution and liver metabolism. In the mouse bacteremia model, the multifunctional nanosystem produced a 1‒2 log reduction of MRSA burden in peripheral organs and blood. The functionalized nanosystem arrested the cytokine/chemokine overexpression greater than the unfunctionalized nanocarriers and free drugs. The combinatory nanosystem also extended the median survival time from 50 to 103 h. No toxicity from the nanoformulation was found based on histology and serum biochemistry. Furthermore, our data proved that the active neutrophil targeting by the versatile nanosystem efficiently alleviated MRSA infection and organ dysfunction caused by bacteremia. Statement of significanceBacteremia-mediated sepsis poses a significant challenge in clinical practice, as there is currently no specific and effective treatment available. In our study, we have developed a novel combinatorial nanosystem to address this issue. Our nanosystem consists of neutrophil-targeted roflumilast-loaded nanocarriers and non-targeted fusidic acid-loaded nanoparticles, enabling the simultaneous mitigation of bacteremia-associated inflammation and MRSA infection. Our nanosystem demonstrated the decreased neutrophil activation, effective inhibition of cytokine release, elimination of MRSA biofilm colonies, and reduced intracellular bacterial counts. In vivo experiments showed prolonged circulation, limited organ distribution, and increased survival rates in a mouse bacteremia model. Importantly, our nanosystem exhibited no toxicity based on comprehensive assessments.

Methicillin-Resistant Staphylococcus aureus Colonization in Intensive Care and Burn Units: A Narrative Review.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common hospital-acquired pathogen and can cause a wide spectrum of infections. In recent years, MRSA has emerged as a significant public health concern, particularly in hospitals. Intensive care units (ICUs) and burn units are high-risk areas for hospital-acquired MRSA infections, which can lead to increased morbidity, mortality, and healthcare costs. MRSA exhibits resistance to multiple antibiotics and can cause serious infections, including but not limited to pneumonia, endocarditis, and cutaneous infections, particularly in patients with burn injuries. The prevention and effective management of MRSA infections in both burn patients and those in ICUs is crucial, with strategies like isolation, regular disinfection, and prophylactic intranasal mupirocin. Early diagnosis of MRSA infection and isolation of patients is vital to prevent the spread of MRSA. Implementation of prevention strategies faces many challenges, such as cost, and the most successful infection management practices are still debated. This review has highlighted the substantial concern of MRSA colonization in intensive care and burn units. MRSA poses a significant risk to vulnerable patients, influenced by factors such as compromised immunity and invasive procedures. The prevalence of MRSA colonization varies, influenced by regional factors and infection control practices. Combating MRSA requires a multifaceted approach, including stringent infection control measures and education for healthcare workers and patients. As we move forward, continued research and cooperation are essential to reduce the burden of MRSA in these critical care settings.

Analysis of the Trends of Methicillin-Resistant Staphylococcus aureus in Gauteng Public Hospitals from 2009 to 2018.

Most investigations into the distribution of methicillin resistant Staphylococcus aureus (MRSA) have focused exclusively on bloodborne infections within individual health care institutions for shorter time periods. This has limited the analysis of a community-spread pathogen to snapshots within the hospital domain. Therefore, in this study we determined the demographic and geographical patterns of MRSA infections and their fluctuation in 10 years within all public hospitals in Gauteng, South Africa. A retrospective analysis of S. aureus samples was done by deduplicating samples in two groups. The sample groups were placed into subsets with respect to demographic and geographical fields and compared across the studied period. Logistic regression was utilized to determine odds ratios for resistant infections in univariate and multivariable configurations. A total of 66,071 unique infectious events were identified from the 148,065 samples received over a 10-year period, out of which 14,356 were identified as bacteremia. MRSA bacteremia rates in Gauteng peaked in 2015 and have since decreased. Within Gauteng, metropolitan areas have the greatest burden of MRSA with children under 5 years of age and males being most affected. Medical wards have the highest S. aureus bacteremia rates, while intensive care units have the highest MRSA bacteremia rates. Patient age, admitting ward, and geographical district are the most important associated factors of resistance. MRSA acquisition rates have shown tremendous growth since 2009 but have since spiked and subsequently decreased. This may be due to the initiation of the National Guidelines on Antimicrobial Stewardship and Infectious Disease Surveillance. Further studies to determine the trajectory of infections are required to support these claims. IMPORTANCE S. aureus is the leading cause of a variety of devastating clinical conditions, including infective endocarditis, bacteremia, and pleuropulmonary infections. It is an important pathogen responsible for substantial morbidity and mortality. MRSA is a variant of interest originally responsible for difficult to treat hospital-acquired infections that has since achieved community spread throughout the world. Most investigations into the distribution of MRSA have focused exclusively on bloodborne infections within individual health care institutions for shorter periods. This has limited the analysis of a community-spread pathogen to snapshots within the hospital domain. This study sought to determine the demographic and geographical patterns of MRSA infections as well as how these have fluctuated over time within all public hospitals. This will also help in understanding the epidemiology and resistance trends of S. aureus, which will help clinicians to understand the clinical prospective and policy makers to design guidelines and strategies for treating such infections.

Combining the dual antibacterial and regenerative activities of platelet-rich plasma with β-lactams to mitigate MRSA-infected skin wounds

The emergence of multidrug-resistant bacteria contributes to the necessity of developing novel infection treatment approaches. This study was designed to evaluate the antimicrobial and wound healing activities of platelet-rich plasma (PRP) in combination with β-lactams (ampicillin and/or oxacillin) for the application on methicillin-resistant Staphylococcus aureus (MRSA)-infected skin. PRP was collected from the peripheral blood of healthy donors. The anti-MRSA activity was tested through a growth inhibition curve, colony-forming unit (CFU), and SYTO 9 assay. The PRP incorporation lowered the minimum inhibitory concentration (MIC) of ampicillin and oxacillin against MRSA. The combination of β-lactams together with PRP showed a three-log CFU reduction of MRSA. The major components of PRP for eliminating MRSA were found to be the complement system and iron sequestration proteins, according to the proteomic analysis. The adhesive bacterial colony in the microplate was decreased from 2.9 × 107 to 7.3 × 105 CFU after the treatment of cocktails containing β-lactams and PRP. The cell-based study indicated that keratinocyte proliferation was stimulated by PRP. The in vitro scratch and transwell experiments revealed that PRP improved keratinocyte migration. In the MRSA-infected mouse skin model, PRP appeared to show a synergistic effect for wound area reduction by 39% when combined with β-lactams. The MRSA burden in the infected area was lessened two-fold after topical administration of the combined β-lactams and PRP. PRP inhibited macrophage infiltration in the wound site to shorten the inflammatory phase and accelerate the initiation of the proliferative phase. No skin irritation was detected with the topical delivery of this combination. Our findings suggested that β-lactams plus PRP was applicable to alleviate the problems associated with MRSA via dual antibacterial and regenerative activities.

Prevalence, antimicrobial susceptibility pattern and multidrug resistance of methicillin-resistant Staphylococcus aureus isolated from clinical samples at a tertiary care teaching hospital: an observational, cross-sectional study from the Himalayan country, Nepal

ObjectiveWe sought to determine the prevalence and antimicrobial susceptibility pattern of methicillin-resistant Staphylococcus aureus (MRSA) isolated from the clinical samples at a tertiary care hospital in Nepal.MethodsCross-sectional, observational study design.Study...

Four-armed host-defense peptidomimetics-augmented vanadium carbide MXene-based microneedle array for efficient photo-excited bacteria-killing

To explore the potential of vanadium compounds in disease treatment, a vanadium-based MXene composite nanosheet 4 K10@V2C was constructed using a simple procedure by electrostatic coating a four-armed host-defense peptidomimetic 4 K10 on vanadium carbide (V2C) MXene. The two-dimensional therapeutics integrate membranolytic, photothermal, and photocatalytic abilities, realizing a great potential for efficient photo-excited bacteria-killing of focal infections via a microneedle-assisted approach. The proposed host-defense peptidomimetic augmenting MXene strategy achieves synergistic membranolytic-photothermal effects against biofilm bacteria by mediating high-selectivity bacteria binding, reducing bacteria heat resistance and increasing MXene-to-bacteria heat transfer efficiency. Moreover, the persistent photocatalytic disinfection and adjuvant effects of V2C degradation products on inhibiting bacterial rebound are highlighted. While the 4 K10@V2C nanosheets demonstrate impressive in vitro antimicrobial activity with a ∼ 99.9996 % (5.5 log) reduction of methicillin-resistant Staphylococcus aureus (MRSA) and 100 % reduction of Pseudomonas aeruginosa at a low photothermal temperature of 54.1 °C, the dissolving microneedle system facilitates the transdermal delivery of 4 K10@V2C nanosheets to eradicate skin infections with an efficacy superior to that of commercial Bactroban and with no significant in vivo toxicity. In a human ex vivo skin infection models, the 4 K10@V2C nanosheets are highly efficacious in eradicating biofilm-associated infections with > 99.98 % (3.86 log) reduction in the skin MRSA burden.

The Potential Threat of Vertical Transmission in Methicillin-Resistant Staphylococcus Aureus Infection: A Systematic Review 2022.

This systematic review paper aimed to assess and analyze the prevalence of maternal colonization of Staphylococcus aureus (S. aureus) also known as methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) in the peripartum period and its significance on vertical transmission to the neonate and if it is a potential threat to the health of newborns. For this, multiple databases, such as PubMed, MEDLINE, ScienceDirect, and the database of Elsevier, were used to scout for relevant articles, and results were reported adhering to the principles set by Preferred Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines 2020. A specific medical subject headings (MeSH) criterion was designed to search for relevant publications on PubMed. A total of 26 articles were finally selected after a meticulous screening process, including detailed inclusion and exclusion criteria, manual reading of titles and abstracts, and availability of accessible full-text articles. A few articles were also selected after going through the citations section of the initially selected papers. Quality appraisal was done on the selected publications. Maternal colonization of S. aureus is determined to be highly prevalentwith the hypothesis that nasal colonization had higher rates than recto-vaginal sites. Increasing maternal age, history of vaginitis, and multiparity were the most common risk factors for MRSA and MSSA colonization. Premature babies were at the highest risk of MRSA colonization. Breast milk is also a risk factor for neonatal MRSA transmission. Through this systematic review, we concluded that although the rate of vertical transmission of MRSA is lower than that of MSSA, we felt that it held significance as neonates with the bug have poor outcomes due to skin and soft tissue infections and there is spread of MRSA to other neonates in the wardsand spread to siblings in cases of triplets and quadruplets and even death due to potential MRSA sepsis. Women in Africa and China had high prevalence rates of MRSA and S. aureus which can probably be attributed to a lack of access to adequate healthcare facilities. We recommend screening with regular recto-vaginal swabs and nasal swabs especially in regions with a high burden of MRSA to be performed at regular intervals after confirmation of pregnancy, as prevention and screening are effective to avoid serious complications.

Planning for Implementation of a Universal Decolonization Process at a Large Healthcare System (Masters of Science in Biomedical Informatics Capstone)

<h3>Background</h3> There is a growing body of literature to promote the use and highlight the effectiveness of universal decolonization (UD) over targeted decolonization (TD) to reduce the burden of methicillin-resistant Staphylococcus aureus (MRSA) on acute care patients. Infection preventionist (IP) leaders and stakeholders at a large urban healthcare system have supported implementing UD in adult intensive care units (ICUs) but have not yet identified a future state electronic health record (EHR) workflow due to technical, legal, and human factor constraints. This project served as a Masters capstone for an IP. <h3>Methods</h3> An IP with biomedical informatics experience identified constraints and requirements associated with UD at the implementation site, collaborated with clinical informaticists, and outlined pathways in the EHR, including triggering events, alerts, and order sets, to accomplish the UD process effectively. The target patient population will include adult ICU patients in 14 acute care hospitals. The IP identified three potential future state workflows in the EHR for effective UD implementation with strengths and weaknesses. <h3>Results</h3> Future state workflows were evaluated based on reliability that all UD components will be carried out to completion in each patient, the workflow will reach the target population, and there will be high compliance. IPs and stakeholders elected to pursue a partial hard-stop alert within the EHR with few override options in order to achieve high compliance, despite possible physician resistance as seen with total hard-stop alerts. In the coming months, this workflow will be built into the System's EHR and implemented. <h3>Conclusions</h3> A viable solution was identified for a future state MRSA UD workflow. The future state workflow successfully satisfied requirements and addressed constraints identified by IPs and stakeholders. This will ultimately lead to higher compliance with the UD process and a decrease in the burden of MRSA within the System is expected following implementation of the workflow.

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.

Epidemiology of Methicillin-Resistant Staphylococcus Aureus in Arab Countries of the Middle East and North African (MENA) Region.

Available data suggest a high burden of methicillin-resistant staphylococcus aureus (MRSA) in Arab countries of the Middle East and North Africa (MENA). To review the MRSA rates and molecular epidemiology in this region, we used PubMed search engine to identify relative articles published from January 2005 to December 2019. Great heterogeneity in reported rates was expectedly seen. Nasal MRSA colonization ranged from 2%–16% in Gulf Cooperation Council (GCC), 1–9% in the Levant, and 0.2%–9% in North African Arab states. Infective MRSA rates ranged from 9%–38% in GCC, 28%–67% in the Levant, and 28%–57% in North African states. Studies demonstrated a wide clonal diversity in the MENA. The most common molecular types belonged to 5 clonal complexes (CC) known to spread worldwide: CC5, CC8, CC22, CC30, and CC80. The most prevalent strains had genotypes related to the European community-acquired MRSA (CA-MRSA), Brazilian/Hungarian hospital-acquired MRSA (HA-MRSA), UK-EMRSA-15 HA-MRSA, and USA300 CA-MRSA. Finally, significant antimicrobial resistance was seen in the region with variation in patterns depending on location and clonal type. For a more accurate assessment of MRSA epidemiology and burden, the Arab countries need to implement national surveillance systems.

The Inhibitory Efficiencies of Geraniol as an Anti-Inflammatory, Antioxidant, and Antibacterial, Natural Agent Against Methicillin-Resistant Staphylococcus aureus Infection in vivo

IntroductionAntibiotics wee widely used as feed additives in animal husbandry. With the increase of drug resistance of bacteria, there is an urgent need to find alternatives to antibiotics. Clinically, methicillin-resistant Staphylococcus aureus (MRSA) infections account for about 25% to 50% of Staphylococcus aureus infections worldwide. Similarly, it is also one of the pathogens that cause serious animal infections.MethodsWe established a mouse model of systemic infection of MRSA to study the preventive effect of geraniol on MRSA and the immunomodulatory effect of geraniol. The mice in the experiment were injected with geraniol by intramuscular injection and were fed intraperitoneally with minimum lethal dose of MRSA. Then, the survival rate, inflammatory cytokines, oxidative stress factors in serum were measured. These values were used to estimate the bacterial load in different organs and to assess histopathological changes in the lungs, liver and kidneys.ResultsThe above-mentioned two ways of using geraniol could prevent MRSA infection in vivo in mice and showed a significant dose–response relationship. In other words, geraniol significantly decreased the concentrations of inflammatory cytokines and oxidative stress factors in MRSA-infected mice. At the same time, the level of glutathione peroxidase also increased in a dose–proportional relationship. In the group of mice treated with geraniol, their superoxide dismutase levels were significantly higher than those in the vancomycin. After treatment with geraniol, the burden of MRSA decreased. No obvious histopathological abnormalities were found in the liver and kidney of MRSA-infected mice. In addition, geraniol improved the inflammatory changes in the lungs.ConclusionThe results indicated that geraniol was a natural substance that could be used as an anti-inflammatory, antioxidant and antibacterial substance to protect mice from MRSA systemic infection. Generally, the research shows that as a natural medicine, geraniol has broad potential in the development and application of antibiotic substitutes.

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.

Infection control measures in nosocomial MRSA outbreaks-Results of a systematic analysis.

There is a lack of data on factors that contribute to the implementation of hygiene measures during nosocomial outbreaks (NO) caused by Methicillin-resistant Staphylococcus aureus (MRSA). Therefore, we first conducted a systematic literature analysis to identify MRSA outbreak reports. The expenditure for infection control in each outbreak was then evaluated by a weighted cumulative hygiene score (WCHS). Effects of factors on this score were determined by multivariable linear regression analysis. 104 NO got included, mostly from neonatology (n = 32), surgery (n = 27), internal medicine and burn units (n = 10 each), including 4,361 patients (thereof 657 infections and 73 deaths) and 279 employees. The outbreak sources remained unknown in 10 NO and were not reported from further 61 NO. The national MRSA prevalence did not correlate with the WCHS (p = .714). There were significant WCHS differences for internal medicine (p = 0.014), burn units (p<0.01), for Japanese NO (p<0.01), and NO with an unknown source (p<0.01). In sum, management of a NO due to MRSA does not depend on the local MRSA burden. However, differences of MRSA management among medical departments do exist. Strict adherence to the Outbreak Reports and Intervention Studies Of Nosocomial infection (ORION) statement is highly recommended for. The WCHS may also serve as a useful tool to quantify infection control effort and could therefore be used for further investigations.

Modular Design of Membrane-Active Antibiotics: From Macromolecular Antimicrobials to Small Scorpionlike Peptidomimetics.

Infections caused by multidrug-resistant bacteria have emerged in recent decades, leading to escalating interest in host defense peptides (HDPs) to reverse this dangerous trend. Inspired by the modular design in bioengineering, herein we report a new class of small amphiphilic scorpionlike peptidomimetics based on this strategy. These HDP mimics show potent antimicrobial activity against both Gram-positive and Gram-negative bacteria without drug resistance but with a high therapeutic index. The membrane-compromising action mode was suggested to be their potential bactericidal mechanism. Pharmacodynamic experiments were conducted using a murine abscess model of methicillin-resistant Staphylococcus aureus (MRSA) infections. The lead compound 12 showed impressive in vivo therapeutic efficacy with ∼99.998% (4.7log) reduction in skin MRSA burden, a significantly higher bactericidal efficiency than ciprofloxacin, and good biocompatibility. These results highlight the potential of these HDP mimics as novel antibiotic therapeutics.

Genomic surveillance of methicillin-resistant Staphylococcus aureus in the Philippines, 2013-2014.

Methicillin-resistant Staphylococcus aureus (MRSA) remains one of the leading causes of both nosocomial and community infections worldwide. In the Philippines, MRSA rates have remained above 50% since 2010, but resistance to other antibiotics, including vancomycin, is low. The MRSA burden can be partially attributed to pathogen-specific characteristics of the circulating clones, but little was known about the S. aureus clones circulating in the Philippines.We sequenced the whole genomes of 116 S. aureus isolates collected in 2013–2014 within the Antimicrobial Resistance Surveillance Program. The multilocus sequence type, spa type, SCCmec type, presence of antimicrobial resistance (AMR) determinants and virulence genes and relatedness between the isolates were all derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined.The MRSA population in the Philippines comprised a limited number of genetic clones, including several international epidemic clones, such as CC30-spa-t019-SCCmec-IV-PVL+, CC5-SCCmec-typeIV and ST239-spa-t030-SCCmec-typeIII. The CC30 genomes were related to the South-West Pacific clone but formed a distinct, diverse lineage, with evidence of global dissemination. We showed independent acquisition of resistance to sulfamethoxazole/trimethoprim in various locations and genetic clones but mostly in paediatric patients with invasive infections. The concordance between phenotypic and genotypic resistance was 99.68% overall for eight antibiotics in seven classes.We have made the first comprehensive genomic survey of S. aureus in the Philippines, which bridges the gap in genomic data from the Western Pacific Region and will constitute the genetic background for contextualizing prospective surveillance.

Evaluation of ebselen in resolving a methicillin-resistant Staphylococcus aureus infection of pressure ulcers in obese and diabetic mice.

Pressure ulcers (PUs) are a source of morbidity in individuals with restricted mobility including individuals that are obese or diabetic. Infection of PUs with pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), impairs ulcers from healing. The present study evaluated ebselen as a topical antibacterial to treat MRSA-infected PUs. Against two different S. aureus strains, including MRSA USA300, resistance to ebselen did not emerge after 14 consecutive passages. Resistance to mupirocin emerged after only five passages. Additionally, ebselen was found to exert a modest postantibiotic effect of five hours against two MRSA strains. Ebselen was subsequently evaluated in MRSA-infected PUs in two models using obese and diabetic mice. In obese mice, topical ebselen (89.2% reduction) and oral linezolid (84.5% reduction) similarly reduced the burden of MRSA in infected PUs. However, in diabetic mice, topical ebselen (45.8% reduction in MRSA burden) was less effective. Histopathological evaluation of ulcers in diabetic mice determined that ebselen treatment resulted in fewer bacterial colonies deep within the dermis and that the treatment exhibited evidence of epithelial regeneration. Topical mupirocin was superior to ebselen in reducing MRSA burden in infected PUs both in obese (98.7% reduction) and diabetic (99.3% reduction) mice. Ebselen’s antibacterial activity was negatively impacted as the bacterial inoculum was increased from 105 CFU/mL to 107 CFU/mL. These results suggest that a higher dose of ebselen, or a longer course of treatment, may be needed to achieve a similar effect as mupirocin in topically treating MRSA-infected pressure ulcers.

Genomic Epidemiology of MRSA During Incarceration at a Large Inner-City Jail.

Congregate settings, such as jails, may be a location where colonized detainees transmit methicillin-resistant Staphylococcus aureus (MRSA). We examined MRSA acquisition during incarceration and characterized the genomic epidemiology of MRSA entering the jail and isolated during incarceration. Males incarcerated at the Cook County Jail were enrolled within 72 h of intake and MRSA surveillance cultures collected. Detainees in jail at Day 30 were re-cultured to determine MRSA acquisition. A survey was administered to identify acquisition predictors. Genomic sequencing of surveillance and clinical isolates was integrated with epidemiologic and jail location data to track MRSA transmission pathways. 800 males were enrolled; 19% MRSA colonized at intake. Of 184 who reached Day 30 visit, 12 acquired MRSA. Heroin use before entering (OR 3.67, P = .05) and sharing personal items during incarceration (OR = 4.92, P = .01) were predictors of acquisition. Sequenced clinical USA300 isolates (n = 112) were more genetically similar than diverse intake USA300 strains (P < .001), suggesting jail transmission. Four acquired colonization isolates were within 20 single-nucleotide variant (SNVs) of other isolates; 4 were within 20 SNVs of an intake isolate, 2 for an acquisition isolate, and 1 for a clinical isolate. Individuals with genetically similar isolates were more likely to have had overlapping stays in the same buildings. There was a high MRSA burden entering jail. Genomic analysis of acquisition and clinical isolates suggests potential spread of incoming strains and networks of spread during incarceration, with spread often occurring among detainees housed in similar locations. Sharing personal items during incarceration is associated with MRSA acquisition and could be a focus for intervention.

Does the Fist Bump Transfer Less Methicillin-Resistant Staphylococcus aureus Than a Handshake?

Background: Contaminated hands are the most important source for transmission of pathogens in healthcare settings. It has been proposed that replacing the handshake with alternative greetings such as the fist bump might reduce the risk for pathogen transmission. Methods: In a cohort of 50 patients with methicillin-resistant Staphylococcus aureus (MRSA) colonization, we compared the frequency of transfer of MRSA by handshake versus fist bump versus cruise tap (ie, a modified fist bump involving knuckle-to-knuckle contact with a single finger). MRSA-colonized patients performed each greeting with research personnel wearing sterile gloves, and cultures were obtained to determine the number of colonies transferred. Transfer by handshake was also assessed after MRSA-colonized patients used alcohol-based hand sanitizer. Quantitative cultures were obtained to compare the burden of MRSA on the palm versus dorsum of the hands of the MRSA carriers. Results: As shown in Fig. 1, there was a significant reduction in the frequency of MRSA transfer for the cruise tap compared to the handshake, but not for the fist bump. Use of alcohol-based hand sanitizer by MRSA carriers also significantly reduced the risk for transfer of MRSA. There was no significant difference in the burden of MRSA on the dorsum versus the palm of the hands (mean +SE colonies recovered, 32.7+12.3 vs 27.3+12.7; P &gt; .05). Conclusions: The fist-bump greeting did not transfer less MRSA than a handshake. However, transfer was significantly reduced by a cruise-tap greeting or by handshake after the use of hand sanitizer. Modified greetings and patient hand hygiene are potential strategies to reduce transmission of healthcare-associated pathogens.Funding: NoneDisclosures: None

Risk Factors Associated With Hospital-Onset MRSA Proportion—National Healthcare Safety Network, 2017–2018

Background:Staphylococcus aureus is frequently implicated in healthcare-associated infections in the United States, and a substantial proportion of these infections are attributed to methicillin-resistant Staphylococcus aureus (MRSA). Although MRSA infections have decreased in health care settings, accurate estimates of the rate of decline call for risk-adjusted methods for calculating the resistant proportion (%R), that is, the proportion of S. aureus resistant to cefoxitin or oxacillin. Risk-adjusted %R also enables more accurate interhospital comparisons and can serve as a quantitative guide and evaluation metric for prevention efforts. Methods: To develop a risk-adjusted %R for S. aureus, we analyzed the antimicrobial susceptibility test (AST) results for S. aureus isolates reported to the CDC NHSN Antimicrobial Resistance Option during 2017–2018. Isolates were reported for cerebrospinal fluid (CSF), blood, lower respiratory tract (LRT), and urine. Isolates without cefoxitin and oxacillin test results, or from the facilities that had &gt;10% missing test results were excluded. Test results were differentiated between those associated with community-onset and hospital-onset (HO) infections by defining the latter group as test results for isolates obtained 3 days or more after hospital admission. Logistic regression was used to evaluate the factors associated with oxacillin/cefoxitin resistance. Hospital, patient and isolate-level variables from NHSN annual survey and AR option were assessed as covariates. Variable entry into the models is based on significance level P &lt; .05. Results: Among 9,992 hospital-onset SA isolates from 9,019 patients in 315 facilities, 5,488 (54.9%) were MRSA. Logistic regression showed that a higher proportion of HO-MRSA was significantly associated with older age, female, particular sources of specimen (urine and LRT), and selected hospital characteristics: hospitals not serving as major teaching hospitals, hospitals with a higher proportion of MRSA among community-onset SA isolates, hospitals with lower percentage of beds in intensive care units, and hospitals outsourcing AST service (Table 1). Conclusions: HO-MRSA is independently associated with community burden of MRSA, older and female patient populations, and hospital teaching status and AST practices, which highlights the importance of public health engagement and regional collaborations to prevent MRSA. To provide a standardized MRSA proportion for public health surveillance, taking some of these factors into account in MRSA proportion standardization should be considered.Funding: NoneDisclosures: None