Methicillin-Resistant Staphylococcus aureus Carriage among Neonate Mothers, Healthcare Workers, and Environmental Samples in Neonatal Intensive Care Units: A Systematic Review.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of morbidity and mortality among neonates admitted to neonatal intensive care units (NICUs). The MRSA colonization of neonates, attributed to various sources, including mothers, healthcare workers, and environmental surfaces, can lead to severe infection, prolonged hospital stays, and even death, imposing substantial economic burdens. Given the pressing need to mitigate MRSA spread in these vulnerable environments, further examination of the subject is warranted. This systematic review is aimed at synthesizing available evidence on MRSA carriage proportions among mothers of newborns, healthcare workers, and environmental surfaces in NICUs. Methodology. We included observational studies published in English or French from database inception to March 21, 2023. These studies focused on MRSA in nonoutbreak NICU settings, encompassing healthy neonate mothers and healthcare workers, and environmental surfaces. Literature search involved systematic scanning of databases, including Medline, Embase, Web of Science, Global Health, and Global Index Medicus. The quality of the selected studies was assessed using the Hoy et al. critical appraisal scale. The extracted data were summarized to calculate the pooled proportion of MRSA positives, with a 95% confidence interval (CI) based on the DerSimonian and Laird random-effects model. Results: A total of 1891 articles were retrieved from which 16 studies were selected for inclusion. Most of the studies were from high-income countries. The pooled proportion of MRSA carriage among 821 neonate mothers across four countries was found to be 2.1% (95% CI: 0.3-5.1; I2 = 76.6%, 95% CI: 36.1-91.5). The proportion of MRSA carriage among 909 HCWs in eight countries was determined to be 9.5% (95% CI: 3.1-18.4; I2 = 91.7%, 95% CI: 87.1-94.6). The proportion of MRSA carriage among HCWs was highest in the Western Pacific Region, at 50.00% (95% CI: 23.71-76.29). In environmental specimens from five countries, a pooled proportion of 16.6% (95% CI: 3.5-36.0; I2 = 97.7%, 95% CI: 96.6-98.4) was found to be MRSA-positive. Conclusion: With a significant heterogeneity, our systematic review found high MRSA carriage rates in neonate mothers, healthcare workers, and across various environmental surfaces in NICUs, posing a potential risk of nosocomial infections. Urgent interventions, including regular screening and decolonization of MRSA carriers, reinforcing infection control measures, and enhancing cleaning and disinfection procedures within NICUs, are crucial. This trial is registered with CRD42023407114.

FacZ is a GpsB-interacting protein that prevents aberrant division-site placement in Staphylococcus aureus.

Staphylococcus aureus is a Gram-positive pathogen responsible for antibiotic-resistant infections. To identify vulnerabilities in cell envelope biogenesis that may overcome resistance, we enriched for S. aureus transposon mutants with defects in cell surface integrity or cell division by sorting for cells that stain with propidium iodide or have increased light-scattering properties, respectively. Transposon sequencing of the sorted populations identified more than 20 previously uncharacterized factors impacting these processes. Cells inactivated for one of these proteins, factor preventing extra Z-rings (FacZ, SAOUHSC_01855), showed aberrant membrane invaginations and multiple FtsZ cytokinetic rings. These phenotypes were suppressed in mutants lacking the conserved cell-division protein GpsB, which forms an interaction hub bridging envelope biogenesis factors with the cytokinetic ring in S. aureus. FacZ was found to interact directly with GpsB in vitro and in vivo. We therefore propose that FacZ is an envelope biogenesis factor that antagonizes GpsB function to prevent aberrant division events in S. aureus.

Dose regimen optimization of cephalothin for surgical prophylaxis against Staphylococcus aureus and coagulase negative staphylococci in dogs by pharmacokinetic/pharmacodynamic modeling.

First generation cephalosporins such cephalothin of cefazolin are indicated for antimicrobial prophylaxis for clean and clean contaminated surgical procedures because its antimicrobial spectrum, relative low toxicity and cost. Anesthesia and surgery could alter the pharmacokinetic behavior of different drugs administered perioperative by many mechanisms that affect distribution, metabolism or excretion processes. Intravenous administration of the antimicrobial within 30 and 60 min before incision is recommended in order to reach therapeutic serum and tissue concentrations and redosing is recommended if the duration of the procedure exceeds two half-life of the antimicrobial. To the author's knowledge there are no pharmacokinetic studies of cephalothin in dogs under anesthesia/surgery conditions. The aim of this study was (1) to evaluate the pharmacokinetics of cephalothin in anesthetized dogs undergoing ovariohysterectomy by a nonlinear mixed-effects model and to determine the effect of anesthesia/surgery and other individual covariates on its pharmacokinetic behavior; (2) to determine the MIC and conduct a pharmacodynamic modeling of time kill curves assay of cephalothin against isolates of Staphylococcus spp. isolated from the skin of dogs; (3) to conduct a PK/PD analysis by integration of the obtained nonlinear mixed-effects models in order to evaluate the antimicrobial effect of changing concentrations on simulated bacterial count; and (4) to determine the PK/PD endpoints and PK/PDco values in order to predict the optimal dose regimen of cephalothin for antimicrobial prophylaxis in dogs. Anesthesia/surgery significantly reduced cephalothin clearance by 18.78%. Based on the results of this study, a cephalothin dose regimen of 25 mg/kg q6h by intravenous administration showed to be effective against Staphylococcus spp. isolates with MIC values ≤2 µg/mL and could be recommended for antimicrobial prophylaxis for clean surgery in healthy dogs.

Should Contact Precautions Be Used for Patients with MRSA Infection and Colonization in Acute Care Settings?

Are Contact Precautions for Patients with MRSA Useful?MRSA infections lead to substantial morbidity and mortality. Hospitals commonly implement "contact precautions" to reduce MRSA transmission; however, recent studies have challenged the effectiveness of this strategy, and the use of contact precautions has been associated with certain adverse events. This article reviews the existing evidence and proposes a randomized trial to assess the efficacy of contact precautions in preventing MRSA transmission.

MRSA throat carriage in two healthcare workers. / MRSA-halsbærerskap hos to helsearbeidere.

Background: Healthcare workers colonised with methicillin-resistant Staphylococcus aureus (MRSA) experience negative consequences due to work restrictions, long-term sick leave, stigmatisation, eradication failures and psychosocial stress. Throat colonisation is associated with prolonged carriage and non-successful treatment. Case presentation: We describe two Norwegian healthcare students with persistent MRSA throat carriage. After several eradication failures, MRSA eradication was successful only after tonsillectomy. Interpretation: Tonsillectomy is not the solution for persistent MRSA throat carriage in healthcare workers. However, their stories illustrate the challenges they faced during repeated eradication attempts. They suffered considerable psychological stress due to the risk of study disruption and limited career options. The impact of laws and strict guidelines for MRSA-colonised healthcare workers, needs to be re-assessed in order to reduce transmission. We argue that healthcare workers without individual risk factors should be able to work in units considered to pose no risk as long as they undergo individual training in basic infection control measures.

In nursing homes, universal decolonization vs. routine care reduced transfers to hospital for infection.

SOURCE CITATION: Miller LG, McKinnell JA, Singh RD, et al. Decolonization in nursing homes to prevent infection and hospitalization. N Engl J Med. 2023;389:1766-1777. 37815935.

Isolation and encapsulation of bacteriophage with chitosan nanoparticles for biocontrol of multidrug-resistant methicillin-resistant Staphylococcus aureus isolated from broiler poultry farms.

This study was divided into two parts. The first part, the determination of methicillin-resistant Staphylococcus aureus (MRSA) prevalence in 25 broiler chicken farms, with the detection of multidrug resistant MRSA strains. The prevalence of MRSA was 31.8% (159 out of 500 samples) at the level of birds and it was 27% (27 out of 100) in the environmental samples. The highest antimicrobial resistance of the recovered MRSA strains was recorded to streptomycin (96%). All isolates (100%) had multidrug resistance (MDR) to four or more antibiotics with 16 distinct antibiotic resistant patterns, and multiple antibiotic resistance index (MARI) of 0.4-1. The second part, implementing novel biocontrol method for the isolated multidrug resistant MRSA strains through the isolation of its specific phage and detection of its survival rate at different pH and temperature degrees and lytic activity with and without encapsulation by chitosan nanoparticles (CS-NPs). Encapsulated and non-encapsulated MRSA phages were characterized using transmission electron microscope (TEM). Encapsulation of MRSA phage with CS-NPs increasing its lytic activity and its resistance to adverse conditions from pH and temperature. The findings of this study suggested that CS-NPs act as a protective barrier for MRSA phage for the control of multidrug resistant MRSA in broiler chicken farms.

Synergistic use of anti-inflammatory ketorolac and gentamicin to target staphylococcal biofilms.

BACKGROUND: While antibiotics remain our primary tools against microbial infection, increasing antibiotic resistance (inherent and acquired) is a major detriment to their efficacy. A practical approach to maintaining or reversing the efficacy of antibiotics is the use of other commonly used therapeutics, which show synergistic antibacterial action with antibiotics. Here, we investigated the extent of antibacterial synergy between the antibiotic gentamicin and the anti-inflammatory ketorolac regarding the dynamics of biofilm growth, the rate of acquired resistance, and the possible mechanism of synergy. METHODS: Control (ATCC 12600, ATCC 35984) and clinical strains (L1101, L1116) of Staphylococcus aureus and Staphylococcus epidermidis with varying antibiotic susceptibility profiles were used in this study to simulate implant-material associated low-risk and high-risk biofilms in vitro. The synergistic action of gentamicin sulfate (GS) and ketorolac tromethamine (KT), against planktonic staphylococcal strains were determined using the fractional inhibitory concentration measurement assay. Nascent (6 h) and established (24 h) biofilms were grown on 316L stainless steel plates and the synergistic biofilm eradication activity was determined and characterized using adherent bacteria count, minimum biofilm eradication concentration (MBEC) measurement for GS, visualization by live/dead imaging, scanning electron microscopy, gene expression of biofilm-associated genes, and bacterial membrane fluidity assessment. RESULTS: Gentamicin-ketorolac (GS-KT) combination demonstrated synergistic antibacterial action against planktonic Staphylococci. Control and clinical strains showed distinct biofilm growth dynamics and an increase in biofilm maturity was shown to confer further resistance to gentamicin for both 'low-risk' and 'high-risk' biofilms. The addition of ketorolac enhanced the antibiofilm activity of gentamicin against acquired resistance in staphylococcal biofilms. Mechanistic studies revealed that the synergistic action of gentamicin-ketorolac interferes with biofilm morphology and subverts bacterial stress response altering bacterial physiology, membrane dynamics, and biofilm properties. CONCLUSION: The results of this study have a significant impact on the local administration of antibiotics and other therapeutic agents commonly used in the prevention and treatment of orthopaedic infections. Further, these results warrant the study of synergy for the concurrent or sequential administration of non-antibiotic drugs for antimicrobial effect.

Discontinuation of Contact Precautions for Methicillin-resistant Staphylococcus aureus in a Pediatric Healthcare System.

BACKGROUND: Many hospitals caring for adult patients have discontinued the requirement for contact precautions (CP) for patients with methicillin-resistant Staphylococcus aureus (MRSA) infection or colonization without reported negative effects. It is not clear whether this experience can be extrapolated to pediatric facilities. METHODS: CP for MRSA were discontinued in all locations except the neonatal intensive care unit at a 3-hospital pediatric healthcare system in September 2019. All hospitalized patients underwent surveillance for LabID healthcare facility-onset MRSA infections. Analysis was done using interrupted time series (ITS) from September 2017 through August 2023 and aggregate before-and-after rate ratios. RESULTS: There were 234 incident healthcare facility-onset MRSA infections during 766 020 patient days of surveillance. After discontinuation of CP for MRSA there was no change in the ITS slope (0.06, 95% CI: -0.35 to 0.47, P = .78) or intercept (0.21, 95% CI: -0.36 to 0.78, P = .47) of the LabID healthcare facility-onset MRSA infection incidence density rate. Additionally, there was no change in the aggregate incidence density rate of these MRSA LabID events (aggregate rate ratio = 0.98, 95% CI: 0.74 to 1.28). MRSA nasal colonization among patients being screened before cardiac surgery did not change (aggregate rate ratio = 0.94, 95% CI: 0.60 to 1.48). The prevalence rate of contact isolation days decreased by 14.0%. CONCLUSIONS: Discontinuation of CP for pediatric patients with MRSA was not associated with increased MRSA infection over 4 years. Our experience supports considering discontinuation of CP for MRSA in similar pediatric healthcare settings in the context of good adherence to horizontal infection prevention measures.

Efficacy of novel staphylococcal surface associated protein vaccines against Staphylococcus aureus and non-aureus staphylococcal mastitis in dairy cows.

Mastitis is an inflammation of the mammary gland commonly caused by bacteria or fungi. Staphylococcus aureus is a major bacterium that causes mastitis in dairy cows. Non-aureus staphylococci are also increasingly reported, with Staphylococcus chromogenes being the most common species. Current staphylococcal mastitis control programs are not fully effective, and treatment with antibiotics is not sustainable. Non-antibiotic sustainable control tools, such as effective vaccines, are critically needed. We previously developed S. aureus surface-associated proteins (SASP) and S. chromogenes surface-associated proteins (SCSP) vaccines that conferred partial protective effects. We hypothesized that vaccination with SASP or SCSP would reduce the incidence of S. aureus mastitis throughout the lactation period. The objective of this study was to evaluate the efficacy of SASP and SCSP vaccines against S. aureus and non-aureus staphylococcal mastitis under natural exposure over 300 days of lactation. Pregnant Holstein dairy cows (n = 45) were enrolled and assigned to receive SASP (n = 15) or SCSP (n = 16) vaccines or unvaccinated control (n = 14). Cows were vaccinated with 1.2 mg of SASP or SCSP with Emulsigen-D adjuvant. Control cows were injected with phosphate-buffered saline with Emulsigen-D adjuvant. Three vaccine injections were given subcutaneously at 60, 40, and 20 days before the expected calving. Booster vaccinations were given at 120 and 240 days in milk. Cows were monitored for mastitis at quarter and cow levels, staphylococcal mastitis incidence, changes in serum and milk anti-SASP and anti-SCSP antibody titers, bacterial counts in milk, adverse reactions, milk yield and milk somatic cells count over 300 days of lactation. The SCSP vaccine conferred a significant reduction in the incidence of staphylococcal mastitis. Milk and serum anti-SASP and anti-SCSP antibody titers were increased in the vaccinated cows compared to unvaccinated control cows. Anti-SASP and anti-SCSP antibody titers decreased at about 120 days in milk, indicating the duration of immunity of about four months. In conclusion, the SASP and SCSP vaccines conferred partial protection from natural infection.

Factors associated with patient-to-healthcare personnel (HCP) and HCP-to-subsequent patient transmission of methicillin-resistant Staphylococcus aureus.

BACKGROUND: Transient acquisition of methicillin-resistant Staphylococcus aureus (MRSA) on healthcare personnel (HCP) gloves and gowns following patient care has been examined. However, the potential for transmission to the subsequent patient has not been studied. We explored the frequency of MRSA transmission from patient to HCP, and then in separate encounters from contaminated HCP gloves and gowns to a subsequent simulated patient as well as the factors associated with these 2 transmission pathways. METHODS: We conducted a prospective cohort study with 2 parts. In objective 1, we studied MRSA transmission from random MRSA-positive patients to HCP gloves and gowns after specific routine patient care activities. In objective 2, we simulated subsequent transmission from random HCP gloves and gowns without hand hygiene to the next patient using a manikin proxy. RESULTS: For the first objective, among 98 MRSA-positive patients with 333 randomly selected individual patient-HCP interactions, HCP gloves or gowns were contaminated in 54 interactions (16.2%). In a multivariable analysis, performing endotracheal tube care had the greatest odds of glove or gown contamination (OR, 4.06; 95% CI, 1.3-12.6 relative to physical examination). For the second objective, after 147 simulated HCP-patient interactions, the subsequent transmission of MRSA to the manikin proxy occurred 15 times (10.2%). CONCLUSION: After caring for a patient with MRSA, contamination of HCP gloves and gown and transmission to subsequent patients following HCP-patient interactions occurs frequently if contact precautions are not used. Proper infection control practices, including the use of gloves and gown, can prevent this potential subsequent transmission.

A novel antibacterial compound decreases MRSA biofilm formation without the use of antibiotics in a murine model.

Despite significant advancements in material science, surgical site infection (SSI) rates remain high and prevention is key. This study aimed to demonstrate the in vivo safety and antibacterial efficacy of titanium implants treated with a novel broad-spectrum biocidal compound (DBG21) against methicillin-resistant Staphylococcus aureus (MRSA). Titanium (Ti) discs were covalently bound with DBG21. Untreated Ti discs were used as controls. All discs were implanted either untreated for 44 control mice or DBG21-treated for 44 treated mice. After implantation, 1 × 107 colony forming units (CFU) of MRSA were injected into the operating site. Mice were killed at 7 and 14 days to determine the number of adherent bacteria (biofilm) on implants and in the peri-implant surrounding tissues. Systemic and local toxicity were assessed. At both 7 and 14 days, DBG21-treated implants yielded a significant decrease in MRSA biofilm (3.6 median log10 CFU [99.97%] reduction [p < 0.001] and 1.9 median log10 CFU [98.7%] reduction [p = 0.037], respectively) and peri-implant surrounding tissues (2.7 median log10 CFU/g [99.8%] reduction [p < 0.001] and 5.6 median log10 CFU/g [99.9997%] reduction [p < 0.001], respectively). There were no significant differences between control and treated mice in terms of systemic and local toxicity. DBG-21 demonstrated a significant decrease in the number of biofilm bacteria without associated toxicity in a small animal implant model of SSI. Preventing biofilm formation has been recognized as a key element of preventing implant-related infections.

Cost-effectiveness of a real-time spatiotemporal mapping surveillance system for meticillin-resistant Staphylococcus aureus prevention.

OBJECTIVES: An infection surveillance system based on a hospital's digital twin [4D-Disease Outbreak Surveillance System (4D-DOSS)] is being developed in Singapore. It offers near-real-time infection surveillance and mapping capabilities. This early economic modelling study was conducted, using meticillin-resistant Staphylococcus aureus (MRSA) as the pathogen of interest, to assess the potential cost-effectiveness of 4D-DOSS. METHODS: A Markov model that simulates the likelihood of MRSA colonization and infection was developed to evaluate the cost-effectiveness of adopting 4D-DOSS for MRSA surveillance from the hospital perspective, compared with current practice. The cycle duration was 1 day, and the model horizon was 30 days. Probabilistic sensitivity analysis was conducted, and the probability of cost-effectiveness was reported. Scenario analyses and a value of information analysis were performed. RESULTS: In the base-case scenario, with 10-year implementation/maintenance costs of 4D-DOSS of $0, there was 68.6% chance that 4D-DOSS would be cost-effective. In a more pessimistic but plausible scenario where the effectiveness of 4D-DOSS in reducing MRSA transmission was one-quarter of the base-case scenario with 10-year implementation/maintenance costs of $1 million, there was 47.7% chance that adoption of 4D-DOSS would be cost-effective. The value of information analysis showed that uncertainty in MRSA costs made the greatest contribution to model uncertainty. CONCLUSIONS: This early-stage modelling study revealed the circumstances for which 4D-DOSS is likely to be cost-effective at the current willingness-to-pay threshold, and identified the parameters for which further research will be worthwhile to reduce model uncertainty. Inclusion of other drug-resistant organisms will provide a more thorough assessment of the cost-effectiveness of 4D-DOSS.

Microbiome dysbiosis: a modifiable state and target to prevent Staphylococcus aureus infections and other diseases in neonates.

Bacterial infections present a significant threat to neonates. Increasingly, studies demonstrate associations between human diseases and the microbiota, the communities of microorganisms on or in the body. A "healthy" microbiota with a great diversity and balance of microorganisms can resist harmful pathogens and protect against infections, whereas a microbiota suffering from dysbiosis, can predispose to pathogen colonization and subsequent infection. For decades, strategies such as bacterial interference, decolonization, prebiotics, and probiotics have been tested to reduce Staphylococcus aureus disease and other infections in neonates. More recently, microbiota transplant has emerged as a strategy to broadly correct dysbiosis, promote colonization resistance, and prevent infections. This paper discusses the benefits of a healthy neonate's microbiota, exposures that alter the microbiota, associations of dysbiosis and neonatal disease, strategies to prevent dysbiosis, such as microbiota transplantation, and presents a framework of microbiome manipulation to reduce Staphylococcus aureus (S. aureus) and other infections in neonates.

Efficacy of Lysostaphin functionalized silicon catheter for the prevention of Staphylococcus aureus biofilm.

Staphylococcus aureus readily forms biofilms on tissue and indwelling catheter surfaces. These biofilms are resistant to antibiotics. Consequently, effective prevention and treatment strategies against staphylococcal biofilms are actively being pursued over the past two decades. One of the proposed strategies involve the incorporation of antibiotics and antiseptics into catheters, however, a persistent concern regarding the possible emergence of antimicrobial resistance is associated with these medical devices. In this study, we developed two types of silicone catheters: one with Lysostaphin (Lst) adsorbed onto the surface, and the other with Lst functionalized on the surface. To confirm the presence of Lst protein on the catheter surface, we conducted FTIR-ATR and SEM-EDS analysis. Both catheters exhibited hemocompatibility, biocompatibility, and demonstrated antimicrobial and biofilm prevention activities against both methicillin-sensitive and resistant strains of S. aureus. Furthermore, the silicone catheters that were surface-functionalized with Lst showed substantially better and more persistent anti-biofilm effects when compared to the catheters where Lst was surface-adsorbed, both under in vitro static and flow conditions, as well as in vivo in BALB/c mice. These results indicate that surface-functionalized Lst catheters have the potential to serve as a promising new medical device for preventing S. aureus biofilm infections in humans.

Effect of contact precautions on preventing meticillin-resistant Staphylococcus aureus transmission in intensive care units: a review and modelling study of field trials.

BACKGROUND: Contact precautions (CPs) have been widely implemented in hospitals, particularly in intensive care units (ICUs), as the standard approach for managing meticillin-resistant Staphylococcus aureus (MRSA). However, the effectiveness of CPs in preventing MRSA transmission remains a subject of debate. AIM: To assess the effectiveness of CPs in reducing MRSA transmission within ICUs. METHODS: A comprehensive analysis was conducted using data from 16 sets of parameters collected from 13 field studies investigating the effectiveness of CPs in ICUs, and an epidemiologic model was developed to simulate the dynamics of MRSA incidence in the hospital setting. FINDINGS: The analysis demonstrated a mean reduction of 20.52% (95% confidence interval -30.52 to 71.60%) in the MRSA transmission rate associated with the implementation of CPs. Furthermore, reducing the time-delay of screening tests and increasing the percentage of patients identified with MRSA through screening at admission were found to contribute to the effectiveness of CPs. CONCLUSION: Proper implementation of CPs, with a particular emphasis on early identification of MRSA-colonized/infected patients, demonstrated a strong association with reduced MRSA transmission within the hospital setting. However, further research is necessary to investigate the effectiveness and safety of decolonization and other interventions used in conjunction with CPs to mitigate the risk of infection among colonized patients.