Reducing Hospitalizations and Multidrug-Resistant Organisms via Regional Decolonization in Hospitals and Nursing Homes.

Importance: Infections due to multidrug-resistant organisms (MDROs) are associated with increased morbidity, mortality, length of hospitalization, and health care costs. Regional interventions may be advantageous in mitigating MDROs and associated infections. Objective: To evaluate whether implementation of a decolonization collaborative is associated with reduced regional MDRO prevalence, incident clinical cultures, infection-related hospitalizations, costs, and deaths. Design, Setting, and Participants: This quality improvement study was conducted from July 1, 2017, to July 31, 2019, across 35 health care facilities in Orange County, California. Exposures: Chlorhexidine bathing and nasal iodophor antisepsis for residents in long-term care and hospitalized patients in contact precautions (CP). Main Outcomes and Measures: Baseline and end of intervention MDRO point prevalence among participating facilities; incident MDRO (nonscreening) clinical cultures among participating and nonparticipating facilities; and infection-related hospitalizations and associated costs and deaths among residents in participating and nonparticipating nursing homes (NHs). Results: Thirty-five facilities (16 hospitals, 16 NHs, 3 long-term acute care hospitals [LTACHs]) adopted the intervention. Comparing decolonization with baseline periods among participating facilities, the mean (SD) MDRO prevalence decreased from 63.9% (12.2%) to 49.9% (11.3%) among NHs, from 80.0% (7.2%) to 53.3% (13.3%) among LTACHs (odds ratio [OR] for NHs and LTACHs, 0.48; 95% CI, 0.40-0.57), and from 64.1% (8.5%) to 55.4% (13.8%) (OR, 0.75; 95% CI, 0.60-0.93) among hospitalized patients in CP. When comparing decolonization with baseline among NHs, the mean (SD) monthly incident MDRO clinical cultures changed from 2.7 (1.9) to 1.7 (1.1) among participating NHs, from 1.7 (1.4) to 1.5 (1.1) among nonparticipating NHs (group × period interaction reduction, 30.4%; 95% CI, 16.4%-42.1%), from 25.5 (18.6) to 25.0 (15.9) among participating hospitals, from 12.5 (10.1) to 14.3 (10.2) among nonparticipating hospitals (group × period interaction reduction, 12.9%; 95% CI, 3.3%-21.5%), and from 14.8 (8.6) to 8.2 (6.1) among LTACHs (all facilities participating; 22.5% reduction; 95% CI, 4.4%-37.1%). For NHs, the rate of infection-related hospitalizations per 1000 resident-days changed from 2.31 during baseline to 1.94 during intervention among participating NHs, and from 1.90 to 2.03 among nonparticipating NHs (group × period interaction reduction, 26.7%; 95% CI, 19.0%-34.5%). Associated hospitalization costs per 1000 resident-days changed from $64 651 to $55 149 among participating NHs and from $55 151 to $59 327 among nonparticipating NHs (group × period interaction reduction, 26.8%; 95% CI, 26.7%-26.9%). Associated hospitalization deaths per 1000 resident-days changed from 0.29 to 0.25 among participating NHs and from 0.23 to 0.24 among nonparticipating NHs (group × period interaction reduction, 23.7%; 95% CI, 4.5%-43.0%). Conclusions and Relevance: A regional collaborative involving universal decolonization in long-term care facilities and targeted decolonization among hospital patients in CP was associated with lower MDRO carriage, infections, hospitalizations, costs, and deaths.

Characterizing predictors of COVID-19 vaccine refusal in an urban southern California jail population.

BACKGROUND: Correctional populations have been disproportionately affected by COVID-19, and many large outbreaks have occurred in jails and prisons. Vaccination is a key strategy to reduce the SARS-CoV-2 transmission in carceral settings. Although implementation can be challenging due to vaccine hesitancy and medical mistrust, correctional settings provide largely equitable healthcare access and present a unique opportunity to identify potential predictors of vaccine hesitancy independent of access issues. METHODS: We retrospectively analyzed electronic health record data for individuals offered COVID-19 vaccination at the Los Angeles County Jail between January 19, 2021, and January 31, 2023, and used multivariable logistic regression to determine predictors of COVID-19 vaccine refusal. RESULTS: Of the 21,424 individuals offered COVID-19 vaccination, 2,060 (9.6 %) refused. Refusal was associated with male sex ([aOR] = 2.3, 95 % CI (1.9, 2.8)), age 18-34 ([aOR] = 1.2, 95 % CI (1.1, 1.4), referent group: age 45-54), Black race ([aOR] = 1.2, 95 % CI (1.1, 1.4)), reporting ever being houseless ([aOR] = 1.2, 95 % CI (1.1, 1.3)), and having a history of not receiving influenza vaccination while incarcerated ([aOR] = 2.4, 95 % CI (2.0, 2.8)). When analyzing male and female populations separately, male-specific trends reflected those seen in the overall population, whereas the only significant predictor of vaccine refusal in the female population was not receiving influenza vaccination while in custody ([aOR] = 6.5, 95 % CI (2.4, 17.6)). CONCLUSION: Identifying predictors of vaccine refusal in correctional populations is an essential first step in the development and implementation of targeted interventions to mitigate vaccine hesitancy.

Skin and soft tissue infection incidence before and during the COVID-19 pandemic.

Skin and Soft Tissue Infections (SSTIs) are common bacterial infections. We hypothesized that due to the COVID-19 pandemic, SSTI rates would significantly decrease due to directives to avoid unneeded care and attenuated SSTIs risk behaviours. We retrospectively examined all patients with an ICD-10 diagnosis code in the Los Angeles County Department of Health Services, the second largest U.S. safety net healthcare system between 16 March 2017 and 15 March 2022. We then compared pre-pandemic with intra-pandemic SSTI rates using an interrupted time series analysis. We found 72,118 SSTIs, 46,206 during the pre-pandemic period and 25,912 during the intra-pandemic period. Pre-pandemic SSTI rate was significantly higher than the intra-pandemic rate (3.27 vs. 2.31 cases per 1,000 empanelled patient-months, P < 0.0001). The monthly SSTI cases decreased by 1.19 SSTIs/1,000 empanelled patient-months between the pre- and intra-pandemic periods (P = 0.0003). SSTI subgroups (inpatient, observation unit, emergency department, and outpatient clinics), all had significant SSTI decreases between the two time periods (P < 0.05) except for observation unit (P = 0.50). Compared to the pre-COVID-19 pandemic period, medically attended SSTI rates in our large U.S. safety net healthcare system significantly decreased by nearly 30%. Whether findings reflect true SSTI decreases or decreased health system utilization for SSTIs requires further examination.

Decolonization in Nursing Homes to Prevent Infection and Hospitalization.

BACKGROUND: Nursing home residents are at high risk for infection, hospitalization, and colonization with multidrug-resistant organisms. METHODS: We performed a cluster-randomized trial of universal decolonization as compared with routine-care bathing in nursing homes. The trial included an 18-month baseline period and an 18-month intervention period. Decolonization entailed the use of chlorhexidine for all routine bathing and showering and administration of nasal povidone-iodine twice daily for the first 5 days after admission and then twice daily for 5 days every other week. The primary outcome was transfer to a hospital due to infection. The secondary outcome was transfer to a hospital for any reason. An intention-to-treat (as-assigned) difference-in-differences analysis was performed for each outcome with the use of generalized linear mixed models to compare the intervention period with the baseline period across trial groups. RESULTS: Data were obtained from 28 nursing homes with a total of 28,956 residents. Among the transfers to a hospital in the routine-care group, 62.2% (the mean across facilities) were due to infection during the baseline period and 62.6% were due to infection during the intervention period (risk ratio, 1.00; 95% confidence interval [CI], 0.96 to 1.04). The corresponding values in the decolonization group were 62.9% and 52.2% (risk ratio, 0.83; 95% CI, 0.79 to 0.88), for a difference in risk ratio, as compared with routine care, of 16.6% (95% CI, 11.0 to 21.8; P<0.001). Among the discharges from the nursing home in the routine-care group, transfer to a hospital for any reason accounted for 36.6% during the baseline period and for 39.2% during the intervention period (risk ratio, 1.08; 95% CI, 1.04 to 1.12). The corresponding values in the decolonization group were 35.5% and 32.4% (risk ratio, 0.92; 95% CI, 0.88 to 0.96), for a difference in risk ratio, as compared with routine care, of 14.6% (95% CI, 9.7 to 19.2). The number needed to treat was 9.7 to prevent one infection-related hospitalization and 8.9 to prevent one hospitalization for any reason. CONCLUSIONS: In nursing homes, universal decolonization with chlorhexidine and nasal iodophor led to a significantly lower risk of transfer to a hospital due to infection than routine care. (Funded by the Agency for Healthcare Research and Quality; Protect ClinicalTrials.gov number, NCT03118232.).

Priorities and Progress in Gram-positive Bacterial Infection Research by the Antibacterial Resistance Leadership Group: A Narrative Review.

The Antibacterial Resistance Leadership Group (ARLG) has prioritized infections caused by gram-positive bacteria as one of its core areas of emphasis. The ARLG Gram-positive Committee has focused on studies responding to 3 main identified research priorities: (1) investigation of strategies or therapies for infections predominantly caused by gram-positive bacteria, (2) evaluation of the efficacy of novel agents for infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci, and (3) optimization of dosing and duration of antimicrobial agents for gram-positive infections. Herein, we summarize ARLG accomplishments in gram-positive bacterial infection research, including studies aiming to (1) inform optimal vancomycin dosing, (2) determine the role of dalbavancin in MRSA bloodstream infection, (3) characterize enterococcal bloodstream infections, (4) demonstrate the benefits of short-course therapy for pediatric community-acquired pneumonia, (5) develop quality of life measures for use in clinical trials, and (6) advance understanding of the microbiome. Future studies will incorporate innovative methodologies with a focus on interventional clinical trials that have the potential to change clinical practice for difficult-to-treat infections, such as MRSA bloodstream infections.

Bayesian modeling of the impact of antibiotic resistance on the efficiency of MRSA decolonization.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of morbidity and mortality. Colonization by MRSA increases the risk of infection and transmission, underscoring the importance of decolonization efforts. However, success of these decolonization protocols varies, raising the possibility that some MRSA strains may be more persistent than others. Here, we studied how the persistence of MRSA colonization correlates with genomic presence of antibiotic resistance genes. Our analysis using a Bayesian mixed effects survival model found that genetic determinants of high-level resistance to mupirocin was strongly associated with failure of the decolonization protocol. However, we did not see a similar effect with genetic resistance to chlorhexidine or other antibiotics. Including strain-specific random effects improved the predictive performance, indicating that some strain characteristics other than resistance also contributed to persistence. Study subject-specific random effects did not improve the model. Our results highlight the need to consider the properties of the colonizing MRSA strain when deciding which treatments to include in the decolonization protocol.

Safety and tolerability of tedizolid as oral treatment for bone and joint infections.

Bone and joint infections (BJIs) are common infections increasingly managed with oral therapy. However, there are limited safe oral options for many Gram-positive pathogens. In animal studies and short-term human use, tedizolid lacks the hematologic and neurologic toxicity of the other available oxazolidinone, linezolid. However, there are limited prospective safety data. We conducted an open-label, non-comparative trial of oral tedizolid for BJI treatment. Primary outcomes were safety and cure rate. Eligible patients had a BJI caused by documented or suspected Gram-positive pathogen, required 4-12 weeks of therapy, and did not have myelosuppression or peripheral/optic neuropathy. Subjects underwent weekly evaluation for cytopenias and neuropathy. We enrolled 44 subjects; five were lost to follow-up. Two subjects did not complete planned treatment because of rash (n = 1) and urgent surgery (n = 1). Of 37 patients with evaluable outcomes, 17 (46%) had hardware-associated infection, 13 (35%) had osteomyelitis, 5 (14%) had prosthetic joint infection, and 2 (5%) had other BJIs. Median (mean, range) treatment duration was 12 (10.1, 4-12) weeks. There were no cases of cytopenias or peripheral or optic neuropathy. Treatment cure occurred in 13 (35%); 19 (51%) required antibiotic continuation after 12 weeks of tedizolid related to retained hardware at the BJI site, and failure occurred in four (11%), two unlikely, one possibly, and one probably due to tedizolid. We found that oral tedizolid was well tolerated for prolonged BJI treatment without significant toxicity. Clinical failure rate was similar to that of other published BJI investigations. (This study has been registered at Clinicaltrials.gov under identifier NCT03009045.) IMPORTANCE Bone and joint infections are common infections with limited effective and safe oral options for Gram-positive infections. The largest prospective clinical trial of tedizolid therapy for bone and joint infections enrolled 44 patients and tested each in person weekly with detailed safety monitoring including tests for leukopenia, anemia, thrombocytopenia, peripheral neuropathy, and optic neuropathy for up to 12 weeks. Findings demonstrated tedizolid was generally well tolerated and there were no incident cases of cytopenias or neuropathy. Cure rates were similar to that in other bone and joint infection studies. In summary, oral tedizolid appears to be a well-tolerated oral option for Gram-positive bone and joint infections.

Clinical and Bacterial Characteristics Associated with Glove and Gown Contamination by Carbapenem-Resistant Klebsiella pneumoniae in the Health Care Setting.

Carbapenem-resistant Klebsiella pneumoniae (CRKp) is a pathogen of significant concern to public health, as it has become increasingly associated with difficult-to-treat community-acquired and hospital-associated infections. Transmission of K. pneumoniae between patients through interactions with shared health care personnel (HCP) has been described as a source of infection in health care settings. However, it is not known whether specific lineages or isolates of K. pneumoniae are associated with increased transmission. Thus, we used whole-genome sequencing to analyze the genetic diversity of 166 carbapenem-resistant K. pneumoniae isolates from five U.S. hospitals in four states as part of a multicenter study examining risk factors for glove and gown contamination by carbapenem-resistant Enterobacterales (CRE). The CRKp isolates exhibited considerable genomic diversity with 58 multilocus sequence types (STs), including four newly designated STs. ST258 was the most prevalent ST, representing 31% (52/166) of the CRKp isolates, but was similarly prevalent among patients who had high, intermediate, and low CRKp transmission. Increased transmission was associated with clinical characteristics including a nasogastric (NG) tube or an endotracheal tube or tracheostomy (ETT/Trach). Overall, our findings provide important insight into the diversity of CRKp associated with transmission from patients to the gloves and gowns of HCP. These findings suggest that certain clinical characteristics and the presence of CRKp in the respiratory tract, rather than specific lineages or genetic content, are more often associated with increased transmission of CRKp from patients to HCP. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae (CRKp) is a significant public health concern that has contributed to the spread of carbapenem resistance and has been linked to high morbidity and mortality. Transmission of K. pneumoniae among patients through interactions with shared health care personnel (HCP) has been described as a source of infection in health care settings; however, it remains unknown whether particular bacterial characteristics are associated with increased CRKp transmission. Using comparative genomics, we demonstrate that CRKp isolates associated with high or intermediate transmission exhibit considerable genomic diversity, and there were no K. pneumoniae lineages or genes that were universally predictive of increased transmission. Our findings suggest that certain clinical characteristics and the presence of CRKp, rather than specific lineages or genetic content of CRKp, are more often associated with increased transmission of CRKp from patients to HCP.

Longitudinal analysis of SARS-CoV-2 infection and vaccination in the LA-SPARTA cohort reveals increased risk of infection in vaccinated Hispanic participants.

Introduction: SARS-CoV-2 is the etiologic agent of coronavirus disease 2019 (COVID-19). Questions remain regarding correlates of risk and immune protection against COVID-19. Methods: We prospectively enrolled 200 participants with a high risk of SARS-CoV-2 occupational exposure at a U.S. medical center between December 2020 and April 2022. Participant exposure risks, vaccination/infection status, and symptoms were followed longitudinally at 3, 6, and 12 months, with blood and saliva collection. Serological response to the SARS-CoV-2 spike holoprotein (S), receptor binding domain (RBD) and nucleocapsid proteins (NP) were quantified by ELISA assay. Results: Based on serology, 40 of 200 (20%) participants were infected. Healthcare and non-healthcare occupations had equivalent infection incidence. Only 79.5% of infected participants seroconverted for NP following infection, and 11.5% were unaware they had been infected. The antibody response to S was greater than to RBD. Hispanic ethnicity was associated with 2-fold greater incidence of infection despite vaccination in this cohort. Discussion: Overall, our findings demonstrate: 1) variability in the antibody response to SARS-CoV-2 infection despite similar exposure risk; 2) the concentration of binding antibody to the SARS-CoV-2 S or RBD proteins is not directly correlated with protection against infection in vaccinated individuals; and 3) determinants of infection risk include Hispanic ethnicity despite vaccination and similar occupational exposure.

Characterization of COVID-19 Vaccine Hesitancy Among Essential Workforce Members of a Large Safety Net Urban Medical Center.

OBJECTIVES: Vaccine hesitancy among essential workers remains a significant public health challenge. We examined psychological constructs of perceived susceptibility, threat, and self-efficacy and their associations with COVID-19 vaccine hesitancy among a racially and ethnically diverse essential workforce population. METHODS: We performed a cross-sectional survey of essential workers from September-December 2020 at a large Los Angeles safety-net medical center as part of a program offering free COVID-19 serology testing. Program participants completed a standardized survey at the time of phlebotomy. Hierarchical logistic regression was utilized to determine factors independently associated with vaccine hesitancy. RESULTS: Among 1327 persons who had serology testing, 1235 (93%) completed the survey. Of these, 958 (78%) were healthcare workers. Based on expressed intent, 22% were vaccine-hesitant 78% were vaccine acceptors. In our multivariate model, vaccine hesitancy was associated with female gender [aOR = 2.09; 95% CI (1.44-3.05)], African American race [aOR = 4.32; (2.16-8.62)], LatinX ethnicity [aOR = 2.47; 95% CI (1.51-4.05)] and history of not/sometimes receiving influenza vaccination [aOR = 4.39; 95% CI (2.98-6.48)]. Compared to nurses, vaccine hesitancy was lower among physicians [aOR = 0.09; 95% CI (0.04-0.23)], non-nursing/non-physician healthcare workers [aOR = 0.55; 95% CI (0.33-0.92)], and non-healthcare care workers [aOR = 0.53; 95% CI (0.36-0.78)]. CONCLUSIONS: Among a racially/ethnically diverse group of safety net medical center essential workers, COVID-19 vaccine hesitancy was associated with racial/ethnic minority groups, employment type, and prior influenza vaccination hesitancy. Interestingly, we found no association with the Health Belief Model construct measures of perceived susceptibility, threat, and self-efficacy. Psychological constructs not assessed may be drivers of vaccine hesitancy in our population.

Post-discharge decolonization of patients harboring methicillin-resistant Staphylococcus aureus (MRSA) USA300 strains: secondary analysis of the CLEAR Trial.

The CLEAR Trial recently found that decolonization reduced infections and hospitalizations in MRSA carriers in the year following hospital discharge. In this secondary analysis, we explored whether decolonization had a similar benefit in the subgroup of trial participants who harbored USA300, using two different definitions for the USA300 strain-type.

Chlorhexidine and Mupirocin for Clearance of Methicillin-Resistant Staphylococcus aureus Colonization After Hospital Discharge: A Secondary Analysis of the Changing Lives by Eradicating Antibiotic Resistance Trial.

BACKGROUND: The CLEAR Trial demonstrated that a multisite body decolonization regimen reduced post-discharge infection and hospitalization in methicillin-resistant Staphylococcus aureus (MRSA) carriers. Here, we describe decolonization efficacy. METHODS: We performed a large, multicenter, randomized clinical trial of MRSA decolonization among adult patients after hospital discharge with MRSA infection or colonization. Participants were randomized 1:1 to either MRSA prevention education or education plus decolonization with topical chlorhexidine, oral chlorhexidine, and nasal mupirocin. Participants were swabbed in the nares, throat, axilla/groin, and wound (if applicable) at baseline and 1, 3, 6, and 9 months after randomization. The primary outcomes of this study are follow-up colonization differences between groups. RESULTS: Among 2121 participants, 1058 were randomized to decolonization. By 1 month, MRSA colonization was lower in the decolonization group compared with the education-only group (odds ration [OR] = 0.44; 95% confidence interval [CI], .36-.54; P ≤ .001). A similar magnitude of reduction was seen in the nares (OR = 0.34; 95% CI, .27-.42; P < .001), throat (OR = 0.55; 95% CI, .42-.73; P < .001), and axilla/groin (OR = 0.57; 95% CI, .43-.75; P < .001). These differences persisted through month 9 except at the wound site, which had a relatively small sample size. Higher regimen adherence was associated with lower MRSA colonization (P ≤ .01). CONCLUSIONS: In a randomized, clinical trial, a repeated post-discharge decolonization regimen for MRSA carriers reduced MRSA colonization overall and at multiple body sites. Higher treatment adherence was associated with greater reductions in MRSA colonization.

Clinical Impact of Ceftriaxone Resistance in Escherichia coli Bloodstream Infections: A Multicenter Prospective Cohort Study.

Background: Ceftriaxone-resistant (CRO-R) Escherichia coli bloodstream infections (BSIs) are common. Methods: This is a prospective cohort of patients with E coli BSI at 14 United States hospitals between November 2020 and April 2021. For each patient with a CRO-R E coli BSI enrolled, the next consecutive patient with a ceftriaxone-susceptible (CRO-S) E coli BSI was included. Primary outcome was desirability of outcome ranking (DOOR) at day 30, with 50% probability of worse outcomes in the CRO-R group as the null hypothesis. Inverse probability weighting (IPW) was used to reduce confounding. Results: Notable differences between patients infected with CRO-R and CRO-S E coli BSI included the proportion with Pitt bacteremia score ≥4 (23% vs 15%, P = .079) and the median time to active antibiotic therapy (12 hours [interquartile range {IQR}, 1-35 hours] vs 1 hour [IQR, 0-6 hours]; P < .001). Unadjusted DOOR analyses indicated a 58% probability (95% confidence interval [CI], 52%-63%) for a worse clinical outcome in CRO-R versus CRO-S BSI. In the IPW-adjusted cohort, no difference was observed (54% [95% CI, 47%-61%]). Secondary outcomes included unadjusted and adjusted differences in the proportion of 30-day mortality between CRO-R and CRO-S BSIs (-5.3% [95% CI, -10.3% to -.4%] and -1.8 [95% CI, -6.7% to 3.2%], respectively), postculture median length of stay (8 days [IQR, 5-13 days] vs 6 days [IQR, 4-9 days]; P < .001), and incident admission to a long-term care facility (22% vs 12%, P = .045). Conclusions: Patients with CRO-R E coli BSI generally have poorer outcomes compared to patients infected with CRO-S E coli BSI, even after adjusting for important confounders.

Modelling methicillin-resistant Staphylococcus aureus decolonization: interactions between body sites and the impact of site-specific clearance.

Methicillin-resistant Staphylococcus aureus (MRSA) can colonize multiple body sites, and carriage is a risk factor for infection. Successful decolonization protocols reduce disease incidence; however, multiple protocols exist, comprising diverse therapies targeting multiple body sites, and the optimal protocol is unclear. Standard methods cannot infer the impact of site-specific components on successful decolonization. Here, we formulate a Bayesian coupled hidden Markov model, which estimates interactions between body sites, quantifies the contribution of each therapy to successful decolonization, and enables predictions of the efficacy of therapy combinations. We applied the model to longitudinal data from a randomized controlled trial (RCT) of an MRSA decolonization protocol consisting of chlorhexidine body and mouthwash and nasal mupirocin. Our findings (i) confirmed nares as a central hub for MRSA colonization and nasal mupirocin as the most crucial therapy and (ii) demonstrated all components contributed significantly to the efficacy of the protocol and the protocol reduced self-inoculation. Finally, we assessed the impact of hypothetical therapy improvements in silico and found that enhancing MRSA clearance at the skin would yield the largest gains. This study demonstrates the use of advanced modelling to go beyond what is typically achieved by RCTs, enabling evidence-based decision-making to streamline clinical protocols.

PARIS and SPARTA: Finding the Achilles' Heel of SARS-CoV-2.

To understand reinfection rates and correlates of protection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we established eight different longitudinal cohorts in 2020 under the umbrella of the PARIS (Protection Associated with Rapid Immunity to SARS-CoV-2)/SPARTA (SARS SeroPrevalence And Respiratory Tract Assessment) studies. Here, we describe the PARIS/SPARTA cohorts, the harmonized assays and analysis that are performed across the cohorts, as well as case definitions for SARS-CoV-2 infection and reinfection that have been established by the team of PARIS/SPARTA investigators. IMPORTANCE Determining reinfection rates and correlates of protection against SARS-CoV-2 infection induced by both natural infection and vaccination is of high significance for the prevention and control of coronavirus disease 2019 (COVID-19). Furthermore, understanding reinfections or infection after vaccination and the role immune escape plays in these scenarios will inform the need for updates of the current SARS-CoV-2 vaccines and help update guidelines suitable for the postpandemic world.

Comparative Genomics Identifies Features Associated with Methicillin-Resistant Staphylococcus aureus (MRSA) Transmission in Hospital Settings.

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious public health concern in the United States. Patients colonized and/or infected can transmit MRSA to healthcare workers and subsequent patients However, the components of this transmission chain are just becoming evident, including certain patient factors, specific patient-healthcare worker interactions, and microbial factors. We conducted a comparative genomic analysis of 388 isolates from four hospitals in three states: Maryland, California, and New York. Isolates from nasal surveillance or clinical cultures were categorized as high, moderate, or low transmission surrogate outcomes based on the number of times the species was identified on the gloves or gowns of healthcare providers. The comparative analyses included a single gene, multigene, and core genome phylogenetic analysis, as well as a genome-wide association analysis to identify molecular signatures associated with the observed transmission surrogate outcomes, geographic origin, or sample source of isolation. Based on the phylogenetic analysis, 95% (n = 372) of the MRSA isolates were from four well-described genomic clades, with most of the isolates being part of the USA300 containing clade (n = 187; 48%). Genome-wide association studies also identified genes that were exclusive or prevalent among specific geographic locations. The identified genes provide insights into the transmission dynamics of MRSA isolates providing additional insights into the basis of the geographical differences of MRSA for molecular diagnostics. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is considered a serious threat to public health and contributes to the dissemination of S. aureus in both the healthcare and community setting. Transmission of MRSA between patients via healthcare worker (HCW) has been described. However, what is not understood are the genetic determinants that contribute to the transmission of MRSA from patients to HCWs. In this study, we demonstrated that certain genes may be associated with transmission in the hospital setting.