Genomic Epidemiology Suggests Community Origins of Healthcare-Associated USA300 Methicillin-Resistant Staphylococcus aureus.

BACKGROUND: Hospital-onset (HO) methicillin-resistant Staphylococcus aureus (MRSA) infections have declined over the past decade due to infection control strategies; community-onset (CO) and healthcare-associated community-onset (HACO) MRSA, particularly USA300, has declined less. We examined the role of community strains to explain the difference. METHODS: We performed whole-genome sequencing (WGS) on MRSA clinical isolates from Cook County Health patients during 2011-2014. We defined infections as CO, HO, or HACO epidemiologically. We integrated genomic, community exposure, and statewide hospital discharge data to infer MRSA origin. RESULTS: Among 1020 individuals with available WGS, most were USA300 wound infections (580 CO, 143 HO, 297 HACO). USA300 HO, CO, and HACO infections were intermixed on the USA300 phylogeny, consistent with common strains circulating across community and healthcare settings. Community exposures (eg, substance abuse, incarceration, homelessness) were associated with HACO and HO infections, and genetically linked individuals from both groups had little overlap in healthcare facilities, supporting community origins. Most repeat infections-over months to years-occurred in individuals persistently carrying their own strains. These individuals were more likely to have genetic linkages, suggesting a role of persistent colonization in transmission. CONCLUSIONS: Efforts to reduce presumed nosocomial USA300 spread may require understanding and controlling community sources and transmission networks, particularly for repeat infections.

MRSA Transmission in Intensive Care Units: Genomic Analysis of Patients, Their Environments, and Healthcare Workers.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA)-and now USA300 MRSA-is a significant intensive care unit (ICU) pathogen; healthcare worker (HCW) contamination may lead to patient cross-transmission. METHODS: From September 2015 to February 2016, to study the spread of MRSA, we enrolled HCWs in 4 adult ICUs caring for patients on MRSA contact precautions. Samples were collected from patient body sites and high-touch surfaces in patient rooms. HCW hands, gloves, and personal protective equipment were sampled pre/post-patient encounter. Whole genome sequencing (WGS) was used to compare isolates from patients, HCWs, and environment. RESULTS: There were 413 MRSA isolates sequenced (38% USA300, 52% USA100) from 66 patient encounters. Six of 66 HCWs were contaminated with MRSA prior to room entry. Isolates from a single patient encounter were typically either USA100 or USA300; in 8 (12%) encounters both USA300 and USA100 were isolated. WGS demonstrated that isolates from patients, HCWs, and environment often were genetically similar, although there was substantial between-encounter diversity. Strikingly, there were 5 USA100 and 1 USA300 clusters that contained similar strains (<22 single-nucleotide variants [SNVs], with most <10 SNVs) within the cluster despite coming from different encounters, suggesting intra- and inter-ICU spread of strains, that is, 4 of these genomic clusters were from encounters in the same ICU; 5 of 6 clusters occurred within 1 week. CONCLUSIONS: We demonstrated frequent spread of MRSA USA300 and USA100 strains among patients, environment, and HCWs. WGS identified possible spread within and even between ICUs. Future analysis with detailed contact tracing in conjunction with genomic data may further elucidate pathways of MRSA spread and points for intervention.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Frequent Methicillin-Resistant Staphylococcus aureus Introductions Into an Inner-city Jail: Indications of Community Transmission Networks.

BACKGROUND: Jails may facilitate spread of methicillin-resistant Staphylococcus aureus (MRSA) in urban areas. We examined MRSA colonization upon entrance to a large urban jail to determine if there are MRSA transmission networks preceding incarceration. METHODS: Males incarcerated in Cook County Jail (Chicago) were enrolled, with enrichment for people living with human immunodeficiency virus (PLHIV), within 72 hours of intake. Surveillance cultures assessed prevalence of MRSA colonization. Whole-genome sequencing (WGS) identified preincarceration transmission networks.We examined methicillin-resistant Staphylococcus aureus (MRSA) isolates to determine if there are transmission networks that precede incarceration. A large proportion of individuals enter jail colonized with MRSA. Molecular epidemiology and colonization risk factors provide clues to community reservoirs for MRSA. RESULTS: There were 718 individuals (800 incarcerations) enrolled; 58% were PLHIV. The prevalence of MRSA colonization at intake was 19%. In multivariate analysis, methamphetamine use, unstable housing, current/recent skin infection, and recent injection drug use were predictors of MRSA. Among PLHIV, recent injection drug use, current skin infection, and HIV care at outpatient clinic A that emphasizes comprehensive care to the lesbian, gay, bisexual, transgender community were predictors of MRSA. Fourteen (45%) of 31 detainees with care at clinic A had colonization. WGS revealed that this prevalence was not due to clonal spread in clinic but rather to an intermingling of distinct community transmission networks. In contrast, genomic analysis supported spread of USA500 strains within a network. Members of this USA500 network were more likely to be PLHIV (P < .01), men who have sex with men (P < .001), and methamphetamine users (P < .001). CONCLUSIONS: A large proportion of individuals enter jail colonized with MRSA. Molecular epidemiology and colonization risk factors provide clues to identify colonized detainees entering jail and potential community reservoirs of MRSA.

Quantitative Results of a National Intervention to Prevent Hospital-Onset Methicillin-Resistant Staphylococcus aureus Bloodstream Infection: A Pre-Post Observational Study.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) remains one of the most common causes of health care-associated infection (HAI). Objective: To evaluate the effect of education and a tiered, evidence-based infection prevention strategy on rates of hospital-onset MRSA bloodstream infection (BSI). Design: Prospective, national, nonrandomized, interventional, 12-month, multiple cohort, pre-post observational quality improvement project. Setting: Acute care, long-term acute care, and critical access hospitals with a disproportionate burden of HAI. Patients: All patients admitted to participating facilities during the project period. Intervention: A multimodal infection prevention intervention consisting of recommendations and tools for prioritizing and implementing evidence-based infection prevention strategies, on-demand educational videos, Internet-based live educational presentations, and access to content experts. Measurements: Rates of hospital-onset MRSA BSI, overall and stratified by hospital type, during 12-month baseline and postintervention periods. Variation in outcomes across hospital types was examined. Results: Between November 2016 and May 2018, 387 hospitals in 23 states and the District of Columbia participated, 353 (91%) submitted MRSA data, and 172 (49%) indicated that MRSA prevention was a priority. Unadjusted overall rates of hospital-onset MRSA BSI were 0.075 (95% CI, 0.065 to 0.085) and 0.071 (CI, 0.063 to 0.080) per 1000 patient-days in the baseline and postintervention periods, respectively. Limitations: The intervention period was short. Participation and adherence to recommended interventions were not fully assessed. Baseline rates of hospital-onset MRSA BSI were relatively low. Prevention of MRSA was a priority in a minority of participating hospitals. Patient characteristics and other MRSA risk factors were not assessed. Conclusion: In hospitals with a disproportionate burden of HAIs, access to tools to assist with implementation of evidence-based prevention strategies and education resources alone may not be sufficient to prevent MRSA BSI. Primary Funding Source: Centers for Disease Control and Prevention.

Policy Recommendations for Optimizing the Infectious Diseases Physician-Scientist Workforce.

The Infectious Diseases Society of America, HIV Medicine Association, and Pediatric Infectious Diseases Society are concerned by the continued decline in the number of infectious diseases trainees pursuing careers as physician-scientists and the attrition of junior and midcareer physician-scientists. The inability to replace the aging physician-scientist workforce will have a negative, long-lasting impact our biomedical research enterprise and its ability to drive the discovery of new treatments for important infectious diseases. We discuss policy recommendations for securing and optimizing the infectious diseases physician-scientist workforce in the areas of education, training, compensation, and mentorship, as well as ways to improve federal research funding, cross-sector collaboration, and workforce diversity.

Genomic and Epidemiological Evidence for Community Origins of Hospital-Onset Methicillin-Resistant Staphylococcus aureus Bloodstream Infections.

Background: We examined whether disparities existed in hospital-onset (HO) Staphylococcus aureus bloodstream infections (BSIs) and used whole-genome sequencing (WGS) to identify factors associated with USA300 transmission networks. Methods: We evaluated HO methicillin-susceptible S. aureus (MSSA) and HO methicillin-resistant S. aureus (MRSA) BSIs for 2009-2013 at 2 hospitals and used an adjusted incidence for modeling. WGS and phylogenetic analyses were performed on a sample of USA300 BSI isolates. Epidemiologic data were analyzed in the context of phylogenetic reconstructions. Results: On multivariate analysis, male sex, African-American race, and non-Hispanic white race/ethnicity were significantly associated with HO-MRSA BSIs whereas Hispanic ethnicity was negatively associated (rate ratio, 0.41; P = .002). Intermixing of community-onset and HO-USA300 strains on the phylogenetic tree indicates that these strains derive from a common pool. African-American race was the only factor associated with genomic clustering of isolates. Conclusions: In a multicenter assessment of HO-S. aureus BSIs, African-American race was significantly associated with HO-MRSA but not MSSA BSIs. There appears to be a nexus of USA300 community and hospital transmission networks, with a community factor being the primary driver. Our data suggest that HO-USA300 BSIs likely are due to colonizing strains acquired in the community before hospitalization. Therefore, prevention efforts may need to extend to the community for maximal benefit.

Genomic Epidemiology of USA300 Methicillin-Resistant Staphylococcus aureus in an Urban Community.

BACKGROUND: In a community, it is unknown what factors account for transmission of methicillin-resistant Staphylococcus aureus (MRSA). We integrated whole genome sequencing (WGS) and epidemiologic data to identify factors associated with MRSA transmission networks in an urban community. METHODS: WGS was performed on colonizing USA300 MRSA isolates from 74 individuals within 72 hours of admission to a public hospital in Chicago, IL. Single nucleotide variants (SNVs) were used to reconstruct the phylogeny of sequenced isolates, and epidemiologic data was overlaid to identify factors associated with transmission networks. RESULTS: The maximum within-patient SNV difference for an individual with multisite colonization was 41 SNVs, with no systematic divergence among body sites. We observed a minimum of 7 SNVs and maximum of 153 SNVs between isolates from different individuals. We identified 4 pairs of individuals whose isolates were within 40 SNVs of each other. Putting our isolates in the context of previously sequenced USA300 isolates from other communities, we identified a 13-member group and two 4-member groups that represent samples from putative local transmission networks. Individuals in these groups were more likely to be African American, to be human immunodeficiency virus-infected, to reside in high detainee release areas, and to be current users of illicit drugs. CONCLUSIONS: Using WGS, we observed potential transmission networks in an urban community and that certain epidemiologic factors were associated with inclusion in these networks. Future work with contact tracing and advanced molecular diagnostics may allow for identification of MRSA "epicenters" in the community where interventions can be targeted.

Genomic Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 in a County Jail.

Background: In the coronavirus disease 2019 (COVID-19) pandemic, correctional facilities are potential hotspots for transmission. We examined the genomic epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the pandemic in one of the country's largest urban jails. Methods: Existing SARS-CoV-2 isolates from 131 detainees at the Cook County Jail in Chicago, Illinois, from March 2020 through May 2020 were analyzed by whole-genome sequencing. Contemporaneous isolates from Rush University Medical Center (Chicago, Illinois) and the Global Initiative on Sharing All Influenza Data (GISAID) were used to identify genetic clusters containing only jail isolates. Transmission windows were identified for each pair of detainees using the date of the SARS-CoV-2-positive test and location data to determine if detainees overlapped in the jail, within a specific building, or within particular living units during transmission windows. Results: We identified 29 jail-only clusters that contained 75 of the 132 SARS-CoV-2 isolates from detainees; of these clusters, 17 (58.6%) had individuals who overlapped in the jail during putative transmission windows. Focusing on specific buildings revealed that 2 buildings, a single- and double-cell style of housing. were associated with having detainees infected with similar SARS-CoV-2 genomes during their infectious time period (P < .001). Conclusions: Our findings suggest that there was transmission of SARS-CoV-2 in the jail, in the setting of extensive importation of COVID-19 from the community. Numerous infection control practices at intake and during incarceration were implemented in the jail to limit viral spread. Our study shows the importance of genomic analysis in this type of settings and how it can be utilized within infection control protocols.

Community-associated methicillin-resistant Staphylococcus aureus colonization burden in HIV-infected patients.

BACKGROUND: The epidemic of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has had a disproportionate impact on patients with human immunodeficiency virus (HIV). METHODS: We evaluated CA-MRSA colonization burden (number of colonized sites per total number sampled) among HIV-infected and HIV-negative inpatients within 72 hours of hospitalization. From March 2011 through April 2012, we obtained cultures from nasal and extranasal sites (throat, axilla, inguinal, perirectal, and chronic wound if present) and collected risk factor data. RESULTS: Of 745 patients (374 HIV-infected, 371 HIV-negative), 15.7% were colonized with CA-MRSA at any site: 20% of HIV and 11% of HIV-negative patients (relative prevalence=1.8, P=.002). HIV-infected patients had a higher prevalence of nasal, extranasal, and exclusive extranasal colonization as well as higher colonization burden. Perirectal and inguinal areas were the extranasal sites most frequently colonized, and 38.5% of colonized patients had exclusive extranasal colonization. Seventy-three percent of isolates were identified as USA300. Among HIV-infected patients, male sex, younger age, and recent incarceration were positively associated whereas Hispanic ethnicity was negatively associated with higher colonization burden. Among HIV-negative patients, temporary housing (homeless, shelter, or substance abuse center) was the only factor associated with higher colonization burden. Predictors of USA300 included HIV, younger age, illicit drug use, and male sex; all but 1 colonized individual with current or recent incarceration carried USA300. CONCLUSIONS: HIV-infected patients were more likely to have a higher CA-MRSA colonization burden and carry USA300. In certain populations, enhanced community and outpatient-based infection control strategies may be needed to prevent CA-MRSA cross-transmission and infection.

Layered Screening and Contact-Limiting Interventions Are Necessary to Reduce SARS-Cov-2 Outbreak Risks in Large Urban Jails.

Highly transmissible infections with short serial intervals, such as SARS-Cov-2 and influenza, can quickly overwhelm healthcare resources in institutional settings such as jails. We assessed the impact of intake screening measures on the risk of SARS-CoV-2 outbreaks in this setting. We identified which elements of the intake process created the largest reductions in caseload. We implemented an individual-based simulation representative of SARS-Cov-2 transmission in a large urban jail utilizing testing at entry, quarantine, and post-quarantine testing to protect its general population from mass infection. We tracked the caseload under each scenario and quantified the impact of screening steps by varying quarantine duration, removing testing, and using a range of test sensitivities. We repeated the simulations under a range of transmissibility and community prevalence levels to evaluate the sensitivity of our results. We found that brief quarantine of newly incarcerated individuals separate from the existing population of the jail to permit pre-quarantine and end-of-quarantine tests reduced SARS-CoV-2 caseload 30-70% depending on test sensitivity. These results were robust to variation in the transmissibility. Further quarantine (up to 14 days) on average created only a 5% further reduction in caseload. A multilayered intake process is necessary to limit the spread of highly transmissible pathogens with short serial intervals. The pre-symptomatic phase means that no single strategy can be effective. We also show that shorter durations of quarantine combined with testing can be nearly as effective at preventing spread as longer-duration quarantine up to 14 days.

SHEA/IDSA/APIC Practice Recommendation: Strategies to prevent methicillin-resistant Staphylococcus aureus transmission and infection in acute-care hospitals: 2022 Update.

Previously published guidelines have provided comprehensive recommendations for detecting and preventing healthcare-associated infections (HAIs). The intent of this document is to highlight practical recommendations in a concise format designed to assist acute-care hospitals in implementing and prioritizing efforts to prevent methicillin-resistant Staphylococcus aureus (MRSA) transmission and infection. This document updates the "Strategies to Prevent Methicillin-Resistant Staphylococcus aureus Transmission and Infection in Acute Care Hospitals" published in 2014.1 This expert guidance document is sponsored by the Society for Healthcare Epidemiology of America (SHEA). It is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America (IDSA), the Association for Professionals in Infection Control and Epidemiology (APIC), the American Hospital Association (AHA), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise.