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Background: Despite large reductions from 2005-2012, hospital-onset methicillin-resistant Staphylococcus aureus bloodstream infections (HO MRSA BSIs) continue be a major source of morbidity and mortality.Aim: To describe risk factors for and underlying sources of HO MRSA BSIs.Methods: We investigated HO MRSA BSIs at eight high-burden short-stay acute care hospitals. A case was defined as first isolation of MRSA from a blood specimen collected in 2016 on hospital day ≥4 from a patient without an MRSA-positive blood culture in the 14 days prior. We reviewed case-patient demographics and risk factors by medical record abstraction. The potential clinical source(s) of infection were determined by consensus by a clinician panel.Findings: Of the 195 eligible cases, 186 were investigated. Case-patients were predominantly male (63%); median age was 57 years (range 0-92). In the two weeks prior to the BSI, 88% of case-patients had indwelling devices, 31% underwent a surgical procedure, and 18% underwent dialysis. The most common locations of attribution were intensive care units (ICUs) (46%) and step-down units (19%). The most commonly identified non-mutually exclusive clinical sources were CVCs (46%), non-surgical wounds (17%), surgical site infections (16%), non-ventilator healthcare-associated pneumonia (13%), and ventilator-associated pneumonia (11%).Conclusions: Device-and procedure-related infections were common sources of HO MRSA BSIs. Prevention strategies focused on improving adherence to existing prevention bundles for device-and procedure-associated infections and on source control for ICU patients, patients with certain indwelling devices, and patients undergoing certain high-risk surgeries are being pursued to decrease HO MRSA BSI burden at these facilities. [ABSTRACT FROM AUTHOR]

Our detailed study on the chemical constituents of the stem bark of Calophyllum benjaminum and Calophyllum javanicum has resulted in one new coumarin benjaminin (1), five xanthones fuscaxanthone C (2), β-mangostin (3), thwaitesixanthone (4), dombakinaxanthone (5) and caloxanthone A (6), together with four common triterpenes friedelin (7), β-sitosterol (8), lupeol (9) and stigmasterol (10). The structures of these compounds were elucidated using NMR, FTIR and GCMS. [ABSTRACT FROM AUTHOR]

The article presents a case of 63-year old woman with increasing abdominal distension for several months and acute onset breathlessness. The woman had experienced a single episode of jaundice and underwent precutaneous liver biopsy. Clinical examinations showed tachypnoea, a clear chest and moderate ascites with no stigma of chronic liver disease. Later in her admission, she suffered a significant fresh hematemesis.

There are various models for acute neurology services in the UK, with considerable variation in practice. Patients are often admitted unnecessarily for neurology review, leading to delay in diagnosis and treatment. Alternative models, such as the Neurology Same Day Emergency Care service (Neuro-SDEC) at University College London Hospital provide a pathway that can prevent admissions and streamline patient care. Headache is one of the commonest presenting symptoms in acute neurology.This study compared the impact of Neuro-SDEC on the care for patients presenting with headache against the standard pathway.A prospective audit was undertaken from November - December 2023 to evaluate all appropriate patients seen by the Neuro-SDEC service or admitted to the ward. For Neuro-SDEC patients, each case was reviewed to see whether an admission, lumbar puncture or neurology outpatient referral was avoided. For admitted patients, length of inpatient stay, time to neurology review and discharge diagnosis was recorded.Fifty-one patients were seen by Neuro-SDEC, twenty-five of whom would have been admitted to hospital on the standard pathway. Thirty general neurology outpatient clinic referrals were prevented and 5 patients avoided a lumbar puncture. In 45% of cases, the working diagnosis changed after the patient was seen by the Neuro-SDEC team. There were seven admitted patients not seen by the service with a combined length of stay of 17 bed days. The average wait time for inpatient neurology review was 42 hours. 3 admitted patients underwent a lumbar puncture. 2 patients were referred on to neuro-SDEC to enable an earlier discharge from hospital. Migraine was the most common final diagnosis in both groups.This study highlights that Neuro-SDEC is effective at reducing hospital admissions, as well as unnecessary tests and referrals to generalneurology outpatients. For admitted patients, the service enabled earlier discharge from hospital and reduced length of stay., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Importance: Multiplex molecular syndromic panels for diagnosis of urinary tract infection (UTI) lack clinical data supporting their use in routine clinical care. They also have the potential to exacerbate inappropriate antibiotic prescribing., Objective: To describe the frequency of unspecified multiplex testing in administrative claims with a primary diagnosis of UTI in the Medicare population over time, to assess costs, and to characterize the health care professionals (eg, clinicians, laboratories, physician assistants, and nurse practitioners) and patient populations using these tests., Design, Setting, and Participants: This cohort study used Centers for Medicare & Medicaid Services (CMS) claims data for Medicare beneficiaries. The study included older community-dwelling adults and nursing home residents with fee-for-service Medicare Part A and Part B benefits from January 1, 2016, to December 31, 2023., Main Outcomes and Measures: Multiplex syndromic panels were identified using carrier claims (ie, claims for clinician office or laboratory services). The annual rate of claims was measured for multiplex syndromic panels with a primary diagnosis of UTI per 10 000 eligible Medicare beneficiaries. The performing and referring specialties of health care professionals listed on claims of interest and the proportion of claims that occurred among beneficiaries residing in a nursing home were described., Results: Between 31 110 656 and 36 175 559 Medicare beneficiaries with fee-for-service coverage annually (2016-2023) were included in this study. In this period, 1 679 328 claims for UTI multiplex testing were identified. The median age of beneficiaries was 77 (IQR, 70-84) years; 34% of claims were from male beneficiaries and 66% were from female beneficiaries. From 2016 to 2023, the observed rate of UTI multiplex testing increased from 2.4 to 148.1 claims per 10 000 fee-for-service beneficiaries annually, and the proportion of claims that occurred among beneficiaries residing in a nursing home ranged from 1% in 2016 to 12% in 2020. In addition to laboratories or pathologists, urology was the most common clinician specialty conducting this testing. The CMS-assigned referring clinician specialty was most frequently urology or advanced practice clinician for claims among community-dwelling beneficiaries compared with internal medicine or family medicine for claims among nursing home residents. In 2023, the median cost of a multiplex test in the US was $585 (IQR, $516-$695 for Q1-Q3), which was more than 70 times higher than the median cost of $8 for a urine culture (IQR, $8-$16 for Q1-Q3)., Conclusions and Relevance: This cohort study of Medicare beneficiaries with fee-for-service coverage from 2016 to 2023 found increasing use of emerging multiplex testing for UTI coupled with high costs to the Medicare program. Monitoring and research are needed to determine the effects of multiplex testing on antimicrobial use and whether there are clinical situations in which this testing may benefit patients.

Background: Nontuberculous mycobacteria (NTM) cause pulmonary and extrapulmonary infections. Although isolation of NTM from clinical specimens has increased nationally, few studies delineated the molecular characteristics of extrapulmonary NTM., Methods: Extrapulmonary isolates were collected by four Emerging Infections Program sites from October 2019 to March 2020 and underwent laboratory characterization, including matrix-assisted laser desorption ionization-time of flight mass spectrometry, Sanger DNA sequencing, and whole genome sequencing. Bioinformatics analyses were employed to identify species, sequence types (STs), antimicrobial resistance (AR), and virulence genes; isolates were further characterized by phylogenetic analyses., Results: Among 45 isolates, the predominant species were Mycobacterium avium (n=20, 44%), Mycobacterium chelonae (n=7, 16%), and Mycobacterium fortuitum (n=6, 13%). The collection represented 31 STs across 10 species; the most common ST was ST11 (M. avium, n=7). Mycobacterium fortuitum and Mycobacterium abscessus isolates harbored multiple genes conferring resistance to aminoglycosides, beta-lactams, and macrolides. No known AR mutations were detected in rpoB, 16S, or 23S rRNAs. Slow-growing NTM species harbored multiple virulence genes including type-VII secretion components, adhesion factors, and phospholipase C., Conclusion: Continued active laboratory- and population-based surveillance will further inform the prevalence of NTM species and STs, monitor emerging clones, and allow AR characterization., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Carbapenem-resistant Enterobacterales (CRE) are among the most concerning antibiotic resistance threats due to high rates of multidrug resistance, transmissibility in health care settings, and high mortality rates. We evaluated the potential for regional genomic surveillance to track the spread of bla KPC -carrying CRE (KPC-CRE) by using isolate collections from health care facilities in three U.S. states. Clinical isolates were collected from Connecticut (2017 to 2018), Minnesota (2012 to 2018), and Tennessee (2016 to 2017) through the U.S. Centers for Disease Control and Prevention's Multi-site Gram-negative Surveillance Initiative (MuGSI) and additional surveillance. KPC-CRE isolates were whole-genome sequenced, yielding 255 isolates from 214 patients across 96 facilities. Case report data on patient comorbidities, facility exposures, and interfacility patient transfer were extracted. We observed that in Connecticut, most KPC-CRE isolates showed evidence of importation from outside the state, with limited local transmission. In Minnesota, cases were mainly from sporadic importation and transmission of bla KPC -carrying Klebsiella pneumoniae ST258, and clonal expansion of bla KPC -carrying Enterobacter hormaechei ST171, primarily at a single focal facility and its satellite facilities. In Tennessee, we observed transmission of diverse strains of bla KPC -carrying Enterobacter and Klesbiella , with evidence that most derived from the local acquisition of bla KPC plasmids circulating in an interconnected regional health care network. Thus, the underlying processes driving KPC-CRE burden can differ substantially across regions and can be discerned through regional genomic surveillance. This study provides proof of concept that integrating genomic data with information on interfacility patient transfers can provide insights into locations and drivers of regional KPC-CRE burden that can enable targeted interventions., Competing Interests: The authors declare no conflict of interest.

Introduction: Racial and ethnic minorities are disproportionately affected by end-stage kidney disease (ESKD). ESKD patients on dialysis are at increased risk for Staphylococcus aureus bloodstream infections, but racial, ethnic, and socioeconomic disparities associated with this outcome are not well described., Methods: Surveillance data from the 2020 National Healthcare Safety Network (NHSN) and the 2017-2020 Emerging Infections Program (EIP) were used to describe bloodstream infections among patients on hemodialysis (hemodialysis patients) and were linked to population-based data sources (CDC/Agency for Toxic Substances and Disease Registry [ATSDR] Social Vulnerability Index [SVI], United States Renal Data System [USRDS], and U.S. Census Bureau) to examine associations with race, ethnicity, and social determinants of health., Results: In 2020, 4,840 dialysis facilities reported 14,822 bloodstream infections to NHSN; 34.2% were attributable to S. aureus . Among seven EIP sites, the S. aureus bloodstream infection rate during 2017-2020 was 100 times higher among hemodialysis patients (4,248 of 100,000 person-years) than among adults not on hemodialysis (42 of 100,000 person-years). Unadjusted S. aureus bloodstream infection rates were highest among non-Hispanic Black or African American (Black) and Hispanic or Latino (Hispanic) hemodialysis patients. Vascular access via central venous catheter was strongly associated with S. aureus bloodstream infections (NHSN: adjusted rate ratio [aRR] = 6.2; 95% CI = 5.7-6.7 versus fistula; EIP: aRR = 4.3; 95% CI = 3.9-4.8 versus fistula or graft). Adjusting for EIP site of residence, sex, and vascular access type, S. aureus bloodstream infection risk in EIP was highest in Hispanic patients (aRR = 1.4; 95% CI = 1.2-1.7 versus non-Hispanic White [White] patients), and patients aged 18-49 years (aRR = 1.7; 95% CI = 1.5-1.9 versus patients aged ≥65 years). Areas with higher poverty levels, crowding, and lower education levels accounted for disproportionately higher proportions of hemodialysis-associated S. aureus bloodstream infections., Conclusions and Implications for Public Health Practice: Disparities exist in hemodialysis-associated S. aureus infections. Health care providers and public health professionals should prioritize prevention and optimized treatment of ESKD, identify and address barriers to lower-risk vascular access placement, and implement established best practices to prevent bloodstream infections., (Copyright © 2023. Published by Elsevier Inc.)

Background: Carbapenem-resistant Enterobacterales (CRE) are usually healthcare-associated but are also emerging in the community., Methods: Active, population-based surveillance was conducted to identify case-patients with cultures positive for Enterobacterales not susceptible to a carbapenem (excluding ertapenem) and resistant to all third-generation cephalosporins tested at 8 US sites from January 2012 to December 2015. Medical records were used to classify cases as health care-associated, or as community-associated (CA) if a patient had no known health care risk factors and a culture was collected <3 days after hospital admission. Enterobacterales isolates from selected cases were submitted to CDC for whole genome sequencing., Results: We identified 1499 CRE cases in 1194 case-patients; 149 cases (10%) in 139 case-patients were CA. The incidence of CRE cases per 100,000 population was 2.96 (95% CI: 2.81, 3.11) overall and 0.29 (95% CI: 0.25, 0.35) for CA-CRE. Most CA-CRE cases were in White persons (73%), females (84%) and identified from urine cultures (98%). Among the 12 sequenced CA-CRE isolates, 5 (42%) harbored a carbapenemase gene., Conclusions: Ten percent of CRE cases were CA; some isolates from CA-CRE cases harbored carbapenemase genes. Continued CRE surveillance in the community is critical to monitor emergence outside of traditional health care settings., (Published by Elsevier Inc.)

Objective: The incidence of infections from extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-E) is increasing in the United States. We describe the epidemiology of ESBL-E at 5 Emerging Infections Program (EIP) sites., Methods: During October-December 2017, we piloted active laboratory- and population-based (New York, New Mexico, Tennessee) or sentinel (Colorado, Georgia) ESBL-E surveillance. An incident case was the first isolation from normally sterile body sites or urine of Escherichia coli or Klebsiella pneumoniae/oxytoca resistant to ≥1 extended-spectrum cephalosporin and nonresistant to all carbapenems tested at a clinical laboratory from a surveillance area resident in a 30-day period. Demographic and clinical data were obtained from medical records. The Centers for Disease Control and Prevention (CDC) performed reference antimicrobial susceptibility testing and whole-genome sequencing on a convenience sample of case isolates., Results: We identified 884 incident cases. The estimated annual incidence in sites conducting population-based surveillance was 199.7 per 100,000 population. Overall, 800 isolates (96%) were from urine, and 790 (89%) were E. coli . Also, 393 cases (47%) were community-associated. Among 136 isolates (15%) tested at the CDC, 122 (90%) met the surveillance definition phenotype; 114 (93%) of 122 were shown to be ESBL producers by clavulanate testing. In total, 111 (97%) of confirmed ESBL producers harbored a bla CTX-M gene. Among ESBL-producing E. coli isolates, 52 (54%) were ST131; 44% of these cases were community associated., Conclusions: The burden of ESBL-E was high across surveillance sites, with nearly half of cases acquired in the community. EIP has implemented ongoing ESBL-E surveillance to inform prevention efforts, particularly in the community and to watch for the emergence of new ESBL-E strains.

Background: Thrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. It presents similarly to spontaneous heparin-induced thrombocytopenia. Twelve cases of cerebral venous sinus thrombosis after vaccination with the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson) have previously been described., Objective: To describe surveillance data and reporting rates of all reported TTS cases after COVID-19 vaccination in the United States., Design: Case series., Setting: United States., Patients: Case patients receiving a COVID-19 vaccine from 14 December 2020 through 31 August 2021 with thrombocytopenia and thrombosis (excluding isolated ischemic stroke or myocardial infarction) reported to the Vaccine Adverse Event Reporting System. If thrombosis was only in an extremity vein or pulmonary embolism, a positive enzyme-linked immunosorbent assay for antiplatelet factor 4 antibodies or functional heparin-induced thrombocytopenia platelet test result was required., Measurements: Reporting rates (cases per million vaccine doses) and descriptive epidemiology., Results: A total of 57 TTS cases were confirmed after vaccination with Ad26.COV2.S ( n  = 54) or a messenger RNA (mRNA)-based COVID-19 vaccine ( n  = 3). Reporting rates for TTS were 3.83 per million vaccine doses (Ad26.COV2.S) and 0.00855 per million vaccine doses (mRNA-based COVID-19 vaccines). The median age of patients with TTS after Ad26.COV2.S vaccination was 44.5 years (range, 18 to 70 years), and 69% of patients were women. Of the TTS cases after mRNA-based COVID-19 vaccination, 2 occurred in men older than 50 years and 1 in a woman aged 50 to 59 years. All cases after Ad26.COV2.S vaccination involved hospitalization, including 36 (67%) with intensive care unit admission. Outcomes of hospitalizations after Ad26.COV2.S vaccination included death (15%), discharge to postacute care (17%), and discharge home (68%)., Limitations: Underreporting and incomplete case follow-up., Conclusion: Thrombosis with thrombocytopenia syndrome is a rare but serious adverse event associated with Ad26.COV2.S vaccination. The different demographic characteristics of the 3 cases reported after mRNA-based COVID-19 vaccines and the much lower reporting rate suggest that these cases represent a background rate., Primary Funding Source: Centers for Disease Control and Prevention.

On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the adenovirus-vectored COVID-19 vaccine (Janssen Biotech, Inc., a Janssen Pharmaceutical company, Johnson & Johnson), and on February 28, 2021, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for its use as a single-dose primary vaccination in persons aged ≥18 years (1,2). On April 13, 2021, CDC and FDA recommended a pause in the use of Janssen COVID-19 vaccine after reports of thrombosis with thrombocytopenia syndrome (TTS), a rare condition characterized by low platelets and thrombosis, including at unusual sites such as the cerebral venous sinus (cerebral venous sinus thrombosis [CVST]), after receipt of the vaccine.* ACIP rapidly convened two emergency meetings to review reported cases of TTS, and 10 days after the pause commenced, ACIP reaffirmed its interim recommendation for use of the Janssen COVID-19 vaccine in persons aged ≥18 years, but included a warning regarding rare clotting events after vaccination, primarily among women aged 18-49 years (3). In July, after review of an updated benefit-risk assessment accounting for risks of Guillain-Barré syndrome (GBS) and TTS, ACIP concluded that benefits of vaccination with Janssen COVID-19 vaccine outweighed risks. Through ongoing safety surveillance and review of reports from the Vaccine Adverse Event Reporting System (VAERS), additional cases of TTS after receipt of Janssen COVID-19 vaccine, including deaths, were identified. On December 16, 2021, ACIP held an emergency meeting to review updated data on TTS and an updated benefit-risk assessment. At that meeting, ACIP made a recommendation for preferential use of mRNA COVID-19 vaccines over the Janssen COVID-19 vaccine, including both primary and booster doses administered to prevent COVID-19, for all persons aged ≥18 years. The Janssen COVID-19 vaccine may be considered in some situations, including for persons with a contraindication to receipt of mRNA COVID-19 vaccines., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Allison Lale reports personal fees from the Medical Library Association, outside the submitted work. No other potential conflicts of interest were disclosed.

Background: Carbapenem-resistant Enterobacterales (CRE) are highly antibiotic-resistant bacteria. Whether CRE resistant only to ertapenem among carbapenems (ertapenem "mono-resistant") represent a unique CRE subset with regards to risk factors, carbapenemase genes, and outcomes is unknown., Methods: We analyzed surveillance data from 9 CDC Emerging Infections Program (EIP) sites. A case was the first isolation of a carbapenem-resistant Enterobacter cloacae complex, Escherichia coli , Klebsiella aerogenes , K. oxytoca , K. pneumoniae, or K. variicola from a normally sterile site or urine in an EIP catchment area resident in 2016-2017. We compared risk factors, carbapenemase genes, antibiotic susceptibility, and mortality of ertapenem "mono-resistant" cases to "other" CRE cases (resistant to ≥1 carbapenem other than ertapenem) and analyzed risk factors for mortality., Results: Of 2009 cases, 1249 (62.2%) were ertapenem-mono-resistant and 760 (37.8%) were other CRE. Ertapenem-mono-resistant CRE cases were more frequently ≥80 years old (29.1% vs 19.5%; P  < .0001) and female (67.9% vs 59.0%; P  < .0001). Ertapenem-mono-resistant isolates were more likely to be Enterobacter cloacae complex (48.4% vs 15.4%; P  < .0001) but less likely to be isolated from a normally sterile site (7.1% vs 11.7%; P  < .01) or to have a carbapenemase gene (2.4% vs 47.4%; P  < .0001). Ertapenem-mono-resistance was not associated with 90-day mortality in logistic regression models. Carbapenemase-positive isolates were associated with mortality (odds ratio, 1.93; 95% CI, 1.30-2.86)., Conclusions: Ertapenem-mono-resistant CRE rarely have carbapenemase genes and have distinct clinical and microbiologic characteristics from other CRE. These findings may inform antibiotic choice and infection prevention practices, particularly when carbapenemase testing is not available., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Four xanthones, α-mangostin ( 1 ), β-mangostin ( 2 ), mangostenol ( 3 ), mangaxanthone B ( 4 ), three benzophenones, mangaphenone ( 5 ), benthamianone ( 6 ), congestiflorone ( 7 ) and one sterol, stigmasterol ( 8 ) were isolated from the stem barks of Garcinia mangostana L. and G. benthamiana (Planch. & Triana) Pipoly. Compounds 1 , 2 , 4 and 5 exhibited significant cytotoxicity through MTT assay towards MCF-7 and MDA-MB-231 cells with the IC 50 values range from 4.4 to 12.0 µM. Remarkably, mangaphenone ( 5) showed non-cytotoxicity against normal Vero cells, revealing its potential as lead compound for anti-breast cancer drug. Structure-activity relationship postulated that the prenyl and hydroxyl groups present in xanthones are important in promoting anti-proliferative effects. Molecular docking simulation study of 1 , 2 , 4 and 5 with 2OCF and 4PIV implied that the induction of apoptosis for both cancer cells involve ER and FAS signaling pathways. Future study on the lead optimization of 5 is highly recommended.

Objectives: Some studies suggested more COVID-19-associated hospitalizations among racial and ethnic minorities. To inform public health practice, the COVID-19-associated Hospitalization Surveillance Network (COVID-NET) quantified associations between race/ethnicity, census tract socioeconomic indicators, and COVID-19-associated hospitalization rates., Methods: Using data from COVID-NET population-based surveillance reported during March 1-April 30, 2020 along with socioeconomic and denominator data from the US Census Bureau, we calculated COVID-19-associated hospitalization rates by racial/ethnic and census tract-level socioeconomic strata., Results: Among 16,000 COVID-19-associated hospitalizations, 34.8% occurred among non-Hispanic White (White) persons, 36.3% among non-Hispanic Black (Black) persons, and 18.2% among Hispanic or Latino (Hispanic) persons. Age-adjusted COVID-19-associated hospitalization rate were 151.6 (95% Confidence Interval (CI): 147.1-156.1) in census tracts with >15.2%-83.2% of persons living below the federal poverty level (high-poverty census tracts) and 75.5 (95% CI: 72.9-78.1) in census tracts with 0%-4.9% of persons living below the federal poverty level (low-poverty census tracts). Among White, Black, and Hispanic persons living in high-poverty census tracts, age-adjusted hospitalization rates were 120.3 (95% CI: 112.3-128.2), 252.2 (95% CI: 241.4-263.0), and 341.1 (95% CI: 317.3-365.0), respectively, compared with 58.2 (95% CI: 55.4-61.1), 304.0 (95%: 282.4-325.6), and 540.3 (95% CI: 477.0-603.6), respectively, in low-poverty census tracts., Conclusions: Overall, COVID-19-associated hospitalization rates were highest in high-poverty census tracts, but rates among Black and Hispanic persons were high regardless of poverty level. Public health practitioners must ensure mitigation measures and vaccination campaigns address needs of racial/ethnic minority groups and people living in high-poverty census tracts., Competing Interests: Dr. Anderson reports consulting for AbbVie, Pfizer, and Sanofi-Pasteur and clinical trials research funding from MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Novavax, Sanofi Pasteur, Micron, and Janssen. He also works on a safety monitoring board for Kentucky Bioprocessing, Inc. All are outside of the submitted work. No other disclosures were reported. Nonetheless, this does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Identifying asymptomatic individuals early through serial testing is recommended to control coronavirus disease 2019 (COVID-19) in nursing homes, both in response to an outbreak ("outbreak testing" of residents and healthcare personnel) and in facilities without outbreaks ("nonoutbreak testing" of healthcare personnel). The effectiveness of outbreak testing and isolation with or without nonoutbreak testing was evaluated., Methods: Using published SARS-CoV-2 transmission parameters, the fraction of SARS-CoV-2 transmissions prevented through serial testing (weekly, every 3 days, or daily) and isolation of asymptomatic persons compared with symptom-based testing and isolation was evaluated through mathematical modeling using a Reed-Frost model to estimate the percentage of cases prevented (ie, "effectiveness") through either outbreak testing alone or outbreak plus nonoutbreak testing. The potential effect of simultaneous decreases (by 10%) in the effectiveness of isolating infected individuals when instituting testing strategies was also evaluated., Results: Modeling suggests that outbreak testing could prevent 54% (weekly testing with 48-hour test turnaround) to 92% (daily testing with immediate results and 50% relative sensitivity) of SARS-CoV-2 infections. Adding nonoutbreak testing could prevent up to an additional 8% of SARS-CoV-2 infections (depending on test frequency and turnaround time). However, added benefits of nonoutbreak testing were mostly negated if accompanied by decreases in infection control practice., Conclusions: When combined with high-quality infection control practices, outbreak testing could be an effective approach to preventing COVID-19 in nursing homes, particularly if optimized through increased test frequency and use of tests with rapid turnaround., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Importance: Cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare and serious condition, has been described in Europe following receipt of the ChAdOx1 nCoV-19 vaccine (Oxford/AstraZeneca), which uses a chimpanzee adenoviral vector. A mechanism similar to autoimmune heparin-induced thrombocytopenia (HIT) has been proposed. In the US, the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson), which uses a human adenoviral vector, received Emergency Use Authorization (EUA) on February 27, 2021. By April 12, 2021, approximately 7 million Ad26.COV2.S vaccine doses had been given in the US, and 6 cases of CVST with thrombocytopenia had been identified among the recipients, resulting in a temporary national pause in vaccination with this product on April 13, 2021., Objective: To describe reports of CVST with thrombocytopenia following Ad26.COV2.S vaccine receipt., Design, Setting, and Participants: Case series of 12 US patients with CVST and thrombocytopenia following use of Ad26.COV2.S vaccine under EUA reported to the Vaccine Adverse Event Reporting System (VAERS) from March 2 to April 21, 2021 (with follow-up reported through April 21, 2021)., Exposures: Receipt of Ad26.COV2.S vaccine., Main Outcomes and Measures: Clinical course, imaging, laboratory tests, and outcomes after CVST diagnosis obtained from VAERS reports, medical record review, and discussion with clinicians., Results: Patients' ages ranged from 18 to younger than 60 years; all were White women, reported from 11 states. Seven patients had at least 1 CVST risk factor, including obesity (n = 6), hypothyroidism (n = 1), and oral contraceptive use (n = 1); none had documented prior heparin exposure. Time from Ad26.COV2.S vaccination to symptom onset ranged from 6 to 15 days. Eleven patients initially presented with headache; 1 patient initially presented with back pain and later developed headache. Of the 12 patients with CVST, 7 also had intracerebral hemorrhage; 8 had non-CVST thromboses. After diagnosis of CVST, 6 patients initially received heparin treatment. Platelet nadir ranged from 9 ×103/µL to 127 ×103/µL. All 11 patients tested for the heparin-platelet factor 4 HIT antibody by enzyme-linked immunosorbent assay (ELISA) screening had positive results. All patients were hospitalized (10 in an intensive care unit [ICU]). As of April 21, 2021, outcomes were death (n = 3), continued ICU care (n = 3), continued non-ICU hospitalization (n = 2), and discharged home (n = 4)., Conclusions and Relevance: The initial 12 US cases of CVST with thrombocytopenia after Ad26.COV2.S vaccination represent serious events. This case series may inform clinical guidance as Ad26.COV2.S vaccination resumes in the US as well as investigations into the potential relationship between Ad26.COV2.S vaccine and CVST with thrombocytopenia.

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the vulnerability of residents and staff members in long-term care facilities (LTCFs) (1). Although skilled nursing facilities (SNFs) certified by the Centers for Medicare & Medicaid Services (CMS) have federal COVID-19 reporting requirements, national surveillance data are less readily available for other types of LTCFs, such as assisted living facilities (ALFs) and those providing similar residential care. However, many state and territorial health departments publicly report COVID-19 surveillance data across various types of LTCFs. These data were systematically retrieved from health department websites to characterize COVID-19 cases and deaths in ALF residents and staff members. Limited ALF COVID-19 data were available for 39 states, although reporting varied. By October 15, 2020, among 28,623 ALFs, 6,440 (22%) had at least one COVID-19 case among residents or staff members. Among the states with available data, the proportion of COVID-19 cases that were fatal was 21.2% for ALF residents, 0.3% for ALF staff members, and 2.5% overall for the general population of these states. To prevent the introduction and spread of SARS-CoV-2, the virus that causes COVID-19, in their facilities, ALFs should 1) identify a point of contact at the local health department; 2) educate residents, families, and staff members about COVID-19; 3) have a plan for visitor and staff member restrictions; 4) encourage social (physical) distancing and the use of masks, as appropriate; 5) implement recommended infection prevention and control practices and provide access to supplies; 6) rapidly identify and properly respond to suspected or confirmed COVID-19 cases in residents and staff members; and 7) conduct surveillance of COVID-19 cases and deaths, facility staffing, and supply information (2)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Rises in the incidence of bacterial infections, such as infective endocarditis (IE), have been reported in conjunction with the opioid crisis. However, recent trends for IE and other serious infections among persons with substance use disorders (SUDs) are unknown., Methods: Using the Premier Healthcare Database, we identified hospitalizations from 2012 through 2017 among adults with primary discharge diagnoses of bacterial infections and secondary SUD diagnoses, using International Classification of Diseases, Clinical Modification Ninth and Tenth Revision codes. We calculated annual rates of infections with SUD diagnoses and evaluated temporal trends. Blood and cardiac tissue specimens were identified from IE hospitalizations to describe the microbiology distribution and temporal trends among hospitalizations with and without SUDs., Results: Among 72 481 weighted IE admissions recorded, SUD diagnoses increased from 19.9% in 2012 to 39.4% in 2017 (P < .0001). Hospitalizations with SUDs increased from 1.1 to 2.1 per 100 000 persons for IE, 1.4 to 2.4 per 100 000 persons for osteomyelitis, 0.5 to 0.9 per 100 000 persons for central nervous system abscesses, and 24.4 to 32.9 per 100 000 persons for skin and soft tissue infections. For adults aged 18-44 years, IE-SUD hospitalizations more than doubled, from 1.6 in 2012 to 3.6 in 2017 per 100 000 persons. Among all IE-SUD hospitalizations, 50.3% had a Staphylococcus aureus infection, compared with 19.4% of IE hospitalizations without SUDs., Conclusions: Rates of hospitalization for serious infections among persons with SUDs are increasing, driven primarily by younger age groups. The differences in the microbiology of IE hospitalizations suggest that SUDs are changing the epidemiology of these infections., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Nursing homes are high-risk settings for outbreaks of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1,2). During the COVID-19 pandemic, U.S. health departments worked to improve infection prevention and control (IPC) practices in nursing homes to prevent outbreaks and limit the spread of COVID-19 in affected facilities; however, limited resources have hampered health departments' ability to rapidly provide IPC support to all nursing homes within their jurisdictions. Since 2008, the Centers for Medicare & Medicaid Services (CMS) has published health inspection results and quality ratings based on their Five-Star Quality Rating System for all CMS-certified nursing homes (3); these ratings might be associated with facility-level risk factors for COVID-19 outbreaks. On April 17, 2020, West Virginia became the first state to mandate and conduct COVID-19 testing for all nursing home residents and staff members to identify and reduce transmission of SARS-CoV-2 in these settings (4). West Virginia's census of nursing home outbreaks was used to examine associations between CMS star ratings and COVID-19 outbreaks. Outbreaks, defined as two or more cases within 14 days (with at least one resident case), were identified in 14 (11%) of 123 nursing homes. Compared with 1-star-rated (lowest rated) nursing homes, the odds of a COVID-19 outbreak were 87% lower among 2- to 3-star-rated facilities (adjusted odds ratio [aOR] = 0.13, 95% confidence interval [CI] = 0.03-0.54) and 94% lower among 4- to 5-star-rated facilities (aOR = 0.06, 95% CI = 0.006-0.39). Health departments could use star ratings to help identify priority nursing homes in their jurisdictions to inform the allocation of IPC resources. Efforts to mitigate outbreaks in high-risk nursing homes are necessary to reduce overall COVID-19 mortality and associated disparities. Moreover, such efforts should incorporate activities to improve the overall quality of life and care of nursing home residents and staff members and address the social and health inequities that have been recognized as a prominent feature of the COVID-19 pandemic in the United States (5)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Despite concerns about the burden of the bacterial and fungal infection syndromes related to injection drug use (IDU), robust estimates of the public health burden of these conditions are lacking. The current article reviews and compares data sources and national burden estimates for infective endocarditis (IE) and skin and soft-tissue infections related to IDU in the United States., Methods: A literature review was conducted for estimates of skin and soft-tissue infection and endocarditis disease burden with related IDU or substance use disorder terms since 2011. A range of the burden is presented, based on different methods of obtaining national projections from available data sources or published data., Results: Estimates using available data suggest the number of hospital admissions for IE related to IDU ranged from 2900 admissions in 2013 to more than 20 000 in 2017. The only source of data available to estimate the annual number of hospitalizations and emergency department visits for skin and soft-tissue infections related to IDU yielded a crude estimate of 98 000 such visits. Including people who are not hospitalized, a crude calculation suggests that 155 000-540 000 skin infections related to IDU occur annually., Discussion: These estimates carry significant limitations. However, regardless of the source or method, the burden of disease appears substantial, with estimates of thousands of episodes of IE among persons with IDU and at least 100 000 persons who inject drugs (PWID) with skin and soft-tissue infections annually in the United States. Given the importance of these types of infections, more robust and reliable estimates are needed to better quantitate the occurrence and understand the impact of interventions., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

We compared methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) captured by culture-based surveillance and MRSA septicemia hospitalizations captured by administrative coding using statewide hospital discharge data in Connecticut from 2010 to 2018. Observed discrepancies between identification methods suggest administrative coding is inappropriate for assessing trends in MRSA BSIs.

Background: Public health and infection control prevention and surveillance efforts in the United States have primarily focused on methicillin-resistant Staphylococcus aureus (MRSA). We describe the public health importance of methicillin-susceptible S. aureus (MSSA) in selected communities., Methods: We analyzed Emerging Infections Program surveillance data for invasive S. aureus (SA) infections (isolated from a normally sterile body site) in 8 counties in 5 states during 2016. Cases were considered healthcare-associated if culture was obtained >3 days after hospital admission; if associated with dialysis, hospitalization, surgery, or long-term care facility (LTCF) residence within 1 year prior; or if a central venous catheter was present ≤2 days prior. Incidence per 100 000 census population was calculated, and a multivariate logistic regression model with random intercepts was used to compare MSSA risk factors with those of MRSA., Results: Invasive MSSA incidence (31.3/100 000) was 1.8 times higher than MRSA (17.5/100 000). Persons with MSSA were more likely than those with MRSA to have no underlying medical conditions (adjusted odds ratio [aOR], 2.06; 95% confidence interval [CI], 1.26-3.39) and less likely to have prior hospitalization (aOR, 0.70; 95% CI, 0.60-0.82) or LTCF residence (aOR, 0.37; 95% CI, 0.29-0.47). MSSA accounted for 59.7% of healthcare-associated cases and 60.1% of deaths., Conclusions: Although MRSA tended to be more closely associated with healthcare exposures, invasive MSSA is a substantial public health problem in the areas studied. Public health and infection control prevention efforts should consider MSSA prevention in addition to MRSA., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

Background: Previous reports suggested that US methicillin-resistant Staphylococcus aureus (MRSA) strain epidemiology has changed since the rise of USA300 MRSA. We describe invasive MRSA trends by strain type., Methods: Data came from 5 Centers for Disease Control and Prevention Emerging Infections Program sites conducting population-based surveillance and collecting isolates for invasive MRSA (ie, from normally sterile body sites), 2005-2013. MRSA bloodstream infection (BSI) incidence per 100 000 population was stratified by strain type and epidemiologic classification of healthcare exposures. Invasive USA100 vs USA300 case characteristics from 2013 were compared through logistic regression., Results: From 2005 to 2013, USA100 incidence decreased most notably for hospital-onset (6.1 vs 0.9/100 000 persons, P < .0001) and healthcare-associated, community-onset (10.7 vs 4.9/100 000 persons, P < .0001) BSIs. USA300 incidence for hospital-onset BSIs also decreased (1.5 vs 0.6/100 000 persons, P < .0001). However, USA300 incidence did not significantly change for healthcare-associated, community-onset (3.9 vs 3.3/100 000 persons, P = .05) or community-associated BSIs (2.5 vs 2.4/100 000 persons, P = .19). Invasive MRSA was less likely to be USA300 in patients who were older (adjusted odds ratio [aOR], 0.97 per year [95% confidence interval {CI}, .96-.98]), previously hospitalized (aOR, 0.36 [95% CI, .24-.54]), or had central lines (aOR, 0.44 [95% CI, .27-.74]), and associated with USA300 in people who inject drugs (aOR, 4.58 [95% CI, 1.16-17.95])., Conclusions: Most of the decline in MRSA BSIs was from decreases in USA100 BSI incidence. Prevention of USA300 MRSA BSIs in the community will be needed to further reduce burden from MRSA BSIs., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

Objective: Describe common pathogens and antimicrobial resistance patterns for healthcare-associated infections (HAIs) that occurred during 2015-2017 and were reported to the Centers for Disease Control and Prevention's (CDC's) National Healthcare Safety Network (NHSN)., Methods: Data from central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated events (VAEs), and surgical site infections (SSIs) were reported from acute-care hospitals, long-term acute-care hospitals, and inpatient rehabilitation facilities. This analysis included device-associated HAIs reported from adult location types, and SSIs among patients ≥18 years old. Percentages of pathogens with nonsusceptibility (%NS) to selected antimicrobials were calculated for each HAI type, location type, surgical category, and surgical wound closure technique., Results: Overall, 5,626 facilities performed adult HAI surveillance during this period, most of which were general acute-care hospitals with <200 beds. Escherichia coli (18%), Staphylococcus aureus (12%), and Klebsiella spp (9%) were the 3 most frequently reported pathogens. Pathogens varied by HAI and location type, with oncology units having a distinct pathogen distribution compared to other settings. The %NS for most pathogens was significantly higher among device-associated HAIs than SSIs. In addition, pathogens from long-term acute-care hospitals had a significantly higher %NS than those from general hospital wards., Conclusions: This report provides an updated national summary of pathogen distributions and antimicrobial resistance among select HAIs and pathogens, stratified by several factors. These data underscore the importance of tracking antimicrobial resistance, particularly in vulnerable populations such as long-term acute-care hospitals and intensive care units.

Objective: To describe common pathogens and antimicrobial resistance patterns for healthcare-associated infections (HAIs) among pediatric patients that occurred in 2015-2017 and were reported to the Centers for Disease Control and Prevention's National Healthcare Safety Network (NHSN)., Methods: Antimicrobial resistance data were analyzed for pathogens implicated in central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated pneumonias (VAPs), and surgical site infections (SSIs). This analysis was restricted to device-associated HAIs reported from pediatric patient care locations and SSIs among patients <18 years old. Percentages of pathogens with nonsusceptibility (%NS) to selected antimicrobials were calculated by HAI type, location type, and surgical category., Results: Overall, 2,545 facilities performed surveillance of pediatric HAIs in the NHSN during this period. Staphylococcus aureus (15%), Escherichia coli (12%), and coagulase-negative staphylococci (12%) were the 3 most commonly reported pathogens associated with pediatric HAIs. Pathogens and the %NS varied by HAI type, location type, and/or surgical category. Among CLABSIs, the %NS was generally lowest in neonatal intensive care units and highest in pediatric oncology units. Staphylococcus spp were particularly common among orthopedic, neurosurgical, and cardiac SSIs; however, E. coli was more common in abdominal SSIs. Overall, antimicrobial nonsusceptibility was less prevalent in pediatric HAIs than in adult HAIs., Conclusion: This report provides an updated national summary of pathogen distributions and antimicrobial resistance patterns among pediatric HAIs. These data highlight the need for continued antimicrobial resistance tracking among pediatric patients and should encourage the pediatric healthcare community to use such data when establishing policies for infection prevention and antimicrobial stewardship.

During 2014-2017, CDC Emerging Infections Program surveillance data reported that the occurrence of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections associated with injection drug use doubled among persons aged 18-49 years residing in Monroe County in western New York.* Unpublished surveillance data also indicate that an increasing proportion of all Candida spp. bloodstream infections in Monroe County and invasive group A Streptococcus (GAS) infections in 15 New York counties are also occurring among persons who inject drugs. In addition, across six surveillance sites nationwide, the proportion of invasive MRSA infections that occurred in persons who inject drugs increased from 4.1% of invasive MRSA cases in 2011 to 9.2% in 2016 (1). To better understand the types and frequency of these infections and identify prevention opportunities, CDC and public health partners conducted a rapid assessment of bacterial and fungal infections among persons who inject drugs in western New York. The goals were to assess which bacterial and fungal pathogens most often cause infections in persons who inject drugs, what proportion of persons who inject use opioids, and of these, how many were offered medication-assisted treatment for opioid use disorder. Medication-assisted treatment, which includes use of medications such as buprenorphine, methadone, and naltrexone, reduces cravings and has been reported to lower the risk for overdose death and all-cause mortality in persons who use opioids (2,3). In this assessment, nearly all persons with infections who injected drugs used opioids (97%), but half of inpatients (22 of 44) and 12 of 13 patients seen only in the emergency department (ED) were not offered medication-assisted treatment. The most commonly identified pathogen was S. aureus (80%), which is frequently found on skin. Health care visits for bacterial and fungal infections associated with injection opioid use are an opportunity to treat the underlying opioid use disorder with medication-assisted treatment. Routine care for patients who continue to inject should include advice on hand hygiene and not injecting into skin that has not been cleaned or to use any equipment contaminated by reuse, saliva, soil, or water (4,5)., Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. Elizabeth Dufort reports that her spouse has a Gilead Foundation FOCUS research grant for expanded hepatitis C virus screening and testing. No other potential conflicts of interest were disclosed.

Introduction: Staphylococcus aureus is one of the most common pathogens in health care facilities and in the community, and can cause invasive infections, sepsis, and death. Despite progress in preventing methicillin-resistant S. aureus (MRSA) infections in health care settings, assessment of the problem in both health care and community settings is needed. Further, the epidemiology of methicillin-susceptible S. aureus (MSSA) infections is not well described at the national level., Methods: Data from the Emerging Infections Program (EIP) MRSA population surveillance (2005-2016) and from the Premier and Cerner Electronic Health Record databases (2012-2017) were analyzed to describe trends in incidence of hospital-onset and community-onset MRSA and MSSA bloodstream infections and to estimate the overall incidence of S. aureus bloodstream infections in the United States and associated in-hospital mortality., Results: In 2017, an estimated 119,247 S. aureus bloodstream infections with 19,832 associated deaths occurred. During 2005-2012 rates of hospital-onset MRSA bloodstream infection decreased by 17.1% annually, but the decline slowed during 2013-2016. Community-onset MRSA declined less markedly (6.9% annually during 2005-2016), mostly related to declines in health care-associated infections. Hospital-onset MSSA has not significantly changed (p = 0.11), and community-onset MSSA infections have slightly increased (3.9% per year, p<0.0001) from 2012 to 2017., Conclusions and Implications for Public Health Practice: Despite reductions in incidence of MRSA bloodstream infections since 2005, S. aureus infections account for significant morbidity and mortality in the United States. To reduce the incidence of these infections further, health care facilities should take steps to fully implement CDC recommendations for prevention of device- and procedure-associated infections and for interruption of transmission. New and novel prevention strategies are also needed., Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: The problem of variable selection for risk factor modeling is an ongoing challenge in statistical practice. Classical methods that select one subset of exploratory risk factors dominate the medical research field. However, this approach has been criticized for not taking into account the uncertainty of the model selection process itself. This limitation can be addressed by a Bayesian model averaging approach: instead of focusing on a single model and a few factors, Bayesian model averaging considers all the models with non-negligible probabilities to make inference., Methods: This paper reports on a simulation study designed to emulate a matched case-control study and compares classical versus Bayesian model averaging selection methods. We used Matthews's correlation coefficient to measure the quality of binary classifications. Both classical and Bayesian model averaging were also applied and compared for the analysis of a matched case-control study of patients with methicillin-resistant Staphylococcus aureus infections after hospital discharge 2011-2013., Results: Bayesian model averaging outperformed the classical approach with much lower false positive rates and higher Matthew's correlation scores. Bayesian model averaging also produced more reliable and robust effect estimates., Conclusion: Bayesian model averaging is a conceptually simple, unified approach that produces robust results. It can be used to replace controversial P-values for case-control study in medical research.