BACKGROUND: Nursing homes (NHs) were disproportionately affected by the COVID-19 pandemic. However, little is known regarding the kinetics of SARS-CoV-2 shedding in NH residents and staff, which could inform treatment and infection prevention. METHODS: We enrolled NH residents and staff in eight US states from April to November 2023 and analyzed the kinetics of SARS-CoV-2 using serial antigen and molecular (RT-PCR) tests, whole genome sequencing, and viral culture (VC). Symptoms, vaccination, and treatment were collected via interviews and chart review. Viral load trajectories were modeled with gamma distribution functional forms. Antigen and VC test positivity over time were assessed using a Chi-squared test. RESULTS: Of the 587 enrolled participants, 86 tested positive and 73 underwent testing for ≥ 10 days; most residents (78%) and staff (87%) had ≥ 3 COVID-19 vaccine doses. The modeled SARS-CoV-2 proliferation period (period prior to reaching peak viral load) had ended for 48% (14/29) of residents and 56% (9/16) of staff when they took the initial RT-PCR test. Both antigen and VC showed higher positivity rates early in the course of disease (Days 0-5 vs. Days ≥ 6) (antigen: p < 0·001, VC: p < 0·001). VC positivity was 15% after Day 5 (14/96); two participants were VC positive after Day 10. CONCLUSIONS: Peak viral load occurs early in the disease, suggesting asymptomatic and presymptomatic transmission may be a significant driver of transmission. Only two participants had a positive VC after Day 10, supporting current isolation and return to work recommendations.

BACKGROUND: Medicare claims are frequently used to study Clostridioides difficile infection (CDI) epidemiology. However, they lack specimen collection and diagnosis dates to assign location of onset. Algorithms to classify CDI onset location using claims data have been published, but the degree of misclassification is unknown. METHODS: We linked patients with laboratory-confirmed CDI reported to four Emerging Infections Program (EIP) sites from 2016-2021 to Medicare beneficiaries with fee-for-service Part A/B coverage. We calculated sensitivity of ICD-10-CM codes in claims within ±28 days of EIP specimen collection. CDI was categorized as hospital, long-term care facility, or community-onset using three different Medicare claims-based algorithms based on claim type, ICD-10-CM code position, duration of hospitalization, and ICD-10-CM diagnosis code presence-on-admission indicators. We assessed concordance of EIP case classifications, based on chart review and specimen collection date, with claims case classifications using Cohen's kappa statistic. RESULTS: Of 12,671 CDI cases eligible for linkage, 9,032 (71%) were linked to a single, unique Medicare beneficiary. Compared to EIP, sensitivity of CDI ICD-10-CM codes was 81%; codes were more likely to be present for hospitalized patients (93.0%) than those who were not (56.2%). Concordance between EIP and Medicare claims algorithms ranged from 68% to 75%, depending on the algorithm used (κ = 0.56-0.66). CONCLUSION: ICD-10-CM codes in Medicare claims data had high sensitivity compared to laboratory-confirmed CDI reported to EIP. Claims-based epidemiologic classification algorithms had moderate concordance with EIP classification of onset location. Misclassification of CDI onset location using Medicare algorithms may bias findings of claims-based CDI studies.

IMPORTANCE: Antimicrobial resistance is a major public health problem in the US. Estimating national rates of antimicrobial-resistant infections commonly associated with health care can aid in targeted public health efforts. OBJECTIVE: To determine the national incidence rates of 6 pathogens over time: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp (VRE), extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella spp (excluding Klebsiella aerogenes) (ESCR-EK), carbapenem-resistant Enterobacterales (CRE), carbapenem-resistant Acinetobacter spp (CRAsp), and multidrug-resistant (MDR) Pseudomonas aeruginosa. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from 2012 to 2022 on inpatient hospitalizations, clinical cultures, and facility-level characteristics. Hospital-months were included in the dynamic cohort if the hospital reported at least 1 culture with microbial growth accompanied by antimicrobial susceptibility testing (AST) results in the month. Data from the PINC-AI and Becton Dickinson Insights databases were used, and cases were defined as incident nonsurveillance cultures yielding an organism of interest with sufficient AST results for a phenotype of interest. Data were collected from January 2012 to December 2022 and analyzed from April 2023 to June 2024. EXPOSURE: Inpatient hospitalizations with a discharge date in an included hospital month. MAIN OUTCOMES AND MEASURES: National annual antimicrobial-resistant cases per 10 000 hospitalizations were obtained using weights based on facility-level characteristics. Cases were defined as community-onset if collected on or before day 3 of hospitalization and hospital-onset if obtained on day 4 or later. RESULTS: This study cohort included 332 to 606 hospitals per year between 2012 to 2022 and 7 158 139 cultures. Antimicrobial-resistant pathogens accounted for an estimated 569 749 (95% CI, 475 949-663 548) cases and 179.6 (95% CI, 163.1-196.1) cases per 10 000 hospitalizations in 2022. Of these cases, 77% (437 657; 95% CI, 364 529-510 785) were community-onset and 23% (132 092; 95% CI, 108 241-155 943) were hospital-onset. MRSA (44% [251 854; 95% CI, 209 558-294 150]) and ESCR-EK (35% [200 884; 95% CI, 163 692-238 077]) made up the largest proportions of total infections in 2022, respectively. Rates of hospital-onset MRSA, VRE, CRE, CRAsp, and MDR P aeruginosa had periods of decline from 2012 to 2019; however, all pathogens experienced an increase in hospital-onset rates in 2020 and 2021. Community-onset ESCR-EK rates increased from 2012 to 2022, while community-onset rates of MRSA, VRE, and MDR P aeruginosa declined. CONCLUSIONS AND RELEVANCE: While antimicrobial resistance rates have experienced uneven declines in the US from 2012 to 2022, the burden of resistance remains substantial. These findings suggest that more effective strategies to reduce antimicrobial resistance are needed.

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: The majority of recent estimates on the direct medical cost attributable to hospital-onset infections (HOIs) has focused on device- or procedure-associated HOIs. The attributable costs of HOIs that are not associated with device use or procedures have not been extensively studied. OBJECTIVE: We developed simulation models of attributable cost for 16 HOIs and estimated the total direct medical cost, including nondevice-related HOIs in the USA for 2011 and 2015. DATA AND METHODS: We used total discharge costs associated with HOI-related hospitalization from the National Inpatient Sample and applied an analogy costing methodology to develop simulation models of the costs attributable to HOIs. The mean attributable cost estimate from the simulation analysis was then multiplied by previously published estimates of the number of HOIs for 2011 and 2015 to generate national estimates of direct medical costs. RESULTS: After adjusting all estimates to 2017 US dollars, attributable cost estimates for select nondevice-related infections attributable cost estimates ranged from $7661 for ear, eye, nose, throat, and mouth (EENTM) infections to $27,709 for cardiovascular system infections in 2011; and from $8394 for EENTM to $26,445 for central nervous system infections in 2016 (based on 2015 incidence data). The national direct medical costs for all HOIs were $14.6 billion in 2011 and $12.1 billion in 2016. Nondevice- and nonprocedure-associated HOIs comprise approximately 26-28% of total HOI costs. CONCLUSION: Results suggest that nondevice- and nonprocedure-related HOIs result in considerable costs to the healthcare system.

BACKGROUND: Detection and containment of hospital outbreaks currently depend on variable and personnel-intensive surveillance methods. Whether automated statistical surveillance for outbreaks of health care-associated pathogens allows earlier containment efforts that would reduce the size of outbreaks is unknown. METHODS: We conducted a cluster-randomized trial in 82 community hospitals within a larger health care system. All hospitals followed an outbreak response protocol when outbreaks were detected by their infection prevention programs. Half of the hospitals additionally used statistical surveillance of microbiology data, which alerted infection prevention programs to outbreaks. Statistical surveillance was also applied to microbiology data from control hospitals without alerting their infection prevention programs. The primary outcome was the number of additional cases occurring after outbreak detection. Analyses assessed differences between the intervention period (July 2019 to January 2022) versus baseline period (February 2017 to January 2019) between randomized groups. A post hoc analysis separately assessed pre-coronavirus disease 2019 (Covid-19) and Covid-19 pandemic intervention periods. RESULTS: Real-time alerts did not significantly reduce the number of additional outbreak cases (intervention period versus baseline: statistical surveillance relative rate [RR]=1.41, control RR=1.81; difference-in-differences, 0.78; 95% confidence interval [CI], 0.40 to 1.52; P=0.46). Comparing only the prepandemic intervention with baseline periods, the statistical outbreak surveillance group was associated with a 64.1% reduction in additional cases (statistical surveillance RR=0.78, control RR=2.19; difference-in-differences, 0.36; 95% CI, 0.13 to 0.99). There was no similarly observed association between the pandemic versus baseline periods (statistical surveillance RR=1.56, control RR=1.66; difference-in-differences, 0.94; 95% CI, 0.46 to 1.92). CONCLUSIONS: Automated detection of hospital outbreaks using statistical surveillance did not reduce overall outbreak size in the context of an ongoing pandemic. (Funded by the Centers for Disease Control and Prevention; ClinicalTrials.gov number, NCT04053075. Support for HCA Healthcare's participation in the study was provided in kind by HCA.).

IMPORTANCE: Universal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization. OBJECTIVE: To compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing. DESIGN, SETTING, AND PARTICIPANTS: Two-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) and intervention (November 1, 2017-April 30, 2019) were included. INTERVENTION: Universal decolonization involving switching to iodophor-CHG (intervention) or continuing mupirocin-CHG (baseline). MAIN OUTCOMES AND MEASURES: ICU-attributable S aureus clinical cultures (primary outcome), MRSA clinical cultures, and all-cause bloodstream infections were evaluated using proportional hazard models to assess differences from baseline to intervention periods between the strategies. Results were also compared with a 2009-2011 trial of mupirocin-CHG vs no decolonization in the same hospital network. The prespecified noninferiority margin for the primary outcome was 10%. RESULTS: Among the 801 668 admissions in 233 ICUs, the participants' mean (SD) age was 63.4 (17.2) years, 46.3% were female, and the mean (SD) ICU length of stay was 4.8 (4.7) days. Hazard ratios (HRs) for S aureus clinical isolates in the intervention vs baseline periods were 1.17 for iodophor-CHG (raw rate: 5.0 vs 4.3/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 4.1 vs 4.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 18.4% [95% CI, 10.7%-26.6%] for mupirocin-CHG, P < .001). For MRSA clinical cultures, HRs were 1.13 for iodophor-CHG (raw rate: 2.3 vs 2.1/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 2.0 vs 2.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 14.1% [95% CI, 3.7%-25.5%] for mupirocin-CHG, P = .007). For all-pathogen bloodstream infections, HRs were 1.00 (2.7 vs 2.7/1000) for iodophor-CHG and 1.01 (2.6 vs 2.6/1000) for mupirocin-CHG (nonsignificant HR difference in differences, -0.9% [95% CI, -9.0% to 8.0%]; P = .84). Compared with the 2009-2011 trial, the 30-day relative reduction in hazards in the mupirocin-CHG group relative to no decolonization (2009-2011 trial) were as follows: S aureus clinical cultures (current trial: 48.1% [95% CI, 35.6%-60.1%]; 2009-2011 trial: 58.8% [95% CI, 47.5%-70.7%]) and bloodstream infection rates (current trial: 70.4% [95% CI, 62.9%-77.8%]; 2009-2011 trial: 60.1% [95% CI, 49.1%-70.7%]). CONCLUSIONS AND RELEVANCE: Nasal iodophor antiseptic did not meet criteria to be considered noninferior to nasal mupirocin antibiotic for the outcome of S aureus clinical cultures in adult ICU patients in the context of daily CHG bathing. In addition, the results were consistent with nasal iodophor being inferior to nasal mupirocin. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03140423.

IMPORTANCE: Characterizing the scale and factors associated with hospital-onset SARS-CoV-2 infections could help inform hospital and public health policies regarding prevention and surveillance needs for these infections. OBJECTIVE: To evaluate associations of hospital-onset SARS-CoV-2 infection rates with different periods of the COVID-19 pandemic, hospital characteristics, and testing practices. DESIGN, SETTING, AND PARTICIPANTS: This cohort study of US hospitals reporting SARS-CoV-2 testing data in the PINC AI Healthcare Database COVID-19 special release files was conducted from July 2020 through June 2022. Data were collected from hospitals that reported at least 1 SARS-CoV-2 reverse transcription-polymerase chain reaction or antigen test during hospitalizations discharged that month. For each hospital-month where the hospital reported sufficient data, all hospitalizations discharged in that month were included in the cohort. SARS-CoV-2 viral tests and results reported in the microbiology files for all hospitalizations in the study period by discharge month were identified. Data analysis was conducted from September 2022 to March 2023. EXPOSURE: Hospitalizations discharged in an included hospital-month. MAIN OUTCOMES AND MEASURES: Multivariable generalized estimating equation negative-binomial regression models were used to assess associations of monthly rates of hospital-onset SARS-CoV-2 infections per 1000 patient-days (defined as a first positive SARS-CoV-2 test during after hospitalization day 7) with the phase of the pandemic (defined as the predominant SARS-CoV-2 variant in circulation), admission testing rates, and hospital characteristics (hospital bed size, teaching status, urban vs rural designation, Census region, and patient distribution variables). RESULTS: A total of 5687 hospital-months from 288 distinct hospitals were included, which contributed 4 421 268 hospitalization records. Among 171 564 hospitalizations with a positive SARS-CoV-2 test, 7591 (4.4%) were found to be hospital onset and 6455 (3.8%) were indeterminate onset. The mean monthly hospital-onset infection rate per 1000 patient-days was 0.27 (95 CI, 0.26-0.29). Hospital-onset infections occurred in 2217 of 5687 hospital-months (39.0%). The monthly percentage of discharged patients tested for SARS-CoV-2 at admission varied; 1673 hospital-months (29.4%) had less than 25% of hospitalizations tested at admission; 2199 hospital-months (38.7%) had 25% to 50% of all hospitalizations tested, and 1815 hospital months (31.9%) had more than 50% of all hospitalizations tested at admission. Postadmission testing rates and community-onset infection rates increased with admission testing rates. In multivariable models restricted to hospital-months testing at least 25% of hospitalizations at admission, a 10% increase in community-onset SARS-CoV-2 infection rate was associated with a 178% increase in the hospital-onset infection rate (rate ratio, 2.78; 95% CI, 2.52-3.07). Additionally, the phase of the COVID-19 pandemic, the admission testing rate, Census region, and bed size were all significantly associated with hospital-onset SARS-CoV-2 infection rates. CONCLUSIONS AND RELEVANCE: In this cohort study of hospitals reporting SARS-CoV-2 infections, there was an increase of hospital-onset SARS-CoV-2 infections when community-onset infections were higher, indicating a need for ongoing and enhanced surveillance and prevention efforts to reduce in-hospital transmission of SARS-CoV-2 infections, particularly when community-incidence of SARS-CoV-2 infections is high.

Background SARS-CoV-2 outbreaks in nursing homes can be large with high case fatality. Identifying asymptomatic individuals early through serial testing is recommended to control COVID-19 in nursing homes, both in response to an outbreak (“outbreak testing” of residents and healthcare personnel) and in facilities without outbreaks (“non-outbreak testing” of healthcare personnel). The effectiveness of outbreak testing and isolation with or without non-outbreak testing was evaluated.Methods Using published SARS-CoV-2 transmission parameters, the fraction of SARS-CoV-2 transmissions prevented through serial testing (weekly, every three days, or daily) and isolation of asymptomatic persons compared to symptom-based testing and isolation was evaluated through mathematical modeling using a Reed-Frost model to estimate the percentage of cases prevented (i.e., “effectiveness”) through either outbreak testing alone or outbreak plus non-outbreak 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 non-outbreak testing could prevent up to an additional 8% of SARS-CoV-2 infections (depending on test frequency and turnaround time). However, added benefits of non-outbreak 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.Summary Mathematical modeling evaluated the effectiveness of serially testing asymptomatic persons in a nursing home in response to a SARS-CoV-2 outbreak with or without serial testing of asymptomatic staff in the absence of known SARS-CoV-2 infections.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was received. All work was conducted as part of government duties.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy (see e.g., 45 C.F.R. part 46, 21 C.F.R. part 56; 42 U.S.C. 241(d); 5 U.S.C 552a; 44 U.S.C. 351 et seq.).All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData provided in supplemental materials or publicly available through links in the manuscript. https://github.com/cdcepi/Nursing-home-SARS-CoV-2-testing-model/

Importance: There are limited data describing SARS-CoV-2-specific immune responses and their durability following infection and vaccination in nursing home residents. Objective(s): To evaluate the quantitative titers and durability of binding antibodies detected after SARSCoV-2 infection and subsequent COVID-19 vaccination. Design(s): A prospective longitudinal evaluation included nine visits over 150 days; visits included questionnaire administration, blood collection for serology, and paired anterior nasal specimen collection for testing by BinaxNOWTM COVID-19 Ag Card (BinaxNOW), reverse transcription polymerase chain reaction (RT-PCR), and viral culture. Setting(s): A nursing home during and after a SARS-CoV-2 outbreak. Participant(s): 11 consenting SARS-CoV-2-positive nursing home residents. Main Outcomes and Measures: SARS-CoV-2 testing (BinaxNOWTM, RT-PCR, viral culture); quantitative titers of binding SARS-CoV-2 antibodies post-infection and post-vaccination (beginning after the first dose of the primary series). Result(s): Of 10 participants with post-infection serology results, 9 (90%) had detectable Pan-Ig, IgG, and IgA antibodies and 8 (80%) had detectable IgM antibodies. At first antibody detection post-infection, two-thirds (6/9, 67%) of participants were RT-PCR-positive but none were culture positive. Ten participants received vaccination; all had detectable Pan-Ig, IgG, and IgA antibodies through their final observation <=90 days post-first dose. Post-vaccination geometric means of IgG titers were 10-200-fold higher than post-infection. Conclusions and Relevance: Nursing home residents in this cohort mounted robust immune responses to SARS-CoV-2 post-infection and post-vaccination. The augmented antibody responses post-vaccination are potential indicators of enhanced protection that vaccination may confer on previously infected nursing home residents. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

One in six nursing home residents and staff with positive SARS-CoV-2 tests 90 days after initial infection had specimen cycle thresholds (Ct) <30. Individuals with specimen Ct<30 were more likely to report symptoms but were not different from individuals with high Ct value specimens by other clinical and testing data.

The authors reply: We thank Calbo and colleagues for highlighting the need to better understand the role of asymptomatic shedding in transmission of SARS-CoV-2 in health care settings. Our study focused on transmission of SARS-CoV-2 from asymptomatic and presymptomatic residents in a skilled nursing facility. As we noted, health care personnel with undetected infection probably contributed to transmission in this facility, but we could not document this because we were unable to test asymptomatic health care personnel as part of this investigation owing to limited testing resources at the time. Since that investigation, the CDC has provided guidance on testing strategies in nursing homes.1 In addition, the CDC recommends universal source control in all health care settings to help prevent transmission from health care personnel with unrecognized SARS-CoV-2 infection.2 | | The data provided by Calbo et al. suggest important hypotheses about the role of patients and health care personnel with asymptomatic SARS-CoV-2 infection in ongoing transmission in acute care facilities, a setting that is distinct from the residential skilled nursing facility described in our article. Further studies may help to better quantify the benefit of active surveillance (including laboratory testing) when added to active symptom screening and universal source control in various health care settings.

OBJECTIVES: The Centers for Disease Control and Prevention (CDC) recommends implementing Enhanced Barrier Precautions (EBP) for all nursing home (NH) residents known to be colonized with targeted multidrug-resistant organisms (MDROs), wounds, or medical devices. Differences in health care personnel (HCP) and resident interactions between units may affect risk of acquiring and transmitting MDROs, affecting EBP implementation. We studied HCP-resident interactions across a variety of NHs to characterize MDRO transmission opportunities. DESIGN: 2 cross-sectional visits. SETTING AND PARTICIPANTS: Four CDC Epicenter sites and CDC Emerging Infection Program sites in 7 states recruited NHs with a mix of unit care types (≥30 beds or ≥2 units). HCP were observed providing resident care. METHODS: Room-based observations and HCP interviews assessed HCP-resident interactions, care type provided, and equipment use. Observations and interviews were conducted for 7-8 hours in 3-6-month intervals per unit. Chart reviews collected deidentified resident demographics and MDRO risk factors (eg, indwelling devices, pressure injuries, and antibiotic use). RESULTS: We recruited 25 NHs (49 units) with no loss to follow-up, conducted 2540 room-based observations (total duration: 405 hours), and 924 HCP interviews. HCP averaged 2.5 interactions per resident per hour (long-term care units) to 3.4 per resident per hour (ventilator care units). Nurses provided care to more residents (n = 12) than certified nursing assistants (CNAs) and respiratory therapists (RTs) (CNA: 9.8 and RT: 9) but nurses performed significantly fewer task types per interaction compared to CNAs (incidence rate ratio (IRR): 0.61, P < .05). Short-stay (IRR: 0.89) and ventilator-capable (IRR: 0.94) units had less varied care compared with long-term care units (P < .05), although HCP visited residents in these units at similar rates. CONCLUSIONS AND IMPLICATIONS: Resident-HCP interaction rates are similar across NH unit types, differing primarily in types of care provided. Current and future interventions such as EBP, care bundling, or targeted infection prevention education should consider unit-specific HCP-resident interaction patterns.

BACKGROUND: Descriptions of changes in invasive bacterial disease (IBD) epidemiology during the COVID-19 pandemic in the United States are limited. METHODS: We investigated changes in the incidence of IBD due to Streptococcus pneumoniae, Haemophilus influenzae, group A Streptococcus (GAS), and group B Streptococcus (GBS). We defined the COVID-19 pandemic period as March 1-December 31, 2020. We compared observed IBD incidences during the pandemic to expected incidences, consistent with January 2014-February 2020 trends. We conducted secondary analysis of a healthcare database to assess changes in testing by blood and cerebrospinal fluid (CSF) culture during the pandemic. RESULTS: Compared with expected incidences, the observed incidences of IBD due to S. pneumoniae, H. influenzae, GAS, and GBS were 58%, 60%, 28%, and 12% lower during the pandemic period of 2020, respectively. Declines from expected incidences corresponded closely with implementation of COVID-19-associated non-pharmaceutical-interventions (NPIs). Significant declines were observed across all age, race groups and surveillance sites for S pneumoniae and H influenzae. Blood and CSF culture testing rates during the pandemic were comparable to previous years. CONCLUSIONS: NPIs likely contributed to the decline in IBD incidence in the United States in 2020; observed declines were unlikely to be driven by reductions in testing.

There are limited data describing SARS-CoV-2-specific immune responses and their durability following infection and vaccination in nursing home residents. We conducted a prospective longitudinal evaluation of 11 consenting SARS-CoV-2-positive nursing home residents to evaluate the quantitative titers and durability of binding antibodies detected after SARS-CoV-2 infection and subsequent COVID-19 vaccination. The evaluation included nine visits over 150 days from October 25, 2020, through April 1, 2021. Visits included questionnaire administration, blood collection for serology, and paired anterior nasal specimen collection for testing by BinaxNOW™ COVID-19 Ag Card (BinaxNOW), reverse transcription polymerase chain reaction (RT-PCR), and viral culture. We evaluated quantitative titers of binding SARS-CoV-2 antibodies post-infection and post-vaccination (beginning after the first dose of the primary series). The median age among participants was 74 years; one participant was immunocompromised. Of 10 participants with post-infection serology results, 9 (90%) had detectable Pan-Ig, IgG, and IgA antibodies, and 8 (80%) had detectable IgM antibodies. At first antibody detection post-infection, two-thirds (6/9, 67%) of participants were RT-PCR-positive, but none were culture- positive. Ten participants received vaccination; all had detectable Pan-Ig, IgG, and IgA antibodies through their final observation ≤90 days post-first dose. Post-vaccination geometric means of IgG titers were 10-200-fold higher than post-infection. Nursing home residents in this cohort mounted robust immune responses to SARS-CoV-2 post-infection and post-vaccination. The augmented antibody responses post-vaccination are potential indicators of enhanced protection that vaccination may confer on previously infected nursing home residents.

Among persons with an initial Clostridioides difficile infection (CDI) across 10 US sites in 2018 compared with 2013, 18.3% versus 21.1% had 1 recurrent CDI (rCDI) within 180 days. We observed a 16% lower adjusted risk of rCDI in 2018 versus 2013 (P<.0001).

The disruptions of the coronavirus disease 2019 (COVID-19) pandemic impacted the delivery and utilization of healthcare services with potential long-term implications for population health and the hospital workforce. Using electronic health record data from over 700 USacute care hospitals, we documented changes in admissions to hospital service areas (inpatient, observation, emergency room [ER], and same-day surgery) during 2019-2020 and examined whether surges of COVID-19 hospitalizations corresponded with increased inpatient disease severity and death rate. We found that in 2020, hospitalizations declined by 50% in April, with greatest declines occurring in same-day surgery (-73%). The youngest patients (0-17) experienced largest declines in ER, observation, and same-day surgery admissions; inpatient admissions declined the most among the oldest patients (65+). Infectious disease admissions increased by 52%. The monthly measures of inpatient case mix index, length of stay, and non-COVID death rate were higher in all months in 2020 compared with respective months in 2019.

We described bacterial/fungal co-infections and antibiotic resistant infections among inpatients diagnosed with COVID-19 and compared findings with inpatients diagnosed with influenza-like-illness. Less than 10% of COVID-19 inpatients had bacterial/fungal co-infection. Longer lengths of stay, critical care stay, and mechanical ventilation contribute to increased incidence of hospital-onset infections among COVID-19 inpatients.

The SARS-CoV-2 Omicron variant has been hypothesized to exhibit faster clearance (time from peak viral concentration to clearance of acute infection), decreased sensitivity of antigen tests, and increased immune escape (the ability of the variant to evade immunity conferred by past infection or vaccination) compared to prior variants. These factors necessitate re-evaluation of prevention and control strategies-particularly in high-risk, congregate settings like nursing homes that have been heavily impacted by other COVID-19 variants. We used a simple model representing individual-level viral shedding dynamics to estimate the optimal strategy for testing nursing home healthcare personnel and quantify potential reduction in transmission of COVID-19. This provides a framework for prospectively evaluating testing strategies in emerging variant scenarios when data are limited. We find that case-initiated testing prevents 38% of transmission within a facility if implemented within a day of an index case testing positive, and screening testing strategies could prevent 30-78% of transmission within a facility if implemented daily, depending on test sensitivity.

When responding to the COVID-19 pandemic, public health entities have had to use available data to rapidly develop policies to reduce transmission, including determining duration of isolation and evaluating interventions such as masking to reduce transmission. Mathematical models often can be used to evaluate interventions when data are sparse, assuming that key parameters are known. SARS-CoV-2 shedding kinetics (corresponding to within-host virus proliferation, peak, and clearance stages) and its association with disease progression and onward transmission inform models that can be used to evaluate the effectiveness of prevention strategies. Jung et al,1 in a timely composite analysis of 2 intensive longitudinal studies in South Korea, shed light on this association.

OBJECTIVES: The coronavirus disease 2019 pandemic caused substantial changes to healthcare delivery and antibiotic prescribing beginning in March 2020. To assess pandemic impact on Clostridioides difficile infection (CDI) rates, we described patients and trends in facility-level incidence, testing rates, and percent positivity during 2019-2020 in a large cohort of US hospitals. METHODS: We estimated and compared rates of community-onset CDI (CO-CDI) per 10,000 discharges, hospital-onset CDI (HO-CDI) per 10,000 patient days, and C. difficile testing rates per 10,000 discharges in 2019 and 2020. We calculated percent positivity as the number of inpatients diagnosed with CDI over the total number of discharges with a test for C. difficile. We used an interrupted time series (ITS) design with negative binomial and logistic regression models to describe level and trend changes in rates and percent positivity before and after March 2020. RESULTS: In pairwise comparisons, overall CO-CDI rates decreased from 20.0 to 15.8 between 2019 and 2020 (P < .0001). HO-CDI rates did not change. Using ITS, we detected decreasing monthly trends in CO-CDI (-1% per month, P = .0036) and HO-CDI incidence (-1% per month, P < .0001) during the baseline period, prior to the COVID-19 pandemic declaration. We detected no change in monthly trends for CO-CDI or HO-CDI incidence or percent positivity after March 2020 compared with the baseline period. CONCLUSIONS: While there was a slight downward trajectory in CDI trends prior to March 2020, no significant change in CDI trends occurred during the COVID-19 pandemic despite changes in infection control practices, antibiotic use, and healthcare delivery.

Mathematical models are used to gauge the impact of interventions for healthcare-associated infections. As with any analytic method, such models require many assumptions. Two common assumptions are that asymptomatically colonized individuals are more likely to be hospitalized and that they spend longer in the hospital per admission because of their colonization status. These assumptions have no biological basis and could impact the estimated effects of interventions in unintended ways. Therefore, we developed a model of methicillin-resistant Staphylococcus aureus transmission to explicitly evaluate the impact of these assumptions. We found that assuming that asymptomatically colonized individuals were more likely to be admitted to the hospital or spend longer in the hospital than uncolonized individuals biased results compared to a more realistic model that did not make either assumption. Results were heavily biased when estimating the impact of an intervention that directly reduced transmission in a hospital. In contrast, results were moderately biased when estimating the impact of an intervention that decolonized hospital patients. Our findings can inform choices modelers face when constructing models of healthcare-associated infection interventions and thereby improve their validity.

BACKGROUND: Multidrug-resistant organisms (MDROs) frequently contaminate hospital environments. We performed a multicenter, cluster-randomized, crossover trial of two methods for monitoring of terminal cleaning effectiveness. METHODS: Six intensive care units (ICUs) at three medical centers received both interventions sequentially, in randomized order. Ten surfaces were surveyed each in five rooms weekly, after terminal cleaning, with ATP monitoring or an ultraviolet fluorescent marker (UV/F). Results were delivered to environmental services staff in real-time with failing surfaces recleaned. We measured monthly rates of MDRO infection or colonization, including methicillin-resistant Staphylococcus aureus, Clostridioides difficile, vancomycin-resistant Enterococcus, and MDR gram-negative bacilli (MDR-GNB) during a 12-month baseline period and sequential 6-month intervention periods, separated by a 2-month washout. Primary analysis compared only the randomized intervention periods, while secondary analysis included the baseline. RESULTS: The ATP method was associated with a reduction in incidence rate of MDRO infection or colonization compared to the UV/F period (incidence rate ratio (IRR) 0.876, 95% confidence-interval (CI) 0.807 - 0.951, P=0.002). Including the baseline period, the ATP method was associated with reduced infection with MDROs (IRR 0.924, 95% CI 0.855 - 0.998, P=0.04), and MDR-GNB infection or colonization (IRR 0.856, 95% CI 0.825 - 0.887, P<0.001). The UV/F intervention was not associated with a statistically significant impact on these outcomes. Room turn-around time increased by a median of one minute with the ATP intervention and 4.5 minutes with UV/F compared to baseline. CONCLUSIONS: Intensive monitoring of ICU terminal room cleaning with an ATP modality is associated with a reduction of MDRO infection and colonization.

Results from sampling healthcare surfaces for pathogens are difficult to interpret without understanding the factors that influence pathogen detection. We investigated the recovery of four healthcare-associated pathogens from three common surface materials, and how a body fluid simulant (artificial test soil, ATS), deposition method, and contamination levels influence the percent of organisms recovered (%R). Known quantities of carbapenemase-producing KPC+ Klebsiella pneumoniae (KPC), Acinetobacter baumannii, vancomycin-resistant Enterococcus faecalis, and Clostridioides difficile spores (CD) were suspended in Butterfield's buffer or ATS, deposited on 323cm2 steel, plastic, and laminate surfaces, allowed to dry 1h, then sampled with a cellulose sponge wipe. Bacteria were eluted, cultured, CFU counted and %R determined relative to the inoculum. The %R varied by organism, from <1% (KPC) to almost 60% (CD) and was more dependent upon the organism's characteristics and presence of ATS than on surface type. KPC persistence as determined by culture also declined by >1 log10 within the 60 min drying time. For all organisms, the %R was significantly greater if suspended in ATS than if suspended in Butterfield's buffer (p<0.05), and for most organisms the %R was not significantly different when sampled from any of the three surfaces. Organisms deposited in multiple droplets were recovered at equal or higher %R than if spread evenly on the surface. This work assists in interpreting data collected while investigating a healthcare infection outbreak or while conducting infection intervention studies.

The Pfizer-BioNTech COVID-19 (BNT162b2) vaccine is a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. On August 23, 2021, the Food and Drug Administration (FDA) approved a Biologics License Application (BLA) for use of the Pfizer-BioNTech COVID-19 vaccine, marketed as Comirnaty (Pfizer, Inc.), in persons aged ≥16 years (1). The Pfizer-BioNTech COVID-19 vaccine is also recommended for adolescents aged 12-15 years under an Emergency Use Authorization (EUA) (1). All persons aged ≥12 years are recommended to receive 2 doses (30 μg, 0.3 mL each), administered 3 weeks apart (2,3). As of November 2, 2021, approximately 248 million doses of the Pfizer-BioNTech COVID-19 vaccine had been administered to persons aged ≥12 years in the United States.* On October 29, 2021, FDA issued an EUA amendment for a new formulation of Pfizer-BioNTech COVID-19 vaccine for use in children aged 5-11 years, administered as 2 doses (10 μg, 0.2 mL each), 3 weeks apart (Table) (1). On November 2, 2021, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation(†) for use of the Pfizer-BioNTech COVID-19 vaccine in children aged 5-11 years for the prevention of COVID-19. To guide its deliberations regarding recommendations for the vaccine, ACIP used the Evidence to Recommendation (EtR) Framework(§) and incorporated a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.(¶) The ACIP recommendation for the use of the Pfizer-BioNTech COVID-19 vaccine in children aged 5-11 years under an EUA is interim and will be updated as additional information becomes available. The Pfizer-BioNTech COVID-19 vaccine has high efficacy (>90%) against COVID-19 in children aged 5-11 years, and ACIP determined benefits outweigh risks for vaccination. Vaccination is important to protect children against COVID-19 and reduce community transmission of SARS-CoV-2.

OBJECTIVES: Widespread use and misuse of prescription and illicit opioids have exposed millions to health risks including serious infectious complications. Little is known, however, about the association between opioid use and sepsis. DESIGN: Retrospective cohort study. SETTING: About 373 U.S. hospitals. PATIENTS: Adults hospitalized between January 2009 and September 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sepsis was identified by clinical indicators of concurrent infection and organ dysfunction. Opioid-related hospitalizations were identified by the International Classification of Diseases, 9th Revision, Clinical Modification codes and/or inpatient orders for buprenorphine. Clinical characteristics and outcomes were compared by sepsis and opioid-related hospitalization status. The association between opioid-related hospitalization and all-cause, in-hospital mortality in patients with sepsis was assessed using mixed-effects logistic models to adjust for baseline characteristics and severity of illness. The cohort included 6,715,286 hospitalizations; 375,479 (5.6%) had sepsis, 130,399 (1.9%) had opioid-related hospitalizations, and 8,764 (0.1%) had both. Compared with sepsis patients without opioid-related hospitalizations (n = 366,715), sepsis patients with opioid-related hospitalizations (n = 8,764) were younger (mean 52.3 vs 66.9 yr) and healthier (mean Elixhauser score 5.4 vs 10.5), had more bloodstream infections from Gram-positive and fungal pathogens (68.9% vs 47.0% and 10.6% vs 6.4%, respectively), and had lower in-hospital mortality rates (10.6% vs 16.2%; adjusted odds ratio, 0.73; 95% CI, 0.60-0.79; p < 0.001 for all comparisons). Of 1,803 patients with opioid-related hospitalizations who died in-hospital, 928 (51.5%) had sepsis. Opioid-related hospitalizations accounted for 1.5% of all sepsis-associated deaths, including 5.7% of sepsis deaths among patients less than 50 years old. From 2009 to 2015, the proportion of sepsis hospitalizations that were opioid-related increased by 77% (95% CI, 40.7-123.5%). CONCLUSIONS: Sepsis is an important cause of morbidity and mortality in patients with opioid-related hospitalizations, and opioid-related hospitalizations contribute disproportionately to sepsis-associated deaths among younger patients. In addition to ongoing efforts to combat the opioid crisis, public health agencies should focus on raising awareness about sepsis among patients who use opioids and their providers.

Replication-competent virus has not been detected in individuals with mild to moderate COVID-19 more than 10 days after symptom onset. It is unknown whether these findings apply to nursing home residents. Of 273 specimens collected from nursing home residents >10 days from the initial positive test, none were culture positive.

Previously reported associations between hospital-level antibiotic use and hospital-onset Clostridioides difficile infection (HO-CDI) were reexamined using 2012-2018 data from a new cohort of US acute-care hospitals. This analysis revealed significant positive associations between total, third-generation, and fourth-generation cephalosporin, fluoroquinolone, carbapenem, and piperacillin-tazobactam use and HO-CDI rates, confirming previous findings.

BACKGROUND: To address high COVID-19 burden in U.S. nursing homes, rapid SARS-CoV-2 antigen tests have been widely distributed in those facilities. However, performance data are lacking, especially in asymptomatic people. OBJECTIVE: To evaluate the performance of SARS-CoV-2 antigen testing when used for facility-wide testing during a nursing home outbreak. DESIGN: A prospective evaluation involving 3 facility-wide rounds of testing where paired respiratory specimens were collected to evaluate the performance of the BinaxNOW antigen test compared with virus culture and real-time reverse transcription polymerase chain reaction (RT-PCR). Early and late infection were defined using changes in RT-PCR cycle threshold values and prior test results. SETTING: A nursing home with an ongoing SARS-CoV-2 outbreak. PARTICIPANTS: 532 paired specimens collected from 234 available residents and staff. MEASUREMENTS: Percentage of positive agreement (PPA) and percentage of negative agreement (PNA) for BinaxNOW compared with RT-PCR and virus culture. RESULTS: BinaxNOW PPA with virus culture, used for detection of replication-competent virus, was 95%. However, the overall PPA of antigen testing with RT-PCR was 69%, and PNA was 98%. When only the first positive test result was analyzed for each participant, PPA of antigen testing with RT-PCR was 82% among 45 symptomatic people and 52% among 343 asymptomatic people. Compared with RT-PCR and virus culture, the BinaxNOW test performed well in early infection (86% and 95%, respectively) and poorly in late infection (51% and no recovered virus, respectively). LIMITATION: Accurate symptom ascertainment was challenging in nursing home residents; test performance may not be representative of testing done by nonlaboratory staff. CONCLUSION: Despite lower positive agreement compared with RT-PCR, antigen test positivity had higher agreement with shedding of replication-competent virus. These results suggest that antigen testing could be a useful tool to rapidly identify contagious people at risk for transmitting SARS-CoV-2 during nascent outbreaks and help reduce COVID-19 burden in nursing homes. PRIMARY FUNDING SOURCE: None.

IMPORTANCE: Risks for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among health care personnel (HCP) are unclear. OBJECTIVE: To evaluate the risk factors associated with SARS-CoV-2 seropositivity among HCP with the a priori hypothesis that community exposure but not health care exposure was associated with seropositivity. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted among volunteer HCP at 4 large health care systems in 3 US states. Sites shared deidentified data sets, including previously collected serology results, questionnaire results on community and workplace exposures at the time of serology, and 3-digit residential zip code prefix of HCP. Site-specific responses were mapped to a common metadata set. Residential weekly coronavirus disease 2019 (COVID-19) cumulative incidence was calculated from state-based COVID-19 case and census data. EXPOSURES: Model variables included demographic (age, race, sex, ethnicity), community (known COVID-19 contact, COVID-19 cumulative incidence by 3-digit zip code prefix), and health care (workplace, job role, COVID-19 patient contact) factors. MAIN OUTCOME AND MEASURES: The main outcome was SARS-CoV-2 seropositivity. Risk factors for seropositivity were estimated using a mixed-effects logistic regression model with a random intercept to account for clustering by site. RESULTS: Among 2 749 HCP, most were younger than 50 years (17 233 [69.6%]), were women (19 361 [78.2%]), were White individuals (15 157 [61.2%]), and reported workplace contact with patients with COVID-19 (12 413 [50.2%]). Many HCP worked in the inpatient setting (8893 [35.9%]) and were nurses (7830 [31.6%]). Cumulative incidence of COVID-19 per 10 000 in the community up to 1 week prior to serology testing ranged from 8.2 to 275.6; 20 072 HCP (81.1%) reported no COVID-19 contact in the community. Seropositivity was 4.4% (95% CI, 4.1%-4.6%; 1080 HCP) overall. In multivariable analysis, community COVID-19 contact and community COVID-19 cumulative incidence were associated with seropositivity (community contact: adjusted odds ratio [aOR], 3.5; 95% CI, 2.9-4.1; community cumulative incidence: aOR, 1.8; 95% CI, 1.3-2.6). No assessed workplace factors were associated with seropositivity, including nurse job role (aOR, 1.1; 95% CI, 0.9-1.3), working in the emergency department (aOR, 1.0; 95% CI, 0.8-1.3), or workplace contact with patients with COVID-19 (aOR, 1.1; 95% CI, 0.9-1.3). CONCLUSIONS AND RELEVANCE: In this cross-sectional study of US HCP in 3 states, community exposures were associated with seropositivity to SARS-CoV-2, but workplace factors, including workplace role, environment, or contact with patients with known COVID-19, were not. These findings provide reassurance that current infection prevention practices in diverse health care settings are effective in preventing transmission of SARS-CoV-2 from patients to HCP.