Multidrug-Resistant Bacterial Infections in U.S. Hospitalized Patients, 2012-2017.

BACKGROUND: Multidrug-resistant (MDR) bacteria that are commonly associated with health care cause a substantial health burden. Updated national estimates for this group of pathogens are needed to inform public health action. METHODS: Using data from patients hospitalized in a cohort of 890 U.S. hospitals during the period 2012-2017, we generated national case counts for both hospital-onset and community-onset infections caused by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE), extended-spectrum cephalosporin resistance in Enterobacteriaceae suggestive of extended-spectrum beta-lactamase (ESBL) production, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant acinetobacter species, and MDR Pseudomonas aeruginosa. RESULTS: The hospital cohort in the study accounted for 41.6 million hospitalizations (>20% of U.S. hospitalizations annually). The overall rate of clinical cultures was 292 cultures per 1000 patient-days and was stable throughout the time period. In 2017, these pathogens caused an estimated 622,390 infections (95% confidence interval [CI], 579,125 to 665,655) among hospitalized patients. Of these infections, 517,818 (83%) had their onset in the community, and 104,572 (17%) had their onset in the hospital. MRSA and ESBL infections accounted for the majority of the infections (52% and 32%, respectively). Between 2012 and 2017, the incidence decreased for MRSA infection (from 114.18 to 93.68 cases per 10,000 hospitalizations), VRE infection (from 24.15 to 15.76 per 10,000), carbapenem-resistant acinetobacter species infection (from 3.33 to 2.47 per 10,000), and MDR P. aeruginosa infection (from 13.10 to 9.43 per 10,000), with decreases ranging from -20.5% to -39.2%. The incidence of carbapenem-resistant Enterobacteriaceae infection did not change significantly (from 3.36 to 3.79 cases per 10,000 hospitalizations). The incidence of ESBL infection increased by 53.3% (from 37.55 to 57.12 cases per 10,000 hospitalizations), a change driven by an increase in community-onset cases. CONCLUSIONS: Health care-associated antimicrobial resistance places a substantial burden on patients in the United States. Further work is needed to identify improved interventions for both the inpatient and outpatient settings. (Funded by the Centers for Disease Control and Prevention.).

Distinct Origins and Transmission Pathways of blaKPC Enterobacterales across Three U.S. States.

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 blaKPC-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 blaKPC-carrying Klebsiella pneumoniae ST258, and clonal expansion of blaKPC-carrying Enterobacter hormaechei ST171, primarily at a single focal facility and its satellite facilities. In Tennessee, we observed transmission of diverse strains of blaKPC-carrying Enterobacter and Klesbiella, with evidence that most derived from the local acquisition of blaKPC 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.

Antibiotic-Resistant Infections Among Inpatients with Coronavirus Disease 2019 (COVID-19) in US Hospitals.

We described bacterial/fungal coinfections and antibiotic-resistant infections among inpatients with a diagnosis of coronavirus disease 2019 (COVID-19) and compared findings in those with a diagnosis of influenza like illness. Less than 10% of inpatients with COVID-19 had bacterial/fungal coinfection. Longer lengths of stay, critical care stay, and mechanical ventilation contribute to increased incidence of hospital-onset infections among inpatients with COVID-19.

Effectiveness of Coronavirus Disease 2019 (COVID-19) Vaccination Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Among Residents of US Nursing Homes Before and During the Delta Variant Predominance, December 2020-November 2021.

BACKGROUND: Residents of nursing homes experience disproportionate morbidity and mortality related to coronavirus disease 2019 (COVID-19) and were prioritized for vaccine introduction. We evaluated COVID-19 vaccine effectiveness (VE) in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among nursing home residents. METHODS: We used a retrospective cohort of 4315 nursing home residents during 14 December 2020-9 November 2021. A Cox proportional hazards model was used to estimate hazard ratios comparing residents with a completed vaccination series with unvaccinated among those with and without prior SARS-CoV-2 infection, by vaccine product, and by time period. RESULTS: Overall adjusted VE was 58% (95% confidence interval [CI], 44% to 69%) among residents without a history of SARS-CoV-2 infection. During the pre-Delta period, the VE within 150 days of receipt of the second dose of Pfizer-BioNTech (67%; 95% CI, 40% to 82%) and Moderna (75%; 95% CI, 32% to 91%) was similar. During the Delta period, VE measured >150 days after the second dose was 33% (95% CI, -2% to 56%) for Pfizer-BioNTech and 77% (95% CI, 48% to 91%) for Moderna. Rates of infection were 78% lower (95% CI, 67% to 85%) among residents with prior SARS-CoV-2 infection and completed vaccination series compared with unvaccinated residents without a history of SARS-CoV-2 infection. CONCLUSIONS: COVID-19 vaccines were effective in preventing SARS-CoV-2 infections among nursing home residents, and history of prior SARS-CoV-2 infection provided additional protection. Maintaining high coverage of recommended doses of COVID-19 vaccines remains a critical tool for preventing infections in nursing homes.

Cruise Ship Travel in the Era of Coronavirus Disease 2019 (COVID-19): A Summary of Outbreaks and a Model of Public Health Interventions.

BACKGROUND: Cruise travel contributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission when there were relatively few cases in the United States. By 14 March 2020, the Centers for Disease Control and Prevention (CDC) issued a No Sail Order suspending US cruise operations; the last US passenger ship docked on 16 April. METHODS: We analyzed SARS-CoV-2 outbreaks on cruises in US waters or carrying US citizens and used regression models to compare voyage characteristics. We used compartmental models to simulate the potential impact of 4 interventions (screening for coronavirus disease 2019 (COVID-19) symptoms; viral testing on 2 days and isolation of positive persons; reduction of passengers by 40%, crew by 20%, and reducing port visits to 1) for 7-day and 14-day voyages. RESULTS: During 19 January to 16 April 2020, 89 voyages on 70 ships had known SARS-CoV-2 outbreaks; 16 ships had recurrent outbreaks. There were 1669 reverse transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infections and 29 confirmed deaths. Longer voyages were associated with more cases (adjusted incidence rate ratio, 1.10, 95% confidence interval [CI]: 1.03-1.17, P < .003). Mathematical models showed that 7-day voyages had about 70% fewer cases than 14-day voyages. On 7-day voyages, the most effective interventions were reducing the number of individuals onboard (43.3% reduction in total infections) and testing passengers and crew (42% reduction in total infections). All four interventions reduced transmission by 80.1%, but no single intervention or combination eliminated transmission. Results were similar for 14-day voyages. CONCLUSIONS: SARS-CoV-2 outbreaks on cruises were common during January-April 2020. Despite all interventions modeled, cruise travel still poses a significant SARS-CoV-2 transmission risk.

National Estimates of Healthcare Costs Associated With Multidrug-Resistant Bacterial Infections Among Hospitalized Patients in the United States.

BACKGROUND: Treating patients with infections due to multidrug-resistant pathogens often requires substantial healthcare resources. The purpose of this study was to report estimates of the healthcare costs associated with infections due to multidrug-resistant bacteria in the United States (US). METHODS: We performed retrospective cohort studies of patients admitted for inpatient stays in the Department of Veterans Affairs healthcare system between January 2007 and October 2015. We performed multivariable generalized linear models to estimate the attributable cost by comparing outcomes in patients with and without positive cultures for multidrug-resistant bacteria. Finally, we multiplied these pathogen-specific, per-infection attributable cost estimates by national counts of infections due to each pathogen from patients hospitalized in a cohort of 722 US hospitals from 2017 to generate estimates of the population-level healthcare costs in the US attributable to these infections. RESULTS: Our analysis cohort consisted of 16 676 patients with community-onset infections and 172 712 matched controls and 8246 patients with hospital-onset infections and 66 939 matched controls. The highest cost was seen in hospital-onset invasive infections, with attributable costs (95% confidence intervals) ranging from $30 998 ($25 272-$36 724) for methicillin-resistant Staphylococcus aureus to $74 306 ($20 377-$128 235) for carbapenem-resistant (CR) Acinetobacter. The highest attributable costs for community-onset invasive infections were seen in CR Acinetobacter ($62 396; $20 370-$104 422). Treatment of these infections cost an estimated $4.6 billion ($4.1 billion-$5.1 billion) in 2017 in the US for community- and hospital-onset infections combined. CONCLUSIONS: We found that antimicrobial-resistant infections led to substantial healthcare costs.

Reducing travel-related SARS-CoV-2 transmission with layered mitigation measures: symptom monitoring, quarantine, and testing.

BACKGROUND: Balancing the control of SARS-CoV-2 transmission with the resumption of travel is a global priority. Current recommendations include mitigation measures before, during, and after travel. Pre- and post-travel strategies including symptom monitoring, antigen or nucleic acid amplification testing, and quarantine can be combined in multiple ways considering different trade-offs in feasibility, adherence, effectiveness, cost, and adverse consequences. METHODS: We used a mathematical model to analyze the expected effectiveness of symptom monitoring, testing, and quarantine under different estimates of the infectious period, test-positivity relative to time of infection, and test sensitivity to reduce the risk of transmission from infected travelers during and after travel. RESULTS: If infection occurs 0-7 days prior to travel, immediate isolation following symptom onset prior to or during travel reduces risk of transmission while traveling by 30-35%. Pre-departure testing can further reduce risk, with testing closer to the time of travel being optimal even if test sensitivity is lower than an earlier test. For example, testing on the day of departure can reduce risk while traveling by 44-72%. For transmission risk after travel with infection time up to 7 days prior to arrival at the destination, isolation based on symptom monitoring reduced introduction risk at the destination by 42-56%. A 14-day quarantine after arrival, without symptom monitoring or testing, can reduce post-travel risk by 96-100% on its own. However, a shorter quarantine of 7 days combined with symptom monitoring and a test on day 5-6 after arrival is also effective (97--100%) at reducing introduction risk and is less burdensome, which may improve adherence. CONCLUSIONS: Quarantine is an effective measure to reduce SARS-CoV-2 transmission risk from travelers and can be enhanced by the addition of symptom monitoring and testing. Optimal test timing depends on the effectiveness of quarantine: with low adherence or no quarantine, optimal test timing is close to the time of arrival; with effective quarantine, testing a few days later optimizes sensitivity to detect those infected immediately before or while traveling. These measures can complement recommendations such as social distancing, using masks, and hand hygiene, to further reduce risk during and after travel.

Evaluating Movement of Patients With Carbapenem-resistant Enterobacteriaceae Infections in the Greater Atlanta Metropolitan Area Using Social Network Analysis.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent threat with potential for rapid spread. We evaluated the role of Medicare patient movement between facilities to model the spread of CRE within a region. METHODS: Through population-based CRE surveillance in the 8-county Atlanta (GA) metropolitan area, all Escherichia coli, Enterobacter spp., or Klebsiella spp. resistant to ≥1 carbapenem were reported from residents. CRE was attributed to a facility based on timing of culture and facility exposures. Centrality metrics were calculated from 2016 Medicare data and compared to CRE-transfer derived centrality metrics by Spearman correlation. RESULTS: During 2016, 283 incident CRE cases with concurrent or prior year facility stays were identified; cases were attributed mostly to acute care hospitals (ACHs; 141, 50%) and skilled nursing facilities (SNFs; 113, 40%), and less frequently to long-term acute care hospitals (LTACHs; 29, 10%). Attribution was widespread, originating at 17 of 20 ACHs (85%), 7 of 8 (88%) LTACHs, but only 35 of 65 (54%) SNFs. Betweenness of Medicare patient transfers strongly correlated with betweenness of CRE case-transfer data in ACHs (r = 0.75; P < .01) and LTACHs (r = 0.77; P = .03), but not in SNFs (r = 0.02; P = 0.85). We noted 6 SNFs with high CRE-derived betweenness but low Medicare-derived betweenness. CONCLUSIONS: CRE infections originate from almost all ACHs and half of SNFs. We identified a subset of SNFs central to the CRE transfer network but not the Medicare transfer network; other factors may explain CRE patient movement in these facilities.

Web-Based Interactive Tool to Identify Facilities at Risk of Receiving Patients with Multidrug-Resistant Organisms.

To identify facilities at risk of receiving patients colonized or infected with multidrug-resistant organisms (MDROs), we developed an interactive web-based interface for visualization of patient-sharing networks among healthcare facilities in Tennessee, USA. Using hospital discharge data and the Centers for Medicare and Medicaid Services' claims and Minimum Data Set, we constructed networks among hospitals and skilled nursing facilities. Networks included direct and indirect transfers, which accounted for <365 days in the community outside of facility admissions. Authorized users can visualize a facility of interest and tailor visualizations by year, network dataset, length of time in the community, and minimum number of transfers. The interface visualizes the facility of interest with its connected facilities that receive or send patients, the number of interfacility transfers, and facilities at risk of receiving transfers from the facility of interest. This tool will help other health departments enhance their MDRO outbreak responses.

Whole-Genome Sequencing To Identify Drivers of Carbapenem-Resistant Klebsiella pneumoniae Transmission within and between Regional Long-Term Acute-Care Hospitals.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an antibiotic resistance threat of the highest priority. Given the limited treatment options for this multidrug-resistant organism (MDRO), there is an urgent need for targeted strategies to prevent transmission. Here, we applied whole-genome sequencing to a comprehensive collection of clinical isolates to reconstruct regional transmission pathways and analyzed this transmission network in the context of statewide patient transfer data and patient-level clinical data to identify drivers of regional transmission. We found that high regional CRKP burdens were due to a small number of regional introductions, with subsequent regional proliferation occurring via patient transfers among health care facilities. While CRKP was predicted to have been imported into each facility multiple times, there was substantial variation in the ratio of intrafacility transmission events per importation, indicating that amplification occurs unevenly across regional facilities. While myriad factors likely influence intrafacility transmission rates, an understudied one is the potential for clinical characteristics of colonized and infected patients to influence their propensity for transmission. Supporting the contribution of high-risk patients to elevated transmission rates, we observed that patients colonized and infected with CRKP in high-transmission facilities had higher rates of carbapenem use, malnutrition, and dialysis and were older. This report highlights the potential for regional infection prevention efforts that are grounded in genomic epidemiology to identify the patients and facilities that make the greatest contribution to regional MDRO prevalence, thereby facilitating the design of precision interventions of maximal impact.

Length of antibiotic therapy among adults hospitalized with uncomplicated community-acquired pneumonia, 2013-2020.

OBJECTIVE: The 2014 US National Strategy for Combating Antibiotic-Resistant Bacteria (CARB) aimed to reduce inappropriate inpatient antibiotic use by 20% for monitored conditions, such as community-acquired pneumonia (CAP), by 2020. We evaluated annual trends in length of therapy (LOT) in adults hospitalized with uncomplicated CAP from 2013 through 2020. METHODS: We conducted a retrospective cohort study among adults with a primary diagnosis of bacterial or unspecified pneumonia using International Classification of Diseases Ninth and Tenth Revision codes in MarketScan and the Centers for Medicare & Medicaid Services databases. We included patients with length of stay (LOS) of 2-10 days, discharged home with self-care, and not rehospitalized in the 3 days following discharge. We estimated inpatient LOT based on LOS from the PINC AI Healthcare Database. The total LOT was calculated by summing estimated inpatient LOT and actual postdischarge LOT. We examined trends from 2013 to 2020 in patients with total LOT >7 days, which was considered an indicator of likely excessive LOT. RESULTS: There were 44,976 and 400,928 uncomplicated CAP hospitalizations among patients aged 18-64 years and ≥65 years, respectively. From 2013 to 2020, the proportion of patients with total LOT >7 days decreased by 25% (68% to 51%) among patients aged 18-64 years and by 27% (68%-50%) among patients aged ≥65 years. CONCLUSIONS: Although likely excessive LOT for uncomplicated CAP patients decreased since 2013, the proportion of patients treated with LOT >7 days still exceeded 50% in 2020. Antibiotic stewardship programs should continue to pursue interventions to reduce likely excessive LOT for common infections.

Hospitalizations for Unspecified Mycoses in a Large Administrative Data Set and Implications for Fungal Disease Burden Estimates, United States, 2019-2021.

Fungal diseases are frequently coded as "unspecified mycoses" in data sets used to estimate disease burden. In a large administrative database, 50.9% of unspecified mycosis hospitalizations during 2019-2021 had positive fungal laboratory testing, most commonly Candida (79.1%), highlighting a potential need for improved coding practices and greater fungal laboratory testing.

Antibiotic Use Among Hospitalized Patients With COVID-19 in the United States, March 2020-June 2022.

We conducted a retrospective study to describe antibiotic use among US adults hospitalized with a COVID-19 diagnosis. Despite a decrease in overall antibiotic use, most patients hospitalized with COVID-19 received antibiotics on admission (88.1%) regardless of critical care status, highlighting that more efforts are needed to optimize antibiotic therapy.

Trimethoprim-sulfamethoxazole resistance patterns among Staphylococcus aureus in the United States, 2012-2018.

We reviewed trimethoprim-sulfamethoxazole antibiotic susceptibility testing data among Staphylococcus aureus using 3 national inpatient databases. In all 3 databases, we observed an increases in the percentage of methicillin-resistant Staphylococcus aureus that were not susceptible to trimethoprim-sulfamethoxazole. Providers should select antibiotic regimens based on local resistance patterns and should report changes to the public health department.

Declines in the utilization of hospital-based care during COVID-19 pandemic.

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 US acute 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.

Trends in Antibiotic Use in United States Hospitals During the Coronavirus Disease 2019 Pandemic.

We described antibiotic use among inpatients with coronavirus disease 2019 (COVID-19). Most COVID-19 inpatients received antibiotic therapy. We also described hospital-wide antibiotic use during 2020 compared with 2019, stratified by hospital COVID-19 burden. Although total antibiotic use decreased between years, certain antibiotic use increased with higher COVID-19 burden.

The projected burden of complex surgical site infections following hip and knee arthroplasties in adults in the United States, 2020 through 2030.

BACKGROUND: As the US population ages, the number of hip and knee arthroplasties is expected to increase. Because surgical site infections (SSIs) following these procedures contribute substantial morbidity, mortality, and costs, we projected SSIs expected to occur from 2020 through 2030. METHODS: We used a stochastic Poisson process to project the number of primary and revision arthroplasties and SSIs. Primary arthroplasty rates were calculated using annual estimates of hip and knee arthroplasty stratified by age and gender from the 2012-2014 Nationwide Inpatient Sample and standardized by census population data. Revision rates, dependent on time from primary procedure, were obtained from published literature and were uniformly applied for all ages and genders. Stratified complex SSI rates for arthroplasties were obtained from 2012-2015 National Healthcare Safety Network data. To evaluate the possible impact of prevention measures, we recalculated the projections with an SSI rate reduced by 30%, the national target established by the US Department of Health and Human Services (HHS). RESULTS: Without a reduction in SSI rates, we projected an increase in complex SSIs following hip and knee arthroplasty of 14% between 2020 and 2030. We projected a total burden of 77,653 SSIs; however, meeting the 30% rate reduction could prevent 23,297 of these SSIs. CONCLUSIONS: Given current SSI rates, we project that complex SSI burden for primary and revision arthroplasty may increase due to an aging population. Reducing the SSI rate to the national HHS target could prevent 23,000 SSIs and reduce subsequent morbidity, mortality, and Medicare costs.