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Vaccination with JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic) to prevent monkeypox commenced shortly after confirmation of the first monkeypox case in the current outbreak in the United States on May 17, 2022 (1). To date, more than 27,000 cases have been reported across all 50 states, the District of Columbia (DC), and Puerto Rico.* JYNNEOS vaccine is licensed by the Food and Drug Administration (FDA) as a 0.5-mL 2-dose series administered subcutaneously 28 days apart to prevent smallpox and monkeypox infections (2) and has been found to provide protection against monkeypox infection during the current outbreak (3). The U.S. Department of Health and Human Services (HHS) allocated 1.1 million vials of JYNNEOS vaccine from the Strategic National Stockpile, with doses allocated to jurisdictions based on case counts and estimated size of population at risk (4). However, initial vaccine supplies were severely constrained relative to vaccine demand during the expanding outbreak. Some jurisdictions with highest incidence responded by prioritizing first dose administration during May-July (5,6). The FDA emergency use authorization (EUA) of 0.1 mL dosing for intradermal administration of JYNNEOS for persons aged ≥18 years on August 9, 2022, substantially expanded available vaccine supply

In November 2021, CDC was notified of a cluster of previously healthy children with hepatitis of unknown etiology evaluated at a single U.S. hospital (1). On April 21, 2022, following an investigation of this cluster and reports of similar cases in Europe (2,3), a health advisory* was issued requesting U.S. providers to report pediatric cases

Summary Background In the USA, COVID-19 vaccines became available in mid-December, 2020, with adults aged 65 years and older among the first groups prioritised for vaccination. We estimated the national-level impact of the initial phases of the US COVID-19 vaccination programme on COVID-19 cases, emergency department visits, hospital admissions, and deaths among adults aged 65 years and older. Methods We analysed population-based data reported to US federal agencies on COVID-19 cases, emergency department visits, hospital admissions, and deaths among adults aged 50 years and older during the period Nov 1, 2020, to April 10, 2021. We calculated the relative change in incidence among older age groups compared with a younger reference group for pre-vaccination and post-vaccination periods, defined by the week when vaccination coverage in a given age group first exceeded coverage in the reference age group by at least 1%; time lags for immune response and time to outcome were incorporated. We assessed whether the ratio of these relative changes differed when comparing the pre-vaccination and post-vaccination periods. Findings The ratio of relative changes comparing the change in the COVID-19 case incidence ratio over the post-vaccine versus pre-vaccine periods showed relative decreases of 53% (95% CI 50 to 55) and 62% (59 to 64) among adults aged 65 to 74 years and 75 years and older, respectively, compared with those aged 50 to 64 years. We found similar results for emergency department visits with relative decreases of 61% (52 to 68) for adults aged 65 to 74 years and 77% (71 to 78) for those aged 75 years and older compared with adults aged 50 to 64 years. Hospital admissions declined by 39% (29 to 48) among those aged 60 to 69 years, 60% (54 to 66) among those aged 70 to 79 years, and 68% (62 to 73), among those aged 80 years and older, compared with adults aged 50 to 59 years. COVID-19 deaths also declined (by 41%, 95% CI –14 to 69 among adults aged 65–74 years and by 30%, –47 to 66 among those aged ≥75 years, compared with adults aged 50 to 64 years), but the magnitude of the impact of vaccination roll-out on deaths was unclear. Interpretation The initial roll-out of the US COVID-19 vaccination programme was associated with reductions in COVID-19 cases, emergency department visits, and hospital admissions among older adults. Funding None.

Although COVID-19 generally results in milder disease in children and adolescents than in adults, severe illness from COVID-19 can occur in children and adolescents and might require hospitalization and intensive care unit (ICU) support (1-3). It is not known whether the B.1.617.2 (Delta) variant,* which has been the predominant variant of SARS-CoV-2 (the virus that causes COVID-19) in the United States since late June 2021,† causes different clinical outcomes in children and adolescents compared with variants that circulated earlier. To assess trends among children and adolescents, CDC analyzed new COVID-19 cases, emergency department (ED) visits with a COVID-19 diagnosis code, and hospital admissions of patients with confirmed COVID-19 among persons aged 0-17 years during August 1, 2020-August 27, 2021. Since July 2021, after Delta had become the predominant circulating variant, the rate of new COVID-19 cases and COVID-19-related ED visits increased for persons aged 0-4, 5-11, and 12-17 years, and hospital admissions of patients with confirmed COVID-19 increased for persons aged 0-17 years. Among persons aged 0-17 years during the most recent 2-week period (August 14-27, 2021), COVID-19-related ED visits and hospital admissions in the states with the lowest vaccination coverage were 3.4 and 3.7 times that in the states with the highest vaccination coverage, respectively. At selected hospitals, the proportion of COVID-19 patients aged 0-17 years who were admitted to an ICU ranged from 10% to 25% during August 2020-June 2021 and was 20% and 18% during July and August 2021, respectively. Broad, community-wide vaccination of all eligible persons is a critical component of mitigation strategies to protect pediatric populations from SARS-CoV-2 infection and severe COVID-19 illness.

Increases in severe respiratory illness and acute flaccid myelitis (AFM) among children and adolescents resulting from enterovirus D68 (EV-D68) infections occurred biennially in the United States during 2014, 2016, and 2018, primarily in late summer and fall. Although EV-D68 annual trends are not fully understood, EV-D68 levels were lower than expected in 2020, potentially because of implementation of COVID-19 mitigation measures (e.g., wearing face masks, enhanced hand hygiene, and physical distancing) (1). In August 2022, clinicians in several geographic areas notified CDC of an increase in hospitalizations of pediatric patients with severe respiratory illness and positive rhinovirus/enterovirus (RV/EV) test results.* Surveillance data were analyzed from multiple national data sources to characterize reported trends in acute respiratory illness (ARI), asthma/reactive airway disease (RAD) exacerbations, and the percentage of positive RV/EV and EV-D68 test results during 2022 compared with previous years. These data demonstrated an increase in emergency department (ED) visits by children and adolescents with ARI and asthma/RAD in late summer 2022. The percentage of positive RV/EV test results in national laboratory-based surveillance and the percentage of positive EV-D68 test results in pediatric sentinel surveillance also increased during this time. Previous increases in EV-D68 respiratory illness have led to substantial resource demands in some hospitals and have also coincided with increases in cases of AFM (2), a rare but serious neurologic disease affecting the spinal cord. Therefore, clinicians should consider AFM in patients with acute flaccid limb weakness, especially after respiratory illness or fever, and ensure prompt hospitalization and referral to specialty care for such cases. Clinicians should also test for poliovirus infection in patients suspected of having AFM because of the clinical similarity to acute flaccid paralysis caused by poliovirus. Ongoing surveillance for EV-D68 is critical to ensuring preparedness for possible future increases in ARI and AFM.

Background Respiratory tract infections are common, often seasonal, and caused by multiple pathogens. We assessed whether seasonal respiratory illness patterns changed during the COVID-19 pandemic. Methods We categorized emergency department (ED) visits reported to the National Syndromic Surveillance Program according to chief complaints and diagnosis codes, excluding visits with diagnosed SARS-CoV-2 infections. For each week during 1 March 2020 through 26 December 2020 (“pandemic period”), we compared the proportion of ED visits in each respiratory category with the proportion of visits in that category during the corresponding weeks of 2017–2019 (“pre–pandemic period”). We analyzed positivity of respiratory viral tests from 2 independent clinical laboratories. Results During March 2020, cough, shortness of breath, and influenza-like illness accounted for twice as many ED visits compared with the pre–pandemic period. During the last 4 months of 2020, all respiratory conditions, except shortness of breath, accounted for a smaller proportion of ED visits than during the pre–pandemic period. Percent positivity for influenza virus, respiratory syncytial virus, human parainfluenza virus, adenoviruses, and human metapneumovirus was lower in 2020 than 2019. Although test volume decreased, percent positivity was higher for rhinovirus/enterovirus during the final weeks of 2020 compared with 2019, with ED visits similar to the pre–pandemic period. Conclusions Broad reductions in respiratory test positivity and respiratory ED visits (excluding COVID-19) occurred during 2020. Interventions for mitigating spread of SARS-CoV-2 likely also reduced transmission of other pathogens. Timely surveillance is needed to understand community health threats, particularly when current trends deviate from seasonal norms.

Beginning in March 2020, the COVID-19 pandemic and response, which included physical distancing and stay-at-home orders, disrupted daily life in the United States. Compared with the rate in 2019, a 31% increase in the proportion of mental health-related emergency department (ED) visits occurred among adolescents aged 12-17 years in 2020 (1). In June 2020, 25% of surveyed adults aged 18-24 years reported experiencing suicidal ideation related to the pandemic in the past 30 days (2). More recent patterns of ED visits for suspected suicide attempts among these age groups are unclear. Using data from the National Syndromic Surveillance Program (NSSP),* CDC examined trends in ED visits for suspected suicide attempts† during January 1, 2019-May 15, 2021, among persons aged 12-25 years, by sex, and at three distinct phases of the COVID-19 pandemic. Compared with the corresponding period in 2019, persons aged 12-25 years made fewer ED visits for suspected suicide attempts during March 29-April 25, 2020. However, by early May 2020, ED visit counts for suspected suicide attempts began increasing among adolescents aged 12-17 years, especially among girls. During July 26-August 22, 2020, the mean weekly number of ED visits for suspected suicide attempts among girls aged 12-17 years was 26.2% higher than during the same period a year earlier; during February 21-March 20, 2021, mean weekly ED visit counts for suspected suicide attempts were 50.6% higher among girls aged 12-17 years compared with the same period in 2019. Suicide prevention measures focused on young persons call for a comprehensive approach, that is adapted during times of infrastructure disruption, involving multisectoral partnerships (e.g., public health, mental health, schools, and families) and implementation of evidence-based strategies (3) that address the range of factors influencing suicide risk.

Hispanic or Latino (Hispanic), non-Hispanic Black or African American (Black), and non-Hispanic American Indian or Alaska Native (AI/AN) persons have experienced disproportionately higher rates of hospitalization and death attributable to COVID-19 than have non-Hispanic White (White) persons (1-4). Emergency care data offer insight into COVID-19 incidence; however, differences in use of emergency department (ED) services for COVID-19 by racial and ethnic groups are not well understood. These data, most of which are recorded within 24 hours of the visit, might be an early indicator of changing patterns in disparities. Using ED visit data from 13 states obtained from the National Syndromic Surveillance Program (NSSP), CDC assessed the number of ED visits with a COVID-19 discharge diagnosis code per 100,000 population during October-December 2020 by age and race/ethnicity. Among 5,794,050 total ED visits during this period, 282,220 (4.9%) were for COVID-19. Racial/ethnic disparities in COVID-19 ED visit rates were observed across age groups. Compared with White persons, Hispanic, AI/AN, and Black persons had significantly more COVID-19-related ED visits overall (rate ratio [RR] range = 1.39-1.77) and in all age groups through age 74 years; compared with White persons aged ≥75 years, Hispanic and AI/AN persons also had more COVID-19-related ED visits (RR = 1.91 and 1.22, respectively). These differences in ED visit rates suggest ongoing racial/ethnic disparities in COVID-19 incidence and can be used to prioritize prevention resources, including COVID-19 vaccination, to reach disproportionately affected communities and reduce the need for emergency care for COVID-19.

During March 29-April 25, 2020, emergency department (ED) visits in the United States declined by 42% after the declaration of a national emergency for COVID-19 on March 13, 2020. Among children aged ≤10 years, ED visits declined by 72% compared with prepandemic levels (1). To assess the continued impact of the COVID-19 pandemic on EDs, CDC examined trends in visits since December 30, 2018, and compared the numbers and types of ED visits by patient demographic and geographic factors during a COVID-19 pandemic period (December 20, 2020-January 16, 2021) with a prepandemic period 1 year earlier (December 15, 2019-January 11, 2020). After an initial decline during March-April 2020 (1), ED visits increased through July 2020, but at levels below those during the previous year, until December 2020-January 2021 when visits again fell to 25% of prepandemic levels. During this time, among patients aged 0-4, 5-11, 12-17, and ≥18 years, ED visits were lower by 66%, 63%, 38%, and 17%, respectively, compared with ED visits for each age group during the same period before the pandemic. Differences were also observed by region and reasons for ED visits during December 2020-January 2021; more visits during this period were for infectious diseases or mental and behavioral health-related concerns and fewer visits were for gastrointestinal and upper-respiratory-related illnesses compared with ED visits during December 2019-January 2020. Although the numbers of ED visits associated with socioeconomic factors and mental or behavioral health conditions are low, the increased visits by both adults and children for these concerns suggest that health care providers should maintain heightened vigilance in screening for factors that might warrant further treatment, guidance, or intervention during the COVID-19 pandemic.

Background Ceftazidime-avibactam has in vitro activity against some carbapenem-resistant gram-negative infections (GNIs), and therefore may be a useful alternative to more toxic antibiotics such as colistin. Understanding ceftazidime-avibactam uptake and usage patterns would inform hospital formularies, stewardship, and antibiotic development. Methods A retrospective cohort study assessed inpatient encounters in the Vizient database. Ceftazidime-avibactam and colistin administrations were categorized into presumed empiric (3 consecutive days of therapy or less with qualifying exclusions) versus targeted therapy (≥4 consecutive days of therapy) for presumed carbapenem-resistant GNIs. Quarterly percentage change (QPC) using modified Poisson regression and relative change in frequency of targeted ceftazidime-avibactam to colistin encounters was calculated. Factors associated with preferentially receiving targeted ceftazidime-avibactam versus colistin were identified using generalized estimating equations. Results Between 2015 quarter (q) 1 and 2017q4, ceftazidime-avibactam was administered 21 215 times across 1901 encounters. Inpatient prescriptions for ceftazidime-avibactam increased from 0.44/10 000 hospitalizations in 2015q1 to 7.7/10 000 in 2017q4 (QPC, +11%; 95% CI, 10–13%; P < .01), while conversely colistin prescriptions decreased quarterly by 5% (95% CI, 4–6%; P < .01). Ceftazidime-avibactam therapy was categorized as empiric 25% of the time, targeted 65% of the time, and indeterminate 10% of the time. Patients with chronic kidney disease were twice as likely to receive targeted ceftazidime-avibactam versus colistin (RR, 2.02; 95% CI, 1.82–2.25), whereas those on dialysis were less likely to receive ceftazidime-avibactam than colistin (RR, 0.71; 95% CI, .61–.83). Conclusions Since approval in 2015, ceftazidime-avibactam use has grown for presumed carbapenem-resistant GNIs, while colistin has correspondingly declined. Renal function drove the choice between ceftazidime-avibactam and colistin as targeted therapy.

The COVID-19 pandemic has negatively affected adult mental health (MH), with racial and ethnic minoritized groups disproportionately affected.To examine changes in adult MH-related emergency department (ED) visits into the Delta variant pandemic period and identify changes and inequities in these visits before and during COVID-19 case surges.This epidemiologic cross-sectional study used National Syndromic Surveillance Program data from US adults aged 18 to 64 years from 1970 to 2352 ED facilities from January 1, 2019, to August 14, 2021. All MH-related ED visits and visits related to 10 disorders (ie, anxiety, depressive, bipolar, schizophrenia spectrum, trauma- and stressor-related, attention-deficit/hyperactivity, disruptive behavioral and impulse, obsessive-compulsive, eating, and tic disorders) were identified.The following periods of MH-related ED visits were compared: (1) high Delta variant circulation (July 18-August 14, 2021) with a pre-Delta period (April 18-May 15, 2021), (2) after a COVID-19 case peak (February 14-March 13, 2021) with during a peak (December 27, 2020-January 23, 2021), and (3) the Delta period and the period after a COVID-19 case peak with the respective corresponding weeks during the prepandemic period.ED visits for 10 mental disorders and all MH-related visits.This cross-sectional study included 107 761 319 ED visits among adults aged 18 to 64 years (59 870 475 [56%] women) from January 1, 2019, to August 14, 2021. There was stability in most MH-related ED visit counts between the Delta and pre-Delta periods (percentage change, -1.4% to -7.5%), except for eating disorders (-11.9%) and tic disorders (-19.8%) and after a COVID-19 case peak compared with during a peak (0.6%-7.4%). Most MH-related ED visit counts declined in the Delta period relative to the prepandemic period (-6.4% to -30.7%); there were fluctuations by disorder when comparing after a COVID-19 case peak with the corresponding prepandemic period (-15.4% to 11.3%). Accounting for ED visit volume, MH-related ED visits were a smaller proportion of visits in the Delta period compared with the pre-Delta period (visit ratio, 0.86; 95% CI, 0.85-0.86) and prepandemic period (visit ratio, 0.80; 95% CI, 0.79-0.80). After a COVID-19 case peak, MH-related ED visits were a larger proportion of ED visits compared with during a peak (visit ratio, 1.04; 95% CI, 1.03-1.04) and the corresponding prepandemic period (visit ratio, 1.11; 95% CI, 1.11-1.12). Of the 2 510 744 ED visits included in the race and ethnicity analysis, 24 592 (1%) were American Indian or Alaska Native persons, 33 697 (1%) were Asian persons, 494 198 (20%) were Black persons, 389 740 (16%) were Hispanic persons, 5000 (0.2%) were Native Hawaiian or Other Pacific Islander persons, and 1 172 683 (47%) were White persons. There was between- and within-group variation in ED visits by race and ethnicity and increases in selected disorders after COVID-19 peaks for adults aged 18 to 24 years.Results of this cross-sectional study suggest that EDs may have increases in MH-related visits after COVID-19 surges, specifically for young adults and individual racial and ethnic minoritized subpopulations. Public health practitioners should consider subpopulation-specific messaging and programmatic strategies that address differences in MH needs, particularly for those historically marginalized.

On September 6, 2019, this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr). As of August 27, 2019, 215 possible cases of severe pulmonary disease associated with the use of electronic cigarette (e-cigarette) products (e.g., devices, liquids, refill pods, and cartridges) had been reported to CDC by 25 state health departments. E-cigarettes are devices that produce an aerosol by heating a liquid containing various chemicals, including nicotine, flavorings, and other additives (e.g., propellants, solvents, and oils). Users inhale the aerosol, including any additives, into their lungs. Aerosols produced by e-cigarettes can contain harmful or potentially harmful substances, including heavy metals such as lead, volatile organic compounds, ultrafine particles, cancer-causing chemicals, or other agents such as chemicals used for cleaning the device (1). E-cigarettes also can be used to deliver tetrahydrocannabinol (THC), the principal psychoactive component of cannabis, or other drugs; for example, "dabbing" involves superheating substances that contain high concentrations of THC and other plant compounds (e.g., cannabidiol) with the intent of inhaling the aerosol. E-cigarette users could potentially add other substances to the devices. This report summarizes available information and provides interim case definitions and guidance for reporting possible cases of severe pulmonary disease. The guidance in this report reflects data available as of September 6, 2019; guidance will be updated as additional information becomes available.

The Centers for Disease Control and Prevention explored use of emergency department (ED) visit data, during 2018-2020, from the National Syndromic Surveillance Program to monitor vaccine-associated adverse events (VAE) among all age groups. A combination of chief complaint terms and administrative diagnosis codes were used to detect VAE-related ED visits. Postvaccination fever was among the top 10 most frequently noted diagnoses. VAE annual trends demonstrated seasonality; visits trended upward starting in September of each year, coinciding with the administration of seasonal influenza vaccines. The 2020 VAE-related visit trend declined below the 2018 and 2019 baselines during March 22-September 5, 2020, before returning to the seasonal pattern. VAE-related visits declined in children aged 3-18 years in 2020 compared with 2018-2019, especially in the back-to-school months. These findings demonstrate that syndromic surveillance can complement traditional VAE reporting systems without an additional demand on data collection resources.

Objectives To obtain timely and detailed data on COVID-19 cases in the United States, the Centers for Disease Control and Prevention (CDC) uses 2 data sources: (1) aggregate counts for daily situational awareness and (2) person-level data for each case (case surveillance). The objective of this study was to describe the sensitivity of case ascertainment and the completeness of person-level data received by CDC through national COVID-19 case surveillance. Methods We compared case and death counts from case surveillance data with aggregate counts received by CDC during April 5–September 30, 2020. We analyzed case surveillance data to describe geographic and temporal trends in data completeness for selected variables, including demographic characteristics, underlying medical conditions, and outcomes. Results As of November 18, 2020, national COVID-19 case surveillance data received by CDC during April 5–September 30, 2020, included 4 990 629 cases and 141 935 deaths, representing 72.7% of the volume of cases (n = 6 863 251) and 71.8% of the volume of deaths (n = 197 756) in aggregate counts. Nationally, completeness in case surveillance records was highest for age (99.9%) and sex (98.8%). Data on race/ethnicity were complete for 56.9% of cases; completeness varied by region. Data completeness for each underlying medical condition assessed was Conclusions Incompleteness in national COVID-19 case surveillance data might limit their usefulness. Streamlining and automating surveillance processes would decrease reporting burdens on jurisdictions and likely improve completeness of national COVID-19 case surveillance data.

IMPORTANCE: The coronavirus disease 2019 (COVID-19) pandemic, associated mitigation measures, and social and economic impacts may affect mental health, suicidal behavior, substance use, and violence. OBJECTIVE: To examine changes in US emergency department (ED) visits for mental health conditions (MHCs), suicide attempts (SAs), overdose (OD), and violence outcomes during the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the Centers for Disease Control and Prevention’s National Syndromic Surveillance Program to examine national changes in ED visits for MHCs, SAs, ODs, and violence from December 30, 2018, to October 10, 2020 (before and during the COVID-19 pandemic). The National Syndromic Surveillance Program captures approximately 70% of US ED visits from more than 3500 EDs that cover 48 states and Washington, DC. MAIN OUTCOMES AND MEASURES: Outcome measures were MHCs, SAs, all drug ODs, opioid ODs, intimate partner violence (IPV), and suspected child abuse and neglect (SCAN) ED visit counts and rates. Weekly ED visit counts and rates were computed overall and stratified by sex. RESULTS: From December 30, 2018, to October 10, 2020, a total of 187 508 065 total ED visits (53.6% female and 46.1% male) were captured; 6 018 318 included at least 1 study outcome (visits not mutually exclusive). Total ED visit volume decreased after COVID-19 mitigation measures were implemented in the US beginning on March 16, 2020. Weekly ED visit counts for all 6 outcomes decreased between March 8 and 28, 2020 (March 8: MHCs = 42 903, SAs = 5212, all ODs = 14 543, opioid ODs = 4752, IPV = 444, and SCAN = 1090; March 28: MHCs = 17 574, SAs = 4241, all ODs = 12 399, opioid ODs = 4306, IPV = 347, and SCAN = 487). Conversely, ED visit rates increased beginning the week of March 22 to 28, 2020. When the median ED visit counts between March 15 and October 10, 2020, were compared with the same period in 2019, the 2020 counts were significantly higher for SAs (n = 4940 vs 4656, P = .02), all ODs (n = 15 604 vs 13 371, P

Background Invasive candidiasis (IC) is a growing concern among US healthcare facilities. A large-scale study evaluating incidence and trends of IC in the United States by species and body site is needed to understand the distribution of infection. Methods An electronic medical record database was used to calculate incidence and trends of IC in the United States by species and infection site from 2009 through 2017. Hospital incidence was calculated using total unique inpatient hospitalizations in hospitals reporting at least 1 Candida case as the denominator. IC incidence trends were assessed using generalized estimating equations with exchangeable correlation structure to fit Poisson regression models, controlling for changes in hospital characteristics and case mix over time. Results Candida albicans remains the leading cause of IC in the United States, followed by Candida glabrata. The overall incidence of IC was 90/100 000 patients, which did not change significantly over time. There were no changes in incidence among C. albicans, C. glabrata, C. parapsilosis, or C. tropicalis; the incidence of other Candida spp. as a whole increased 7.2% annually. While there was no change in candidemia 2009–2017, abdominal and nonabdominal sterile site IC increased significantly. Conclusions Nonbloodstream IC is increasing in the United States. Understanding the epidemiology of IC should facilitate improved management of infected patients.

RATIONALE: The risk of all-cause mortality of nontuberculous mycobacterial lung disease (NTMLD) in the United States (US) population is not well established. OBJECTIVES: This study aims to assess the public health burden of NTMLD in the US by comparing the relative risk of all-cause mortality in the NTMLD population with an age- and sex-matched cohort from the general population. METHODS: Patients with physician claims for NTMLD (ICD-9 0.031; ICD-10 A31.0) were identified between 2007 and 2016 from a large US national managed care insurance plan covering approximately 15–18 million members annually. A control group with no NTMLD ICD-9 or 10 codes was randomly selected from the general population and matched 3:1 to the NTMLD sample according to birth year, gender, and insurance benefit coverage. The date of first NTMLD diagnosis of each patient was assigned to the matched controls as the index date. The Cox proportional hazard method compared survival between cohorts, adjusting for demographic factors and baseline comorbidities. RESULTS: A total of 2005 patients with NTMLD and 6014 controls were identified, with a mean follow-up duration of 3.4 years and 3.7 years, respectively. The NTMLD group had substantially higher proportions of patients with asthma (23.3% versus 3.5%), bronchiectasis (36.5% versus 0.1%), COPD (52.0% versus 5.9%), arrhythmia (22.6% versus 6.5%), coronary artery disease (18.5% versus 6.6%), heart failure (11.9% versus 4.1%), and cancer (18.5% versus 5.0%). The unadjusted rate of all-cause mortality from the index date was 20.7 per 1000 person-years in the NTMLD group vs 5.6 per 1000 person-years in the control group (rate ratio=3.73; 95% CI: 2.93–4.75). Multivariable Cox regression, adjusted for the above variables as well as all other important baseline covariates, showed a doubling risk of all-cause mortality (hazard ratio [HR]=2.06; CI: 1.52–2.79; P

Treatment guidelines exist for pulmonary Mycobacterium avium complex (MAC) infection, although studies suggest poor concordance in clinician practice. Using a national database including hospital encounters of laboratory-confirmed MAC patients, we sought to characterise US treatment practices. We assessed patients in the Premier Healthcare Database from 2009 to 2013 with two or more MAC-positive cultures or one MAC-positive culture and the International Classification of Diseases (9th revision) code for pulmonary nontuberculous mycobacteria (PNTM). Treatment was characterised by patient-, provider- and facility-level factors; significant differences were assessed (p, Few MAC patients receive recommended therapy and improved treatment is needed to prevent resistance http://ow.ly/4F0S30lIihn

Rationale: Pulmonary nontuberculous mycobacteria (NTM) disease represents a significant threat to patients with cystic fibrosis (CF), with an estimated annual prevalence of 12%. Prior studies reported an increasing annual NTM prevalence in the general population, though similar trends in persons with CF have not been assessed. Objectives: In this study we aimed to identify the prevalence, geographic patterns, temporal trends, and risk factors for NTM positivity by mycobacterial species among persons with CF throughout the United States. Methods: Using annualized CF Patient Registry (CFFPR) data from 2010 to 2014, we identified patients with mycobacterial culture results to estimate the annual and period prevalence of pathogenic NTM species by demographic and geographic factors. Regression models were used to estimate the annual percent change over time and risk factors for NTM isolation. Geographic patterns were described and mapped. Results: Of 16,153 included persons with CF, 3,211 (20%) had a pathogenic NTM species isolated at least once over the 5-year period; 1,949 (61%) had Mycobacterium avium complex (MAC), and 1,249 (39%) had M. abscessus. The period prevalence was 12% for MAC (confidence interval [CI], 12–13%), 8% for M. abscessus (CI, 7–8%), and 4% for other NTM species (CI, 3.8–4.3%). The period prevalence for MAC was nearly three times greater among patients ≥60 years old with a body mass index < 19 (33% [CI, 16–51%]); this trend was not present for patients with M. abscessus (4% [CI, 0–11%]). NTM prevalence showed a significant relative increase of 5% per year, from 11.0% in 2010 to 13.4% in 2014 (P = 0.0008), although this varied by geographic area. For M. abscessus, the states with the highest prevalence were Hawaii (50%), Florida (17%), and Louisiana (16%), and for MAC they were Nevada (24%), Kansas (21%), and Hawaii and Arizona (both 20%). Study participants with either MAC or M. abscessus were significantly more likely to have been diagnosed with CF at an older age (P < 0.0001), have a lower body mass index (P < 0.0001), higher forced expiratory volume in 1 second % predicted (P < 0.01), and fewer years on chronic macrolide therapy (P < 0.0001). Conclusions: NTM remains highly prevalent among adults and children with CF in the United States, with one in five affected, and appears to be increasing over time. Prevalence varies by geographic region and by patient-level factors, including older age and receiving an initial CF diagnosis later in life. Routine screening for NTM, including mycobacterial speciation, especially in high-risk geographic areas, is critical to increase our understanding of its epidemiology and changes in prevalence over time.

Background: Delayed or in vitro inactive empiric antibiotic therapy may be detrimental to survival in patients with bloodstream infections (BSIs). Understanding the landscape of delayed or discordant empiric antibiotic therapy (DDEAT) across different patient, pathogen, and hospital types, as well as by their baseline resistance milieu, may enable providers, antimicrobial stewardship programs, and policy makers to optimize empiric prescribing. Methods: Inpatients with clinically suspected serious infection (based on sampling of blood cultures and receiving systemic antibiotic therapy on the same or next day) found to have BSI were identified in the Cerner Healthfacts EHR database. Patients were considered to have received DDEAT when, on culture sampling day, they received either no antibiotic(s) or none that displayed in vitro activity against the pathogenic bloodstream isolate. Antibiotic-resistant phenotypes were defined by in vitro resistance to taxon-specific prototype antibiotics (eg, methicillin/oxacillin resistance in S. aureus) and were used to estimate baseline resistance prevalence encountered by the hospital. The probability of DDEAT was examined by bacterial taxon, by time of BSI onset, and by presence versus absence of antibiotic-resistance phenotypes, sepsis or septic shock, hospital type, and baseline resistance. Results: Of 26,036 assessable patients with a BSI at 131 US hospitals between 2005 and 2014, 14,658 (56%) had sepsis, 3,623 (14%) had septic shock, 5,084 (20%) had antibiotic-resistant phenotypes, and 8,593 (33%) received DDEAT. Also, 4,428 (52%) recipients of DDEAT received no antibiotics on culture sampling day, whereas the remaining 4,165 (48%) received in vitro discordant therapy. DDEAT occurred most often in S. maltophilia (87%) and E. faecium (80%) BSIs; however, 75% of DDEAT cases and 76% of deaths among recipients of DDEAT collectively occurred among patients with S. aureus and Enterobacteriales BSIs. For every 8 bacteremic patients presenting with septic shock, 1 patient did not receive any antibiotics on culture day (Fig. 1A). Patients with BSIs of hospital (vs community) onset were twice as likely to receive no antibiotics on culture day, whereas those with bloodstream pathogens displaying antibiotic-resistant (vs susceptible) phenotypes were 3 times as likely to receive in vitro discordant therapy (Fig. 1B). The median proportion of DDEAT ranged between 25% (14, 37%) in eight Conclusions: Delayed or in vitro discordant empiric antibiotic therapy is common among patients with BSI in US hospitals regardless of hospital size, teaching status, or local resistance patterns. Prompt empiric antibiotic therapy in septic shock and hospital-onset BSI needs more support. Reliable detection of S. aureus and Enterobacteriales bloodstream pathogens and their resistance patterns earlier with rapid point-of-care diagnostics may mitigate the population-level impact of DDEAT in BSI.Funding: This study was funded in part by the National Institutes of Health Clinical Center, National Institutes of Allergy and Infectious Diseases, National Cancer Institute (NCI contract no. HHSN261200800001E) and the Agency for Healthcare Research and Quality.Disclosures: None

The prevalence and effects of inappropriate empirical antibiotic therapy for bloodstream infections are unclear. We aimed to establish the population-level burden, predictors, and mortality risk of in-vitro susceptibility-discordant empirical antibiotic therapy among patients with bloodstream infections.Our retrospective cohort analysis of electronic health record data from 131 hospitals in the USA included patients with suspected-and subsequently confirmed-bloodstream infections who were treated empirically with systemic antibiotics between Jan 1, 2005, and Dec 31, 2014. We included all patients with monomicrobial bacteraemia caused by common bloodstream pathogens who received at least one systemic antibiotic either on the day blood cultures were drawn or the day after, and for whom susceptibility data were available. We calculated the prevalence of discordant empirical antibiotic therapy-which was defined as receiving antibiotics on the day blood culture samples were drawn to which the cultured isolate was not susceptible in vitro-overall and by hospital type by using regression tree analysis. We used generalised estimating equations to identify predictors of receiving discordant empirical antibiotic therapy, and used logistic regression to calculate adjusted odds ratios for the relationship between in-hospital mortality and discordant empirical antibiotic therapy.21 608 patients with bloodstream infections received empirical antibiotic therapy on the day of first blood culture collection. Of these patients, 4165 (19%) received discordant empirical antibiotic therapy. Discordant empirical antibiotic therapy was independently associated with increased risk of mortality (adjusted odds ratio 1·46 [95% CI, 1·28-1·66]; p0·0001), a relationship that was unaffected by the presence or absence of resistance or sepsis or septic shock. Infection with antibiotic-resistant species strongly predicted receiving discordant empirical therapy (adjusted odds ratio 9·09 [95% CI 7·68-10·76]; p0·0001). Most incidences of discordant empirical antibiotic therapy and associated deaths occurred among patients with bloodstream infections caused by Staphylococcus aureus or Enterobacterales.Approximately one in five patients with bloodstream infections in US hospitals received discordant empirical antibiotic therapy, receipt of which was closely associated with infection with antibiotic-resistant pathogens. Receiving discordant empirical antibiotic therapy was associated with increased odds of mortality overall, even in patients without sepsis. Early identification of bloodstream pathogens and resistance will probably improve population-level outcomes.US National Institutes of Health, US Centers for Disease Control and Prevention, and US Agency for Healthcare Research and Quality.

Vaping Syndromic Surveillance Increases in EVALI were identified in 2019. Using the National Syndromic Surveillance Program, which includes about 70% of U.S. EDs, researchers found a gradual increa...

Difficult-to-treat resistance (DTR; ie, co-resistance to all first-line antibiotics) in gram-negative bloodstream infection (GNBSI) is associated with decreased survival in administrative data models. We externally validated DTR prevalence and associated mortality risk in GNBSI using detailed clinical data from electronic health records to adjust for baseline differences in acute illness severity.

At 128 US hospitals, from 2009–2014, a 17% decline occurred annually in central venous catheter tips sent for culture: a 6-fold decrease from blood culture sampling trends. The positive predictive value was low (23%). Tip culture use often does not conform to recommendations and offers limited independent treatment opportunities.

Bacteria thrive in showerheads and throughout household water distribution systems. While most of these bacteria are innocuous, some are potential pathogens, including members of the genus Mycobacterium that can cause nontuberculous mycobacterial (NTM) lung infection, an increasing threat to public health. We found that showerheads in households across the United States and Europe often harbor abundant mycobacterial communities that vary in composition depending on geographic location, water chemistry, and water source, with households receiving water treated with chlorine disinfectants having particularly high abundances of certain mycobacteria. The regions in the United States where NTM lung infections are most common were the same regions where pathogenic mycobacteria were most prevalent in showerheads, highlighting the important role of showerheads in the transmission of NTM infections., Bacteria within the genus Mycobacterium can be abundant in showerheads, and the inhalation of aerosolized mycobacteria while showering has been implicated as a mode of transmission in nontuberculous mycobacterial (NTM) lung infections. Despite their importance, the diversity, distributions, and environmental predictors of showerhead-associated mycobacteria remain largely unresolved. To address these knowledge gaps, we worked with citizen scientists to collect showerhead biofilm samples and associated water chemistry data from 656 households located across the United States and Europe. Our cultivation-independent analyses revealed that the genus Mycobacterium was consistently the most abundant genus of bacteria detected in residential showerheads, and yet mycobacterial diversity and abundances were highly variable. Mycobacteria were far more abundant, on average, in showerheads receiving municipal water than in those receiving well water and in U.S. households than in European households, patterns that are likely driven by differences in the use of chlorine disinfectants. Moreover, we found that water source, water chemistry, and household location also influenced the prevalence of specific mycobacterial lineages detected in showerheads. We identified geographic regions within the United States where showerheads have particularly high abundances of potentially pathogenic lineages of mycobacteria, and these “hot spots” generally overlapped those regions where NTM lung disease is most prevalent. Together, these results emphasize the public health relevance of mycobacteria in showerhead biofilms. They further demonstrate that mycobacterial distributions in showerhead biofilms are often predictable from household location and water chemistry, knowledge that advances our understanding of NTM transmission dynamics and the development of strategies to reduce exposures to these emerging pathogens.

Population-based studies of pulmonary nontuberculous mycobacterial disease in the USA indicate increasing prevalence. Prevalence is higher among women, older populations, and persons of Asian ancestry. The most frequent species is Mycobacterium avium complex, although the proportion varies geographically, with high rates of Mycobacterium abscessus in areas including the Southeast. Both host and environmental factors modulate disease risk. Environmental risk factors include high vapor pressure and low soil pH, while host risk factors include structural lung disease, thoracic skeletal abnormalities, and immunomodulatory medications.

Annual prevalence estimates for pulmonary nontuberculous mycobacterial (PNTM) disease in the contiguous United States range from 1.4 to 13.9 per 100,000 persons, while one study found an annual prevalence of up to 44 per 100,000 persons in Hawaii. PNTM prevalence varies by region, sex, and race/ethnicity, with higher prevalence among women and persons of Asian ancestry, as well as in the Southern United States and Hawaii. Studies consistently indicate that PNTM prevalence is increasing, with estimates ranging from 2.5 to 8% per year. Most PNTM disease is associated with Mycobacterium avium complex (MAC), although the proportion of disease attributed to MAC varies by region. Host factors identified as influencing disease risk include structural lung disease, immunomodulatory medication, as well as variants in connective tissue, mucociliary clearance, and immune genes. Environmental variables including measures of atmospheric moisture and concentrations of certain soil factors have also been shown to correlate with higher PNTM prevalence. Prevalence of extrapulmonary NTM disease is lower, stable, and associated with different risk factors, including primary immune deficiencies or HIV infection.

BACKGROUND: Resistance to all first-line antibiotics necessitates the use of less effective or more toxic “reserve” agents. Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for ≥1 active first-line antibiotic. METHODS: The Premier Database was analyzed for inpatients with select GNBSIs. DTR was defined as intermediate/resistant in vitro to all ß-lactam categories, including carbapenems and fluoroquinolones. Prevalence and aminoglycoside resistance of DTR episodes were compared with carbapenem-resistant, extended-spectrum cephalosporin-resistant, and fluoroquinolone-resistant episodes using CDC definitions. Predictors of DTR were identified. The adjusted relative risk (aRR) of mortality was examined for DTR, CDC-defined phenotypes susceptible to ≥1 first-line agent, and graded loss of active categories. RESULTS: Between 2009–2013, 471 (1%) of 45011 GNBSI episodes at 92 (53.2%) of 173 hospitals exhibited DTR, ranging from 0.04% for Escherichia coli to 18.4% for Acinetobacter baumannii. Among patients with DTR, 79% received parenteral aminoglycosides, tigecycline, or colistin/polymyxin-B; resistance to all aminoglycosides occurred in 33%. Predictors of DTR included urban healthcare and higher baseline illness. Crude mortality for GNBSIs with DTR was 43%; aRR was higher for DTR than for carbapenem-resistant (1.2; 95% confidence interval, 1.0–1.4; P = .02), extended-spectrum cephalosporin-resistant (1.2; 1.1–1.4; P = .001), or fluoroquinolone-resistant (1.2; 1.0–1.4; P = .008) infections. The mortality aRR increased 20% per graded loss of active first-line categories, from 3–5 to 1–2 to 0. CONCLUSION: Nonsusceptibility to first-line antibiotics is associated with decreased survival in GNBSIs. DTR is a simple bedside prognostic measure of treatment-limiting coresistance.

The high rate documented in this study highlights the need for increased surveillance. Lassa Virus Seroprevalence, Mali, Lassa virus (LASV) is endemic to several nations in West Africa. In Mali, LASV was unknown until an exported case of Lassa fever was reported in 2009. Since that time, rodent surveys have found evidence of LASV-infected Mastomys natalensis rats in several communities in southern Mali, near the border with Côte d’Ivoire. Despite increased awareness, to date only a single case of Lassa fever has been confirmed in Mali. We conducted a survey to determine the prevalence of LASV exposure among persons in 3 villages in southern Mali where the presence of infected rodents has been documented. LASV IgG seroprevalence ranged from 14.5% to 44% per village. No sex bias was noted; however, seropositivity rates increased with participant age. These findings confirm human LASV exposure in Mali and suggest that LASV infection/Lassa fever is a potential public health concern in southern Mali.

Invasive candidiasis is a major nosocomial fungal disease in the United States associated with high rates of illness and death. We analyzed inpatient hospitalization records from the Healthcare Cost and Utilization Project to estimate incidence of invasive candidiasis-associated hospitalizations in the United States. We extracted data for 33 states for 2002-2012 by using codes from the International Classification of Diseases, 9th Revision, Clinical Modification, for invasive candidiasis; we excluded neonatal cases. The overall age-adjusted average annual rate was 5.3 hospitalizations/100,000 population. Highest risk was for adults >65 years of age, particularly men. Median length of hospitalization was 21 days; 22% of patients died during hospitalization. Median unadjusted associated cost for inpatient care was $46,684. Age-adjusted annual rates decreased during 2005-2012 for men (annual change -3.9%) and women (annual change -4.5%) and across nearly all age groups. We report a high mortality rate and decreasing incidence of hospitalizations for this disease.

Microbiologically based criteria such as sputum culture conversion to negative have traditionally been used to define treatment success for mycobacterial diseases. There are, however, limited data regarding whether nontuberculous mycobacterial sputum culture conversion or semiquantitative culture analysis correlates with subjective or nonmicrobiologic objective indices of treatment response.To determine whether a semiquantitative mycobacterial culture scale correlated with clinical disease status and was predictive of long-term sputum mycobacterial culture conversion to negative in a cohort of patients with nodular/bronchiectatic Mycobacterium avium complex lung disease undergoing therapy.One hundred and eighty patients undergoing standard macrolide-based therapy for M. avium complex lung disease were monitored at standard frequent intervals with symptomatic, radiographic, and microbiologic data collected, including semiquantitative mycobacterial culture analysis. Analyses were used to evaluate clinical and microbiologic predictors of long-term sputum conversion to culture negative.After 12 months of therapy, 148 (82%) patients had sputum conversion to culture negative. Baseline semiquantitative sputum culture scores did not differ between patients with sputum conversion and those without. The change in sputum culture semiquantitative score from baseline to Month 3 was highly predictive of subsequent sputum long-term conversion status indicative of treatment success, as was improvement in cough, and especially early radiographic improvement.Early semiquantitative sputum agar plate culture results can be used to predict symptomatic and radiographic improvement as well as long-term sputum culture conversion to negative in this population. We suggest that semiquantitative sputum culture scores can be a useful tool for evaluating new nontuberculous mycobacterial lung disease therapies.

Blastomycosis is a disease caused by endemic fungi that ranges from severe pulmonary or disseminated to mild or asymptomatic. Environmental factors associated with it are not well described throughout the endemic area. We used the intramural State Inpatient Database from the Agency for Healthcare Research and Quality and ArcMap GIS to identify geographic high-risk clusters of blastomycosis hospitalizations in 13 states in the US endemic regions (AR, IA, IL, IN, KY, LA, MI, MN, MO, MS, OH, TN, and WI). We then used logistic regression to identify risk factors associated with these high-risk clusters. We describe six clusters of counties in which there was an elevated incidence of blastomycosis hospitalizations. We identified maximum mean annual temperature, percentage of persons aged ≥65 years, and mercury and copper soil content as being associated with high-risk clusters. Specifically, the odds of a county being part of a high-risk cluster was associated with increasing percentage of population over age 65, decreasing maximum temperature, increasing mercury, and decreasing copper soil content. Healthcare providers should be aware of these high-risk areas so that blastomycosis can be included, as appropriate, in a differential diagnosis for patients currently or previously residing in these areas.

Nontuberculous mycobacteria are an important cause of morbidity in the United States, although patient outcomes vary greatly by species. Currently, nationally representative data on the distribution of mycobacterial species from clinical isolates are limited.Using a national hospitalization database capturing microbiologic data for nearly 6 million patient encounters, we describe the geographic distribution of, and patient demographic features associated with, clinical mycobacterial isolates in the United States.Linked demographic and microbiologic data from the Premier Healthcare Database were extracted for all patient encounters from 2009 to 2013. Patients with at least one positive potentially pathogenic nontuberculous mycobacterial culture were identified as cases. The period prevalence was calculated, and patient-, encounter-, and hospital-level factors were analyzed. Regional differences in species distribution were analyzed; a subanalysis was conducted among patients with International Classification of Diseases, Ninth Revision, codes for pulmonary nontuberculous mycobacterial disease. Significant differences were assessed (P 0.05).Of 5,928,830 unique patients included during the 5-year study period, 7,812 (0.13%) had at least one positive nontuberculous mycobacterial culture. The mean age of cases was 64 years (range,1-89 yr), and most were female (52%) and white (70%). Hospitals with cases were more often labeled "urban" (96%), "teaching" (56%), and had at least 500 beds (78%). Species distribution differed significantly by geographic area. Mycobacterium avium complex ranged from 61 to 91% of isolates and were most frequent in the South and Northeast regions; M. abscessus/M. chelonae ranged from 2 to 18% of isolates and were most frequent in the West; and other species, including M. fortuitum and M. kansasii, ranged from 7 to 26% and were also most frequent in the West.Significant geographic variation exists in the distribution of nontuberculous mycobacterial species in the United States. Whereas M. avium complex was the most common species isolated in the South, M. abscessus/M. chelonae was proportionately higher in the West. Greater clinical awareness in regions with increased levels of harder-to-treat mycobacteria are needed, given differences in treatment options and implications for patient outcomes.