BACKGROUND: We investigated hospitalized carbapenem-resistant Enterobacterales (CRE) and extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) cases with and without COVID-19, as identified through Emerging Infections Program surveillance in 10 sites from 2020 to 2022. METHODS: We defined a CRE case as the first isolation of Escherichia coli, Enterobacter cloacae complex, Klebsiella aerogenes, K oxytoca, K pneumoniae, or K variicola resistant to any carbapenem. We defined an ESBL-E case as the first isolation of E coli, K pneumoniae, or K oxytoca resistant to any third-generation cephalosporin and nonresistant to all carbapenems tested. Specimens were drawn from a normally sterile site or urine among hospitalized residents of the surveillance area in a 30-day period. We defined COVID-19 as a positive SARS-CoV-2 test result (SC2(+)) within 14 days before CRE or ESBL-E specimen collection and performed multivariable logistic regression analyses. RESULTS: Of 1595 CRE and 1866 ESBL-E hospitalized cases, 38 (2.4%) and 60 (3.2%), respectively, had a SC2(+). Among these cases, a SC2(+) was associated with intensive care unit admission (adjusted odds ratio [aOR], 1.69 [95% CI, 1.14-2.50]; aOR, 1.48 [95% CI, 1.03-2.12]) and 30-day mortality (aOR, 1.79 [95% CI, 1.22-2.64]; aOR, 1.94 [95% CI, 1.39-2.70]). CONCLUSIONS: CRE and ESBL-E infections among hospitalized patients with preceding COVID-19 were uncommon but had worse outcomes when compared with cases without COVID-19. COVID-19 prevention in patients at risk of CRE and ESBL-E infections is needed, as well as continued infection control measures and antibiotic stewardship for patients with COVID-19.

INTRODUCTION: Mounting evidence indicates that an individual's humoral adaptive immune response plays a critical role in the setting of SARS-CoV-2 infection, and that the efficiency of the response correlates with disease severity. The relationship between the adaptive immune dynamics in the lower airways with those in the systemic circulation, and how these relate to an individual's clinical response to SARS-CoV-2 infection, are less understood and are the focus of this study. MATERIAL AND METHODS: We investigated the adaptive immune response to SARS-CoV-2 in paired samples from the lower airways and blood from 27 critically ill patients during the first wave of the pandemic (median time from symptom onset to intubation 11 days). Measurements included clinical outcomes (mortality), bronchoalveolar lavage fluid (BALF) and blood specimen antibody levels, and BALF viral load. RESULTS: While there was heterogeneity in the levels of the SARS-CoV-2-specific antibodies, we unexpectedly found that some BALF specimens displayed higher levels than the paired concurrent plasma samples, despite the known dilutional effects common in BALF samples. We found that survivors had higher levels of anti-spike, anti-spike-N-terminal domain and anti-spike-receptor-binding domain IgG antibodies in their BALF (p<0.05), while there was no such association with antibody levels in the systemic circulation. DISCUSSION: Our data highlight the critical role of local adaptive immunity in the airways as a key defence mechanism against primary SARS-CoV-2 infection.

BACKGROUND: Understanding the epidemiology of carbapenem-resistant A. baumannii complex (CRAB) and the patients impacted is an important step towards informing better infection prevention and control practices and improving public health response. METHODS: Active, population-based surveillance was conducted for CRAB in 9 U.S. sites from January 1-December 31, 2019. Medical records were reviewed, isolates were collected and characterized including antimicrobial susceptibility testing and whole genome sequencing. RESULTS: Among 136 incident cases in 2019, 66 isolates were collected and characterized; 56.5% were from cases who were male, 54.5% were from persons of Black or African American race with non-Hispanic ethnicity, and the median age was 63.5 years. Most isolates, 77.2%, were isolated from urine, and 50.0% were collected in the outpatient setting; 72.7% of isolates harbored an acquired carbapenemase gene (aCP), predominantly bla(OXA-23) or bla(OXA-24/40); however, an isolate with bla(NDM) was identified. The antimicrobial agent with the most in vitro activity was cefiderocol (96.9% of isolates were susceptible). CONCLUSIONS: Our surveillance found that CRAB isolates in the U.S. commonly harbor an aCP, have an antimicrobial susceptibility profile that is defined as difficult-to-treat resistance, and epidemiologically are similar regardless of the presence of an aCP.

BACKGROUND: We described changes in 2016─2020 carbapenem-resistant Enterobacterales (CRE) incidence rates in 7 US sites that conduct population-based CRE surveillance. METHODS: An incident CRE case was defined as the first isolation of Escherichia coli, Klebsiella spp., or Enterobacter spp. resistant to ≥1 carbapenem from a sterile site or urine in a surveillance area resident in a 30-day period. We reviewed medical records and classified cases as hospital-onset (HO), healthcare-associated community-onset (HACO), or community-associated (CA) CRE based on healthcare exposures and location of disease onset. We calculated incidence rates using census data. We used Poisson mixed effects regression models to perform 2016─2020 trend analyses, adjusting for sex, race/ethnicity, and age. We compared adjusted incidence rates between 2016 and subsequent years using incidence rate ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Of 4996 CRE cases, 62% were HACO, 21% CA, and 14% HO. The crude CRE incidence rate per 100 000 was 7.51 in 2016 and 6.08 in 2020 and was highest for HACO, followed by CA and HO. From 2016 to 2020, the adjusted overall CRE incidence rate decreased by 24% (RR, 0.76 [95% CI, .70-.83]). Significant decreases in incidence rates in 2020 were seen for HACO (RR, 0.75 [95% CI, .67-.84]) and CA (0.75 [.61-.92]) but not for HO CRE. CONCLUSIONS: Adjusted CRE incidence rates declined from 2016 to 2020, but changes over time varied by epidemiologic class. Continued surveillance and effective control strategies are needed to prevent CRE in all settings.

The rapid expansion of telemedicine has highlighted challenges and opportunities to improve antibiotic use and effectively adapt antibiotic stewardship best practices to outpatient telemedicine settings. Antibiotic stewardship integration into telemedicine is essential to optimize antibiotic prescribing for patients and ensure health care quality. We performed a narrative review of published literature on antibiotic prescribing and stewardship in outpatient telemedicine to inform the adaptation of the Core Elements of Outpatient Antibiotic Stewardship framework to outpatient telemedicine settings. Our narrative review suggests that in-person antibiotic stewardship interventions can be adapted to outpatient telemedicine settings. We present considerations for applying the Core Elements of Outpatient Antibiotic Stewardship to outpatient telemedicine which builds upon growing evidence describing care delivery and quality improvement in this setting. Additional applied implementation research is necessary to inform the application of effective, sustainable, and equitable antibiotic stewardship interventions across the spectrum of outpatient telemedicine.

We performed a scoping review of articles published from 1 January 2000 to 4 January 2022 to characterize inequities in antibiotic prescribing and use across healthcare settings in the United States to inform antibiotic stewardship interventions and research. We included 34 observational studies, 21 cross-sectional survey studies, 4 intervention studies, and 2 systematic reviews. Most studies (55 of 61 [90%]) described the outpatient setting, 3 articles were from dentistry, 2 were from long-term care, and 1 was from acute care. Differences in antibiotic prescribing were found by patient's race and ethnicity, sex, age, socioeconomic factors, geography, clinician's age and specialty, and healthcare setting, with an emphasis on outpatient settings. Few studies assessed stewardship interventions. Clinicians, antibiotic stewardship experts, and health systems should be aware that prescribing behavior varies according to both clinician- and patient-level markers. Prescribing differences likely represent structural inequities; however, no studies reported underlying drivers of inequities in antibiotic prescribing.

Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.

OBJECTIVE: Urgent care (UC) clinicians frequently prescribe inappropriate antibiotics for upper respiratory illnesses. In a national survey, pediatric UC clinicians reported family expectations as a primary driver for prescribing inappropriate antibiotics. Communication strategies effectively reduce unnecessary antibiotics while increasing family satisfaction. We aimed to reduce inappropriate prescribing practices in otitis media with effusion (OME), acute otitis media (AOM), and pharyngitis in pediatric UC clinics by a relative 20% within 6 months using evidence-based communication strategies. METHODS: We recruited participants via e-mails, newsletters, and Webinars from pediatric and UC national societies. We defined antibiotic-prescribing appropriateness based on consensus guidelines. Family advisors and UC pediatricians developed script templates based on an evidence-based strategy. Participants submitted data electronically. We reported data using line graphs and shared deidentified data during monthly Webinars. We used χ2 tests to evaluate change in appropriateness at the beginning and end of the study period. RESULTS: The 104 participants from 14 institutions submitted 1183 encounters for analysis in the intervention cycles. Using a strict definition of inappropriateness, overall inappropriate antibiotic prescriptions for all diagnoses trended downward from 26.4% to 16.6% (P = 0.13). Inappropriate prescriptions trended upward in OME from 30.8% to 46.7% (P = 0.34) with clinicians' increased use of "watch and wait" for this diagnosis. Inappropriate prescribing for AOM and pharyngitis improved from 38.6% to 26.5% (P = 0.03) and 14.5% to 8.8% (P = 0.44), respectively. CONCLUSIONS: Using templates to standardize communication with caregivers, a national collaborative decreased inappropriate antibiotic prescriptions for AOM and had downward trend in inappropriate antibiotic prescriptions for pharyngitis. Clinicians increased the inappropriate use of "watch and wait" antibiotics for OME. Future studies should evaluate barriers to the appropriate use of delayed antibiotic prescriptions.

OBJECTIVES: To describe acute respiratory illnesses (ARI) visits and antibiotic prescriptions in 2011 and 2018 across outpatient settings to evaluate progress in reducing unnecessary antibiotic prescribing for ARIs. DESIGN: Cross-sectional study. SETTING AND PATIENTS: Outpatient medical and pharmacy claims captured in the IBM MarketScan commercial database, a national convenience sample of privately insured individuals aged <65 years. METHODS: We calculated the annual number of ARI visits and visits with oral antibiotic prescriptions per 1,000 enrollees overall and by age category, sex, and setting in 2011 and 2018. We compared these and calculated prevalence rate ratios (PRRs). We adapted existing tiered-diagnosis methodology for International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes. RESULTS: In our study population, there were 829 ARI visits per 1,000 enrollees in 2011 compared with 760 ARI visits per 1,000 enrollees in 2018. In 2011, 39.3% of ARI visits were associated with ≥1 oral antibiotic prescription versus 36.2% in 2018. In 2018 compared with 2011, overall ARI visits decreased 8% (PRR, 0.92; 99.99% confidence interval [CI], 0.92-0.92), whereas visits with antibiotic prescriptions decreased 16% (PRR, 0.84; 99.99% CI, 0.84-0.85). Visits for antibiotic-inappropriate ARIs decreased by 9% (PRR, 0.91; 99.99% CI, 0.91-0.92), and visits with antibiotic prescriptions for these conditions decreased by 32% (PRR, 0.68; 99.99% CI, 0.67-0.68) from 2011 to 2018. CONCLUSIONS: Both the rate of antibiotic prescriptions per 1,000 enrollees and the percentage of visits with antibiotic prescriptions decreased modestly from 2011 to 2018 in our study population. These decreases were greatest for antibiotic-inappropriate ARIs; however, additional reductions in inappropriate antibiotic prescribing are needed.

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.

The distributions of antibiotic prescriptions by geography, antibiotic class, and prescriber specialty are similar in the US Centers for Medicare and Medicaid Services (CMS) Part D Prescriber Public Use Files and IQVIA Xponent dataset. Public health organizations and healthcare systems can use these data to track antibiotic use and guide antibiotic stewardship interventions for older adults.

BACKGROUND: Studies have shown that the Southern United States has higher rates of outpatient antibiotic prescribing rates compared with other regions in the country, but the reasons for this variation are unclear. We aimed to determine whether the regional variability in outpatient antibiotic prescribing for respiratory diagnoses can be explained by differences in prescriber clinical factors found in a commercially insured population. METHODS: We analyzed the 2017 IBM MarketScan Commercial Database of commercially insured individuals aged <65 years. We included visits with acute respiratory tract infection (ARTI) diagnoses from retail clinics, urgent care centers, emergency departments, and physician offices. ARTI diagnoses were categorized based on antibiotic indication. We calculated risk ratios and 95% CIs stratified by ARTI tier and region using log-binomial models controlling for patient age, comorbidities, care setting, prescriber type, and diagnosis. RESULTS: Of the 14.9 million ARTI visits, 40% received an antibiotic. The South had the highest proportion of visits with an antibiotic prescription (43%), and the West the lowest (34%). ARTI visits in the South are 34% more likely receive an antibiotic for rarely antibiotic-appropriate ARTI visits when compared with the West in multivariable modeling (relative risk, 1.34; 95% CI, 1.33-1.34). CONCLUSIONS: It is likely that higher antibiotic prescribing in the South is in part due to nonclinical factors such as regional differences in clinicians' prescribing habits and patient expectations. There is a need for future studies to define and characterize these factors to better inform regional and local stewardship interventions and achieve greater health equity in antibiotic prescribing.

Background: Inappropriate antibiotic use for SARS-CoV-2 infection has the potential to increase the burden of antibiotic resistance. Brazil experienced spread of a new SARS-CoV-2 variant in the fourth quarter (Q4) of 2020, resulting in the highest case counts in Latin America, raising concerns of antibiotic overuse. To better understand antibiotic use during the COVID-19 pandemic, we evaluated prescribing changes in antibiotics commonly used for outpatient respiratory infections (amoxicillin-clavulanate, azithromycin, and levofloxacin or moxifloxacin [AALM]) among adults aged ≥20 years in Brazil in 2020 versus 2019. Methods: We analyzed the IQVIA MIDAS medical data set for AALM prescribing by age group (20–39, 40–59, 60–64, 65–74, ≥75 years), comparing Q4 2020 rates to those in Q4 2019. We estimated crude rate ratios and 95% CIs using prescription number as the numerator (assuming Poisson counts) and age-adjusted population as the denominator. We also determined the most common prescribing specialties for each antibiotic across both time points. Results: Compared to Q4 2019, Q4 2020 azithromycin prescribing increased among all ages, ranging from 90.7% (95% CI, 90.0%–91.4%) in those aged 20–39 years to 927.2% (95% CI, 912.9%–941.7%) in those aged 65–74 years (Fig. 1). Amoxicillin-clavulanate prescribing decreased for most ages, ranging from −78.4% (95% CI, −78.7% to −78.1%) in those aged 60–64 years to −25.8% (95% CI, −26.6% to −25.0%) in those aged 65–74 years. Prescribing of levofloxacin or moxifloxacin decreased for most ages, ranging from −39.1% (95% CI, −39.4% to −38.8%) in those aged 20–39 years to −16.9% (95% CI, −18.1% to −15.7%) in those aged 60–64 years. For those aged ≥75 years, prescribing of amoxicillin-clavulanate and levofloxacin or moxifloxacin increased by 13.2% (95% CI, 11.9%–14.5%) and 43.1% (95% CI, 41.7%–44.5%), respectively. In Q4 2019 and Q4 2020, the 2 most common prescribing specialties for azithromycin were general practice (48%–50% of prescriptions) and gynecology (19%–25%). Compared to Q4 2019, infectious disease specialists in Q4 2020 saw the largest decline in percentage of azithromycin prescriptions (10% to 1%) and surgeons saw the largest increase (0% to 7%). General practitioners were also the most common prescribers of the remaining antibiotics (43%–54%), followed by gynecology for levofloxacin or moxifloxacin (25%–29%) and otolaryngology for amoxicillin-clavulanate (14%–20%). Conclusions: Despite decreases in prescribing of amoxicillin-clavulanate and respiratory fluoroquinolones for most adults, azithromycin prescribing increased dramatically across all adults during the COVID-19 pandemic. Targeting inappropriate outpatient antibiotic use in Brazil, particularly azithromycin prescribing among general practitioners, gynecologists, and surgeons, may be high-yield targets for antibiotic stewardship.Funding: NoneDisclosures: None

Healthcare disparities and inequities exist in a variety of environments and manifest in diagnostic and therapeutic measures. In this commentary, we highlight our experience examining our organization's urgent care respiratory encounter antibiotic prescribing practices. We identified differences in prescribing based on several individual characteristics including patient age, race, ethnicity, preferred language, and patient and/or clinician gender. Our approach can serve as an electronic health record (EHR)-based methodology for disparity and inequity audits in other systems and for other conditions.

The CDC's Emerging Infections Program (EIP) conducted population- and laboratory-based surveillance of US carbapenem-resistant Pseudomonas aeruginosa (CRPA) from 2016 through 2018. To characterize the pathotype, 1,019 isolates collected through this project underwent antimicrobial susceptibility testing and whole-genome sequencing. Sequenced genomes were classified using the seven-gene multilocus sequence typing (MLST) scheme and a core genome (cg)MLST scheme was used to determine phylogeny. Both chromosomal and horizontally transmitted mechanisms of carbapenem resistance were assessed. There were 336 sequence types (STs) among the 1,019 sequenced genomes, and the genomes varied by an average of 84.7% of the cgMLST alleles used. Mutations associated with dysfunction of the porin OprD were found in 888 (87.1%) of the genomes and were correlated with carbapenem resistance, and a machine learning model incorporating hundreds of genetic variations among the chromosomal mechanisms of resistance was able to classify resistant genomes. While only 7 (0.1%) isolates harbored carbapenemase genes, 66 (6.5%) had acquired non-carbapenemase β-lactamase genes, and these were more likely to have OprD dysfunction and be resistant to all carbapenems tested. The genetic diversity demonstrates that the pathotype includes a variety of strains, and clones previously identified as high-risk make up only a minority of CRPA strains in the United States. The increased carbapenem resistance in isolates with acquired non-carbapenemase β-lactamase genes suggests that horizontally transmitted mechanisms aside from carbapenemases themselves may be important drivers of the spread of carbapenem resistance in P. aeruginosa.

OBJECTIVES: To compare the antibiotic treatment failure and recurrence rates between antibiotic agents (amoxicillin, amoxicillin-clavulanate, cefdinir, and azithromycin) for children with uncomplicated acute otitis media (AOM) STUDY DESIGN: We completed a retrospective cohort study of children 6 months-12 years of age with uncomplicated AOM identified in a nationwide claims database. The primary exposure was antibiotic agent, and the primary outcomes were treatment failure and recurrence. Logistic regression was used to estimate odds ratios and analyses were stratified by primary exposure, patient age and antibiotic duration. RESULTS: Among the 1,051,007 children included in the analysis, 56.6% were prescribed amoxicillin, 13.5% amoxicillin-clavulanate, 20.6% cefdinir, and 9.3% azithromycin. Most prescriptions (93%) were for 10 days and 98% were filled within 1 day of the medical encounter. Treatment failure or recurrence occurred in 2.2% (95%CI: 2.1, 2.2) and 3.3% (3.2, 3.3) of children, respectively. Combined failure and recurrence rates were low for all agents including amoxicillin (1.7%; 1.7, 1.8) amoxicillin-clavulanate 11.3% (11.1, 11.5); cefdinir 10.0% (9.8, 10.1); azithromycin 9.8% (9.6, 10.0). CONCLUSIONS: Despite microbiologic changes in AOM etiology, treatment failure and recurrence were uncommon for all antibiotic agents and were lower for amoxicillin than for other agents. These findings support the continued use of amoxicillin as a first-line agent for AOM when antibiotics are prescribed.

BACKGROUND: Widespread inappropriate antibiotic prescribing is a major driver of resistance. Little is known about antifungal prescribing practices in the United States, which is concerning given emerging resistance in fungi, particularly to azole antifungals. OBJECTIVE: We analyzed outpatient U.S. antifungal prescribing data to inform stewardship efforts. DESIGN: Descriptive analysis of outpatient antifungal prescriptions dispensed during 2018 in the IQVIA Xponent database. METHODS: Prescriptions were summarized by drug, sex, age, geography, and healthcare provider specialty. Census denominators were used to calculate prescribing rates among demographic groups. RESULTS: Healthcare providers prescribed 22.4 million antifungal courses in 2018 (68 prescriptions per 1,000 persons). Fluconazole was the most common drug (75%), followed by terbinafine (11%) and nystatin (10%). Prescription rates were higher among females vs. males (110 vs. 25 per 1,000) and adults vs. children (82 vs. 27 per 1,000). Prescription rates were highest in the South (81 per 1,000 persons) and lowest in the West (48 per 1,000 persons). Nurse practitioners and family practitioners prescribed the most antifungals (43% of all prescriptions), but the highest prescribing rates were among obstetrician-gynecologists (84 per provider). CONCLUSIONS: Prescribing of antifungal drugs in the outpatient setting was common, with enough courses dispensed for one in every 15 U.S. residents in 2018. Fluconazole use patterns suggest vulvovaginal candidiasis as a common indication. Regional prescribing differences could reflect inappropriate use or variations in disease burden. Further study of higher antifungal use in the South could help target antifungal stewardship practices.

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

This study of Medicare claims data examines the prescribing of antibiotics to older US patients who had outpatient visits for COVID-19 in an effort to address unnecessary antibiotic use for viral infections.

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

Antibiotic prescribing can lead to adverse drug events and antibiotic resistance, which pose ongoing urgent public health threats (1). Adults aged ≥65 years (older adults) are recipients of the highest rates of outpatient antibiotic prescribing and are at increased risk for antibiotic-related adverse events, including Clostridioides difficile and antibiotic-resistant infections and related deaths (1). Variation in antibiotic prescribing quality is primarily driven by prescribing patterns of individual health care providers, independent of patients' underlying comorbidities and diagnoses (2). Engaging higher-volume prescribers (the top 10% of prescribers by antibiotic volume) in antibiotic stewardship interventions, such as peer comparison audit and feedback in which health care providers receive data on their prescribing performance compared with that of other health care providers, has been effective in reducing antibiotic prescribing in outpatient settings and can be implemented on a large scale (3-5). This study analyzed data from the Centers for Medicare & Medicaid Services (CMS) Part D Prescriber Public Use Files (PUFs)* to describe higher-volume antibiotic prescribers in outpatient settings compared with lower-volume prescribers (the lower 90% of prescribers by antibiotic volume). Among the 59.4 million antibiotic prescriptions during 2019, 41% (24.4 million) were prescribed by the top 10% of prescribers (69,835). The antibiotic prescribing rate of these higher-volume prescribers (680 prescriptions per 1,000 beneficiaries) was 60% higher than that of lower-volume prescribers (426 prescriptions per 1,000 beneficiaries). Identifying health care providers responsible for a higher volume of antibiotic prescribing could provide a basis for additional assessment of appropriateness and outreach. Public health organizations and health care systems can use publicly available data to guide focused interventions to optimize antibiotic prescribing to limit the emergence of antibiotic resistance and improve patient outcomes.

Using a machine-learning model, we examined drivers of antibiotic prescribing for antibiotic-inappropriate acute respiratory illnesses in a large US claims data set. Antibiotics were prescribed in 11% of the 42 million visits in our sample. The model identified outpatient setting type, patient age mix, and state as top drivers of prescribing.

Respiratory failure is associated with increased mortality in COVID-19 patients. There are no validated lower airway biomarkers to predict clinical outcome. We investigated whether bacterial respiratory infections were associated with poor clinical outcome of COVID-19 in a prospective, observational cohort of 589 critically ill adults, all of whom required mechanical ventilation. For a subset of 142 patients who underwent bronchoscopy, we quantified SARS-CoV-2 viral load, analysed the lower respiratory tract microbiome using metagenomics and metatranscriptomics and profiled the host immune response. Acquisition of a hospital-acquired respiratory pathogen was not associated with fatal outcome. Poor clinical outcome was associated with lower airway enrichment with an oral commensal (Mycoplasma salivarium). Increased SARS-CoV-2 abundance, low anti-SARS-CoV-2 antibody response and a distinct host transcriptome profile of the lower airways were most predictive of mortality. Our data provide evidence that secondary respiratory infections do not drive mortality in COVID-19 and clinical management strategies should prioritize reducing viral replication and maximizing host responses to SARS-CoV-2.

Time constraints have been suggested as a potential driver of antibiotic overuse for acute respiratory tract infections. In this cross-sectional analysis of national data from visits to offices and emergency departments, we identified no statistically significant association between antibiotic prescribing and the duration of visits for acute respiratory tract infections.

Antibiotics are the double-edged swords we love to wield. They save lives, but they also cause harm with adverse drug events and the promotion of antibiotic resistance. Antibiotic stewardship is the effort to optimize the use of antibiotics to the right antibiotic at the right time and for the right duration. Stewardship encourages us to ask ourselves: can we decrease the biological costs of using these powerful tools, even a little, if we put them away earlier? Evidence has accumulated that we can give shorter courses of antibiotics, at least to adult patients, for many conditions, including for pneumonia, urinary tract infections, sinusitis, and cellulitis.1 This is welcome news to anyone who has taken antibiotics themselves or given their child an antibiotic and experienced diarrhea or a yeast infection; adverse events and effects are common, especially in children.2 However, in children, evidence regarding the efficacy of shorter antibiotic courses is lacking for most common conditions. At least in part because of this uncertainty, most antibiotic courses prescribed to children in the US for common infections, including pneumonia, are 10 days in duration.3 This may be owing in part to the lack of strong evidence to guide recommendations for duration of therapy for many infections.

BACKGROUND: The objective of our study was to describe trends in U.S. outpatient antibiotic prescriptions from January through May 2020 and compare with trends in previous years (2017-2019). METHODS: We used data from the IQVIA Total Patient Tracker to estimate the monthly number of patients dispensed antibiotic prescriptions from retail pharmacies in January 2017-May 2020. We averaged estimates from 2017-2019 and defined expected seasonal change as the average percent change from January to May 2017-2019. We calculated percentage point and volume changes in the number of patients dispensed antibiotics from January to May 2020 exceeding expected seasonal changes. We also calculated average percent change in number of patients dispensed antibiotics per month in 2017- 2019 versus 2020. Data were analyzed overall and by agent, class, patient age, state, and prescriber specialty. RESULTS: From January to May 2020, the number of patients dispensed antibiotic prescriptions decreased from 20.3 to 9.9 million, exceeding seasonally expected decreases by 33 percentage points and 6.6 million patients. The largest changes in 2017-2019 versus 2020 were observed in April (-39%) and May (-42%). The number of patients dispensed azithromycin increased from February to March 2020 then decreased. Overall, beyond-expected decreases were greatest among children (≤19 years) and agents used for respiratory infections, dentistry, and surgical prophylaxis. CONCLUSIONS: From January 2020 to May 2020, the number of outpatients with antibiotic prescriptions decreased substantially more than would be expected due to seasonal trends alone, possibly related to the COVID-19 pandemic and associated mitigation measures.

BACKGROUND: Candidemia is a common healthcare-associated bloodstream infection with high morbidity and mortality. There are no current estimates of candidemia burden in the United States. METHODS: In 2017, the Centers for Disease Control and Prevention (CDC) conducted active population-based surveillance for candidemia through the Emerging Infections Program (EIP) in 45 counties in nine states encompassing ~17 million persons (5% of the national population). Laboratories serving the catchment area population reported all blood cultures with Candida, and a standard case definition was applied to identify cases that occurred in surveillance area residents. Burden of cases and mortality was estimated by extrapolating surveillance area cases to national numbers using 2017 national census data. RESULTS: We identified 1,226 candidemia cases across nine surveillance sites in 2017. Based on this, we estimated 22,660 (95% confidence interval [CI]: 20,210-25,110) cases of candidemia occurred in the United States in 2017. Overall estimated incidence was 7.0 cases per 100,000 persons, with highest rates in adults >/=65 years (20.1/100,000), males (7.9/100,000), and those of black race (12.3/100,000). An estimated 3,380 (95% CI: 1,318-5,442) deaths occurred within seven days of a positive Candida blood culture and 5,628 (95% CI: 2,465-8,791) deaths occurred during the hospitalization with candidemia. CONCLUSIONS: Our analysis highlights the substantial burden of candidemia in the U.S. Because candidemia is only one form of invasive candidiasis, the true burden of invasive infections due to Candida is higher. Ongoing surveillance can support future burden estimates and help assess the impact of prevention interventions.

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.

Candidemia, a bloodstream infection caused by Candida species, is typically considered a health care-associated infection, with known risk factors including the presence of a central venous catheter, receipt of total parenteral nutrition or broad-spectrum antibiotics, recent abdominal surgery, admission to an intensive care unit, and prolonged hospitalization (1,2). Injection drug use (IDU) is not a common risk factor for candidemia; however, in the context of the ongoing opioid epidemic and corresponding IDU increases, IDU has been reported as an increasingly common condition associated with candidemia (3) and methicillin-resistant Staphylococcus aureus bacteremia (4). Little is known about the epidemiology of candidemia among persons who inject drugs. The Colorado Department of Public Health and Environment (CDPHE) conducts population-based surveillance for candidemia in the five-county Denver metropolitan area, encompassing 2.7 million persons, through CDC's Emerging Infections Program (EIP). As part of candidemia surveillance, CDPHE collected demographic, clinical, and IDU behavior information for persons with Candida-positive blood cultures during May 2017-August 2018. Among 203 candidemia cases reported, 23 (11%) occurred in 22 patients with a history of IDU in the year preceding their candidemia episode. Ten (43%) of the 23 cases were considered community-onset infections, and four (17%) cases were considered community-onset infections with recent health care exposures. Seven (32%) of the 22 patients had disseminated candidiasis with end-organ dysfunctions; four (18%) died during their hospitalization. In-hospital IDU was reported among six (27%) patients, revealing that IDU can be a risk factor in the hospital setting as well as in the community. In addition to community interventions, opportunities to intervene during health care encounters to decrease IDU and unsafe injection practices might prevent infections, including candidemia, among persons who inject drugs.