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Background.  Antibiotic use predisposes patients to Clostridium difficile infections (CDI), and approximately 32% of these infections are community-associated (CA) CDI. The population-level impact of antibiotic use on adult CA-CDI rates is not well describ

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., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Background: Protection against symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019 [COVID-19]) can limit transmission and the risk of post-COVID conditions, and is particularly important among healthcare personnel. However, lower vaccine effectiveness (VE) has been reported since predominance of the Omicron SARS-CoV-2 variant., Methods: We evaluated the VE of a monovalent messenger RNA (mRNA) booster dose against COVID-19 from October 2021 to June 2022 among US healthcare personnel. After matching case-participants with COVID-19 to control-participants by 2-week period and site, we used conditional logistic regression to estimate the VE of a booster dose compared with completing only 2 mRNA doses >150 days previously, adjusted for multiple covariates., Results: Among 3279 case-participants and 3998 control-participants who had completed 2 mRNA doses, we estimated that the VE of a booster dose against COVID-19 declined from 86% (95% confidence interval, 81%-90%) during Delta predominance to 65% (58%-70%) during Omicron predominance. During Omicron predominance, VE declined from 73% (95% confidence interval, 67%-79%) 14-60 days after the booster dose, to 32% (4%-52%) ≥120 days after a booster dose. We found that VE was similar by age group, presence of underlying health conditions, and pregnancy status on the test date, as well as among immunocompromised participants., Conclusions: A booster dose conferred substantial protection against COVID-19 among healthcare personnel. However, VE was lower during Omicron predominance, and waning effectiveness was observed 4 months after booster dose receipt during this period. Our findings support recommendations to stay up to date on recommended doses of COVID-19 vaccines for all those eligible., Competing Interests: Potential conflicts of interest. M. B. owned stock in Moderna from November 2022 to April 2023, as part of portfolio managed by Parametric Investments Portfolio. All other authors report no potential conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

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

Background: Most multicenter studies of US pediatric sepsis epidemiology use administrative data or focus on pediatric intensive care units. We conducted a detailed medical record review to describe sepsis epidemiology in children and young adults., Methods: In a convenience sample of hospitals in 10 states, patients aged 30 days-21 years, discharged during 1 October 2014-30 September 2015, with explicit diagnosis codes for severe sepsis or septic shock, were included. Medical records were reviewed for patients with documentation of sepsis, septic shock, or similar terms. We analyzed overall and age group-specific patient characteristics., Results: Of 736 patients in 26 hospitals, 442 (60.1%) had underlying conditions. Most patients (613 [83.3%]) had community-onset sepsis, although most community-onset sepsis was healthcare associated (344 [56.1%]). Two hundred forty-one patients (32.7%) had outpatient visits 1-7 days before sepsis hospitalization, of whom 125 (51.9%) received antimicrobials ≤30 days before sepsis hospitalization. Age group-related differences included common underlying conditions (<5 years: prematurity vs 5-12 years: chronic pulmonary disease vs 13-21 years: chronic immunocompromise); medical device presence ≤30 days before sepsis hospitalization (1-4 years: 46.9% vs 30 days-11 months: 23.3%); percentage with hospital-onset sepsis (<5 years: 19.6% vs ≥5 years: 12.0%); and percentage with sepsis-associated pathogens (30 days-11 months: 65.6% vs 13-21 years: 49.3%)., Conclusions: Our data suggest potential opportunities to raise sepsis awareness among outpatient providers to facilitate prevention, early recognition, and intervention in some patients. Consideration of age-specific differences may be important as approaches are developed to improve sepsis prevention, risk prediction, recognition, and management., Competing Interests: Potential conflicts of interest. G. D.: personal fees from Seres Therapeutics. R. L.: payment for serving as Associate Editor of the American Academy of Pediatrics Red Book (donated to the Minnesota Department of Health); support for attending meetings and/or travel as a member of the IDWeek Program Committee; support for attending meetings and/or travel as an Executive Board Member of the Council for State and Territorial Epidemiologists; support for attending meetings and/or travel as an Executive Board Member of the National Foundation for Infectious Diseases; and support for attending meetings and/or travel from the American Academy of Pediatrics, Committee on Infectious Diseases. M. K.: reimbursement for time participating in the CSF Seqirus Asia-Pacific Advisory Council; and compensation and travel support for service on the board of the Infectious Disease Consulting Corporation. M. M.: recipient of Public Health Scholarship support for meeting attendance/travel to the Society for Healthcare Epidemiology of America 2019 spring meeting. All authors affiliated with EIP sites report support for their institutions from the Centers for Disease Control and Prevention. All other authors report no potential conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

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.

To determine risk factors for coronavirus disease (COVID-19) among US healthcare personnel (HCP), we conducted a case-control analysis. We collected data about activities outside the workplace and COVID-19 patient care activities from HCP with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results (cases) and from HCP with negative test results (controls) in healthcare facilities in 5 US states. We used conditional logistic regression to calculate adjusted matched odds ratios and 95% CIs for exposures. Among 345 cases and 622 controls, factors associated with risk were having close contact with persons with COVID-19 outside the workplace, having close contact with COVID-19 patients in the workplace, and assisting COVID-19 patients with activities of daily living. Protecting HCP from COVID-19 may require interventions that reduce their exposures outside the workplace and improve their ability to more safely assist COVID-19 patients with activities of daily living.

An antimicrobial stewardship intervention consisting of a urinary antibiogram and an electronic health record best-practice advisory promoted narrower-spectrum antibiotics for uncomplicated urinary tract infections in hospitalized patients. Over 20 months, the intervention significantly reduced ceftriaxone orders by 48% ( P < .001) and increased cefazolin use 19 times from baseline ( P < .001)., Competing Interests: All authors report no conflicts of interest relevant to this article., (© The Society for Healthcare Epidemiology of America 2021.)

Infections caused by extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli are a significant cause of morbidity and health care costs. Globally, the prevailing clonal type is ST131 in association with the bla CTX-M-15 β-lactamase gene. However, other ESBLs, such as bla CTX-M-14 and bla CTX-M-27 , can also be prevalent in some regions. We identified ST38 ESBL-producing E. coli from different regions in the United States which carry bla CTX-M-27 embedded on two distinct plasmid types, suggesting the potential emergence of new ESBL lineages.

Throughout the COVID-19 pandemic, health care personnel (HCP) have been at high risk for exposure to SARS-CoV-2, the virus that causes COVID-19, through patient interactions and community exposure (1). The Advisory Committee on Immunization Practices recommended prioritization of HCP for COVID-19 vaccination to maintain provision of critical services and reduce spread of infection in health care settings (2). Early distribution of two mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) to HCP allowed assessment of the effectiveness of these vaccines in a real-world setting. A test-negative case-control study is underway to evaluate mRNA COVID-19 vaccine effectiveness (VE) against symptomatic illness among HCP at 33 U.S. sites across 25 U.S. states. Interim analyses indicated that the VE of a single dose (measured 14 days after the first dose through 6 days after the second dose) was 82% (95% confidence interval [CI] = 74%-87%), adjusted for age, race/ethnicity, and underlying medical conditions. The adjusted VE of 2 doses (measured ≥7 days after the second dose) was 94% (95% CI = 87%-97%). VE of partial (1-dose) and complete (2-dose) vaccination in this population is comparable to that reported from clinical trials and recent observational studies, supporting the effectiveness of mRNA COVID-19 vaccines against symptomatic disease in adults, with strong 2-dose protection., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Deverick Anderson is the owner of Infection Control Education for Major Sports, LLC, and reports grants from the Agency for Healthcare Research and Quality and personal fees from UpToDate, outside the submitted work. Ghinwa Dumyati reports grants from Pfizer and personal fees from Roche Diagnostics. Gregory Moran reports grants from I-Mab Biopharma and BeiGene and personal fees from Light AI. Mark Steele reports personal fees from Light AI, during the conduct of the study. No other potential conflicts of interest were disclosed.

Importance: Hospital antimicrobial consumption data are widely available; however, large-scale assessments of the quality of antimicrobial use in US hospitals are limited., Objective: To evaluate the appropriateness of antimicrobial use for hospitalized patients treated for community-acquired pneumonia (CAP) or urinary tract infection (UTI) present at admission or for patients who had received fluoroquinolone or intravenous vancomycin treatment., Design, Setting, and Participants: This cross-sectional study included data from a prevalence survey of hospitalized patients in 10 Emerging Infections Program sites. Random samples of inpatients on hospital survey dates from May 1 to September 30, 2015, were identified. Medical record data were collected for eligible patients with 1 or more of 4 treatment events (CAP, UTI, fluoroquinolone treatment, or vancomycin treatment), which were selected on the basis of common infection types reported and antimicrobials given to patients in the prevalence survey. Data were analyzed from August 1, 2017, to May 31, 2020., Exposure: Antimicrobial treatment for CAP or UTI or with fluoroquinolones or vancomycin., Main Outcomes and Measures: The percentage of antimicrobial use that was supported by medical record data (including infection signs and symptoms, microbiology test results, and antimicrobial treatment duration) or for which some aspect of use was unsupported. Unsupported antimicrobial use was defined as (1) use of antimicrobials to which the pathogen was not susceptible, use in the absence of documented infection signs or symptoms, or use without supporting microbiologic data; (2) use of antimicrobials that deviated from recommended guidelines; or (3) use that exceeded the recommended duration., Results: Of 12 299 patients, 1566 patients (12.7%) in 192 hospitals were included; the median age was 67 years (interquartile range, 53-79 years), and 864 (55.2%) were female. A total of 219 patients (14.0%) were included in the CAP analysis, 452 (28.9%) in the UTI analysis, 550 (35.1%) in the fluoroquinolone analysis, and 403 (25.7%) in the vancomycin analysis; 58 patients (3.7%) were included in both fluoroquinolone and vancomycin analyses. Overall, treatment was unsupported for 876 of 1566 patients (55.9%; 95% CI, 53.5%-58.4%): 110 of 403 (27.3%) who received vancomycin, 256 of 550 (46.6%) who received fluoroquinolones, 347 of 452 (76.8%) with a diagnosis of UTI, and 174 of 219 (79.5%) with a diagnosis of CAP. Among patients with unsupported treatment, common reasons included excessive duration (103 of 174 patients with CAP [59.2%]) and lack of documented infection signs or symptoms (174 of 347 patients with UTI [50.1%])., Conclusions and Relevance: The findings suggest that standardized assessments of hospital antimicrobial prescribing quality can be used to estimate the appropriateness of antimicrobial use in large groups of hospitals. These assessments, performed over time, may inform evaluations of the effects of antimicrobial stewardship initiatives nationally.

Heteroresistance is a form of antibiotic resistance where a bacterial strain is comprised of a minor resistant subpopulation and a majority susceptible subpopulation. We showed previously that colistin heteroresistance can mediate the failure of colistin therapy in an in vivo infection model, even for isolates designated susceptible by clinical diagnostics. We sought to characterize the extent of colistin heteroresistance among the highly drug-resistant carbapenem-resistant Enterobacterales (CRE). We screened 408 isolates for colistin heteroresistance. These isolates were collected between 2012 and 2015 in eight U.S. states as part of active surveillance for CRE. Colistin heteroresistance was detected in 10.1% (41/408) of isolates, and it was more common than conventional homogenous resistance (7.1%, 29/408). Most (93.2%, 38/41) of these heteroresistant isolates were classified as colistin susceptible by standard clinical diagnostic testing. The frequency of colistin heteroresistance was greatest in 2015, the last year of the study. This was especially true among Enterobacter isolates, of which specific species had the highest rates of heteroresistance. Among Klebsiella pneumoniae isolates, which were the majority of isolates tested, there was a closely related cluster of colistin-heteroresistant ST-258 isolates found mostly in Georgia. However, cladistic analysis revealed that, overall, there was significant diversity in the genetic backgrounds of heteroresistant K. pneumoniae isolates. These findings suggest that due to being largely undetected in the clinic, colistin heteroresistance among CRE is underappreciated in the United States. IMPORTANCE Heteroresistance is an underappreciated phenomenon that may be the cause of some unexplained antibiotic treatment failures. Misclassification of heteroresistant isolates as susceptible may lead to inappropriate therapy. Heteroresistance to colistin was more common than conventional resistance and was overwhelmingly misclassified as susceptibility by clinical diagnostic testing. Higher proportions of colistin heteroresistance observed in certain Enterobacter species and clustering among heteroresistant Klebsiella pneumoniae strains may inform colistin treatment recommendations. Overall, the rate of colistin nonsusceptibility was more than double the level detected by clinical diagnostics, suggesting that the prevalence of colistin nonsusceptibility among CRE may be higher than currently appreciated in the United States., (Copyright © 2021 Band et al.)

We assessed viral co-infections in 155 patients with community-associated Clostridioides difficile infection in five U.S. sites during December 2012-February 2013. Eighteen patients (12%) tested positive for norovirus (n = 10), adenovirus (n = 4), rotavirus (n = 3), or sapovirus (n = 1). Co-infected patients were more likely than non-co-infected patients to have nausea or vomiting (56% vs 31%; p = 0.04), suggesting that viral co-pathogens contributed to symptoms in some patients. There were no significant differences in prior healthcare or medication exposures or in CDI complications., Competing Interests: No authors have competing interests.

Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae pose significant treatment and infection prevention challenges. Escherichia coli sequence type (ST) 131 associated with the bla CTX-M-15 gene has been the dominant lineage of ESBL-producing E. coli in the US and worldwide. In this study, our objective was to determine the β-lactamase profile, means of dissemination, prevalence, and the clonal identity of ESBL-producing E. coli in our region of Western New York. Whole-genome SNP-based phylogenomics was used to assess 89 ceftriaxone-resistant (CTR) E. coli . Isolates were collected from both inpatients and outpatients and from urine and sterile-sites over a 2 month period in 2017 or throughout the year, respectively. ST131 was the predominant ST (46.0%), followed by ST38 (15.7%). The bla CTX-M-15 gene was commonly found in 53.7% of ST131 isolates, whereas the bla CTX-M-27 gene was found in 26.8% of ST131, though was significantly associated with ST38, and was found in 71.4% of those strains. When compared to ST131, ST38 E. coli exhibited increased frequency of resistance to nitrofurantoin and decreased frequency of resistance to ciprofloxacin and ampicillin-sulbactam. Using Nanopore long-read sequencing technology, an analysis of the ESBL genetic context showed that the bla CTX-M-15 gene was chromosomal in 68.2% of ST131, whereas the bla CTX-M-27 gene was plasmid-borne in all ST131 and 90% of ST38 isolates. Notably, the bla CTX-M-27 gene in ST38 resided on highly-related (99.0-100.0% identity and 65.0-98.0% query coverage) conjugative IncF plasmids of distinct plasmid multi-locus sequence types (pMLSTs) from those in ST131. Furthermore, ST131 and ST38 were found to harbor different antibiotic resistance gene and virulence factor profiles. These findings raise the possibility of an emerging ESBL-producing E. coli lineage in our region., (Copyright © 2020 Mostafa, Cameron, Taffner, Wang, Malek, Dumyati, Hardy and Pecora.)

Importance: Current information on the characteristics of patients who develop sepsis may help in identifying opportunities to improve outcomes. Most recent studies of sepsis epidemiology have focused on changes in incidence or have used administrative data sets that provided limited patient-level data., Objective: To describe sepsis epidemiology in adults., Design, Setting, and Participants: This retrospective cohort study reviewed the medical records, death certificates, and hospital discharge data of adult patients with sepsis or septic shock who were discharged from the hospital between October 1, 2014, and September 30, 2015. The convenience sample was obtained from hospitals in the Centers for Disease Control and Prevention Emerging Infections Program in 10 states (California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee). Patients 18 years and older with discharge diagnosis codes for severe sepsis or septic shock were randomly selected. Data were analyzed between May 1, 2018, and January 31, 2019., Main Outcomes and Measures: The population's demographic characteristics, health care exposures, and sepsis-associated infections and pathogens were described, and risk factors for death within 30 days after sepsis diagnosis were assessed., Results: Among 1078 adult patients with sepsis (569 men [52.8%]; median age, 64 years [interquartile range, 53-75 years]), 973 patients (90.3%) were classified as having community-onset sepsis (ie, sepsis diagnosed within 3 days of hospital admission). In total, 654 patients (60.7%) had health care exposures before their hospital admission for sepsis; 260 patients (24.1%) had outpatient encounters in the 7 days before admission, and 447 patients (41.5%) received medical treatment, including antimicrobial drugs, chemotherapy, wound care, dialysis, or surgery, in the 30 days before admission. A pathogen associated with sepsis was found in 613 patients (56.9%); the most common pathogens identified were Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Clostridioides difficile. After controlling for other factors, an association was found between underlying comorbidities, such as cirrhosis (odds ratio, 3.59; 95% CI, 2.03-6.32), immunosuppression (odds ratio, 2.52; 95% CI, 1.81-3.52), vascular disease (odds ratio, 1.54; 95% CI, 1.10-2.15), and 30-day mortality., Conclusions and Relevance: Most adults experienced sepsis onset outside of the hospital and had recent encounters with the health care system. A sepsis-associated pathogen was identified in more than half of patients. Future efforts to improve sepsis outcomes may benefit from examination of health maintenance practices and recent health care exposures as potential opportunities among high-risk patients.

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

Pseudomonas aeruginosa is intrinsically resistant to many antimicrobial drugs, making carbapenems crucial in clinical management. During July-October 2015 in the United States, we piloted laboratory-based surveillance for carbapenem-resistant P. aeruginosa (CRPA) at sentinel facilities in Georgia, New Mexico, Oregon, and Tennessee, and population-based surveillance in Monroe County, NY. An incident case was the first P. aeruginosa isolate resistant to antipseudomonal carbapenems from a patient in a 30-day period from any source except the nares, rectum or perirectal area, or feces. We found 294 incident cases among 274 patients. Cases were most commonly identified from respiratory sites (120/294; 40.8%) and urine (111/294; 37.8%); most (223/280; 79.6%) occurred in patients with healthcare facility inpatient stays in the prior year. Genes encoding carbapenemases were identified in 3 (2.3%) of 129 isolates tested. The burden of CRPA was high at facilities under surveillance, but carbapenemase-producing CRPA were rare.

The convergence of hypervirulence and multidrug resistance in Klebsiella pneumoniae is a significant concern. Here, we report the first screen for hypermucoviscosity, a trait associated with increased virulence, using a U.S. surveillance collection of carbapenem-resistant (CR) K. pneumoniae isolates. We identified one hypermucoviscous isolate, which carried a gene encoding the KPC-3 carbapenemase, among numerous resistance genes. The strain further exhibited colistin heteroresistance undetected by diagnostics. This convergence of diverse resistance mechanisms and increased virulence underscores the need for enhanced K. pneumoniae surveillance., (Copyright © 2019 American Society for Microbiology.)

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

International guidelines recommend using local susceptibility data to direct empiric therapy for acute uncomplicated cystitis. We evaluated outpatient urinary isolate susceptibility trends in New York State. Nitrofurantoin had the lowest resistance prevalence whereas trimethoprim-sulfamethoxazole and fluoroquinolones had higher prevalences. This study highlights the need for local outpatient antimicrobial stewardship programs.

In the United States, age-adjusted opioid overdose death rates increased by >200% during 1999-2015, and heroin overdose death rates increased nearly 300% during 2011-2015 (1). During 2011-2013, the rate of heroin use within the past year among U.S. residents aged ≥12 years increased 62.5% overall and 114.3% among non-Hispanic whites, compared with 2002-2004 (2). Increases in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections related to increases in injection drug use have been recently highlighted (3,4); likewise, invasive bacterial infections, including endocarditis, osteomyelitis, and skin and soft tissue infections, have increased in areas where the opioid epidemic is expanding (5-7). To assess the effects of the opioid epidemic on invasive methicillin-resistant Staphylococcus aureus (MRSA) infections during 2005-2016, surveillance data from CDC's Emerging Infections Program (EIP) were analyzed (8). Persons who inject drugs were estimated to be 16.3 times more likely to develop invasive MRSA infections than others. The proportion of invasive MRSA cases that occurred among persons who inject drugs increased from 4.1% in 2011 to 9.2% in 2016. Infection types were frequently those associated with nonsterile injection drug use. Continued increases in nonsterile injection drug use are likely to result in increases in invasive MRSA infections, underscoring the importance of public health measures to curb the opioid epidemic., Competing Interests: William Schaffner reports personal fees from Pfizer, Merck, Dynavax, Seqirus, SutroVax, and Shionogi outside the submitted work. No other conflicts of interest were reported.

In healthcare settings, Acinetobacter spp. bacteria commonly demonstrate antimicrobial resistance, making them a major treatment challenge. Nearly half of Acinetobacter organisms from clinical cultures in the United States are nonsusceptible to carbapenem antimicrobial drugs. During 2012-2015, we conducted laboratory- and population-based surveillance in selected metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee to determine the incidence of carbapenem-nonsusceptible A. baumannii cultured from urine or normally sterile sites and to describe the demographic and clinical characteristics of patients and cases. We identified 621 cases in 537 patients; crude annual incidence was 1.2 cases/100,000 persons. Among 598 cases for which complete data were available, 528 (88.3%) occurred among patients with exposure to a healthcare facility during the preceding year; 506 (84.6%) patients had an indwelling device. Although incidence was lower than for other healthcare-associated pathogens, cases were associated with substantial illness and death.

Background: An increasing proportion of Clostridium difficile infections (CDI) in the United States are community-associated (CA). We conducted a case-control study to identify CA-CDI risk factors., Methods: We enrolled participants from 10 US sites during October 2014-March 2015. Case patients were defined as persons age ≥18 years with a positive C. difficile specimen collected as an outpatient or within 3 days of hospitalization who had no admission to a health care facility in the prior 12 weeks and no prior CDI diagnosis. Each case patient was matched to one control (persons without CDI). Participants were interviewed about relevant exposures; multivariate conditional logistic regression was performed., Results: Of 226 pairs, 70.4% were female and 52.2% were ≥60 years old. More case patients than controls had prior outpatient health care (82.1% vs 57.9%; P < .0001) and antibiotic (62.2% vs 10.3%; P < .0001) exposures. In multivariate analysis, antibiotic exposure-that is, cephalosporin (adjusted matched odds ratio [AmOR], 19.02; 95% CI, 1.13-321.39), clindamycin (AmOR, 35.31; 95% CI, 4.01-311.14), fluoroquinolone (AmOR, 30.71; 95% CI, 2.77-340.05) and beta-lactam and/or beta-lactamase inhibitor combination (AmOR, 9.87; 95% CI, 2.76-340.05),-emergency department visit (AmOR, 17.37; 95% CI, 1.99-151.22), white race (AmOR 7.67; 95% CI, 2.34-25.20), cardiac disease (AmOR, 4.87; 95% CI, 1.20-19.80), chronic kidney disease (AmOR, 12.12; 95% CI, 1.24-118.89), and inflammatory bowel disease (AmOR, 5.13; 95% CI, 1.27-20.79) were associated with CA-CDI., Conclusions: Antibiotics remain an important risk factor for CA-CDI, underscoring the importance of appropriate outpatient prescribing. Emergency departments might be an environmental source of CDI; further investigation of their contribution to CDI transmission is needed.

Background: Sepsis is a serious and often fatal clinical syndrome, resulting from infection. Information on patient demographics, risk factors, and infections leading to sepsis is needed to integrate comprehensive sepsis prevention, early recognition, and treatment strategies., Methods: To describe characteristics of patients with sepsis, CDC and partners conducted a retrospective chart review in four New York hospitals. Random samples of medical records from adult and pediatric patients with administrative codes for severe sepsis or septic shock were reviewed., Results: Medical records of 246 adults and 79 children (aged birth to 17 years) were reviewed. Overall, 72% of patients had a health care factor during the 30 days before sepsis admission or a selected chronic condition likely to require frequent medical care. Pneumonia was the most common infection leading to sepsis. The most common pathogens isolated from blood cultures were Escherichia coli in adults aged ≥18 years, Klebsiella spp. in children aged ≥1 year, and Enterococcus spp. in infants aged <1 year; for 106 (33%) patients, no pathogen was isolated. Eighty-two (25%) patients with sepsis died, including 65 (26%) adults and 17 (22%) infants and children., Conclusions: Infection prevention strategies (e.g., vaccination, reducing transmission of pathogens in health care environments, and appropriate management of chronic diseases) are likely to have a substantial impact on reducing sepsis. CDC, in partnership with organizations representing clinicians, patients, and other stakeholders, is launching a comprehensive campaign to demonstrate that prevention of infections that cause sepsis, and early recognition of sepsis, are integral to overall patient safety.

Preventing transmission of carbapenemase-producing, carbapenem-resistant Enterobacteriaceae (CP-CRE) is a public health priority. A phenotype-based definition that reliably identifies CP-CRE while minimizing misclassification of non-CP-CRE could help prevention efforts. To assess possible definitions, we evaluated enterobacterial isolates that had been tested and deemed nonsusceptible to >1 carbapenem at US Emerging Infections Program sites. We determined the number of non-CP isolates that met (false positives) and CP isolates that did not meet (false negatives) the Centers for Disease Control and Prevention CRE definition in use during our study: 30% (94/312) of CRE had carbapenemase genes, and 21% (14/67) of Klebsiella pneumoniae carbapenemase-producing Klebsiella isolates had been misclassified as non-CP. A new definition requiring resistance to 1 carbapenem rarely missed CP strains, but 55% of results were false positive; adding the modified Hodge test to the definition decreased false positives to 12%. This definition should be considered for use in carbapenemase-producing CRE surveillance and prevention.

The Healthcare-Associated Infections Community Interface (HAIC), launched in 2009, is the newest major activity of the Emerging Infections Program. The HAIC activity addresses population- and laboratory-based surveillance for Clostridium difficile infections, candidemia, and multidrug-resistant gram-negative bacilli. Other activities include special projects: the multistate Healthcare-Associated Infections and Antimicrobial Use Prevalence Survey and projects that evaluate new approaches for improving surveillance. The HAIC activity has provided information about the epidemiology and adverse health outcomes of health care-associated infections and antimicrobial drug use in the United States and informs efforts to improve patient safety through prevention of these infections.

Background.  Antibiotic use predisposes patients to Clostridium difficile infections (CDI), and approximately 32% of these infections are community-associated (CA) CDI. The population-level impact of antibiotic use on adult CA-CDI rates is not well described. Methods.  We used 2011 active population- and laboratory-based surveillance data from 9 US geographic locations to identify adult CA-CDI cases, defined as C difficile-positive stool specimens (by toxin or molecular assay) collected from outpatients or from patients ≤3 days after hospital admission. All patients were surveillance area residents and aged ≥20 years with no positive test ≤8 weeks prior and no overnight stay in a healthcare facility ≤12 weeks prior. Outpatient oral antibiotic prescriptions dispensed in 2010 were obtained from the IMS Health Xponent database. Regression models examined the association between outpatient antibiotic prescribing and adult CA-CDI rates. Methods.  Healthcare providers prescribed 5.2 million courses of antibiotics among adults in the surveillance population in 2010, for an average of 0.73 per person. Across surveillance sites, antibiotic prescription rates (0.50-0.88 prescriptions per capita) and unadjusted CA-CDI rates (40.7-139.3 cases per 100 000 persons) varied. In regression modeling, reducing antibiotic prescribing rates by 10% among persons ≥20 years old was associated with a 17% (95% confidence interval, 6.0%-26.3%; P = .032) decrease in CA-CDI rates after adjusting for age, gender, race, and type of diagnostic assay. Reductions in prescribing penicillins and amoxicillin/clavulanic acid were associated with the greatest decreases in CA-CDI rates. Conclusions and Relevance.  Community-associated CDI prevention should include reducing unnecessary outpatient antibiotic use. A modest reduction of 10% in outpatient antibiotic prescribing can have a disproportionate impact on reducing CA-CDI rates.

Objective: The current central line-associated bloodstream infection (CLABSI) surveillance rate calculation does not account for multiple concurrent central venous catheters (CVCs). The presence of multiple CVCs creates more points of entry into the bloodstream, potentially increasing CLABSI risk. Multiple CVCs may be used in sicker patients, making it difficult to separate the relative contributions of multiple CVCs and comorbidities to CLABSI risk. We explored the relative impact of multiple CVCs, patient comorbidities, and disease severity on the risk of CLABSI., Design: Case-control study., Setting: A total of 197 case patients and 201 control subjects with a CVC inserted during hospitalization at a tertiary care academic medical center from January 1, 2008, to December 31, 2010., Methods: Multiple CVCs was the exposure of interest; the primary outcome was CLABSI. Multivariable logistic regression was conducted to estimate odds ratios (ORs) and 95% confidence intervals (CIs) describing the association between CLABSI and multiple CVCs with and without controlling for Acute Physiology and Chronic Health Evaluation (APACHE) II and Charlson comorbidity index (CCI) scores as measures of disease severity and patient comorbidities, respectively., Results: Patients with multiple CVCs (n = 78) showed a 4.2 (95% CI, 2.2-8.4) times greater risk of CLABSI compared with patients with 1 CVC after adjusting for CLABSI risk factors. When including APACHE II and CCI scores, multiple CVCs remained an independent risk factor for CLABSI (OR, 3.4 [95% CI, 1.7-6.9])., Conclusions: Multiple CVCs is an independent risk factor for CLABSI even after adjusting for severity of illness. Adjustment for this risk may be necessary to accurately compare rates between hospitals.

We describe the adoption of nucleic acid amplification tests (NAAT) for Clostridium difficile diagnosis and their impact on stool rejection policies and C. difficile positivity rates. Of the laboratories with complete surveys, 51 (43%) reported using NAAT in 2011. Laboratories using NAAT had stricter rejection policies and increased positivity rates.

Objective: To evaluate the accuracy of weekly sampling of central line-associated bloodstream infection (CLABSI) denominator data to estimate central line-days (CLDs)., Design: Obtained CLABSI denominator logs showing daily counts of patient-days and CLD for 6-12 consecutive months from participants and CLABSI numerators and facility and location characteristics from the National Healthcare Safety Network (NHSN)., Setting and Participants: Convenience sample of 119 inpatient locations in 63 acute care facilities within 9 states participating in the Emerging Infections Program., Methods: Actual CLD and estimated CLD obtained from sampling denominator data on all single-day and 2-day (day-pair) samples were compared by assessing the distributions of the CLD percentage error. Facility and location characteristics associated with increased precision of estimated CLD were assessed. The impact of using estimated CLD to calculate CLABSI rates was evaluated by measuring the change in CLABSI decile ranking., Results: The distribution of CLD percentage error varied by the day and number of days sampled. On average, day-pair samples provided more accurate estimates than did single-day samples. For several day-pair samples, approximately 90% of locations had CLD percentage error of less than or equal to ±5%. A lower number of CLD per month was most significantly associated with poor precision in estimated CLD. Most locations experienced no change in CLABSI decile ranking, and no location's CLABSI ranking changed by more than 2 deciles., Conclusions: Sampling to obtain estimated CLD is a valid alternative to daily data collection for a large proportion of locations. Development of a sampling guideline for NHSN users is underway.

Background: Long-term care facility (LTCF) residents are at increased risk of Clostridium difficile infection (CDI). However, little is known about the incidence, recurrence, and severity of CDI in LTCFs or the extent to which acute care exposure contributes to CDI in LTCFs. We describe the epidemiology of CDI in a cohort of LTCF residents in Monroe County, New York, where recent estimates suggest a CDI incidence in hospitals of 9.2 cases per 10,000 patient-days., Design: Population-based surveillance study., Setting: Monroe County, New York. Patients. LTCF residents with onset of CDI while in the LTCF or less than 4 calendar-days after hospital admission from the LTCF from January 1 through December 31, 2010., Methods: We conducted surveillance for CDI in residents of 33 LTCFs. A CDI case was defined as a stool specimen positive for C. difficile obtained from a patient without a C. difficile-positive specimen in the previous 8 weeks; recurrence was defined as a stool specimen positive for C. difficile obtained between 2 and 8 weeks after the last C. difficile-positive stool specimen., Results: There were 425 LTCF-onset cases and 184 recurrences, which yielded an incidence of 2.3 cases per 10,000 resident-days (interquartile range [IQR], 1.2-3.3) and a recurrence rate of 1.0 case per 10,000 resident-days (IQR, 0.3-1.4). The cases occurred in 394 LTCF residents, and 52% of these residents developed CDI within 4 weeks after hospital discharge. Hospitalization for CDI occurred in 70 cases (16%). Of those cases that involved hospitalization for CDI, 70% were severe CDI, and 23% ended in death within 30 days after hospital admission., Conclusion: CDI incidence in Monroe County LTCFs is one-fourth the incidence among hospitalized patients. Approximately 50% of LTCF-onset cases occurred more than 4 weeks after hospital discharge, which emphasizes that prevention of CDI transmission should go beyond acute care settings.

We conducted active sentinel surveillance in Monroe County, New York, USA, to compare incidence of community-associated Clostridium difficile infections (CA-CDIs) with that of health care-associated infections (HA-CDIs) and identify exposure and strain type differences between CA and HA cases. Patients positive for C. difficile toxin and with no documented health care exposure in the previous 12 weeks were defined as possible CA case-patients. Patients with onset in a health care setting or recent health care exposure were defined as HA case-patients. Eighteen percent of CDIs were CA; 76% were in persons who reported antimicrobial drug use in the 12 weeks before CDI diagnosis. Strain type distribution was similar between CA and HA cases; North American pulsed-field 1 was the primary strain (31% CA, 42% HA; p = 0.34). CA-CDI is an emergent disease affecting patients recently exposed to antimicrobial drugs. Community strains are similar to those found in health care settings.

Six hospitals joined to perform surveillance for central line-associated bloodstream infections outside of intensive care units (ICUs). To facilitate the counting of device-days, a weekly measure of the device use ratio was validated as an estimate of central line-days outside the ICU.

We describe clinical and laboratory characteristics of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections with vancomycin MICs of 2 μg/ml and compare heteroresistant-intermediate S. aureus (hVISA) to non-hVISA. Health care-associated community-onset infections were the most common and resulted in frequent complications and relapses. hVISA-infected patients were more likely to have been hospitalized in the year prior to MRSA culture.

This study characterizes 1,984 methicillin-resistant Staphylococcus aureus (MRSA) isolates collected in 2005 and 2006 from normally sterile sites in patients with invasive MRSA infection. These isolates represent a convenience sample of all invasive MRSA cases reported as part of the Active Bacterial Core surveillance system in eight states in the United States. The majority of isolates were from blood (83.8%), joints (4.1%), and bone (4.2%). Isolates were characterized by pulsed-field gel electrophoresis (PFGE); SCCmec typing; susceptibility to 15 antimicrobial agents; and PCR analysis of staphylococcal enterotoxin A (SEA) to SEH, toxic shock syndrome toxin 1, and Panton-Valentine leukocidin. Thirteen established PFGE types were recognized among these isolates, although USA100 and USA300 predominated, accounting for 53.2% and 31.4% of the isolates, respectively. As expected, isolates from hospital onset cases were predominantly USA100, whereas those from community-associated cases were predominantly USA300. USA100 isolates were diverse (Simpson's discriminatory index [DI] = 0.924); generally positive only for enterotoxin D (74.5%); and resistant to clindamycin (98.6%), erythromycin (99.0%), and levofloxacin (99.6%), in addition to beta-lactam agents. USA300 isolates were less diverse (DI = 0.566), positive for Panton-Valentine leukocidin (96.3%), and resistant to erythromycin (94.1%) and, less commonly, levofloxacin (54.6%), in addition to beta-lactam agents. This collection provides a reference collection of MRSA isolates associated with invasive disease, collected in 2005 and 2006 in the United States, for future comparison and ongoing studies.

To determine frequency of methicillin-resistant Staphylococcus aureus infections caused by strains typically associated with community-acquired infections (USA300) among persons with healthcare-related risk factors (HRFs), we evaluated surveillance data. Of patients with HRFs, 18%-28% had a "community-associated" strain, primarily USA300; of patients without HRFs, 26% had a "healthcare-associated" strain, typically USA100.