Carbapenem-resistant Acinetobacter baumannii complex in the United States - an epidemiological and molecular description of isolates collected through the Emerging Infections Program, 2019.

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 blaOXA-23 or blaOXA-24/40; however, an isolate with blaNDM 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.

Trends in Incidence of Carbapenem-Resistant Enterobacterales in 7 US Sites, 2016─2020.

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.

Carbapenem-Resistant enterobacterales in individuals with and without health care risk factors -Emerging infections program, United States, 2012-2015.

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.

Epidemiology of extended-spectrum ß-lactamase-producing Enterobacterales in five US sites participating in the Emerging Infections Program, 2017.

OBJECTIVE: The incidence of infections from extended-spectrum ß-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.

Molecular Characterization of Carbapenem-Resistant Enterobacterales Collected in the United States.

Carbapenem-resistant Enterobacterales (CRE) are a growing public health concern due to resistance to multiple antibiotics and potential to cause health care-associated infections with high mortality. Carbapenemase-producing CRE are of particular concern given that carbapenemase-encoding genes often are located on mobile genetic elements that may spread between different organisms and species. In this study, we performed phenotypic and genotypic characterization of CRE collected at eight U.S. sites participating in active population- and laboratory-based surveillance of carbapenem-resistant organisms. Among 421 CRE tested, the majority were isolated from urine (n = 349, 83%). Klebsiella pneumoniae was the most common organism (n = 265, 63%), followed by Enterobacter cloacae complex (n = 77, 18%) and Escherichia coli (n = 50, 12%). Of 419 isolates analyzed by whole genome sequencing, 307 (73%) harbored a carbapenemase gene; variants of blaKPC predominated (n = 299, 97%). The occurrence of carbapenemase-producing K. pneumoniae, E. cloacae complex, and E. coli varied by region; the predominant sequence type within each genus was ST258, ST171, and ST131, respectively. None of the carbapenemase-producing CRE isolates displayed resistance to all antimicrobials tested; susceptibility to amikacin and tigecycline was generally retained.

Assessment of the Appropriateness of Antimicrobial Use in US Hospitals.

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.

Antimicrobial Use in US Hospitals: Comparison of Results From Emerging Infections Program Prevalence Surveys, 2015 and 2011.

BACKGROUND: In the 2011 US hospital prevalence survey of healthcare-associated infections and antimicrobial use 50% of patients received antimicrobial medications on the survey date or day before. More hospitals have since established antimicrobial stewardship programs. We repeated the survey in 2015 to determine antimicrobial use prevalence and describe changes since 2011. METHODS: The Centers for Disease Control and Prevention's Emerging Infections Program sites in 10 states each recruited ≤25 general and women's and children's hospitals. Hospitals selected a survey date from May-September 2015. Medical records for a random patient sample on the survey date were reviewed to collect data on antimicrobial medications administered on the survey date or day before. Percentages of patients on antimicrobial medications were compared; multivariable log-binomial regression modeling was used to evaluate factors associated with antimicrobial use. RESULTS: Of 12 299 patients in 199 hospitals, 6084 (49.5%; 95% CI, 48.6-50.4%) received antimicrobials. Among 148 hospitals in both surveys, overall antimicrobial use prevalence was similar in 2011 and 2015, although the percentage of neonatal critical care patients on antimicrobials was lower in 2015 (22.8% vs 32.0% [2011]; P = .006). Fluoroquinolone use was lower in 2015 (10.1% of patients vs 11.9% [2011]; P < .001). Third- or fourth-generation cephalosporin use was higher (12.2% vs 10.7% [2011]; P = .002), as was carbapenem use (3.7% vs 2.7% [2011]; P < .001). CONCLUSIONS: Overall hospital antimicrobial use prevalence was not different in 2011 and 2015; however, differences observed in selected patient or antimicrobial groups may provide evidence of stewardship impact.

Changes in Prevalence of Health Care-Associated Infections in U.S. Hospitals.

BACKGROUND: A point-prevalence survey that was conducted in the United States in 2011 showed that 4% of hospitalized patients had a health care-associated infection. We repeated the survey in 2015 to assess changes in the prevalence of health care-associated infections during a period of national attention to the prevention of such infections. METHODS: At Emerging Infections Program sites in 10 states, we recruited up to 25 hospitals in each site area, prioritizing hospitals that had participated in the 2011 survey. Each hospital selected 1 day on which a random sample of patients was identified for assessment. Trained staff reviewed medical records using the 2011 definitions of health care-associated infections. We compared the percentages of patients with health care-associated infections and performed multivariable log-binomial regression modeling to evaluate the association of survey year with the risk of health care-associated infections. RESULTS: In 2015, a total of 12,299 patients in 199 hospitals were surveyed, as compared with 11,282 patients in 183 hospitals in 2011. Fewer patients had health care-associated infections in 2015 (394 patients [3.2%; 95% confidence interval {CI}, 2.9 to 3.5]) than in 2011 (452 [4.0%; 95% CI, 3.7 to 4.4]) (P<0.001), largely owing to reductions in the prevalence of surgical-site and urinary tract infections. Pneumonia, gastrointestinal infections (most of which were due to Clostridium difficile [now Clostridioides difficile]), and surgical-site infections were the most common health care-associated infections. Patients' risk of having a health care-associated infection was 16% lower in 2015 than in 2011 (risk ratio, 0.84; 95% CI, 0.74 to 0.95; P=0.005), after adjustment for age, presence of devices, days from admission to survey, and status of being in a large hospital. CONCLUSIONS: The prevalence of health care-associated infections was lower in 2015 than in 2011. To continue to make progress in the prevention of such infections, prevention strategies against C. difficile infection and pneumonia should be augmented. (Funded by the Centers for Disease Control and Prevention.).

Carbapenem-Nonsusceptible Acinetobacter baumannii, 8 US Metropolitan Areas, 2012-2015.

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.

Outbreak of group A Streptococcus infections in an outpatient wound clinic-Colorado, 2014.

BACKGROUND: In September 2014, wound clinic A reported a cluster of group A Streptococcus (GAS) infections to public health authorities. Although clinic providers were individually licensed, the clinic, affiliated with hospital A, was not licensed or subject to regulation. We investigated to identify cases, determine risk factors, and implement control measures. METHODS: A case was defined as GAS isolation from a wound or blood specimen during March 28-November 19, 2014, from a patient treated at wound clinic A or by a wound clinic A provider within the previous 7 days. All wound clinic A staff were screened for GAS carriage. Wound care procedures were assessed for adherence to infection control principles and possible GAS transmission routes. RESULTS: We identified 16 patients with 19 unique infections: 9 (56%) patients required hospitalization, and 7 (44%) required surgical debridement procedures. One patient died. Six (37%) patients received negative pressure wound therapy at GAS onset. Staff self-screening found no GAS carriers. Breaches in infection control and poor wound care practices were widespread. CONCLUSIONS: This GAS outbreak was associated with a wound care clinic not subject to state or federal regulation. Lapses in infection control practices and inadequate oversight contributed to the outbreak.

Epidemiology of Carbapenem-Resistant Enterobacteriaceae in 7 US Communities, 2012-2013.

IMPORTANCE: Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly reported worldwide as a cause of infections with high-mortality rates. Assessment of the US epidemiology of CRE is needed to inform national prevention efforts. OBJECTIVE: To determine the population-based CRE incidence and describe the characteristics and resistance mechanism associated with isolates from 7 US geographical areas. DESIGN, SETTING, AND PARTICIPANTS: Population- and laboratory-based active surveillance of CRE conducted among individuals living in 1 of 7 US metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, and Oregon. Cases of CRE were defined as carbapenem-nonsusceptible (excluding ertapenem) and extended-spectrum cephalosporin-resistant Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae complex, Klebsiella pneumoniae, or Klebsiella oxytoca that were recovered from sterile-site or urine cultures during 2012-2013. Case records were reviewed and molecular typing for common carbapenemases was performed. EXPOSURES: Demographics, comorbidities, health care exposures, and culture source and location. MAIN OUTCOMES AND MEASURES: Population-based CRE incidence, site-specific standardized incidence ratios (adjusted for age and race), and clinical and microbiological characteristics. RESULTS: Among 599 CRE cases in 481 individuals, 520 (86.8%; 95% CI, 84.1%-89.5%) were isolated from urine and 68 (11.4%; 95% CI, 8.8%-13.9%) from blood. The median age was 66 years (95% CI, 62.1-65.4 years) and 284 (59.0%; 95% CI, 54.6%-63.5%) were female. The overall annual CRE incidence rate per 100<000 population was 2.93 (95% CI, 2.65-3.23). The CRE standardized incidence ratio was significantly higher than predicted for the sites in Georgia (1.65 [95% CI, 1.20-2.25]; P < .001), Maryland (1.44 [95% CI, 1.06-1.96]; P = .001), and New York (1.42 [95% CI, 1.05-1.92]; P = .048), and significantly lower than predicted for the sites in Colorado (0.53 [95% CI, 0.39-0.71]; P < .001), New Mexico (0.41 [95% CI, 0.30-0.55]; P = .01), and Oregon (0.28 [95% CI, 0.21-0.38]; P < .001). Most cases occurred in individuals with prior hospitalizations (399/531 [75.1%; 95% CI, 71.4%-78.8%]) or indwelling devices (382/525 [72.8%; 95% CI, 68.9%-76.6%]); 180 of 322 (55.9%; 95% CI, 50.0%-60.8%) admitted cases resulted in a discharge to a long-term care setting. Death occurred in 51 (9.0%; 95% CI, 6.6%-11.4%) cases, including in 25 of 91 cases (27.5%; 95% CI, 18.1%-36.8%) with CRE isolated from normally sterile sites. Of 188 isolates tested, 90 (47.9%; 95% CI, 40.6%-55.1%) produced a carbapenemase. CONCLUSIONS AND RELEVANCE: In this population- and laboratory-based active surveillance system in 7 states, the incidence of CRE was 2.93 per 100<000 population. Most CRE cases were isolated from a urine source, and were associated with high prevalence of prior hospitalizations or indwelling devices, and discharge to long-term care settings.

Improved Phenotype-Based Definition for Identifying Carbapenemase Producers among Carbapenem-Resistant Enterobacteriaceae.

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.

Prevalence of antimicrobial use in US acute care hospitals, May-September 2011.

IMPORTANCE: Inappropriate antimicrobial drug use is associated with adverse events in hospitalized patients and contributes to the emergence and spread of resistant pathogens. Targeting effective interventions to improve antimicrobial use in the acute care setting requires understanding hospital prescribing practices. OBJECTIVE: To determine the prevalence of and describe the rationale for antimicrobial use in participating hospitals. DESIGN, SETTING, AND PARTICIPANTS: One-day prevalence surveys were conducted in acute care hospitals in 10 states between May and September 2011. Patients were randomly selected from each hospital's morning census on the survey date. Data collectors reviewed medical records retrospectively to gather data on antimicrobial drugs administered to patients on the survey date and the day prior to the survey date, including reasons for administration, infection sites treated, and whether treated infections began in community or health care settings. MAIN OUTCOMES AND MEASURES: Antimicrobial use prevalence, defined as the number of patients receiving antimicrobial drugs at the time of the survey divided by the total number of surveyed patients. RESULTS: Of 11,282 patients in 183 hospitals, 5635 (49.9%; 95% CI, 49.0%-50.9%) were administered at least 1 antimicrobial drug; 77.5% (95% CI, 76.6%-78.3%) of antimicrobial drugs were used to treat infections, most commonly involving the lower respiratory tract, urinary tract, or skin and soft tissues, whereas 12.2% (95% CI, 11.5%-12.8%) were given for surgical and 5.9% (95% CI, 5.5%-6.4%) for medical prophylaxis. Of 7641 drugs to treat infections, the most common were parenteral vancomycin (1103, 14.4%; 95% CI, 13.7%-15.2%), ceftriaxone (825, 10.8%; 95% CI, 10.1%-11.5%), piperacillin-tazobactam (788, 10.3%; 95% CI, 9.6%-11.0%), and levofloxacin (694, 9.1%; 95% CI, 8.5%-9.7%). Most drugs administered to treat infections were given for community-onset infections (69.0%; 95% CI, 68.0%-70.1%) and to patients outside critical care units (81.6%; 95% CI, 80.4%-82.7%). The 4 most common treatment antimicrobial drugs overall were also the most common drugs used for both community-onset and health care facility-onset infections and for infections in patients in critical care and noncritical care locations. CONCLUSIONS AND RELEVANCE: In this cross-sectional evaluation of antimicrobial use in US hospitals, use of broad-spectrum antimicrobial drugs such as piperacillin-tazobactam and drugs such as vancomycin for resistant pathogens was common, including for treatment of community-onset infections and among patients outside critical care units. Further work is needed to understand the settings and indications for which reducing antimicrobial use can be most effectively and safely accomplished.

Carbapenem-resistant Klebsiella pneumoniae producing New Delhi metallo-ß-lactamase at an acute care hospital, Colorado, 2012.

OBJECTIVE: To investigate an outbreak of New Delhi metallo-ß-lactamase (NDM)-producing carbapenem-resistant Enterobacteriaceae (CRE) and determine interventions to interrupt transmission. DESIGN, SETTING, AND PATIENTS: Epidemiologic investigation of an outbreak of NDM-producing CRE among patients at a Colorado acute care hospital. METHODS: Case patients had NDM-producing CRE isolated from clinical or rectal surveillance cultures (SCs) collected during the period January 1, 2012, through October 20, 2012. Case patients were identified through microbiology records and 6 rounds of SCs in hospital units where they had resided. CRE isolates were tested by real-time polymerase chain reaction for blaNDM. Medical records were reviewed for epidemiologic links; relatedness of isolates was evaluated by pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS). Infection control (IC) was assessed through staff interviews and direct observations. RESULTS: Two patients were initially identified with NDM-producing CRE during July-August 2012. A third case patient, admitted in May, was identified through microbiology records review. SC identified 5 additional case patients. Patients had resided in 11 different units before identification. All isolates were highly related by PFGE. WGS suggested 3 clusters of CRE. Combining WGS with epidemiology identified 4 units as likely transmission sites. NDM-producing CRE positivity in certain patients was not explained by direct epidemiologic overlap, which suggests that undetected colonized patients were involved in transmission. CONCLUSIONS: A 4-month outbreak of NDM-producing CRE occurred at a single hospital, highlighting the risk for spread of these organisms. Combined WGS and epidemiologic data suggested transmission primarily occurred on 4 units. Timely SC, combined with targeted IC measures, were likely responsible for controlling transmission.