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Background: The Centers for Disease Control and Prevention’s Emerging Infections Program conducts active laboratory- and population-based surveillance for carbapenem-resistant Enterobacterales (CRE) and extended spectrum beta-lactamase-producing Enterobacterales (ESBL-E). To better understand the U.S. epidemiology of these organisms among children, we determined the incidence of pediatric CRE and ESBL-E cases and described their clinical characteristics. Methods: Surveillance was conducted among children <18 years of age for CRE from 2016–2020 in 10 sites, and for ESBL-E from 2019–2020 in 6 sites. Among catchment-area residents, an incident CRE case was defined as the first isolation of Escherichia coli, Enterobacter cloacae complex, Klebsiella aerogenes, K. oxytoca, or K. pneumoniae in a 30-day period resistant to ≥1 carbapenem from a normally sterile site or urine. An incident ESBL-E case was defined as the first isolation of E. coli, K. pneumoniae, or K. oxytoca in a 30-day period resistant to any third-generation cephalosporin and non-resistant to all carbapenems from a normally sterile site or urine. Case records were reviewed. Results: Among 159 CRE cases, 131 (82.9%) were isolated from urine and 19 (12.0%) from blood; median age was 5 years (IQR 1–10) and 94 (59.1%) were female. Combined CRE incidence rate per 100,000 population by year ranged from 0.47 to 0.87. Among 207 ESBL-E cases, 160 (94.7%) were isolated from urine and 6 (3.6%) from blood; median age was 6 years (IQR 2–15) and 165 (79.7%) were female. Annual ESBL incidence rate per 100,000 population was 26.5 in 2019 and 19.63 in 2020. Incidence rates of CRE and ESBL-E were >2-fold higher in infants (children <1 year) than other age groups. Among those with data available, CRE cases were more likely than ESBL-E cases to have underlying conditions (99/158 [62.7%] versus 59/169 [34.9%], P<0.0001), prior healthcare exposures (74/158 [46.8%] versus 38/169 [22.5%], P<0.0001), and be hospitalized for any reason around time of their culture collection (75/158 [47.5%] versus 38/169 [22.5%], P<0.0001); median duration of admission was 18 days [IQR 3–103] for CRE versus 10 days [IQR 4–43] for ESBL-E. Urinary tract infection was the most frequent infection for CRE (89/158 [56.3%]) and ESBL-E (125/169 [74.0%]) cases. Conclusion: CRE infections occurred less frequently than ESBL-infections in U.S. children but were more often associated with healthcare risk factors and hospitalization. Infants had highest incidence of CRE and ESBL-E. Continued surveillance, infection prevention and control efforts, and antibiotic stewardship outside and within pediatric care are needed
Background: In June 2019, the Maryland Department of Health (MDH) was notified of a hospitalized patient with Candida auris bloodstream infection. The MDH initiated a contact investigation to identify additional patients with C. auris colonization. Many of the contacts had been discharged home from the hospital and were therefore not available for screening. Healthcare facilities in Maryland, Virginia, and Washington, DC, submit patient data to a regional health information exchange (HIE) called the Chesapeake Regional Information System for our Patients (CRISP). CRISP includes a notification system that alerts providers when flagged patients have healthcare encounters. We aimed to use this system to identify discharged C. auris contacts on their next inpatient encounter to rapidly screen them and to detect new cases. Methods:C. auris contacts were defined as patients located on an inpatient unit on the same day, receiving wound care from the same team, or having a procedure in the same operating room on the same day as the index patient or any patients subsequently identified as having C. auris infection or colonization detected either during the normal course of clinical care or through screening. Contacts who remained hospitalized were screened during inpatient point prevalence surveys (PPSs). Contacts discharged to postacute-care facilities were screened by facility staff. Contacts who had been discharged home were flagged in CRISP, and MDH staff received CRISP encounter alerts when these patients were readmitted. MDH staff then contacted the admitting facilities to recommend screening for C. auris. Axilla and groin swabs were collected and tested by rt-PCR at the Mid-Atlantic Regional Antibiotic Resistance Laboratory Network laboratory. Results: As of October 8, 2019, 4,017 contacts were identified. Among these, 936 (23%) contacts at 56 healthcare facilities (33 acute-care hospitals and 23 postacute-care facilities) were screened for C. auris, and 10 patients with C. auris colonization were identified (1.1% of contacts who underwent C. auris screening). Of these, 6 (60%) were identified through CRISP notification and 4 (40%) were identified by PPSs conducted in acute-care hospitals. Conclusions: In this ongoing C. auris outbreak, a large proportion of colonized patients was identified using an electronic encounter notification system within a regional HIE. This approach was effective for identifying opportunities to screen contacts at their next healthcare encounter and can augment other means of case detection, like PPSs. HIEs should incorporate mechanisms to facilitate contact tracing for public health investigations.
Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important cause of healthcare-associated infections with limited treatment options and high mortality. To describe risk factors for mortality, we evaluated characteristics associated with 30-day mortality in patients with CRAB identified through the Emerging Infections Program (EIP). Methods: From January 2012 through December 2017, 8 EIP sites (CO, GA, MD, MN, NM, NY, OR, TN) participated in active, laboratory-, and population-based surveillance for CRAB. An incident case was defined as patient’s first isolation in a 30-day period of A. baumannii complex from sterile sites or urine with resistance to ≥1 carbapenem (excluding ertapenem). Medical records were abstracted. Patients were matched to state vital records to assess mortality within 30 days of incident culture collection. We developed 2 multivariable logistic regression models (1 for sterile site cases and 1 for urine cases) to evaluate characteristics associated with 30-day mortality. Results: We identified 744 patients contributing 863 cases, of which 185 of 863 cases (21.4%) died within 30 days of culture, including 113 of 257 cases (44.0%) isolated from a sterile site and 72 of 606 cases (11.9%) isolated from urine. Among 628 hospitalized cases, death occurred in 159 cases (25.3%). Among hospitalized fatal cases, death occurred after hospital discharge in 27 of 57 urine cases (47.4%) and 21 of 102 cases from sterile sites (20.6%). Among sterile site cases, female sex, intensive care unit (ICU) stay after culture, location in a healthcare facility, including a long-term care facility (LTCF), 3 days before culture, and diagnosis of septic shock were associated with increased odds of death in the model (Fig. 1). In urine cases, age 40–54 or ≥75 years, ICU stay after culture, presence of an indwelling device other than a urinary catheter or central line (eg, endotracheal tube), location in a LTCF 3 days before culture, diagnosis of septic shock, and Charlson comorbidity score ≥3 were associated with increased odds of mortality (Fig. 2). Conclusion: Overall 30-day mortality was high among patients with CRAB, including patients with CRAB isolated from urine. A substantial fraction of mortality occurred after discharge, especially among patients with urine cases. Although there were some differences in characteristics associated with mortality in patients with CRAB isolated from sterile sites versus urine, LTCF exposure and severe illness were associated with mortality in both patient groups. CRAB was associated with major mortality in these patients with evidence of healthcare experience and complex illness. More work is needed to determine whether prevention of CRAB infections would improve outcomes.
Background: Automated testing instruments (ATIs) are commonly used by clinical microbiology laboratories to perform antimicrobial susceptibility testing (AST), whereas public health laboratories may use established reference methods such as broth microdilution (BMD). We investigated discrepancies in carbapenem minimum inhibitory concentrations (MICs) among Enterobacteriaceae tested by clinical laboratory ATIs and by reference BMD at the CDC. Methods: During 2016–2018, we conducted laboratory- and population-based surveillance for carbapenem-resistant Enterobacteriaceae (CRE) through the CDC Emerging Infections Program (EIP) sites (10 sites by 2018). We defined an incident case as the first isolation of Enterobacter spp (E. cloacae complex or E. aerogenes), Escherichia coli, Klebsiella pneumoniae, K. oxytoca, or K. variicola resistant to doripenem, ertapenem, imipenem, or meropenem from normally sterile sites or urine identified from a resident of the EIP catchment area in a 30-day period. Cases had isolates that were determined to be carbapenem-resistant by clinical laboratory ATI MICs (MicroScan, BD Phoenix, or VITEK 2) or by other methods, using current Clinical and Laboratory Standards Institute (CLSI) criteria. A convenience sample of these isolates was tested by reference BMD at the CDC according to CLSI guidelines. Results: Overall, 1,787 isolates from 112 clinical laboratories were tested by BMD at the CDC. Of these, clinical laboratory ATI MIC results were available for 1,638 (91.7%); 855 (52.2%) from 71 clinical laboratories did not confirm as CRE at the CDC. Nonconfirming isolates were tested on either a MicroScan (235 of 462; 50.9%), BD Phoenix (249 of 411; 60.6%), or VITEK 2 (371 of 765; 48.5%). Lack of confirmation was most common among E. coli (62.2% of E. coli isolates tested) and Enterobacter spp (61.4% of Enterobacter isolates tested) (Fig. 1A), and among isolates testing resistant to ertapenem by the clinical laboratory ATI (52.1%, Fig. 1B). Of the 1,388 isolates resistant to ertapenem in the clinical laboratory, 1,006 (72.5%) were resistant only to ertapenem. Of the 855 nonconfirming isolates, 638 (74.6%) were resistant only to ertapenem based on clinical laboratory ATI MICs. Conclusions: Nonconfirming isolates were widespread across laboratories and ATIs. Lack of confirmation was most common among E. coli and Enterobacter spp. Among nonconfirming isolates, most were resistant only to ertapenem. These findings may suggest that ATIs overcall resistance to ertapenem or that isolate transport and storage conditions affect ertapenem resistance. Further investigation into this lack of confirmation is needed, and CRE case identification in public health surveillance may need to account for this phenomenon.
Background: Carbapenem-resistant Enterobacteriaceae (CRE) are a major public health problem. Ceftazidime-avibactam (CZA) is a treatment option for CRE approved in 2015; however, it does not have activity against isolates with metallo-β-lactamases (MBLs). Emerging resistance to CZA is a cause for concern. Our objective was to describe the microbiologic and epidemiologic characteristics of CZA-resistant (CZA-R) CRE. Methods: From 2015 to 2017, 9 states participated in laboratory- and population-based surveillance for carbapenem-resistant Escherichia coli, Klebsiella pneumoniae, K. oxytoca, K. aerogenes, and Enterobacter cloacae complex isolates from a normally sterile site or urine. A convenience sample of isolates from this surveillance were sent to the CDC for antimicrobial susceptibility testing (AST) using reference broth microdilution (BMD) including an MBL screen, species confirmation with MALDI-TOF, and real-time PCR to detect blaKPC, blaNDM, and blaOXA-48–like genes. Additional AST by BMD was performed on CZA-R isolates using meropenem-vaborbactam (MEV), imipenem-relebactam (IMR), plazomicin (PLZ), and eravacycline (ERV). Epidemiologic data were obtained from a medical record review. Community-associated cases were defined as having no healthcare exposures in the year prior to culture, no devices in place 2 days prior to culture, and culture collected before calendar day 3 after hospital admission. Data were analyzed in 3 groups: CRE that were CZA-susceptible (CZA-S), CZA-R that were due to blaNDM, and CZA-R without blaNDM. Results: Among 606 confirmed CRE tested with CZA, 33 (5.4%) were CZA-R. Of the CZA-R isolates, 16 (48.5%) harbored a blaNDM gene, of which 2 coharbored blaNDM and blaOXA-48-like genes; 9 (27.3%) harbored only a blaKPC gene. Of the 17 CZA-R isolates without blaNDM, all were MBL screen negative. CZA-R due to blaNDM were more frequently community-associated (43.8%) than CZA-S or CZA-R without blaNDM (11.0% and 5.9%, respectively); a higher percentage of CZA-R cases due to blaNDM also had recent international travel (25%) compared to the other groups (1.8% and 5.9%, respectively). CZA-R without blaNDM were more susceptible to MEV (76%), IMR (71%), PLZ (88%), and ERV (65%) compared to CZA-R due to blaNDM (19%, 6%, 56%, and 44%, respectively). Conclusions: The emergence of CZA-R isolates without blaNDM are concerning; however, these isolates are more susceptible to newer antimicrobials than those with blaNDM. In addition to high rates of resistance to newer antimicrobials, isolates with blaNDM are more frequently community-associated than other CRE. This underscores the need for more aggressive measures to stop the spread of CRE.
Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a frequent cause of healthcare-associated infections (HAIs). The CDC Emerging Infections Program (EIP) conducted population and laboratory-based surveillance of CRPA in selected areas in 8 states from August 1, 2016, through July 31, 2018. We aimed to describe the molecular epidemiology and mechanisms of resistance of CRPA isolates collected through this surveillance. Methods: We defined a case as the first isolate of P. aeruginosa resistant to imipenem, meropenem, or doripenem from the lower respiratory tract, urine, wounds, or normally sterile sites identified from a resident of the EIP catchment area in a 30-day period; EIP sites submitted a systematic random sample of isolates to CDC for further characterization. Of 1,021 CRPA clinical isolates submitted, 707 have been sequenced to date using an Illumina MiSeq. Sequenced genomes were classified using the 7-gene multilocus sequence typing (MLST) scheme, and a core genome MLST (cgMLST) scheme was used to determine phylogeny. Antimicrobial resistance genes were identified using publicly available databases, and chromosomal mechanisms of carbapenem resistance were determined using previously validated genetic markers. Results: There were 189 sequence types (STs) among the 707 sequenced genomes (Fig. 1). The most frequently occurring were high-risk clones ST235 (8.5%) and ST298 (4.7%), which were found across all EIP sites. Carbapenemase genes were identified in 5 (<1%) isolates. Overall, 95.6% of the isolates had chromosomal mutations associated with carbapenem resistance: 93.2% had porinD-associated mutations that decrease membrane permeability to the drugs; 24.8% had mutations associated with overexpression of the multidrug efflux pump MexAB-OprM; and 22.9% had mutations associated with overexpression of the endogenous β-lactamase ampC. More than 1 such chromosomal resistance mutation type was present in 37.8% of the isolates. Conclusions: The diversity of the sequence types demonstrates that HAIs caused by CRPA can arise from a variety of strains and that high-risk clones are broadly disseminated across the EIP sites but are a minority of CRPA strains overall. Carbapenem resistance in P. aeruginosa was predominantly driven by chromosomal mutations rather than acquired mechanisms (ie, carbapenemases). The diversity of the CRPA isolates and the lack of carbapenemase genes suggest that this ubiquitous pathogen can readily evolve chromosomal resistance mechanisms, but unlike carbapenemases, these cannot be easily spread through horizontal transfer.
Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a serious threat to patient safety due to limited treatment options and propensity to spread in healthcare settings. Using Emerging Infections Program (EIP) data, we describe changes in CRAB incidence and epidemiology. Methods: During January 2012 to December 2018, 9 sites (Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee) participated in active laboratory- and population-based surveillance. An incident case was defined as the first isolation of A. baumannii complex, in a 30-day period, resistant to ≥1 carbapenem (excluding ertapenem) from a normally sterile site or urine of a surveillance area resident. Cases were considered hospital-onset (HO) if the culture was collected >3 days after hospital admission; all others were community-onset (CO). Cases were classified as device-associated (DA) if the patient had 1 or more medical devices (ie, urinary catheter, central venous catheter (CVC), endotracheal/nasotracheal tube, tracheostomy, or another indwelling device) present in the 2 days prior to culture collection. Temporal trends were estimated using generalized linear models adjusted for age, race, sex, and EIP site. Results: Overall, 984 incident CRAB cases were identified, representing 849 patients. Among these patients, 291 (34%) were women, 510 (61%) were nonwhite, and the median age was 62 years (mean, 59; range, 0–102). Among the cases, 226 (23%) were HO; 758 (77%) were CO; and 793 (81%) were DA. Overall incidence rates in 2012 and 2018 were 1.58 (95% CI, 1.29–1.90) and 0.60 (95% CI, 0.40–0.67) per 100,000 population, respectively. There was a 15% annual decrease in incidence (adjusted rate ratio [aRR] 0.85; 95% CI: 0.82-0.88, P < .0001). Decreases were observed among sterile site (aRR 0.88; 95% CI, 0.84–0.93) and urine cases (aRR 0.83; 95% CI, 0.80–0.87). Annual decreases occurred for HO cases (aRR, 0.78; 95% CI, 0.73–0.85) and CO cases (aRR, 0.86; 95% CI, 0.83–0.9). The DA cases decreased 16% annually overall (aRR, 0.84; 95% CI, 0.81–0.88). Decreases among cases in patients with CVC (aRR, 0.85; 95% CI, 0.80–0.90) and urinary catheters (aRR, 0.84; 95% CI, 0.80–0.88) were smaller than what was seen in patients with other indwelling devices (aRR, 0.81; 95% CI, 0.77–0.86). Discussion: Overall, from 2012 to 2018, the incidence of CRAB decreased >60%. Decreases were observed in all case groups, regardless of source, infection onset location, or types of devices. Smaller annual decreases in rates of CO-CRAB than HO-CRAB suggest that there may be opportunities to accelerate prevention outside the hospital to further reduce the incidence of these difficult-to-treat infections.
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