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.

Distinctive Features of Ertapenem-Mono-Resistant Carbapenem-Resistant Enterobacterales in the United States: A Cohort Study.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) are highly antibiotic-resistant bacteria. Whether CRE resistant only to ertapenem among carbapenems (ertapenem "mono-resistant") represent a unique CRE subset with regards to risk factors, carbapenemase genes, and outcomes is unknown. METHODS: We analyzed surveillance data from 9 CDC Emerging Infections Program (EIP) sites. A case was the first isolation of a carbapenem-resistant Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, K. oxytoca, K. pneumoniae, or K. variicola from a normally sterile site or urine in an EIP catchment area resident in 2016-2017. We compared risk factors, carbapenemase genes, antibiotic susceptibility, and mortality of ertapenem "mono-resistant" cases to "other" CRE cases (resistant to ≥1 carbapenem other than ertapenem) and analyzed risk factors for mortality. RESULTS: Of 2009 cases, 1249 (62.2%) were ertapenem-mono-resistant and 760 (37.8%) were other CRE. Ertapenem-mono-resistant CRE cases were more frequently ≥80 years old (29.1% vs 19.5%; P < .0001) and female (67.9% vs 59.0%; P < .0001). Ertapenem-mono-resistant isolates were more likely to be Enterobacter cloacae complex (48.4% vs 15.4%; P < .0001) but less likely to be isolated from a normally sterile site (7.1% vs 11.7%; P < .01) or to have a carbapenemase gene (2.4% vs 47.4%; P < .0001). Ertapenem-mono-resistance was not associated with 90-day mortality in logistic regression models. Carbapenemase-positive isolates were associated with mortality (odds ratio, 1.93; 95% CI, 1.30-2.86). CONCLUSIONS: Ertapenem-mono-resistant CRE rarely have carbapenemase genes and have distinct clinical and microbiologic characteristics from other CRE. These findings may inform antibiotic choice and infection prevention practices, particularly when carbapenemase testing is not available.

Prevalence of colistin heteroresistance in carbapenem-resistant Pseudomonas aeruginosa and association with clinical outcomes in patients: an observational study.

OBJECTIVES: To describe the prevalence of colistin heteroresistance in carbapenem-resistant Pseudomonas aeruginosa (CRPA) and evaluate the association with clinical outcomes. METHODS: Colistin heteroresistance was evaluated in CRPA isolates collected from patients without cystic fibrosis in Atlanta, Georgia, USA using two definitions: HR1, growth at 4 and 8 mg/L of colistin at a frequency ≥1 × 10-6 the main population; and HR2, growth at a colistin concentration ≥8× the MIC of the main population at a frequency ≥1 × 10-7. A modified population analysis profile (mPAP) technique was compared with reference PAP for detecting heteroresistance. For adults hospitalized at the time of or within 1 week of CRPA culture, multivariable logistic regression estimated the association between heteroresistance and 90 day mortality. RESULTS: Of 143 colistin-susceptible CRPA isolates, 8 (6%) met the HR1 definition and 37 (26%) met the HR2 definition. Compared with the reference PAP, mPAP had a sensitivity and specificity of 50% and 100% for HR1 and 32% and 99% for HR2. Of 82 hospitalized patients, 45 (56%) were male and the median age was 63 years (IQR 49-73). Heteroresistance was not associated with 90 day mortality using HR1 (0% in heteroresistant versus 22% in non-heteroresistant group; P = 0.6) or HR2 (12% in heteroresistant versus 24% in non-heteroresistant group; P = 0.4; adjusted OR 0.8; 95% CI 0.2-3.4). CONCLUSIONS: Colistin heteroresistance was identified in up to 26% of patients with CRPA in our sample, although the prevalence varied depending on the definition. We did not observe an apparent association between colistin heteroresistance and 90 day mortality.

Mortality in patients with carbapenem-resistant Pseudomonas aeruginosa with and without susceptibility to traditional antipseudomonal ß-lactams.

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates can frequently retain susceptibility to traditional antipseudomonal ß-lactams including cefepime, ceftazidime and piperacillin/tazobactam. OBJECTIVES: This observational study aimed to determine the proportion of CRPA isolates that were susceptible to all tested other traditional antipseudomonal ß-lactams (S-CRPA) and assess whether patients with S-CRPA had improved 30 day mortality compared with patients with NS-CRPA (non-susceptible to cefepime, ceftazidime or piperacillin/tazobactam). METHODS: Patients with CRPA isolated from normally sterile sites, urine, lower respiratory tracts and wounds were identified using active population- and laboratory-based surveillance through the Georgia Emerging Infections Program from August 2016 to July 2018 in Atlanta, GA, USA. Only unique patients who were hospitalized at the time of, or within 1 week of, culture were included. We excluded patients with cystic fibrosis. Multivariable logistic regression estimated the association between S-CRPA and 30 day mortality. RESULTS: Among 635 adults hospitalized with CRPA, 219 (34%) had S-CRPA. Patients with S-CRPA were more likely to be white (50% versus 38%, P = 0.01) and live in a private residence prior to culture (44% versus 28%, P < 0.01), and less likely to have required ICU care within the prior week (23% versus 36%, P < 0.01) compared with patients with NS-CRPA. Compared with those with NS-CRPA, patients with S-CRPA had an increased 30 day mortality (18% versus 15%, adjusted OR 1.9; 95% CI 1.2-3.1). CONCLUSIONS: S-CRPA was associated with higher 30 day mortality than NS-CRPA in hospitalized patients. The reason for this observed increase in mortality deserves further investigation.

Carbapenem-resistant Enterobacterales bacteriuria and subsequent bacteremia: A population-based study.

OBJECTIVE: To describe the epidemiology of carbapenem-resistant Enterobacterales (CRE) bacteriuria and to determine whether urinary catheters increase the risk of subsequent CRE bacteremia. DESIGN: Using active population- and laboratory-based surveillance we described a cohort of patients with incident CRE bacteriuria and identified risk factors for developing CRE bacteremia within 1 year. SETTING: The study was conducted among the 8 counties of Georgia Health District 3 (HD3) in Atlanta, Georgia. PATIENTS: Residents of HD3 with CRE first identified in urine between 2012 and 2017. RESULTS: We identified 464 patients with CRE bacteriuria (mean yearly incidence, 1.96 cases per 100,000 population). Of 425 with chart review, most had a urinary catheter (56%), and many resided in long-term care facilities (48%), had a Charlson comorbidity index >3 (38%) or a decubitus ulcer (37%). 21 patients (5%) developed CRE bacteremia with the same organism within 1 year. Risk factors for subsequent bacteremia included presence of a urinary catheter (odds ratio [OR], 8.0; 95% confidence interval [CI], 1.8-34.9), central venous catheter (OR, 4.3; 95% CI, 1.7-10.6) or another indwelling device (OR, 4.3; 95% CI, 1.6-11.4), urine culture obtained as an inpatient (OR, 5.7; 95% CI, 1.3-25.9), and being in the ICU in the week prior to urine culture (OR, 2.9; 95% CI, 1.1-7.8). In a multivariable analysis, urinary catheter increased the risk of CRE bacteremia (OR, 5.3; 95% CI, 1.2-23.6). CONCLUSIONS: In patients with CRE bacteriuria, urinary catheters increase the risk of CRE bacteremia. Future interventions should aim to reduce inappropriate insertion and early removal of urinary catheters.

Evaluating Movement of Patients With Carbapenem-resistant Enterobacteriaceae Infections in the Greater Atlanta Metropolitan Area Using Social Network Analysis.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent threat with potential for rapid spread. We evaluated the role of Medicare patient movement between facilities to model the spread of CRE within a region. METHODS: Through population-based CRE surveillance in the 8-county Atlanta (GA) metropolitan area, all Escherichia coli, Enterobacter spp., or Klebsiella spp. resistant to ≥1 carbapenem were reported from residents. CRE was attributed to a facility based on timing of culture and facility exposures. Centrality metrics were calculated from 2016 Medicare data and compared to CRE-transfer derived centrality metrics by Spearman correlation. RESULTS: During 2016, 283 incident CRE cases with concurrent or prior year facility stays were identified; cases were attributed mostly to acute care hospitals (ACHs; 141, 50%) and skilled nursing facilities (SNFs; 113, 40%), and less frequently to long-term acute care hospitals (LTACHs; 29, 10%). Attribution was widespread, originating at 17 of 20 ACHs (85%), 7 of 8 (88%) LTACHs, but only 35 of 65 (54%) SNFs. Betweenness of Medicare patient transfers strongly correlated with betweenness of CRE case-transfer data in ACHs (r = 0.75; P < .01) and LTACHs (r = 0.77; P = .03), but not in SNFs (r = 0.02; P = 0.85). We noted 6 SNFs with high CRE-derived betweenness but low Medicare-derived betweenness. CONCLUSIONS: CRE infections originate from almost all ACHs and half of SNFs. We identified a subset of SNFs central to the CRE transfer network but not the Medicare transfer network; other factors may explain CRE patient movement in these facilities.