What is the prevalence of carbapenem-resistant Enterobacterales among individuals with and without health risk factors?

By Pooja Toshniwal PahariaAug 3 2022Reviewed by Aimee Molineux

In a recent study published in the American Journal of Infection Control, researchers assessed carbapenem-resistant Enterobacterales (CRE) epidemiology across eight United States (US) metropolitan areas between 1 January 2012 and 31 December 2015.

Background

CREs rapidly transmit bacteria usually associated with healthcare settings and can cause complicated infections. Carbapenemase-producing (CP) CREs are of great concern since carbapenemase can inactivate β-lactam antibiotics and can be encoded on plasmids, facilitating CRE transmission. However, CRE infections have been reported among individuals with no healthcare exposure, and epidemiological data on CRE infections in such individuals are lacking.

Several surveillance studies have been conducted under the Centers for Disease Control and Prevention’s (CDC’s) emerging infections program (EIP) on CRE and other gram-negative bacteria resistant to drugs through the multi-site gram-negative surveillance initiative (MuGSI) beginning in 2012.

About the study

In the present study, researchers analyzed MuGSI CRE surveillance data to comparatively assess the epidemiology of healthcare-associated-CRE (HCA-CRE) cases and community-associated-CRE (CA-CRE) cases in the US.

Active, laboratory- and population-based surveillance data were analyzed to identify case patients who were CRE-positive, showed no susceptibility to carbapenems (ertapenem was excluded) and were resistant to all third-generation cephalosporin antibiotics tested. Medical records were retrospectively obtained for classifying cases as HCA-CRE or CA-CRE in patients without known health risk factors. Cultures were obtained within three days of hospital admissions.

In addition, Enterobacterales isolates were submitted to the CDC for whole genome sequencing (WGS) analysis using antibiotic resistance (AR) genes databases such as the NCBI (national center for biotechnology information), pubMLST (publicly available multilocus sequence typing) and ResFinder through 27 December 2019.

The CRE isolates were further characterized by CDC using several tests, which were: (i) matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF) for identification of species, (ii) Metallo-β-lactamase (MBL) screen testing for determining antimicrobial susceptibility, (iii) modified Hodge test (MHT) for detecting carbapenemase production and (iv) real-time polymerase chain reaction (PCR) for identifying Metallo-β-lactamase genes such as bla_NDM, bla_OXA-48-like, bla_VIM, bla_KPC, and plasma-mediated mobilized colistin resistance genes (mcr)-1,2.  CDC reports of CRE isolates as of 7 August 2020 were considered final.

The study sites included Georgia, Minnesota, Oregon, Colorado, Maryland, New Mexico, New York, Tennessee, Atlanta, St. Paul, Minneapolis, Portland, Denver, Baltimore, Albuquerque, Rochester, and Nashville, and the total surveillance population was 15 million. CRE isolates identified from local laboratories with MICs (minimum inhibitory concentrations) ≥2 mg/mL to meropenem, doripenem, or imipenem, and MICs of ≥16 mg/mL and ≥4 mg/mL to ceftazidime and ceftriaxone/cefotaxime, respectively, were considered for the analysis.

Inpatient records of short-stay acute care hospital (ACH), long-term ACH (LTACH), and long-term care facility (LTCF) from the previous year of the specimen collection date were analyzed. Outpatient records obtained five days before the collection date were analyzed. Descriptive analysis was performed, and the crude rates of CRE case incidence and Charlson comorbidity index (CCI) scores were calculated.

Results

Out of 1,585 CRE infection incident cases identified, 1,499 and 1,194 cases and case patients were analyzed, respectively. Among the CRE infection cases, 10% (n=149) and 90% (n=1,350) were CA-CRE and HCA-CRE cases, respectively. The overall and CA-CRE crude incidence rates were 2.9 and 0.3 cases for every 100,000 individuals, respectively.

The highest crude CRE incidence rates for HCA-CRE were observed in Georgia and Maryland and for CA-CRE cases in New York and New Mexico. Most cases of CA-CRE were observed in White individuals (73%), and females (84%) from urine specimens (98%). Urinary tract infections (UTIs) were the most commonly reported infections, more frequently reported among CA-CRE cases (83%) than HCA-CRE cases (67%). Five of 12 (42%) sequenced CA-CRE isolates (42%) were CP-positive with distinct MLST.

Among the specimens, K. pneumoniae (53%, n = 800) was most frequently detected, followed by Escherichia coli (18%, n = 275), and a greater fraction of HCA-CRE cases (58%) occurred due to K. pneumoniae infections than CA-CRE cases (19%). On the contrary, E. coli was the causative organism for most CA-CRE cases (40%) than HCA-CRE cases (16%). However, E. cloacae and K. aerogenes were most prevalent in both case types in Oregon and Minnesota, respectively.

Out of 15 reported cases, 14 case-patients (two CA-CRE patients and 13 HCA-CRE patients) had traveled outside the US to Alaska and/or Hawaii in the previous two months of specimen collection. Among the CRE isolates, 45% (n=664) were susceptible to ≥1 β-lactam antibiotic, including 81% and 41% of CA-CRE and HCA-CRE cases, respectively.

Out of 64 CRE isolates from CA-CRE cases submitted to the CDC, five CP isolates were detected by PCR analysis, of which three, one, and one harbored KPC genes for K. pneumoniae, KPC genes for E. cloacae complex, and NDM genes for E. coli, respectively. The median CCI scores for CP-CA-CRE and non-CP-CA-CRE cases were two and one, respectively.

Overall, the study findings showed that 10% of CRE cases occurred in community-residing individuals without known health risk factors and some CA-CRE isolates comprised carbapenemase genes. The findings underscore the need for continual CRE surveillance in community settings for monitoring CRE emergence beyond healthcare settings and identifying changes in CRE epidemiology.