Carbapenem-resistant Enterobacteriaceae, 2016
Carbapenem-resistant Enterobacteriaceae (CRE) are Gram-negative bacilli that most commonly occur among patients with significant health care exposures, co-morbid conditions, invasive devices, and those who have received extended courses of antibiotics. Invasive infections caused by CRE, such as carbapenem-resistant Klebsiella pneumoniae, are associated with higher morbidity and mortality than those caused by carbapenem-susceptible Enterobacteriaceae. Another opportunistic pathogen associated with health care settings, Acinetobacter baumannii, can also become resistant to carbapenems. Carbapenem-resistant A. baumannii (CRA) is being increasingly recognized as one of the leading causes of health care-associated infections worldwide, and is associated with high mortality rates and unfavorable clinical outcomes.
Carbapenem resistance can be acquired through a variety of mechanisms. Some CRE and CRA carry resistance genes that produce enzymes known as carbapenemases. Certain carbapenemases (e.g., K. pneumoniae carbapenemase [KPC]), are encoded by transmissible genetic elements that can easily spread between bacteria of similar species. KPC is the predominant carbapenemase in the United States. Other carbapenemases have been identified in the United States (e.g., New Delhi metallo-β-lactamase [NDM], Verona integron-encoded metallo-β- lactamase [VIM], active on imipenem [IMP], and oxacillinase [OXA-48]), although they are more frequently identified in other countries.
Carbapenem resistance can also be acquired through the production of a β-lactamase effective against third generation cephalosporins (e.g., AmpC β-lactamases or extended-spectrum β-lactamases [ESBLs]) when combined with porin mutations that prevent carbapenem antibiotics from entering the cell).
Carbapenem-resistant organisms have been increasingly recognized as an important cause of health care-associated infections (HAIs). CDC identified CRE as one of three “urgent” antibiotic resistance threats requiring immediate and aggressive action. In 2017, the World Health Organization ranked 12 bacteria that posed the greatest threat to human health; CRE and CRA, as well as carbapenem-resistant Pseudomonas aeruginosa, are the three bacteria most urgently in need of development of new antibiotics.
MDH first identified a KPC-producing CRE in February 2009 and began voluntary CRE reporting including isolate submission. In 2012, we used standardized CRE and CRA definitions developed by the CDC EIP Multi-site Gram-negative Surveillance Initiative (MuGSI), and began active laboratory- and population-based surveillance in Hennepin and Ramsey Counties. This surveillance includes all isolates of A. baumannii, Escherichia coli, Enterobacter spp., or Klebsiella spp., from normally sterile sites or urine, that are resistant to imipenem, meropenem, doripenem, or ertapenem using current Clinical and Laboratory Standards Institute breakpoints (ertapenem excluded for Acinetobacter isolates). In Hennepin and Ramsey Counties, all carbapenem-resistant species of Enterobacteriaceae from any body site are reportable. An incident case is defined as the first eligible isolate of each species collected from a Hennepin or Ramsey County resident within 30 days. Statewide surveillance for CRE was initiated in 2016. For statewide surveillance, the MuGSI definition is expanded to include isolates of E. coli, Enterobacter spp., Klebsiella spp., or Citrobacter spp. from all body sites. The PHL tested all submitted 2016 isolates by PCR for KPC and NDM carbapenemase genes, and utilized other molecular and phenotypic assays (e.g., CarbaNP) to assess for additional carbapenemases when applicable.
During 2016, 380 incident CRE cases representing 367 patients were identified in Minnesota residents. Twenty-three (6%) isolates (representing 19 patients) were KPC positive (K. pneumoniae , Enterobacter cloacae , Citrobacter freundii , E. coli , and Serratia marcescens . Of note, 2 (11%) patients were positive for the same organism in the calendar year prior to the date of initial culture. Seven (2%) incident cases (representing 7 patients) were NDM positive (K. pneumoniae , C. freundii , E. coli , and Providencia rettgeri . All but 1 had exposure to health care overseas (Asia, Africa). Of the 380 incident cases, 2 (0.5%) isolates (representing 2 patients) were IMP positive (P. rettgeri ).
In 2016, 19 CRA isolates from 18 patients were identified in Minnesota residents. One isolate was NDM positive, with the patient having received health care exposure outside of the United States prior to initial culture. No other carbapenemases in CRA isolates were identified.
Of the 19 Minnesota residents with KPC-positive isolates, the median age was 63 years (range, 24 to 94); 11 (58%) were male, and 9 (47%) were residents of Hennepin or Ramsey County. Eleven (58%) patients were white, 3 (16%) were black, 2 (11%) were American Indian, 1 (5%) was Asian, and 2 (11%) were of unknown race. Hispanic ethnicity was reported for 2 (11%) patients. Urine (12) was the most common source followed by wounds (2), blood (2), sputum (1) and other sites (2). Thirteen (68%) were hospitalized (8 hospitalized ≥;3 days prior to culture); median length of stay was 12 days (range, 1 to 58). Six patients (32%) required ICU care; in-hospital mortality was 21% with 1 patient having CRE isolated from a sterile site within 7 days of death. Other KPC-positive CRE isolates were collected in patients from outpatient settings (4), and long-term care facilities (2) without subsequent hospitalization within 30 days.
A total of 135 CRE incident cases (representing 126 patients) were reported for MuGSI during 2016. Of the 135 cases, 66 were Enterobacter spp., 42 were Klebsiella spp., and 27 were E. coli. KPC was identified in 5 (4%) of MuGSI CRE (K. pneumoniae  and E. cloacae . Again, CRE was most frequently isolated from urine (127) followed by blood (7), and CSF (1). A total of 4 incident cases (representing 4 patients) of CRA were reported for MuGSI during this time period; all were isolated from urine.
During 2016, 11 NDM-producing CRE and 1 NDM-producing CRA were detected. To date, a total of 28 NDM-producing organisms (K. pneumoniae , E. coli , K. oxytoca , C. freundii , P. rettgeri , A. baumannii , and Pseudomonas aeruginosa ) from 21 patients treated in Minnesota have been detected. This includes 9 Minnesota residents and 12 nonresidents, all but one of whom had received medical care outside the United States (20 patients) or in a non-Minnesota U.S. facility (3 patients) prior to their NDM-positive culture in Minnesota. In 2016, the PHL identified, and CDC confirmed, 2 IMP-producing CRE (P. rettgeri ) from Minnesota residents (no history of travel or foreign health care exposures) and 1 VIM-producing S. marcescens from a non-resident with significant health care exposure outside the United States prior to receiving healthcare in Minnesota.
In summary, 8% of Enterobacteriaceae isolates tested by the PHL during 2016 were KPC-positive; 2 patients with KPC-positive isolates had a history of KPC-positive CRE from previous years, both of them from multiple body sites. Detection of NDM and VIM serves as a reminder to clinicians that a travel history, including receipt of medical care outside the United States, is a critical component of early detection of CRE isolates with carbapenemases. CDC recommends performing rectal screening cultures to detect CRE colonization in newly admitted patients with known hospitalization outside the United States within the last 6 months. CRE and CRA bacteria can spread in healthcare facilities (e.g., on the hands of healthcare workers or contaminated equipment) and have been associated with outbreaks in these settings in other states and countries. The spread of these pathogens can be halted with early detection and implementation of appropriate infection prevention measures, and proper communication of infection status upon patient transfer. Healthcare facilities should consider screening in-house patients with epidemiologic links to a patient colonized or infected with CRE, including any roommates. Screening might also be expanded to patients cared for by the same healthcare workers, those on the same unit, and/or patients who have had similar procedures (e.g., endoscopic procedures).
- For up to date information see>> Carbapenem-resistant Enterobacteriaceae (CRE)
- Full issue>> Annual Summary of Communicable Diseases Reported to the Minnesota Department of Health, 2016