Carbapenem-resistant Enterobacteriaceae, 2014
Enterobacteriaceae are a large family of Gram-negative bacilli that cause community-and health care-associated infections (HAI). Carbapenem-resistant Enterobacteriaceae (CRE) infections 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 are associated with higher morbidity and mortality than those caused by carbapenem-susceptible Enterobacteriaceae.
Carbapenem resistance can be acquired through a variety of mechanisms. Some CRE carry resistance genes that produce enzymes known as carbapenemases. Certain carbapenemases (e.g., Klebsiella 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 also been identified (e.g., New Delhi metallo-β-lactamase [NDM], Verona integron-encoded metallo-β-lactamase [VIM], IMP metallo-β-lactamase, and oxacillinase [OXA-48]) though 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.
In recent years, CRE have been increasingly recognized as an important cause of HAI. CRE are often resistant to most available antibiotics, leaving clinicians with few treatment options.
MDH first identified a KPC-producing CRE in February 2009, and at that time began voluntary reporting of CRE, including isolate submission. In 2012, we adopted a standardized CRE definition developed by the EIP Multi-site Gram-negative Surveillance Initiative (MuGSI), and initiated active laboratory-and population-based surveillance in Hennepin and Ramsey Counties. This surveillance includes all isolates of Escherichia coli, Enterobacter spp., or Klebsiella spp. from normally sterile sites or urine that are non-susceptible to imipenem, meropenem, or doripenem and resistant to all tested third-generation cephalosporins using current Clinical and Laboratory Standards Institute (CLSI) breakpoints. An incident case is defined as the first eligible isolate of each species collected from a Hennepin or Ramsey County resident in 30 days. For statewide surveillance, the MuGSI definition is expanded to include isolates of any Enterobacteriaceae species from all body sites, including all isolates that are positive for carbapenemase production. The PHL tests all submitted isolates by PCR for KPC and NDM genes, and selected isolates for OXA-48.
During 2014, 141 incident CRE cases were reported in 140 patients. Of 134 isolates submitted (representing 133 patients), 21 (16%) isolates (representing 20 patients) were KPC positive (K. pneumoniae , E. cloacae , K. oxytoca , and C. freundii ); 1 patient had KPC-positive E. cloacae and K. oxytoca detected from different body sites during a single hospital stay. Of note, 2 (10%) patients were positive for the same organism in the year prior to the date of initial culture and 3 (15%) patients were positive >1 year prior. None of the tested isolates was NDM positive. Of the 20 patients with KPC-positive isolates, the median age was 62 years (range, 24 to 80); 17 (85%) were male and 12 (60%) were residents of Hennepin or Ramsey County. Fourteen (70%) patients were white, 3 (15%) were black, 1 (5%) was American Indian, 1 (5%) was multi-racial and 1 (5%) was of unknown race. Hispanic ethnicity was reported for 2 (13%) patients. Urine (8) was the most common source followed by sputum (5) and blood (3). Fifteen (75%) were hospitalized (8 hospitalized >3 days prior to culture); median length of stay was 19 days (range, 3 to 147). 9 (56%) required ICU care; in-hospital mortality was 10% with one 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 (2), long-term acute care hospitals (1), or long-term care facilities (2) without subsequent hospitalization within 30 days.
A total of 43 incident cases (representing 38 patients) of CRE were reported for MuGSI during 2014. Of the 43 cases, 29 were Enterobacter spp., 9 were Klebsiella spp., and 5 were E. coli. KPC was identified in 23% of MuGSI CRE (K. pneumoniae [6/8] and E. cloacae [4/11]). Again, CRE was most frequently isolated from urine (40) followed by blood (3).
During 2014, 5 NDM-producing CRE (E. coli  and K. pneumoniae ) were detected, all in non-residents. To date, a total of 10 NDM-producing CRE (E. coli  and K. pneumoniae ) from 8 patients have been detected. This includes 1 Minnesota resident and 7 non-residents, all of whom received medical care outside Minnesota (1 patient) or the United States. (7 patients) prior to their initial NDM-positive culture. In 2014, the PHL identified and CDC confirmed the second OXA-48-producing CRE (K. pneumoniae) detected in Minnesota from a non-resident with significant health care exposure outside the United States prior to receiving health care in Minnesota.
In summary, less than one quarter of CRE isolates tested by the PHL during 2014 were KPC positive; 1 patient had KPC-positive isolates of different species cultured from the different body sites during a single hospital stay. Detection of NDM and OXA-48 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 that are less common in the United States. CDC recommends performing rectal screening cultures to detect colonization in newly admitted patients with known hospitalization outside the United States. within the last 6 months. CRE bacteria can spread in health care facilities (e.g., on the hands of health care workers or contaminated equipment) and have been associated with outbreaks in these settings in other states and countries. The spread of CRE can be halted with early detection and implementation of appropriate infection prevention measures, and proper communication of CRE status upon patient transfer. Healthcare facilities should consider screening epidemiologically linked patients including roommate(s) of a patient colonized or infected with CRE who are still in-house. Screening might also be expanded to patients with the same health care workers, those on the same unit, and/or patients who have had similar procedures (e.g., endoscopic procedures). No outbreaks or transmission of CRE were reported to MDH in 2014.
- For up to date information see>> Carbapenem-resistant Enterobacteriaceae (CRE)
- Full issue>> Annual Summary of Communicable Diseases Reported to the Minnesota Department of Health, 2014