Carbapenem-resistant Enterobacteriaceae, 2013

Enterobacteriaceae are a large family of Gram-negative bacilli that are common causes of community- and health care-associated infections (HAI). Carbapenem-resistant Enterobacteriaceae (CRE) are resistant to most available antibiotics, including carbapenems. In recent years, CRE have been increasingly recognized as an important cause of HAI. 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 carbapenem-susceptible Enterobacteriaceae.

Carbapenem resistance can be acquired through different mechanisms. Some CRE harbor 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 among CRE in the United States. Other types of carbapenemases have been identified in the United States (i.e. New Delhi metallo-β-lactamase [NDM], Verona integron-encoded metallo-βlactamase [VIM], active on imipenem [IMP], and oxacillinase [OXA-48]) though these carbapenemases are more common in other countries. Resistance to carbapenems can also be acquired through the production of a β-lactamase effective against third-generation cephalosporins (i.e. AmpC β-lactamases or extended-spectrum β-lactamases [ESBLs]) when combined with porin mutations that prevent carbapenem antibiotics from entering the cell.

MDH first identified a KPC-producing CRE in February 2009, and began voluntary reporting of CRE to track the emergence of these highly resistant organisms in Minnesota. In 2012, MDH adopted a standardized CRE definition developed by the CDC 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 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 collected in Minnesota residents, including all isolates that are positive for carbapenemase production. The PHL tests all submitted CRE isolates by PCR for KPC and NDM genes.

In 2013, 103 CRE were reported. Of 92 isolates submitted (representing 90 patients), 26 ([28%] representing 24 patients) were KPC positive (K. pneumoniae [11], E. cloacae [11], K. oxytoca [2], C. freundii [1], and C. koseri [1]); 2 cases had isolates of different species detected from the same body site. Of note, 2 KPC-positive isolates were susceptible to carbapenems tested by the submitting laboratory. None of the tested isolates were NDM positive. Of the 24 patients with KPC-positive isolates, the median age was 60 years (range,17 to 89); 13 (54%) were male and 13 (54%) were residents of Hennepin or Ramsey County. Urine (11) was the most common source followed by blood (4) and sputum (4). Seventeen (71%) were hospitalized (8 hospitalized >3 days prior to culture); median length of stay was 17 days (range, 1 to 68). Six (35%) required ICU care; in-hospital mortality was 6%. Other KPC-positive CRE isolates were collected in patients from outpatient settings (3), long-term acute care hospitals (2), or long-term care facilities (2).

A total of 41 incident CRE cases (representing 36 patients) were reported for MuGSI during 2013. Species identified were Enterobacter spp. (23), Klebsiella spp. (13), and E. coli (5). KPC was identified in 31% of MuGSI CRE (K. pneumoniae [7/11] and E. cloacae [4/7]). Again, CRE was most frequently isolated from urine (36) followed by blood (3) and other sterile body sites (2).

To date, 2 NDM-producing CRE (E. coli and K. pneumoniae from a single patient) have been detected in Minnesota residents and 3 (E. coli [1] and K. pneumoniae [2]) in 2 non-Minnesota residents. All 3 patients had received prior medical care in countries where NDM is more common. In 2013, the PHL identified, and CDC confirmed, the first OXA-48-producing CRE (K. pneumoniae) in Minnesota, also from a non-resident. The OXA-48-positive urine culture was collected during an outpatient dialysis visit. The patient had significant health care exposure outside the United States prior to receiving health care in Minnesota.

In summary, approximately one third of reported CRE isolates were KPC-positive; 2 cases had KPC-positive isolates of different species cultured from the same body site. Detection of NDM and OXA-48 serves as a reminder to clinicians that a travel history, including hospitalization 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) 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 who have shared the same health care workers and/or those on the same unit. No outbreaks or transmission of CRE were reported among Minnesota facilities that conducted active surveillance testing during 2013.

• For up to date information see>> Carbapenem-resistant Enterobacteriaceae (CRE)
  
• Full issue>> Annual Summary of Communicable Diseases Reported to the Minnesota Department of Health, 2013