Carbapenem-resistant Enterobacteriaceae, 2015

Enterobacteriaceae are a large family of Gram-negative bacilli that cause community- and healthcare-associated infections (HAIs). Carbapenem-resistant Enterobacteriaceae (CRE) infections most commonly occur among patients with significant healthcare 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 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]), 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 HAIs. CRE are often resistant to most available antibiotics, leaving clinicians with few treatment options. In 2013, CDC identified CRE as one of three "urgent" antibiotic resistance threats requiring immediate and aggressive action.

MDH first identified a KPC-producing CRE in February 2009, and voluntary reporting of CRE began, 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 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 was expanded to include isolates of any Enterobacteriaceae species from all body sites collected in Minnesota residents. The PHL tests all submitted isolates by PCR for KPC and NDM carbapenemase genes, and utilizes other molecular and phenotypic assays (e.g., CarbaNP) to detect additional carbapenemases when applicable.

During 2015, 271 isolates from 233 patients (including non-residents) were submitted to the PHL for further testing. Of these, 155 incident CRE cases representing 150 patients were identified in Minnesota residents. Of these 155 isolates, 33 (21%) (representing 27 patients) were KPC positive (E. cloacae [16], K. pneumoniae [12], E. coli [2], K. oxytoca [1], E. asburiae [1], and L. adecarboxylata [1]). Of note, 2 (6%) patients were positive for the same organism in the calendar year prior to the date of initial culture. No tested isolates were NDM-positive.

Of the 27 residents with KPC-positive isolates, the median age was 60 years (range, 21 to 83); 16 (59%) were male and 10 (37%) were residents of Hennepin or Ramsey County. Fourteen (52%) patients were white, 2 (7%) were black, 2 (7%) were American Indian, 2 (7%) were Asian, and 6 (22%) were of unknown race. Hispanic ethnicity was reported for 2 (7%) patients. Urine (15) was the most common source followed by sputum (3), bronchial lavage (3), wounds (2), and other sites (4). Twenty-one (78%) were hospitalized (7 hospitalized ≥3 days prior to culture); median length of stay was 11 days (range, 2 to 113). Nine patients (33%) required ICU care; in-hospital mortality was 11% 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 (3), long-term acute care hospitals (1), or long-term care facilities (2) without subsequent hospitalization within 30 days.

A total of 53 incident CRE cases (representing 49 patients) were reported during 2015. Of these cases, 33 were Enterobacter spp., 11 were Klebsiella spp., and 9 were E. coli. KPC was identified in 11% of MuGSI CRE (K. pneumoniae [3/11], E. cloacae [2/10], and E. coli [1/9]). Again, CRE was most frequently isolated from urine (47) followed by blood (4), peritoneal fluid (1), and pleural fluid (1).

During 2015, 1 NDM-producing CRE (E. coli) was detected in a non-resident. To date, a total of 11 NDM-producing CRE (E. coli [5] and K. pneumoniae [6]) from 9 patients have been detected. This includes 1 resident and 8 non-residents, all of whom had received medical care outside the United States (8 patients) or in a non-Minnesota U.S. facility (1 patient) prior to their initial NDM-positive culture. In 2015, the PHL identified, and CDC confirmed, 2 OXA-48-producing CRE (K. pneumoniae [2]) detected from non-Minnesota residents with significant healthcare exposure outside the United States prior to receiving healthcare in Minnesota.

In summary, 14% of CRE isolates tested by the PHL during 2015 were KPC-positive; 4 cases with KPC-positive isolates had a history of KPC positive CRE from previous years, all 4 of them from multiple body sites. 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 CRE colonization in newly admitted patients with known hospitalization outside the United States within the last 6 months. CRE 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 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 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, 2015