Carbapenem-resistant Enterobacteriaceae (CRE), Acinetobacter baumannii (CRA), and Pseudomonas aeruginosa (CRPA), 2019

Carbapenem-resistant Enterobacteriaceae (CRE), Acinetobacter baumannii (CRA), and Pseudomonas aeruginosa (CRPA) are Gram-negative bacilli that 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, such as carbapenem-resistant Klebsiella pneumoniae, are associated with higher morbidity and mortality than those caused by carbapenem-susceptible Enterobacteriaceae. Carbapenem-resistant A. baumannii (CRA) is increasingly recognized as one of the leading causes of healthcare-associated infections worldwide, and is associated with high mortality rates and unfavorable clinical outcomes. Invasive infections caused by CRPA are associated with higher morbidity and mortality than those caused by carbapenem-susceptible P. aeruginosa. Carbapenem resistance can be acquired through a variety of mechanisms including transmissible genetic elements. Some CRE, CRA, and CRPA carry resistance genes that produce enzymes called carbapenemases. Certain carbapenemases (e.g., K. pneumoniae carbapenemase [KPC]) can easily spread between bacteria of similar species. KPC is the predominant carbapenemase in the United States. Other carbapenemases (e.g., New Delhi metallo-β-lactamase [NDM], Verona integron-encoded metallo-β- lactamase [VIM], and oxacillinase-48 [OXA-48]) are more frequently identified in other countries. 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.

We first identified a KPC-producing CRE in February 2009, and voluntary reporting, including isolate submission for all Enterobacteriaceae and A. baumannii resistant to imipenem, meropenem, doripenem, or ertapenem using current Clinical and Laboratory Standards Institute (CLSI) breakpoints (ertapenem excluded for Acinetobacter isolates) began. In 2012, we used standardized CRE and CRA definitions developed by the EIP Multi-site Gram-negative Surveillance Initiative (MuGSI), and initiated active laboratory- and population-based surveillance in Hennepin and Ramsey Counties. As a subset of statewide reporting, MuGSI surveillance includes all isolates from normally sterile sites or urine of the three most common types of CRE (Escherichia coli, Enterobacter spp., or Klebsiella spp.) and A. baumannii that are resistant to imipenem, meropenem, doripenem, or ertapenem using current CLSI breakpoints (ertapenem excluded for Acinetobacter isolates). A MuGSI incident case is defined as the first eligible isolate of each species collected from a Hennepin or Ramsey County resident in 30 days. In 2016, we initiated statewide CRE surveillance for E. coli, Enterobacter spp., Klebsiella spp., and Citrobacter spp.; MDH also tracks other Enterobacteriaceae including, but not limited to, Morganella spp., Proteus spp., and Providencia spp. PHL tests all CRE isolates for carbapenemase production using a phenotypic assay (modified carbapenem inactivation method [mCIM] or CarbaNP), and conducts PCR on isolates with a positive phenotypic test for KPC, NDM, OXA-48-like, VIM, and IMP genes. All CRA isolates are tested by PCR for KPC, NDM, OXA-48, VIM, and IMP genes, along with Acinetobacter-specific OXA genes (OXA-23, OXA-24, and OXA-58).

In 2019, 558 CRE incident cases representing 515 patients were identified from clinical cultures among Minnesota residents. The most common cases were Enterobacter spp. (219) and Klebsiella spp. (138), followed by E. coli (87), Citrobacter spp. (40), Serratia spp. (31), Providencia spp. (17), Proteus spp. (12), Raoultella spp. (6), Morganella spp. (3), and other Enterobacteriaceae (5). Among the 558 incident cases, there were 157 CRE MuGSI incident cases (representing 145 patients) reported among residents of Hennepin and Ramsey Counties. For MuGSI cases, 66 (42%) cases were Enterobacter spp., 57 (36%) were Klebsiella spp., and 34 (22%) were E. coli. MuGSI isolates harbored carbapenemases KPC (5), NDM (4), and OXA-48 (2). CRE MuGSI incident cases were most frequently isolated from urine (143) followed by blood (8), other sterile sites (5), and pleural fluid (1).

We identified 29 additional CRE surveillance cases (from 23 patients) through colonization screening including 11 residents identified during an outbreak of NDM-producing K. pneumoniae at a long-term care facility. Among surveillance cases with known organism, there were K. pneumoniae (19), E. coli (5), C. freundii (1), E. cloacae (1), and Pluralibacter spp. (1) isolates harboring carbapenemases NDM (21), KPC (5), and OXA-48 (3).

Among the 558 CRE incident cases, 51 (9%) were carbapenemase-producing organisms. Nineteen cases (from 14 patients) were KPC positive (K. pneumoniae [10], C. freundii [2], E. cloacae [2], E. coli [2], K. oxytoca [2], and P. mirabilis [1]). Seventeen cases (from 11 patients) were NDM positive (K. pneumoniae [9], E. coli [6], E. cloacae [1], and P. rettgeri [1]. Twelve cases (from 11 patients) were IMP positive (P. rettgeri [9], P. mirabilis [2], and M. morgannii [1] and 3 cases were OXA-48 positive (E. coli [2] and R. ornithinolytica [1]. For colonization screening among non-outbreak cases, 5 cases (42%) had healthcare exposure outside of the United States or from an area in the United States where carbapenemases are more common.

Among 39 Minnesota residents with carbapenemase-producing isolates, the median age was 66 years (range, 10 to 97); 21 (54%) were female. There were cases in 19 counties; 10 (26%) were residents of Hennepin or Ramsey County, 4 were residents of Dakota County (10%), 3 were residents of Anoka County (8%), and 3 were residents of Waseca County (8%). Twenty (51%) were inpatient at the time of specimen collection, 16 (41%) were in outpatient settings, 2 (5%) were in long-term acute care hospitals, and 1 (3%) was in a long-term care facility. Urine (25) was the most common isolate source followed by blood (4), wound (4), sputum (2), and other sites (4).

Detection of NDM and OXA-48 serve as a reminder to clinicians that assessing travel history to identify receipt of healthcare outside the United States is a critical component of early detection of CRE isolates with carbapenemases that are less common in the United States. In April 2019, MDH released recommendations for admission colonization screening to detect carbapenemase-producing organisms (CPO). In line with CDC recommendations, MDH strongly recommends that Minnesota hospitals screen on admission patients who received healthcare abroad in the last 12 months; healthcare abroad includes ambulatory surgery, hemodialysis, or an overnight stay at a healthcare facility outside of the United States. Furthermore, MDH recommends Minnesota hospitals consider screening patients on admission who received healthcare in U.S. regions where CPO are more common.

In 2018, CDC released the Containment Strategy which provides guidance to state and local public health departments when responding to cases of novel or rare multidrug resistant organisms (MDRO) including CPOs. Novel or rare MDROs are epidemiologically important because these organisms cause severe, difficult-to- treat infections and have the potential to spread within healthcare settings. MDH utilizes the Containment Strategy in response to all single cases of carbapenemase-producing CRE, CRA, and CRPA in Minnesota. This rapid and aggressive action includes prompt identification of the organism, notification and investigation with healthcare facilities, and response or “containing the spread” in an effort to slow the spread of novel or rare MDROs in Minnesota.

In 2019, 21 CRA incident cases representing 18 patients were identified from clinical cultures among Minnesota residents. Wound (6) was the most common isolate source followed by urine (5), sputum (5), lower respiratory tract (2), blood (1), bone (1), and other sterile site (1). Fifteen (71%) cases were hospitalized at the time of culture collection. Other CRA isolates were collected from patients in outpatient settings (3), long-term care facilities (2), and long-term acute care hospitals (1). Eight CRA isolates possessed genes for carbapenemase production (6 with OXA-23 and 2 with OXA-24). Of 21 CRA incident cases, 4 incident cases were reported for MuGSI and all were isolated from urine; 2 cases were found to harbor a carbapenemase, both of which were OXA-23.

Active laboratory- and population-based surveillance for carbapenem-resistant P. aeruginosa (CRPA) was initiated on August 1, 2016 in Hennepin and Ramsey Counties as part of MuGSI and ended on July 31, 2018. This surveillance included all CRPA isolates collected from normally sterile sites, wounds, urine, sputum, throat cultures from cystic fibrosis (CF) patients, or other lower respiratory sites that are resistant to imipenem, meropenem, or doripenem using current CLSI breakpoints. An incident case was defined as the first report of CRPA, or a subsequent report of CRPA ≥30 days after the last incident report. Despite surveillance discontinuation in 2018, PHL continued to test any submitted CRPA isolates for carbapenemase production. In 2019, 2 CRPA isolates demonstrated carbapenemase-production (VIM and NDM).

• Find up to date information at>> Carbapenem-resistant Enterobacteriaceae (CRE), Carbapenem Resistant Pseudomonas aeruginosa (CRPA)
• Full issue>> Annual Summary of Communicable Diseases Reported to the Minnesota Department of Health, 2019