Carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas aeruginosa (CRPA), 2017
Carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas aeruginosa (CRPA) 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 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. P. aeruginosa most commonly causes pneumonia in individuals with chronic lung diseases, particularly cystic fibrosis (CF), or those who are immunocompromised. 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 known as 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], active on imipenem [IMP], and oxacillinase [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).
MDH first identified a KPC-producing CRE in February 2009, and began voluntary reporting, including isolate submission. 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. 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 (CLSI) breakpoints (ertapenem excluded for Acinetobacter isolates). An incident case is defined as the first eligible isolate of each species collected from a Hennepin or Ramsey County resident in 30 days. Statewide CRE surveillance was initiated in 2016 and includes Citrobacter spp. as well as E. coli, Enterobacter spp. and Klebsiella spp. The PHL tested all isolates for carbapenemase production using either a phenotypic assay (carbapenem inactivation method [CIM], modified carbapenem inactivation method [mCIM], or CarbaNP), or a PCR targeting KPC and NDM genes.
In 2017, 468 Enterobacteriaceae incident cases representing 441 patients were identified. Twenty-nine (6%) isolates (from 22 patients) were KPC positive (E. cloacae , K. pneumoniae , K. oxytoca , C. freundii , E. coli , and R. planticola . Of note, 2 patients were positive for two different organisms producing KPC in the same calendar year. Six incident cases (representing 6 patients) were NDM positive (K. pneumoniae , E. coli , and K. oxytoca ]. All but 1 had exposure to health care overseas (Asia, Africa). Of the incident cases, 3 isolates (representing 3 patients) were IMP positive (P. rettgeri , M. morgannii ).
In 2017, 21 CRA incident cases from 17 patients were identified. One isolate was NDM positive, with the patient having received health care outside of the United States prior to initial culture.
Of the 22 Minnesota residents with KPC-positive isolates, the median age was 64 years (range, 23 to 94); 15 (68%) were male, and 8 (36%) were residents of Hennepin or Ramsey County. Twelve (55%) patients were white, 2 (9%) were black, 1 (5%) was American Indian, and 7 (32%) were of unknown race. Urine (12) was the most common source followed by wounds (3), sputum (3), lower respiratory tract (2), and other sites (3). Sixteen (72%) were hospitalized (10 hospitalized ≥3 days prior to culture); median length of stay was 14 days (range, 4 to 223). Seven patients (32%) required ICU care; in hospital mortality was 5%. 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 143 incident CRE cases (representing 137 patients) were reported in 2017. Of these, 90 were Enterobacter spp., 28 were Klebsiella spp., and 25 were E. coli. KPC was identified in 6 (4%) MuGSI CRE (E. cloacae  and K. pneumoniae ). CRE was most frequently isolated from urine (135) followed by blood (3), bone (2), and other sites (3). One incident case of CRA was reported for MuGSI, isolated from urine.
In 2017, 9 NDM-producing CRE and 1 NDM-producing CRA were detected. To date, 37 NDM-producing organisms (K. pneumoniae , E. coli , K. oxytoca , C. freundii , P. rettgeri , A. baumannii , and Pseudomonas aeruginosa ) from 28 patients treated in Minnesota have been detected. This includes 14 Minnesota residents and 14 nonresidents, all but two of whom had received medical care outside the United States (23 patients) or in a non-Minnesota U.S. facility (3 patients) prior to their NDM-positive culture in Minnesota. In 2017, the PHL identified, and CDC confirmed, 3 IMP-producing CRE (P. rettgeri , M. morgannii ) from Minnesota residents (no history of travel or foreign health care exposures) and 4 OXA-48- producing isolates (E. coli  and R. ornithinolytica ) from two residents with significant health care exposure outside the United States prior to receiving healthcare in Minnesota, and two non-residents with no significant health care exposure outside the United States.
In summary, 8% of Enterobacteriaceae isolates tested by the PHL during 2017 were KPC-positive; 2 patients had multiple KPC-producing organisms isolated. 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). Active laboratory- and population based surveillance for CRPA was initiated on August 1, 2016 in Hennepin and Ramsey Counties as part of MuGSI. This surveillance includes all isolates of P. aeruginosa collected from normally sterile sites, wounds, urine, sputum, throat cultures from 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. The PHL tested all isolates submitted in 2017 for carbapenemase production. In 2017, 954 CRPA cases, representing 506 patients, were identified; 551 cases from 256 unique patients were reported in Hennepin and Ramsey County residents and met the MuGSI case definition; 380 (69%) cases were classified as incident. Thirty-seven (14%) patients had CF, accounting for 170 (31%) total CRPA MuGSI reports; 91 (54%) cases were considered incident. CF patients had an average of five separate reports of CRPA per year during 2017, while patients without CF had an average of one report of CRPA. Nine (2%) isolates from three patients were carbapenemase positive by a phenotypic screening test. Eight isolates were PCR-confirmed as carbapenemase-producers (CP), including 7 IMP-positive isolates and 1 VIM-positive isolate. Both patients with CP-CRPA were recent immigrants to the United States and had international healthcare exposure. One isolate collected from a Minnesota resident with no history of overseas healthcare exposure was found, by whole genome sequencing, to be carrying two potentially inducible genes (PDC-3 and OXA-50) capable of hydrolyzing carbapenems.
Of the 219 patients who did not have CF, the median age was 62 (range, 1 to 93); 119 (54%) were male; 128 (58%) were white, 51 (23%) were of unknown race, 29 (13%) were black, 7 (3%) were Asian/Pacific Islander, and 3 (1%) were American Indian. Sputum (149) was the most common source, followed by urine (122), wounds (66), lower respiratory sites (45), and other sterile sources (18). One hundred ninety-nine (52%) were hospitalized at the time of specimen collection, 90 (24%) were outpatients, 59 (15%) were in a longterm acute care hospital, and 29 (8%) were in a skilled nursing facility. Among the 37 CF patients, the median age was 35 years (range, 19-66); 18 (49%) were male; 27 (73%) were white, 8 (22%) were of unknown race, and 2 (5%) were Asian/Pacific Islander. All isolates were collected from a respiratory site; 89% were collected from sputum. Thirty-two patients were hospitalized at the time of specimen collection, while the majority, 137 (81%) were seen in outpatient care settings.
CDC identified CRE as one of three urgent antibiotic resistance threats requiring immediate and aggressive action. In 2017, the World Health Organization (WHO) ranked the 12 bacteria that posed the greatest threat to human health: CRE, CRA, as well as CRPA are the three bacteria most urgently in need of development of new antibiotics.
- For up to date information see>> Carbapenem-resistant Enterobacteriaceae (CRE)
- Full issue>> Annual Summary of Communicable Diseases Reported to the Minnesota Department of Health, 2017