Commentary: Continuing Challenges for the Clinical Laboratory for Detection of Carbapenem-Resistant Enterobacteriaceae

Abstract

Over the last decade, carbapenem-resistant Enterobacteriaceae (CRE) have become an urgent threat to health in the United States and elsewhere in the world (1, 2). The Centers for Disease Control and Prevention (CDC) have reported a steady increase in the burden of disease from CRE, particularly, carbapenem-resistant Klebsiella pneumoniae, in the United States (3, 4). Surveillance data from Chicago showed that 30% of residents of long-termacute-care hospitals (LTACHs) and 3.3% of patients in hospital intensive care units (ICUs) were CRE carriers, suggesting that CRE infections are now endemic in parts of the United States (5). The spread of CRE in the U.S. health care system comes at a great cost because there are limited available treatment options and high attributable mortality from CRE (6, 7).Spread of CRE in the United States appears to be driven by movement of patients though the health care system (8, 9). For instance, the CDC epicenters program demonstrated that patient transfers led to regional spread of CRE across 26 health care facilities in four counties (8). The transfer of CRE-colonized patients not only moves these organisms between institutions but also accelerates the epidemic through subsequent patient transmission events at each institution as the incidence of CRE increases (10) (11). To this point, a study of New York hospitals found that the odds of a patient acquiring CRE increased by 15% for each 1% increase in overall patient colonization at the facility (12).Recent research has shown some promising findings for curbing the spread of CRE. Hayden and colleagues demonstrated that the use of an infection prevention bundle that included chlorhexidine bathing and strict isolation practices in a high-CRE-burden LTACH was able to significantly reduce the rates of both new CRE acquisitions and bacteremia cases (13). Computer model estimates suggest that a coordinated regional response, compared to individual hospital actions, has the potential to reduce or even eliminate CRE transmission (10, 11).Such interventions require an understanding of the prevalence of CRE at the institutional level. However, the true burden of CRE at the local, regional, or national level remains poorly understood. Our limited understanding of CRE burden is due in part to challenges faced by the clinical laboratory at identifying CRE-in both clinical and surveillance cultures. In 2010, the Clinical and Laboratory Standards Institute (CLSI) revised the carbapenem breakpoints for the Enterobacteriaceae, and the U.S. Food and Drug Administration (FDA) followed suit by revising the drug product labeling to include these revised breakpoints. However, no manufacturer of commercial automated antimicrobial susceptibility test (AST) systems has obtained FDA clearance for these new standards, despite over 5 years having passed since their approval. Almost all laboratories in the United States rely on these systems for routine AST, and few have the resources to conduct the studies required to establish the performance of these syste...

Use of Ancillary Carbapenemase Tests To Improve Specificity of Phenotypic Definitions for Carbapenemase-Producing Enterobacteriaceae

“…The specificities for carbapenemase were only 21% in the initial studies by CDC and 6.1% in the present study. Of concern, the use of this highly sensitive but nonspecific definition in routine practice has the potential to negatively impact patient care, as many hospitals place patients who meet CRE definitions in contact precautions for life (22). Some states, including Illinois, have gone to added measures of tracking these patients via CRE registries to help expedite the implementation of contact precautions and enhanced infection control measures when these patients are admitted to a new health care facility.…”

Emergence of Ceftazidime-Avibactam Resistance Due to Plasmid-Borne bla KPC-3 Mutations during Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infections

“…Such misidentification was inevitable since carbapenemase screening by our laboratory, as at many centers, is triggered by elevated carbapenem MICs. Routine molecular screening for bla KPC has been advocated for rapid detection of carbapenem resistance (28). However, such assays will need to detect specific genes, since KPC variants have different antibiotic affinities and hydrolytic properties.…”

Development of selective medium for IMP-type carbapenemase-producing Enterobacteriaceae in stool specimens

“…The main reservoir of CPE is the intestinal tract, and faecal specimens are conventionally used for the screening of CPE. However, isolation of CPE from faecal specimens is difficult because CPE usually exists as a small proportion of the overall bacterial load [4, 5]. Furthermore, among several types of carbapenemases, enzymes such as OXA-48 and IMP have low capability of hydrolysing carbapenems [6].…”