title: What Is the Appropriate Meropenem MIC for Screening of Carbapenemase-Producing Enterobacteriaceae in Low-Prevalence Settings?
abstract: Infection with carbapenemase-producing Enterobacteriaceae (CPE) has been shown to cause significant illness among hospitalized patients. Given the paucity of treatment options, there is a critical need to stop the spread of CPE. However, screening for the presence of CPE in laboratory settings has been challenging. In order to assess the effectiveness of current CPE detection guidelines, we analyzed the meropenem MIC distribution for a large set of clinical Enterobacteriaceae isolates. A total of 1,022 isolates submitted to the Public Health Ontario Laboratories (PHOL) from January 2011 to March 2014 were examined. Only isolates displaying a meropenem or ertapenem MIC of ≥ 0.25 or ≥ 1 μg/ml, respectively, were included. Carbapenemase-positive isolates were identified by multiplex PCR. We identified 189 isolates positive for carbapenemases, which primarily comprised NDM, KPC, and OXA-48-like carbapenemases, and these isolates were largely Klebsiella spp., Escherichia coli, and Enterobacter spp. Interestingly, 14 to 20% of these isolates displayed meropenem MICs within the susceptible range on the basis of CLSI and EUCAST breakpoint interpretive criteria. While the majority of meropenem-susceptible CPE isolates were observed to be E. coli, meropenem susceptibility was not exclusive to any one species/genus or carbapenemase type. Application of CLSI screening recommendations captured only 86% of carbapenemase-producing isolates, whereas application of EUCAST recommendations detected 98.4% of CPE isolates. In a region with a low carbapenemase prevalence, meropenem-based screening approaches require a cutoff MIC near the epidemiological wild-type threshold in order to achieve nearly optimal CPE identification.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Ramzi
authors.initials: R
authors.lastname: Fattouh
authors.affiliation: Public Health Ontario Laboratories, Public Health Ontario, Toronto, ON, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Tijet
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Division of Infectious Diseases, Department of Medicine, University Health Network/Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Allison
authors.initials: A
authors.lastname: McGeer
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Division of Infectious Diseases, Department of Medicine, University Health Network/Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Poutanen
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Public Health Ontario Laboratories, Public Health Ontario, Toronto, ON, Canada.
authors.forename: Roberto G
authors.initials: RG
authors.lastname: Melano
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Public Health Ontario Laboratories, Public Health Ontario, Toronto, ON, Canada samir.patel@oahpp.ca.
authors.forename: Samir N
authors.initials: SN
authors.lastname: Patel
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism*; D004754:Enterobacter / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D004756:Enterobacteriaceae Infections / Q000188:drug therapy / Q000382:microbiology; D000077727:Ertapenem; D004926:Escherichia coli / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D006801:Humans; D007709:Klebsiella / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D060885:Multiplex Polymerase Chain Reaction; D013845:Thienamycins / Q000494:pharmacology*; D001618:beta-Lactamases / Q000378:metabolism*; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D013845:Thienamycins; D047090:beta-Lactams; D001618:beta-Lactamases; C000601047:beta-lactamase OXA-48, E coli; C063912:carbapenemase; D000077731:Meropenem; D000077727:Ertapenem