Improved Phenotype-Based Definition for Identifying Carbapenemase Producers among Carbapenem-Resistant<i>Enterobacteriaceae</i>

Chea, Nora; Bulens, Sandra N.; Kongphet-Tran, Thiphasone; Lynfield, Ruth; Shaw, Kristin M.; Vagnone, Paula Snippes; Kainer, Marion A.; Muleta, Daniel; Wilson, Lucy; Vaeth, Elisabeth; Dumyati, Ghinwa; Concannon, Cathleen; Phipps, Erin C; Culbreath, Karissa; Janelle, Sarah J.; Bamberg, Wendy; Guh, Alice; Limbago, Brandi; Kallen, Alexander J.

doi:10.3201/eid2109.150198

Cited by 61 publications

(50 citation statements)

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“…The authors suggested that the use of a second phenotypic test for carbapenemase, such as the modified Hodge test (MHT), improved specificity for the identification of CP-CRE. However, this was most effective for isolates of K. pneumoniae and Escherichia coli, whereas 26% of Enterobacter species isolates demonstrated false-positive MHT results (18). The MHT is also associated with false-negative results for NDM-producing CRE (6).…”

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confidence: 96%

“…Similarly, some isolates without carbapenemases are resistant to imipenem, meropenem, and/or doripenem due to changes in porin proteins, often in conjunction with low-level AmpC or ESBL activities, albeit such isolates are less common (19). For instance, one study using the CDC definition found that 55% of isolates labeled as CP-CRE did not harbor carbapenemase genes (18). The authors suggested that the use of a second phenotypic test for carbapenemase, such as the modified Hodge test (MHT), improved specificity for the identification of CP-CRE.…”

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confidence: 99%

“…In 2015, the CDC published a new surveillance definition for CRE in an attempt to help laboratories and epidemiologists to identify CP-CRE (18). This definition includes all members of the Enterobacteriaceae that are resistant to any carbapenem tested (ertapenem at Ն2 g/ml, meropenem at Ն4 g/ml, imipenem at Ն4 g/ml, and/or doripenem at Ն4 g/ml) and any isolate that harbors a carbapenemase gene or has a positive phenotypic test for carbapenemase.…”

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

2017

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Carbapenemase-producing Enterobacteriaceae (CPE) are a significant threat to public health. In 2015, CDC revised the surveillance definition for CPE to include all Enterobacteriaceae resistant to any carbapenem tested. However, this definition is associated with poor specificity. We evaluated the performance of this definition, compared to carbapenemase PCR, for a collection of 125 Enterobacteriaceae. We also investigated the impact of ancillary testing for carbapenemase of isolates that met the CDC CPE surveillance definition. The two ancillary tests evaluated were the Xpert Carba-R assay, a molecular test, and the carbapenem inactivation method (CIM). Two variables were evaluated for the CIM: suspension of organisms in double-distilled water (ddH 2 O) versus tryptic soy broth (TSB) to incubate disks, and incubation of plates for 6 h versus 18 to 20 h. The sensitivity and specificity of the Carba-R assay were 100% compared to the results of in-house PCR. The sensitivities of the CIM performed with TSB were 94.6% when read at 6 h and 97.7% when read at 18 to 20 h; the sensitivities with ddH 2 O were 88.0% when read at 6 h and 93.0% when incubated for 18 to 20 h. The specificity was 100% for all variables tested. Without ancillary testing, the sensitivity of the CDC definition was 98.9% for CPE, and the specificity was 6.1%. Testing isolates that screened positive by the CDC definition with the Xpert Carba-R did not change the sensitivity, and it improved the specificity to 100%. Similarly, the use of the CIM (TSB and 18 to 20 h of incubation) to confirm screen-positive isolates resulted in a sensitivity of 95.6% and specificity of 100%.KEYWORDS Carba-R, Enterobacteriaceae, carbapenamase, carbapenem inactivation method C arbapenem-resistant Enterobacteriaceae (CRE), particularly those that are resistant due to carbapenemase production, are a significant threat to public health. Infections caused by CRE are associated with a high attributable mortality (1), and U.S. surveillance data have demonstrated a steady increase in the burden of disease caused by CRE since 2000 (2). The U.S. CRE epidemic is driven, in part, by Klebsiella pneumoniae isolates of sequence type (ST) 258 that express the K. pneumoniae carbapenemase (KPC) (3). Transfer of patients colonized or infected with this organism between health care institutions is thought to have led to the dissemination of ST 258 K. pneumoniae across the country. One particularly well documented outbreak described by the Centers for Disease Control and Prevention Epicenter Program demonstrated that patient transfers between 26 health care facilities across four counties lead to the spread of KPCproducing CRE to 40 patients over a 1-year period (4). Subsequent studies in this region documented that nearly 1 in 3 residents of long-term acute care facilities were colonized with KPC-producing CRE (5). CRE harboring other carbapenem-hydrolyzing enzymes, such as NDM, VIM, IMP, or the OXA-48 type, common in other areas of the world (6), are also spreading in the Unite...

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

2017

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“…This change was also made despite the recognition that this definition would capture some CRE that were not carbapenemase producers. The former definition and other definitions that do not include ertapenem have the potential to not detect CRE producing OXA-48-like carbapenemases, which are now emerging in the United States (16). One way to refine this definition, and thus improve its specificity for CP-CRE, is to perform a carbapenemase test on all CRE detected.…”

Section: Detection Of Carbapenemase-producing Carbapenem-resistant Enmentioning

confidence: 99%

The Problem of Carbapenemase-Producing-Carbapenem-Resistant-Enterobacteriaceae Detection

2016

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The emergence and spread of carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) are a significant clinical and public health concern. Reliable detection of CP-CRE is the first step in combating this problem. There are both phenotypic and molecular methods available for CP-CRE detection. There is no single detection method that is ideal for all situations.G ram-negative bacteria, specifically Enterobacteriaceae, are common causes of both community-acquired and hospitalacquired infections, including urinary tract, bloodstream, and lower respiratory tract infections. These bacteria can acquire genes encoding multiple antibiotic resistance mechanisms, including extended-spectrum ␤-lactamases (ESBLs), AmpCs, and carbapenemases (1). ␤-Lactam drugs are often the primary therapeutic option for serious infections, and carbapenems in particular are often considered agents of last resort. Thus, the emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) are a significant clinical and public health concern. CRE are often resistant to all ␤-lactam drugs and frequently carry mechanisms conferring resistance to other antimicrobial classes, further limiting treatment options. Although CRE infections are relatively infrequent, they have become more common in the United States since their emergence (2, 3, 4). Infections with these resistant bacteria are associated with higher mortality rates than those for infections caused by carbapenem-susceptible organisms (5).The epidemiologic description and phenotypic detection of CRE are complicated by the fact that Enterobacteriaceae may be nonsusceptible (intermediate or resistant) to carbapenems via a variety of mechanisms. Proteus, Providencia, and Morganella species demonstrate intrinsically elevated MICs to imipenem (6). Enterobacteriaceae can also produce ␤-lactamase enzymes such as AmpCs (chromosomal or acquired) and ESBLs that do not readily inactivate carbapenems on their own but can confer carbapenem resistance when combined with chromosomal porin mutations that prevent accumulation of ␤-lactam agents in the bacteria. Finally, the production of carbapenemase enzymes, typically found on mobile genetic elements, that inactivate carbapenem and other ␤-lactam antibiotics is increasingly common (1, 2). These carbapenemase-producing CRE (CP-CRE) frequently carry multiple resistance mechanisms, which can include redundant ␤-lactamases such as AmpCs and ESBLs and genes conferring resistance to other antimicrobial classes.Among the various types of CRE, CP-CRE have received the most attention because they have the greatest potential to contribute to the overall problem of antimicrobial resistance. Production of a carbapenemase usually confers resistance on its own, without requiring additional chromosomal mutations or accessory mechanisms. Because carbapenemase genes are carried on mobile genetic elements, these genes can be spread horizontally to naive bacteria, thus contributing to the reservoir of resistance in both environmental and clinical Enterob...

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“…CP-CRE are particularly concerning from an infection control standpoint, as the genes encoding carbapenemases are generally located on mobile genetic elements (i.e., plasmids, transposons, and insertion sequences) and are easily transmissible to other Gramnegative organisms (1). In the United States, carbapenemase genes are most commonly bla KPC (2). However, other carbapenemase genes (e.g., bla NDM , bla VIM , bla IMP , and bla OXA ) have been increasingly encountered, due in large part to international migration and medical tourism (3).…”

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Determining the Optimal Carbapenem MIC That Distinguishes Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae

Tamma

Huang

Opene

et al. 2016

Antimicrob Agents Chemother

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c Carbapenemase-producing (CP) Enterobacteriaceae are largely responsible for the rapid spread of carbapenem-resistant Enterobacteriaceae (CRE). Distinguishing CP-CRE from non-CP-CRE has important infection control implications. In a cohort of 198 CRE isolates, for isolates that remained susceptible or intermediate to some carbapenem antibiotics, an ertapenem MIC of 0.5 g/ml and meropenem, imipenem, and doripenem MICs of 2 g/ml were best able to distinguish CP-CRE from non-CP-CRE isolates.

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Improved Phenotype-Based Definition for Identifying Carbapenemase Producers among Carbapenem-ResistantEnterobacteriaceae

Abstract: A new, less restrictive definition increases detection of Klebsiella pneumoniae carbapenemase producers.

Cited by 61 publications

References 11 publications

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

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

The Problem of Carbapenemase-Producing-Carbapenem-Resistant-Enterobacteriaceae Detection

Determining the Optimal Carbapenem MIC That Distinguishes Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae

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