TY - JOUR
T1 - Development and Validation of a Novel Anaerobic Carbapenem Inactivation Method (Ana-CIM) for the Detection of Carbapenemase Production in Bacteroides fragilis
AU - Eberly, Allison R.
AU - Wallace, Meghan A.
AU - Shannon, Samantha
AU - Heitman, Angela K.
AU - Schuetz, Audrey N.
AU - Burnham, Carey Ann D.
AU - Jean, Sophonie
N1 - Funding Information:
We thank Nathan Ledeboer of the Medical College of Wisconsin for providing the B. fragilis WIS-ImiR-001 positive-control isolate and Katie Riese of the Mayo Clinic for technical assistance with this study.
Publisher Copyright:
© 2022 American Society for Microbiology. All Rights Reserved.
PY - 2022/4
Y1 - 2022/4
N2 - Antibiotic resistance, particularly to carbapenems, is of increasing concern in Bacteroides fragilis. Carbapenem resistance in B. fragilis is most often mediated by the activation of chromosomally encoded metallo-b-lactamase cfiA by the presence of an upstream insertion sequence (IS). While traditional phenotypic susceptibility methods and molecular tests to detect carbapenem resistance in B. fragilis exist, they are not available in most clinical microbiology laboratory settings. Here, we describe the development of the anaerobic carbapenem inactivation method (Ana-CIM) for predicting carbapenemase production in B. fragilis based off the principles of the well-established modified carbapenem inactivation method (mCIM) for Enterobacterales and Pseudomonas aeruginosa. We also present the clinical validation and reproducibility of the Ana-CIM at three clinical laboratory sites (with 60 clinical isolates, 45% ertapenem resistant). Compared to ertapenem susceptibility by Etest interpreted by CLSI M100 Ed30, the Ana-CIM accurately detected carbapenem resistance in B. fragilis with categorical agreement (CA) of 87% (52/60) and 0% (0/21) very major error (VME), 11% (4/36) major error (ME), and 7% (4/60) minor error (mE) rates across all sites. Additionally, the Ana-CIM demonstrated high reproducibility with 5 clinical and 3 quality control (QC) isolates tested in triplicate with 3 commercial Mueller-Hinton media across all sites, with 93% (604/648) of replicates within a 2-mm zone size of the mode for each isolate. We conclude that the Ana-CIM can be readily deployed in clinical laboratories at a low cost for detection of carbapenemase-mediated resistance in B. fragilis.
AB - Antibiotic resistance, particularly to carbapenems, is of increasing concern in Bacteroides fragilis. Carbapenem resistance in B. fragilis is most often mediated by the activation of chromosomally encoded metallo-b-lactamase cfiA by the presence of an upstream insertion sequence (IS). While traditional phenotypic susceptibility methods and molecular tests to detect carbapenem resistance in B. fragilis exist, they are not available in most clinical microbiology laboratory settings. Here, we describe the development of the anaerobic carbapenem inactivation method (Ana-CIM) for predicting carbapenemase production in B. fragilis based off the principles of the well-established modified carbapenem inactivation method (mCIM) for Enterobacterales and Pseudomonas aeruginosa. We also present the clinical validation and reproducibility of the Ana-CIM at three clinical laboratory sites (with 60 clinical isolates, 45% ertapenem resistant). Compared to ertapenem susceptibility by Etest interpreted by CLSI M100 Ed30, the Ana-CIM accurately detected carbapenem resistance in B. fragilis with categorical agreement (CA) of 87% (52/60) and 0% (0/21) very major error (VME), 11% (4/36) major error (ME), and 7% (4/60) minor error (mE) rates across all sites. Additionally, the Ana-CIM demonstrated high reproducibility with 5 clinical and 3 quality control (QC) isolates tested in triplicate with 3 commercial Mueller-Hinton media across all sites, with 93% (604/648) of replicates within a 2-mm zone size of the mode for each isolate. We conclude that the Ana-CIM can be readily deployed in clinical laboratories at a low cost for detection of carbapenemase-mediated resistance in B. fragilis.
KW - Bacteroides fragilis
KW - anaerobes
KW - antimicrobial susceptibility testing
KW - carbapenem resistance
KW - carbapenemase production
UR - http://www.scopus.com/inward/record.url?scp=85128802164&partnerID=8YFLogxK
U2 - 10.1128/jcm.02188-21
DO - 10.1128/jcm.02188-21
M3 - Article
C2 - 35313739
AN - SCOPUS:85128802164
SN - 0095-1137
VL - 60
JO - Journal of clinical microbiology
JF - Journal of clinical microbiology
IS - 4
ER -