TY - JOUR
T1 - Informing antibiotic treatment decisions
T2 - Evaluating rapid molecular diagnostics to identify susceptibility and resistance to carbapenems against Acinetobacter spp. In PRIMERS III
AU - the Antibacterial Resistance Leadership Group (ARLG)
AU - Evans, Scott R.
AU - Hujer, Andrea M.
AU - Jiang, Hongyu
AU - Hill, Carol B.
AU - Hujer, Kristine M.
AU - Mediavilla, Jose R.
AU - Manca, Claudia
AU - Tran, Thuy Tien T.
AU - Domitrovic, T. Nicholas
AU - Higgins, Paul G.
AU - Seifert, Harald
AU - Kreiswirth, Barry N.
AU - Patel, Robin
AU - Jacobs, Michael R.
AU - Chen, Liang
AU - Sampath, Rangarajan
AU - Hall, Thomas
AU - Marzan, Christine
AU - Fowler, Vance G.
AU - Chambers, Henry F.
AU - Bonomo, Robert A.
N1 - Funding Information:
Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH) under award number UM1AI104681. Additional NIH support to R.A.B. includes R01AI100560, R01AI063517, and R01AI072219. This study was also supported in part by funds and/or facilities provided by the Cleveland Department of Veterans Affairs, award number 1I01BX001974 to R.A.B. from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development and the Geriatric Research Education and Clinical Center VISN 10 to R.A.B.
Publisher Copyright:
Copyright © 2016 American Society for Microbiology. All Rights Reserved.
PY - 2017/1
Y1 - 2017/1
N2 - The widespread dissemination of carbapenem-resistant Acinetobacter spp. has created significant therapeutic challenges. At present, rapid molecular diagnostics (RMDs) that can identify this phenotype are not commercially available. Two RMD platforms, PCR combined with electrospray ionization mass spectrometry (PCR/ESI-MS) and molecular beacons (MB), for detecting genes conferring resistance/susceptibility to carbapenems in Acinetobacter spp. were evaluated. An archived collection of 200 clinical Acinetobacter sp. isolates was tested. Predictive values for susceptibility and resistance were estimated as a function of susceptibility prevalence and were based on the absence or presence of beta-lactamase (bla) NDM, VIM, IMP, KPC, and OXA carbapenemase genes (e.g., blaOXA-23, blaOXA-24/40, and blaOXA-58 found in this study) against the reference standard of MIC determinations. According to the interpretation of MICs, 49% (n = 98) of the isolates were carbapenem resistant (as defined by either resistance or intermediate resistance to imipenem). The susceptibility sensitivities (95% confidence interval [CI]) for imipenem were 82% (74%, 89%) and 92% (85%, 97%) for PCR/ESI-MS and MB, respectively. Resistance sensitivities (95% CI) for imipenem were 95% (88%, 98%) and 88% (80%, 94%) for PCR/ESI-MS and MB, respectively. PRIMERS III establishes that RMDs can discriminate between carbapenem resistance and susceptibility in Acinetobacter spp. In the context of a known prevalence of resistance, SPVs and RPVs can inform clinicians regarding the best choice for empiric antimicrobial therapy against this multidrug-resistant pathogen.
AB - The widespread dissemination of carbapenem-resistant Acinetobacter spp. has created significant therapeutic challenges. At present, rapid molecular diagnostics (RMDs) that can identify this phenotype are not commercially available. Two RMD platforms, PCR combined with electrospray ionization mass spectrometry (PCR/ESI-MS) and molecular beacons (MB), for detecting genes conferring resistance/susceptibility to carbapenems in Acinetobacter spp. were evaluated. An archived collection of 200 clinical Acinetobacter sp. isolates was tested. Predictive values for susceptibility and resistance were estimated as a function of susceptibility prevalence and were based on the absence or presence of beta-lactamase (bla) NDM, VIM, IMP, KPC, and OXA carbapenemase genes (e.g., blaOXA-23, blaOXA-24/40, and blaOXA-58 found in this study) against the reference standard of MIC determinations. According to the interpretation of MICs, 49% (n = 98) of the isolates were carbapenem resistant (as defined by either resistance or intermediate resistance to imipenem). The susceptibility sensitivities (95% confidence interval [CI]) for imipenem were 82% (74%, 89%) and 92% (85%, 97%) for PCR/ESI-MS and MB, respectively. Resistance sensitivities (95% CI) for imipenem were 95% (88%, 98%) and 88% (80%, 94%) for PCR/ESI-MS and MB, respectively. PRIMERS III establishes that RMDs can discriminate between carbapenem resistance and susceptibility in Acinetobacter spp. In the context of a known prevalence of resistance, SPVs and RPVs can inform clinicians regarding the best choice for empiric antimicrobial therapy against this multidrug-resistant pathogen.
KW - Acinetobacter
KW - Beta-lactams
KW - Carbapenemases
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UR - http://www.scopus.com/inward/citedby.url?scp=85008394504&partnerID=8YFLogxK
U2 - 10.1128/JCM.01524-16
DO - 10.1128/JCM.01524-16
M3 - Article
C2 - 27795336
AN - SCOPUS:85008394504
SN - 0095-1137
VL - 55
SP - 134
EP - 144
JO - Journal of clinical microbiology
JF - Journal of clinical microbiology
IS - 1
ER -