title: Informing Antibiotic Treatment Decisions: Evaluating Rapid Molecular Diagnostics To Identify Susceptibility and Resistance to Carbapenems against Acinetobacter spp. in PRIMERS III.
abstract: 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-58found 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.
authors: Center for Biostatistics in AIDS Research and the Department of Biostatistics, Harvard University, Boston, Massachusetts, USA evans@sdac.harvard.edu robert.bonomo@va.gov.
authors: Scott R
authors: SR
authors: Evans
authors: Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.|Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.
authors: Andrea M
authors: AM
authors: Hujer
authors: Center for Biostatistics in AIDS Research and the Department of Biostatistics, Harvard University, Boston, Massachusetts, USA.
authors: Hongyu
authors: H
authors: Jiang
authors: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors: Carol B
authors: CB
authors: Hill
authors: Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.|Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.
authors: Kristine M
authors: KM
authors: Hujer
authors: Public Health Research Institute Center, New Jersey Medical School-Rutgers University, Newark, New Jersey, USA.
authors: Jose R
authors: JR
authors: Mediavilla
authors: Public Health Research Institute Center, New Jersey Medical School-Rutgers University, Newark, New Jersey, USA.
authors: Claudia
authors: C
authors: Manca
authors: Center for Biostatistics in AIDS Research and the Department of Biostatistics, Harvard University, Boston, Massachusetts, USA.
authors: Thuy Tien T
authors: TT
authors: Tran
authors: Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.|Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.
authors: T Nicholas
authors: TN
authors: Domitrovic
authors: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.|German Center for Infection Research (DZIF), Partner Site Bonn, Cologne, Germany.
authors: Paul G
authors: PG
authors: Higgins
authors: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.|German Center for Infection Research (DZIF), Partner Site Bonn, Cologne, Germany.
authors: Harald
authors: H
authors: Seifert
authors: Public Health Research Institute Center, New Jersey Medical School-Rutgers University, Newark, New Jersey, USA.
authors: Barry N
authors: BN
authors: Kreiswirth
authors: Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors: Robin
authors: R
authors: Patel
authors: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors: Michael R
authors: MR
authors: Jacobs
authors: Public Health Research Institute Center, New Jersey Medical School-Rutgers University, Newark, New Jersey, USA.
authors: Liang
authors: L
authors: Chen
authors: IBIS Biosciences Inc., an Abbott Company, Carlsbad, California, USA.
authors: Rangarajan
authors: 0000-0002-2951-6372
authors: R
authors: Sampath
authors: IBIS Biosciences Inc., an Abbott Company, Carlsbad, California, USA.
authors: Thomas
authors: T
authors: Hall
authors: IBIS Biosciences Inc., an Abbott Company, Carlsbad, California, USA.
authors: Christine
authors: C
authors: Marzan
authors: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA.|Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
authors: Vance G
authors: VG
authors: Fowler
authors: University of California, San Francisco General Hospital, San Francisco, California, USA.
authors: Henry F
authors: HF
authors: Chambers
authors: Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA evans@sdac.harvard.edu robert.bonomo@va.gov.|Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.|Departments of Pharmacology, Molecular Biology and Microbiology, Biochemistry, and Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors: Robert A
authors: RA
authors: Bonomo
mesh_terms: D000150:Acinetobacter / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D015780:Carbapenems / Q000494:pharmacology*; D017931:DNA Primers; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods*; D057089:Pathology, Molecular / Q000379:methods*; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D013997:Time Factors; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D017931:DNA Primers; D001618:beta-Lactamases; C063912:carbapenemase
keywords: Acinetobacter; beta-lactams; carbapenemases