Informing Antibiotic Treatment Decisions: Evaluating Rapid Molecular Diagnostics To Identify Susceptibility and Resistance to Carbapenems against Acinetobacter spp. in PRIMERS III

Scott R Evans; Andrea M Hujer; Hongyu Jiang; Carol B Hill; Kristine M Hujer; Jose R Mediavilla; Claudia Manca; Thuy Tien T Tran; T Nicholas Domitrovic; Paul G Higgins; Harald Seifert; Barry N Kreiswirth; Robin Patel; Michael R Jacobs; Liang Chen; Rangarajan Sampath; Thomas Hall; Christine Marzan; Vance G Fowler Jr; Henry F Chambers; Robert A Bonomo

doi:10.1128/JCM.01524-16

Informing Antibiotic Treatment Decisions: Evaluating Rapid Molecular Diagnostics To Identify Susceptibility and Resistance to Carbapenems against Acinetobacter spp. in PRIMERS III

J Clin Microbiol. 2016 Dec 28;55(1):134-144. doi: 10.1128/JCM.01524-16. Print 2017 Jan.

Authors

Scott R Evans¹, Andrea M Hujer^{2

3}, Hongyu Jiang⁴, Carol B Hill⁵, Kristine M Hujer^{2

3}, Jose R Mediavilla⁶, Claudia Manca⁶, Thuy Tien T Tran⁴, T Nicholas Domitrovic^{2

3}, Paul G Higgins^{7

8}, Harald Seifert^{7

8}, Barry N Kreiswirth⁶, Robin Patel⁹, Michael R Jacobs¹⁰, Liang Chen⁶, Rangarajan Sampath¹¹, Thomas Hall¹¹, Christine Marzan¹¹, Vance G Fowler Jr^{5

12}, Henry F Chambers¹³, Robert A Bonomo^{14

3

15}

Affiliations

¹ Center for Biostatistics in AIDS Research and the Department of Biostatistics, Harvard University, Boston, Massachusetts, USA [email protected] [email protected].
² Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
³ Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.
⁴ Center for Biostatistics in AIDS Research and the Department of Biostatistics, Harvard University, Boston, Massachusetts, USA.
⁵ Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA.
⁶ Public Health Research Institute Center, New Jersey Medical School-Rutgers University, Newark, New Jersey, USA.
⁷ Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
⁸ German Center for Infection Research (DZIF), Partner Site Bonn, Cologne, Germany.
⁹ Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
¹⁰ Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
¹¹ IBIS Biosciences Inc., an Abbott Company, Carlsbad, California, USA.
¹² Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
¹³ University of California, San Francisco General Hospital, San Francisco, California, USA.
¹⁴ Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA [email protected] [email protected].
¹⁵ Departments of Pharmacology, Molecular Biology and Microbiology, Biochemistry, and Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

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., bla_OXA-23, bla_OXA-24/40, and bla_OXA-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.

Keywords: Acinetobacter; beta-lactams; carbapenemases.

Publication types

Comparative Study
Evaluation Study

MeSH terms

Acinetobacter / drug effects
Acinetobacter / enzymology
Acinetobacter / genetics*
Anti-Bacterial Agents / pharmacology*
Bacterial Proteins / genetics*
Carbapenems / pharmacology*
DNA Primers
Humans
Microbial Sensitivity Tests / methods*
Pathology, Molecular / methods*
Predictive Value of Tests
Sensitivity and Specificity
Time Factors
beta-Lactam Resistance*
beta-Lactamases / genetics*

Substances

Anti-Bacterial Agents
Bacterial Proteins
Carbapenems
DNA Primers
beta-Lactamases
carbapenemase

Abstract

Publication types

MeSH terms

Substances

Grants and funding