1604. Informing Antibiotic Treatment Decisions: Evaluating Rapid Molecular Diagnostics (RMDs) to Identify Susceptibility and Resistance to Carbapenems against Acinetobacter spp. PRIMERS –III
Session: Poster Abstract Session: ESBL and CRE Diagnostics
Saturday, October 10, 2015
Room: Poster Hall

Background: Due to rising antimicrobial resistance, carbapenems are the cornerstone of therapy for the treatment of serious infections due to Acinetobacter spp. Unfortunately, the widespread dissemination of metallo-beta-lactamases (MBLs) and OXA carbepenemases has created significant therapeutic challenges. In the US, ~12,000 cases of multidrug-resistant Acinetobacter infections occur, associated with ~500 deaths per year. More than half of the isolates encountered are resistant to carbapenems; knowing when to use alternative therapies can be lifesaving. At present, RMDs that can identify carbapenem resistance are not available.

Methods: Two RMD platforms (PCR/ESI-MS and Molecular Beacons™ [MB]) for identifying resistance/susceptibility to carbapenems in Acinetobacter spp. were evaluated. An archived collection of 200 clinical Acinetobacter isolates from the Northeast and Midwest US were tested using Microscan. The very major error (VME) and major error (ME) rates were estimated based on the absence or presence of blaMBLs and blaOXA genes (e.g., OXA-23, -40, -58, NDM, KPC, VIM, IMP) against the reference standard of MIC determination. Predictive values for susceptibility and resistance were estimated as a function of susceptibility prevalence.


Results: 48.5% (n=97) of the isolates were carbapenem-resistant. The rates of MEs for imipenem (n=103) were 17% (11%, 26%) and 8% (3%, 15%) for PCR/ESI-MS and MB, respectively. The rates of VMEs (n=97) were 4% (1%, 9%) and 11% (6%, 19%) for PCR/ESI-MS and MB, respectively. Results for meropenem and doripenem were similar (Figure 1). Assuming 40% imipenem susceptibility, the susceptibility predictive values were 93% (87%, 99%) and 85% (77%, 92%) for PCR/ESI-MS and MB, respectively, while resistance predictive values were 89% (85%, 93%) and 94% (91%, 98%) for PCR/ESI-MS and MB, respectively.

Conclusion: Using a collection with a significant percentage of carbapenem-resistant isolates, MB and PCR/ESI-MS can discriminate between carbapenem susceptibility and resistance, thus demonstrating the potential to inform empiric antimicrobial therapy against Acinetobacter spp. The complexity of the carbapenem-resistant phenotype (porin mutations, efflux pumps) may explain misclassified isolates.

Figure 1

Scott Evans, PhD, MS1, Hongyu Jiang, MS2, Andrea Hujer, BS3, Kristine M. Hujer, BS4, Jose Mediavilla, MPH, MBS5, Claudia Manca, PhD6, Carol Hill, PhD7, Barry N. Kreiswirth, PhD8, Robin Patel, MD, FIDSA, FRCP(C), D(ABMM), FACP, F(AAM)9, Michael R. Jacobs, MD, PhD10, Liang Chen, PhD6, Rangarajan Sampath, PhD11, Thomas Hall, PhD12, Christine Marzan, PhD12, Vance G. Fowler Jr., MD13, Henry Chambers, MD, FIDSA14 and Robert A. Bonomo, MD15, (1)Harvard University, Boston, MA, (2)Biostatistics, Harvard School of Public Health, Boston, MA, (3)Case Western Reserve University, Cleveland, OH, (4)Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, (5)Public Health Research Institute–Rutgers University, Newark, NJ, (6)Public Health Research Institute - Rutgers University, Newark, NJ, (7)Duke Clinical Research Institute, Durham, NC, (8)University of Medicine and Dentistry of NJ, PHRI TB Center, Newark, NJ, (9)Divisions Of Clinical Microbiology and Infectious Diseases, Mayo Clinic, Rochester, MN, (10)Case Western Reserve University/University Hospitals of Cleveland, Cleveland, OH, (11)Ibis Biosciences, Inc, Carlsbad, CA, (12)Ibis Biosciences, Carlsbad, CA, (13)Duke University, Durham, NC, (14)Medicine, University of California San Francisco, San Francisco, CA, (15)Pharmacology, Molecular Biology, and Microbiology, Case Western Reserve University, Cleveland, OH


S. Evans, None

H. Jiang, None

A. Hujer, None

K. M. Hujer, None

J. Mediavilla, None

C. Manca, None

C. Hill, None

B. N. Kreiswirth, None

R. Patel, nanoMR: Grant Investigator , Research grant
Curetis: Grant Investigator , Research grant
Check-Points: Grant Investigator , Research grant
3M: Grant Investigator , Research grant
Cubist/Merck: Grant Investigator , Research grant
Hutchison Biofilm Medical Solutions: Grant Investigator , Research grant
Accelerate Diagnostics: Grant Investigator , Research grant
Actavis: Grant Investigator , Research grant
Curetis: Consultant , Consulting fee
NA: holding patents on B. pertussis/parapertussis PCR, an anti-biofilm substance, and a device/method for sonication , Patent

M. R. Jacobs, None

L. Chen, None

R. Sampath, Abbott: Employee , Salary

T. Hall, Ibis Biosciences, an Abbott Company: Employee , Salary

C. Marzan, Ibis Biosciences, an Abbott Company: Employee , Salary

V. G. Fowler Jr., NIH: Grant Investigator , Grant recipient and Research grant
MedImmune: Grant Investigator , Research grant
Forest/Cerexa: Grant Investigator , Research grant
Pfizer: Consultant and Grant Investigator , Consulting fee and Research grant
Merck: Board Member and Grant Investigator , Research grant
Advanced Liquid Logics: Grant Investigator , Research grant
Theravance: Grant Investigator , Research grant
Novartis: Consultant and Grant Investigator , Consulting fee and Research grant
Cubist: Consultant and Grant Investigator , Consulting fee and Research grant
Galderma: Consultant , Consulting fee
Novadigm: Consultant , Consulting fee
Durata: Consultant , Consulting fee
Debiopharm: Consultant , Consulting fee
Genentech: Consultant , Consulting fee
Achaogen: Consultant , Consulting fee
Affinium: Consultant , Consulting fee
Medicines Co.: Consultant , Consulting fee
Cerexa: Consultant , Consulting fee
Tetraphase: Consultant , Consulting fee
Trius: Consultant , Consulting fee
MedImmune: Consultant , Consulting fee
Bayer: Consultant , Consulting fee
Theravance: Consultant , Consulting fee
Basilea: Consultant , Consulting fee
Duke University Medical Center: Employee , Salary
NCGR: Patent , Patent
UpToDate: Royalties , Royalties
Green Cross: Development of educational pursuits , Development of educational pursuits

H. Chambers, Cubist: Grant Investigator , Grant recipient
AstraZeneca: Scientific Advisor , Consulting fee
Pfizer: Scientific Advisor , Consulting fee
Theravance: Scientific Advisor , Consulting fee
Merck: Shareholder , Stock holder
Genentech: Investigator and Scientific Advisor , Consulting fee and Research grant

R. A. Bonomo, AstraZeneca: Grant Investigator , Research grant
Merck: Grant Investigator , Research grant
Melinta: Grant Investigator , Research grant
VA Merit Review Board: Grant Investigator , Research grant
NIH: Grant Investigator , Research grant

Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 7th with the exception of research findings presented at the IDWeek press conferences.