Program Schedule

Can Rapid Molecular Diagnostics Assist in the Choice of b-Lactam Antibiotics? An Analysis of Data from PRIMERS-II of the Antibiotic Resistance Leadership Group (ARLG)

Session: Oral Abstract Session: New Approaches to Antibiotic Stewardship
Friday, October 10, 2014: 8:45 AM
Room: The Pennsylvania Convention Center: 107-AB

Background: In PRIMERS-I, the ARLG assessed the performance characteristics of PCR/ESI-MS, molecular beacons (MB), microarrays, and ion torrent sequencing (IT) to detect b-lactam (b-L) resistance in highly drug resistant Escherichia coli (Ec) and Klebsiella pneumoniae (Kp).  In PRIMERS-II, PCR/ESI-MS and MB tested in a blinded fashion a heterogeneous collection of Ec and Kp and asked how well these 2 platforms predicted b-L susceptibility (S) or resistance (R).


Methods: S/R to 14 b-Ls were determined (CLSI) using 196 Ec and Kp isolates.  The probabilities of identifying genetic markers of b-L susceptibility/non-susceptibility based on the absence/presence of bla genes (vs. MIC phenotype as the standard) were estimated using 95% confidence intervals (CIs) for each b-L for each platform.  The performance of each platform was compared.


Results: Select estimated probabilities of detecting genotypic susceptibility/non-susceptibility MIC-defined phenotypes are summarized (Table).  In a community that has a prevalence of 15% ceftazidime resistance and 5% carbapenem resistance, the susceptibility predictive values (SPV) of PLEX-ID and MB are 100%, and 96% for ceftazidime; 100%, and 99% for imipenem.  The non-susceptibility predictive values (nSPV) of PLEX-ID and MB are 69%, and 73% for ceftazidime; 41%, and 50% for imipenem.


Conclusion: Advancing the findings of PRIMERS-I, detecting R/S genotypes in Ec and Kp predicts the probability of a corresponding phenotype identified by susceptibility testing.  Informed decisions regarding the choice of b-L  therapy depends upon the geographic prevalence of bla resistance genes


Table 1:  Estimated probabilities (95% CIs) of detecting genotypic non-susceptibility (i.e., presence of bla genes)





1.00 (0.96, 1.00)

0.77 (0.66, 0.85)


1.00 (0.96, 1.00)

0.77 (0.66, 0.85)


1.00 (0.96, 1.00)

0.77 (0.66, 0.85)


0.82 (0.71, 0.91)

0.68 (0.55, 0.78)


0.93 (0.84, 0.98)

0.75 (0.62, 0.85)

Estimated probabilities (95% CIs) of detecting genotypic susceptibility (i.e., absence of bla genes)





0.92 (0.85, 0.96)

0.95 (0.90, 0.99)


0.88 (0.80, 0.93)

0.95 (0.90, 0.98)


0.93 (0.88, 0.97)

0.96 (0.91, 0.98)


Andrea M. Hujer, BS1, Scott Evans, PhD2, Hongyu Jiang, PhD3, Kristine M. Hujer, BS4, Thomas Hall, PhD5, Christine Marzan, PhD5, Michael Jacobs, MD, PhD6, Ranga Sampath, PhD7, David J. Ecker, PhD5, T. Nicholas Domitrovic, BA4, Claudia Manca, PhD8, Kalyan Chavda, PhD8, Pan Zhang, MD PhD9, Liang Chen, PhD10, Carol Hill, PhD11, Federico Perez, MD12, Barry Kreiswirth, PhD13, Vance Fowler, MD11, Henry Chambers, MD, FIDSA14, Robert Bonomo, MD4,15 and Antimicrobial Resistance Leadership Group, (1)Case Western Reserve University, Cleveland, OH, (2)Center for Biostatistics in AIDS Research, Harvard University, Boston, MA, (3)Biostatistics, Harvard School of Public Health, Boston, MA, (4)Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, (5)Ibis Biosciences, Carlsbad, CA, (6)Case Western Reserve University/University Hospitals of Cleveland, Cleveland, OH, (7)Ibis Biosciences, Inc., A Division of Abbott, Carlsbad, CA, (8)PHRI UMDNJ, Newark, NJ, (9)Weill Cornell Medical College, New York, NY, (10)PHRI and UMDNJ, Newark, NJ, (11)Duke University Medical Center, Durham, NC, (12)Cleveland VAMC Case Western Reserve University, Cleveland Heights, OH, (13)University of Medicine and Dentistry of NJ, PHRI TB Center, Newark, NJ, (14)University of California, San Francisco General Hospital, San Francisco, CA, (15)Medicine, Pharmacology and Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH


A. M. Hujer, None

S. Evans, None

H. Jiang, None

K. M. Hujer, None

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

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

M. Jacobs, None

R. Sampath, Ibis Biosciences, Abbott: Employee, Salary

D. J. Ecker, Ibis Biosciences, Abbott: Employee, Salary

T. N. Domitrovic, None

C. Manca, Public Health Research Institute: Employee and patent US6596281 (also published as US6087163) titled "Mycobacterum tuberculosis specific proteins and genes, mixes of antigens and uses thereof", none financial benefit involved

K. Chavda, None

P. Zhang, None

L. Chen, None

C. Hill, None

F. Perez, None

B. Kreiswirth, None

V. Fowler, None

H. Chambers, None

R. Bonomo, AstraZeneca: Grant Investigator, Grant recipient
Merck: Grant Investigator, Grant recipient
Rib-X: Grant Investigator, Grant recipient
Steris: Grant Investigator, Grant recipient
TetraPhase: Scientific Advisor, nothing
NIH: Grant Investigator, Grant recipient
VA Merit Review: Grant Investigator, Grant recipient

Findings in the abstracts are embargoed until 12:01 a.m. EDT, Oct. 8th with the exception of research findings presented at the IDWeek press conferences.

Sponsoring Societies:

© 2014, All Rights Reserved.

Follow IDWeek