2050. Choosing Ceftazidime/Avibactam and Ceftolozane/Tazobactam as Empiric Therapies against Pseudomonas aeruginosa (Pa) using Rapid Molecular Diagnostics (RMDs): PRIMERS IV
Session: Poster Abstract Session: Antimicrobial Resistant Infections: Treatment
Saturday, October 29, 2016
Room: Poster Hall
Background:

Overcoming b-lactam resistance in Pa is a major clinical challenge as diverse mechanisms (bla genes, porin changes, efflux pump overexpression, changes in PBPs, etc.) produce this phenotype. Novel therapeutics are available [ceftazidime/avibactam (taz/avi) and ceftolozane/tazobactam (tol/tazo)] that may overcome many of these resistance mechanisms. We investigated whether representative RMDs can inform the empiric use of tol/tazo and taz/avi against multidrug-resistant (MDR) Pa.

Methods:

3 RMD platforms [Nanosphere, PCR/ESI-MS, and Molecular Beacons (MBs)] were employed to identify genes potentially conferring resistance/susceptibility to taz/avi and tol/tazo in Pa. The absence or presence of blaNDM, -VIM, -IMP, and blaKPC genes was queried against the reference standard of MIC determinations. A worldwide collection of 197 archived clinical MDR Paisolates were tested. Analytical methods employing susceptibility and resistance sensitivities were estimated with 95% confidence intervals. Predictive values for susceptibility and resistance were also estimated as a function of susceptibility prevalence using an adjusted logit transformation.


Results:

In this collection, 27% (n=53) of the isolates were resistant to tol/tazo and 23% (n=45) were resistant to taz/avi by MICs. Susceptibility sensitivity was >99% for both combination antibiotics. However, resistance sensitivities were lower: tol/tazo (62% to 66%) and taz/avi (31% to 33%). Assuming 95% prevalence of susceptibility for both combinations, the susceptibility predictive value was >97% across all platforms. In contrast, the resistance predictive values (RPVs) of MBs were 62% (34, 84) for tol/tazo and 48% (22, 75) for taz/avi. Estimated RPVs of nanosphere and PCR/ESI-MS were similar: 72% (39, 92) and 60% (26, 86) for tol/tazo and taz/avi, respectively (Figure 1).  

Conclusion:

Using taz/avi and tol/tazo empiric therapy against Pa can be assisted by results of RMDs. Clinicians need to be mindful of the benefits and risks of resistance gene detection in Pathat impacts these novel agents, especially when the prevalence of resistance is still undefined and likely to change.

Figure 1. Estimate of Sensitivities and Predictive Values by Drug and Platform with 95% Confidence Intervals

Scott Evans, PhD, MS1, Thuy Tien T. Tran, MS2, Andrea Hujer, BS3, Carol Hill, PhD4, Kristine M. Hujer, BS5, Jose R. Mediavilla, MPH, MBS6, Claudia Manca, PhD7, T. Nicholas Domitrovic, BA5, Barry N. Kreiswirth, PhD8, Robin Patel, MD, FIDSA, D(ABMM)9, Michael R. Jacobs, MD, PhD10, Federico Perez, MD11, Liang Chen, PhD6, Rangarajan Sampath, PhD12, Thomas Hall, PhD13, Christine Marzan, PhD13, Vance Fowler, MD14, Henry Chambers, MD, FIDSA15, Robert A. Bonomo, MD16,17 and The Antibacterial Resistance Leadership Group (ARLG), (1)Department of Biostatistics and the Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA, (2)Harvard T.H. Chan School of Public Health, Boston, MA, (3)Case Western Reserve University, Cleveland, OH, (4)Duke Clinical Research Institute, Durham, NC, (5)Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, (6)Public Health Research Institute, Rutgers University, Newark, NJ, (7)Public Health Research Institute - Rutgers University, Newark, NJ, (8)Public Health Research Institute Tuberculosis Center, Rutgers University, 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)Louis Stokes Cleveland VA M, Cleveland, OH, (12)Ibis Biosciences, Inc., Carlsbad, CA, (13)Ibis Biosciences, Carlsbad, CA, (14)Duke University, Durham, NC, (15)University of California, San Francisco, San Francisco, CA, (16)Pharmacology, Molecular Biology, and Microbiology, Case Western Reserve University, Cleveland, OH, (17)Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH

Disclosures:

S. Evans, None

T. T. T. Tran, None

A. Hujer, None

C. Hill, None

K. M. Hujer, None

J. R. Mediavilla, None

C. Manca, None

T. N. Domitrovic, None

B. N. Kreiswirth, None

R. Patel, USMLE: Question writer , Honorarium
Up-to-Date: Writer , Honorarium
Infectious Diseases Board Review Course: Speaker , Honorarium

M. R. Jacobs, None

F. Perez, Pfizer: Grant Investigator , Grant recipient
Actavis: Consultant , Consulting fee

L. Chen, None

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

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

C. Marzan, None

V. Fowler, Pfizer: Consultant and Grant Investigator , Consulting fee and Research grant
Novartis: Consultant , Consulting fee
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 and Grant Investigator , Consulting fee and Grant recipient
Tetraphase: Consultant , Consulting fee
Trius: Consultant , Consulting fee
MedImmune: Consultant and Grant Investigator , Consulting fee and Grant recipient
Bayer: Consultant , Consulting fee
Theravance: Grant Investigator and Scientific Advisor , Research grant
Cubist/Merck: Consultant and Grant Investigator , Consulting fee and Research grant
Basilea: Consultant , Consulting fee
Affinergy: Consultant and Grant Investigator , Consulting fee and Research support
Janssen: Consultant , Consulting fee
Actavis/Forest/Cerexa: Grant Investigator , Grant recipient
Advanced Liquid Logics: Grant Investigator , Research support
Novartis: Consultant , Consulting fee
Medical Biosurfaces: Grant Investigator , Research support
Locus: Grant Investigator , Research support
Contrafect: Grant Investigator , Grant recipient
Karius: Grant Investigator , Grant recipient
Green Cross: Consultant , Speaker honorarium

H. Chambers, None

R. A. Bonomo, Merck: Grant Investigator and Scientific Advisor , Consulting fee and Research grant
Allergan: Grant Investigator , Research grant
Wockhardt: Grant Investigator , Research grant
GlaxoSmithKline: Grant Investigator , Research grant
AstraZeneca: Grant Investigator , Research grant
Actavis: Invited Speaker , Speaker honorarium

Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.