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Clin Infect Dis. 2019 May 17;68(11):1823-1830. doi: 10.1093/cid/ciy801.

Rapid Molecular Diagnostics to Inform Empiric Use of Ceftazidime/Avibactam and Ceftolozane/Tazobactam Against Pseudomonas aeruginosa: PRIMERS IV.

Author information

1
The Biostatistics Center and the Department of Epidemiology and Biostatistics, George Washington University, Rockville, Maryland.
2
Department of Medicine, Case Western Reserve University School of Medicine.
3
Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio.
4
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
5
Public Health Research Institute Center, New Jersey Medical School-Rutgers University, Newark.
6
OpGen, Gaithersburg, Maryland.
7
Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
8
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
9
Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
10
University of California, San Francisco General Hospital.
11
Departments of Pharmacology, Molecular Biology and Microbiology, Biochemistry, and Proteomics and Bioinformatics, Case Western Reserve University School of Medicine.
12
CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Ohio.

Abstract

BACKGROUND:

Overcoming β-lactam resistance in pathogens such as Pseudomonas aeruginosa is a major clinical challenge. Rapid molecular diagnostics (RMDs) have the potential to inform selection of empiric therapy in patients infected by P. aeruginosa.

METHODS:

In this study, we used a heterogeneous collection of 197 P. aeruginosa that included multidrug-resistant isolates to determine whether 2 representative RMDs (Acuitas Resistome test and VERIGENE gram-negative blood culture test) could identify susceptibility to 2 newer β-lactam/β-lactamase inhibitor (BL-BLI) combinations, ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (TOL/TAZO).

RESULTS:

We found that the studied RMD platforms were able to correctly identify BL-BLI susceptibility (susceptibility sensitivity, 100%; 95% confidence interval [CI], 97%, 100%) for both BLs-BLIs. However, their ability to detect resistance to these BLs-BLIs was lower (resistance sensitivity, 66%; 95% CI, 52%, 78% for TOL/TAZO and 33%; 95% CI, 20%, 49% for CZA).

CONCLUSIONS:

The diagnostic platforms studied showed the most potential in scenarios where a resistance gene was detected or in scenarios where a resistance gene was not detected and the prevalence of resistance to TOL/TAZO or CZA is known to be low. Clinicians need to be mindful of the benefits and risks that result from empiric treatment decisions that are based on resistance gene detection in P. aeruginosa, acknowledging that such decisions are impacted by the prevalence of resistance, which varies temporally and geographically.

KEYWORDS:

Pseudomonas aeruginosa ; antimicrobial resistance; ceftazidime/avibactam; ceftolozane/tazobactam

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