1. Rapid Molecular Diagnostics, Antibiotic Treatment Decisions, and Developing Approaches to Inform Empiric Therapy: PRIMERS I and II
- Author
-
Robert A. Bonomo, Hongyu Jiang, Liang Chen, Kristine M. Hujer, Rangarajan Sampath, Christine Marzan, Helen Fernandez, David J. Ecker, Barry N. Kreiswirth, Scott R. Evans, Michael R. Jacobs, Andrea M. Hujer, José R. Mediavilla, Angela M. Caliendo, Claudia Manca, Kalyan D. Chavda, Thomas A. Hall, Pan Zhang, Federico Perez, Vance G. Fowler, Carol Hill, and Henry F. Chambers
- Subjects
0301 basic medicine ,Microbiology (medical) ,Carbapenem ,Imipenem ,Time Factors ,Genotyping Techniques ,030106 microbiology ,Ceftazidime ,Microbial Sensitivity Tests ,Computational biology ,Tazobactam ,beta-Lactam Resistance ,Microbiology ,03 medical and health sciences ,Correspondence ,Escherichia coli ,medicine ,Humans ,Articles and Commentaries ,business.industry ,Enterobacteriaceae Infections ,Molecular diagnostics ,Anti-Bacterial Agents ,Klebsiella pneumoniae ,Infectious Diseases ,Molecular Diagnostic Techniques ,Piperacillin/tazobactam ,business ,Empiric therapy ,medicine.drug ,Piperacillin - Abstract
Rapid molecular diagnostic (RMD) platforms may lead to better antibiotic use. Our objective was to develop analytical strategies to enhance the interpretation of RMDs for clinicians.We compared the performance characteristics of 4 RMD platforms for detecting resistance against β-lactams in 72 highly resistant isolates of Escherichia coli and Klebsiella pneumoniae (PRIMERS I). Subsequently, 2 platforms were used in a blinded study in which a heterogeneous collection of 196 isolates of E. coli and K. pneumoniae (PRIMERS II) were examined. We evaluated the genotypic results as predictors of resistance or susceptibility against β-lactam antibiotics. We designed analytical strategies and graphical representations of platform performance, including discrimination summary plots and susceptibility and resistance predictive values, that are readily interpretable by practitioners to inform decision-making.In PRIMERS I, the 4 RMD platforms detected β-lactamase (bla) genes and identified susceptibility or resistance in95% of cases. In PRIMERS II, the 2 platforms identified susceptibility against extended-spectrum cephalosporins and carbapenems in90% of cases; however, against piperacillin/tazobactam, susceptibility was identified in80% of cases. Applying the analytical strategies to a population with 15% prevalence of ceftazidime-resistance and 5% imipenem-resistance, RMD platforms predicted susceptibility in95% of cases, while prediction of resistance was 69%-73% for ceftazidime and 41%-50% for imipenem.RMD platforms can help inform empiric β-lactam therapy in cases where bla genes are not detected and the prevalence of resistance is known. Our analysis is a first step in bridging the gap between RMDs and empiric treatment decisions.
- Published
- 2015