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. 2016 Jan 15;62(2):181-9.
doi: 10.1093/cid/civ837. Epub 2015 Sep 25.

Rapid Molecular Diagnostics, Antibiotic Treatment Decisions, and Developing Approaches to Inform Empiric Therapy: PRIMERS I and II

Scott R Evans  1 , Andrea M Hujer  2 , Hongyu Jiang  1 , Kristine M Hujer  2 , Thomas Hall  3 , Christine Marzan  3 , Michael R Jacobs  4 , Rangarajan Sampath  3 , David J Ecker  3 , Claudia Manca  5 , Kalyan Chavda  5 , Pan Zhang  6 , Helen Fernandez  6 , Liang Chen  5 , Jose R Mediavilla  5 , Carol B Hill  7 , Federico Perez  2 , Angela M Caliendo  8 , Vance G Fowler Jr  9 , Henry F Chambers  10 , Barry N Kreiswirth  5 , Robert A Bonomo  11 ; Antibacterial Resistance Leadership Group
Affiliations

Rapid Molecular Diagnostics, Antibiotic Treatment Decisions, and Developing Approaches to Inform Empiric Therapy: PRIMERS I and II

Scott R Evans et al. Clin Infect Dis. .

Abstract

Background: 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.

Methods: 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.

Results: In PRIMERS I, the 4 RMD platforms detected β-lactamase (bla) genes and identified susceptibility or resistance in >95% of cases. In PRIMERS II, the 2 platforms identified susceptibility against extended-spectrum cephalosporins and carbapenems in >90% of cases; however, against piperacillin/tazobactam, susceptibility was identified in <80% of cases. Applying the analytical strategies to a population with 15% prevalence of ceftazidime-resistance and 5% imipenem-resistance, RMD platforms predicted susceptibility in >95% of cases, while prediction of resistance was 69%-73% for ceftazidime and 41%-50% for imipenem.

Conclusions: 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.

Keywords: empiric therapy; molecular diagnostics; β-lactams.

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Figures

Figure 1.
Figure 1.
Phenotypic profiles derived from antimicrobial susceptibility testing of isolates included in (A) PRIMERS I and (B) PRIMERS II. Notes: S highlighted with green denotes a susceptible interpretation for the drug, based on Clinical and Laboratory Standards Institute (CLSI) breakpoints. R highlighted with red denotes a resistant (or intermediate) interpretation, based on CLSI breakpoints.
Figure 2.
Figure 2.
Estimates of the susceptibility and resistance sensitivities displayed using discrimination summary plots. Results for (A) polymerase chain reaction combined with electrospray ionization mass spectrometry and for (B) molecular beacons.
See this image and copyright information in PMC

Comment in

  • For Rapid Molecular Detection, Why Not a Whole Genome Approach?
    Lesho EP, Clifford RJ. Lesho EP, et al. Clin Infect Dis. 2016 Aug 15;63(4):570-1. doi: 10.1093/cid/ciw332. Epub 2016 May 25. Clin Infect Dis. 2016. PMID: 27225237 No abstract available.
  • Reply to Lesho and Clifford.
    Evans S, Kreiswirth B, Fowler V, Chambers H, Patel R, Hujer AM, Perez F, Bonomo RA. Evans S, et al. Clin Infect Dis. 2016 Aug 15;63(4):571-2. doi: 10.1093/cid/ciw336. Epub 2016 May 25. Clin Infect Dis. 2016. PMID: 27225238 Free PMC article. No abstract available.

References

    1. Nathan C, Cars O. Antibiotic resistance—problems, progress, and prospects. New Engl J Med 2014; 371:1761–3. - PubMed
    1. Bartlett JG, Gilbert DN, Spellberg B. Seven ways to preserve the miracle of antibiotics. Clin Infect Dis 2013; 56:1445–50. - PubMed
    1. Caliendo AM, Gilbert DN, Ginocchio CC et al. . Better tests, better care: improved diagnostics for infectious diseases. Clin Infect Dis 2013; 57(suppl 3):S139–70. - PMC - PubMed
    1. Baldwin CD, Howe GB, Sampath R et al. . Usefulness of multilocus polymerase chain reaction followed by electrospray ionization mass spectrometry to identify a diverse panel of bacterial isolates. Diagn Microbiol Infect Dis 2009; 63:403–8. - PubMed
    1. Endimiani A, Hujer AM, Hujer KM et al. . Evaluation of a commercial microarray system for detection of SHV-, TEM-, CTX-M-, and KPC-type beta-lactamase genes in gram-negative isolates. J Clin Microbiol 2010; 48:2618–22. - PMC - PubMed

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