The online version of this article (doi:10.1186/cc9294) contains supplementary material, which is available to authorized users.
LEL, GJK and FS received research funding, reagents and equipment from Roche Diagnostics for the underlying project. BH is an employee of the manufacturer of the PCR assay. MHK declares that he has no competing interests.
LEL has made substantial contributions to study conception and design, data collection and analysis, and wrote the manuscript. He was treating ICU physician in a participating site utilizing PCR. BH has made substantial contributions to study conception, developed the method section and did the calculations. Of note, the formulas and calculations were cross-checked, verified and supplemented with statistical calculations by HW Steinberg, Baseline GmbH (see Acknowledgments). GJK has made substantial contributions to study conception and design, data analysis, and strongly contributed to the study definitions and graphical content. MHK has made substantial contributions to study design, data acquisition and data analysis regarding outcomes associated with inadequate antibiosis in ICU sepsis. He contributed regarding tailoring content to the ICU readership. He is head of ICU in the participating site where the association between early inadequate treatment and outcomes was studied. FS has made substantial contributions to study conception, study design and data interpretation. He is head of ICU in a participating site where the PCR assay is implemented.
Delays in adequate antimicrobial treatment contribute to high cost and mortality in sepsis. Polymerase chain reaction (PCR) assays are used alongside conventional cultures to accelerate the identification of microorganisms. We analyze the impact on medical outcomes and healthcare costs if improved adequacy of antimicrobial therapy is achieved by providing immediate coverage after positive PCR reports.
A mathematical prediction model describes the impact of PCR-based rapid adjustment of antimicrobial treatment. The model is applied to predict cost and medical outcomes for 221 sepsis episodes of 189 post-surgical and intensive care unit (ICU) sepsis patients with available PCR data from a prospective, observational trial of a multiplex PCR assay in five hospitals. While this trial demonstrated reduction of inadequate treatment days, data on outcomes associated with reduced inadequate initial antimicrobial treatment had to be obtained from two other, bigger, studies which involved 1,147 (thereof 316 inadequately treated) medical or surgical ICU patients. Our results are reported with the (5% to 95%) percentile ranges from Monte Carlo simulation in which the input parameters were randomly and independently varied according to their statistical characterization in the three underlying studies. The model allows predictions also for different patient groups or PCR assays.
A total of 13.1% of PCR tests enabled earlier adequate treatment. We predict that cost for PCR testing (300 €/test) can be fully recovered for patients above 717 € (605 € to 1,710 €) daily treatment cost. A 2.6% (2.0 to 3.2%) absolute reduction of mortality is expected. Cost per incremental survivor calculates to 11,477 € (9,321 € to 14,977 €) and incremental cost-effectiveness ratio to 3,107 € (2,523 € to 4,055 €) per quality-adjusted life-year. Generally, for ICU patients with >25% incidence of inadequate empiric antimicrobial treatment, and at least 15% with a positive blood culture, PCR represents a cost-neutral adjunct method.
Rapid PCR identification of microorganisms has the potential to become a cost-effective component for managing sepsis. The prediction model tested with data from three observational trials should be utilized as a framework to deepen insights when integrating more complementary data associated with utilization of molecular assays in the management of sepsis.
Additional file 1: Cost per PCR test. This additional file explains the cost components for one PCR test. Furthermore, two graphs represent how the key results would change with different PCR costs. (PDF 216 KB)13054_2010_8787_MOESM1_ESM.PDF
Additional file 2: Substitution factors. Description: For institutions that presently have only culture based data available, the substitutions in this additional data file allow utilization of the model to estimate potential gains from PCR. (PDF 270 KB)13054_2010_8787_MOESM2_ESM.PDF
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- Cost and mortality prediction using polymerase chain reaction pathogen detection in sepsis: evidence from three observational trials
Lutz E Lehmann
Gerald J Kost
Marin H Kollef
- BioMed Central
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