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Impact of multiplex PCR on antimicrobial treatment in febrile neutropenia: a randomized controlled study

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Abstract

Multiplex PCR (mPCR) directly from blood has been suggested as a promising method for rapid identification of pathogens causing sepsis. This study aimed to investigate whether mPCR has any impact on antimicrobial treatment. Hematological patients with febrile neutropenia were randomized into two groups. In the study group, mPCR was performed as an addition to standard diagnostics, and PCR finding was immediately communicated to the clinicians, thus being available for decision making. In the control group, clinicians were not aware of PCR result. PCR samples were collected simultaneously with clinically indicated blood culture specimens from peripheral vein and/or central venous catheter at fever onset and once again if fever persisted up to 72 h. Overall, 74 patients of the study group and 76 patients of the control group were enrolled and 253 samples collected. Therapy was changed to targeted antimicrobial therapy (AMT) in 12 patients (16.2 %) in the study group and in 12 patients (15.8 %) in the control group. For patients with changes, the median time to change to the targeted AMT was 21.4 h in the study group and 47.5 h in the control group (p = 0.018). In the study group, 57.1 % (8/14) of changes to targeted AMT was due to PCR finding. PCR led to AMT change in 9.5 % (7/74) of study group patients, i.e., in 33.3 % (7/21) of patients who had positive PCR finding. There were no significant differences in patient outcomes (secondary endpoints). In conclusion, PCR method accelerates change to the targeted AMT in febrile neutropenic patients.

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Acknowledgments

This study was part of a joint project of a Münster-Berlin–Munich Molecular Diagnostics of Sepsis Study Group aiming at improvement of diagnostics, AMT and pharmaco-economics of sepsis. The authors are indebted to all members of the study group not listed as authors, including M. Deja, Berlin, C. Spies, Berlin, H. Bunzemeier, Münster, R. Grube, Munich, J. Schulze, Berlin, D. Voss, Münster and M. Wilke, Munich. The authors are thankful to M. Schulte, M. Reher and J. Radtke for excellent technical assistance and to the staff of the Department of Medicine A, University Hospital Münster, for support. This work was partly supported by Roche Diagnostics and Pfizer, Germany. Roche Diagnostics provided SeptiFast kits and made LightCycler 2.0 available at the study site for the study period. Pfizer provided a restricted grant for study activities.

Conflict of interest

Lecture fees were received from Pfizer (EAI, GS, YN, ST, IN, WEB) and Roche Diagnostics (ST, IN, WEB). KB received lecture fees, grants and travel support from Pfizer and Roche Diagnostics. All other authors report no conflict of interest.

Ethical standard

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Correspondence to Karsten Becker.

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Evgeny A. Idelevich and Gerda Silling have contributed equally to this work.

ClinicalTrials.gov registration NCT01114165.

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Idelevich, E.A., Silling, G., Niederbracht, Y. et al. Impact of multiplex PCR on antimicrobial treatment in febrile neutropenia: a randomized controlled study. Med Microbiol Immunol 204, 585–592 (2015). https://doi.org/10.1007/s00430-014-0385-7

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