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University of Groningen

Do we need new trials of procalcitonin-guided antibiotic therapy? A response

van Oers, Jos A. H.; Nijsten, Maarten W.; de lange, Dylan W.

Published in: Critical Care DOI:

10.1186/s13054-018-2008-y

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.

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Publication date: 2018

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

van Oers, J. A. H., Nijsten, M. W., & de lange, D. W. (2018). Do we need new trials of procalcitonin-guided antibiotic therapy? A response. Critical Care, 22(83). https://doi.org/10.1186/s13054-018-2008-y

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LETTER

Open Access

Do we need new trials of

procalcitonin-guided antibiotic therapy? A response

Jos A. H. van Oers

1*

, Maarten W. Nijsten

2

and Dylan W. de Lange

3

See related Commentary by Lisboa et al.,https://ccforum.biomedcentral.com/articles/10.1186/s13054-018-1948-6

Antibiotic treatment needs to be short, appropriate (focused on the right pathogen), and adequate (at the right dosage). And still, many physicians treat patients for too long. A recent meta-analysis on procalcitonin (PCT)-guided antibiotic treatment in acute respiratory infections [1] showed that antibiotics could be shortened form 8.1 to 5.7 days. The key question is, why do physi-cians treat for so long? The answer may be fear! Fear of undertreatment.

We read with great interest the commentary by Lisboa and colleagues in Critical Care [2] in which they ques-tion the clinical utility of this meta-analysis [1]. They concluded that populations in previous trials were not receiving best care, had less adherence to PCT algo-rithms, and lacked information on specific conditions and populations. As authors of the largest study in-cluded in this meta-analysis, the Stop Antibiotics on Procalcitonin guidance Study (SAPS) [3], we want to respond. SAPS was a pragmatic randomized controlled trial in the Netherlands with 1546 adult ICU patients with antibiotics for a presumed infection. We demon-strated a highly significant reduction in initial antibiotic duration (5.0 vs 7.0 days). The median duration of anti-biotic treatment (DOT) in the control group of the total population was 7 days (interquartile range (IQR) 4–11 days). Of these patients, 65% had a presumed pulmonary infection. Dutch national guidelines recommend an anti-biotic duration for moderate-severe community-acquired pneumonia (CAP) of 5 days [4]. No such advice exists for severe pneumonia admitted to the ICU. The median DOT in the control group in CAP was 7 days (IQR 4–10 days), 6 days (IQR 4–10 days) in hospital-acquired pneumonia and 7 days (IQR 5–11 days) in ventilator-associated pneumonia. The wide IQR suggests that physicians are reluctant to trust guidelines and prefer to prolong antibiotic treatment if they

believe it is necessary. Moreover, physicians may perform even better in clinical trials, because they know they are be-ing watched, commonly referred to as the“Hawthorne ef-fect”. In SAPS the patients were already on antibiotics. When a PCT-stopping criterion was reached antibiotics were stopped in 53% of the patients within 48 h. It was a stopping advice. Sensitivity and specificity are not high enough to withhold antibiotics on PCT alone. And indeed, PCT is no holy grail. Like other biomarkers, there are nu-merous non-infectious inflammatory processes, i.e., trauma, surgery, and acute kidney injury, in which PCT can be ele-vated. But such conditions were well balanced between both groups.

Acknowledgements Not applicable. Funding No funding.

Availability of data and materials Not applicable.

Authors’ contributions

JO, MN, and DL made equal contributions. All authors read and approved the final manuscript.

Ethics approval and consent to participate Not applicable.

Consent for publication Not applicable. Competing interests

No financial or non-financial competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Author details

1

Department of Intensive Care Medicine, Elisabeth Tweesteden Ziekenhuis, P.O. Box 90151, 5000 LC Tilburg, the Netherlands.2Department of Critical

Care, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.3Department of Intensive Care Medicine,

University Medical Centre Utrecht, Utrecht, The Netherlands. * Correspondence:jah.vanoers@etz.nl

1Department of Intensive Care Medicine, Elisabeth Tweesteden Ziekenhuis,

P.O. Box 90151, 5000 LC Tilburg, the Netherlands

Full list of author information is available at the end of the article

© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. van Oerset al. Critical Care (2018) 22:83

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Received: 15 February 2018 Accepted: 26 February 2018

References

1. Schuetz P, Wirz Y, Sager R, et al. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect Dis. 2018;18:95–107.

2. Lisboa T, Salluh J, Povoa P. Do we need new trials of procalcitonin guided antibiotic therapy? Crit Care. 2018;22:17.

3. De Jong E, van Oers JA, Beishuizen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomized controlled, open-label trial. Lancet Infect Dis. 2016;16:819–27.

4. Wiersinga W, Bonten MJ, Boersma WG, et al. Management of community-acquired pneumonia in adults: 2016 guideline update from the Dutch Working Party on Antibiotic Policy (SWAB) and Dutch Association of Chest Physicians (NVALT). Neth J Med. 2018;76:4–13.

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