Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections

a patient level meta-analysis

Philipp Schuetz, Yannick Wirz, Ramon Sager, Mirjam Christ-Crain, Daiana Stolz, Michael Tamm, Lila Bouadma, Charles E. Luyt, Michel Wolff, Jean Chastre, Florence Tubach, Kristina B. Kristoffersen, Olaf Burkhardt, Tobias Welte, Stefan Schroeder, Vandack Nobre, Long Wei, Heiner C. Bucher, Djillali Annane, Konrad Reinhart & 20 others Ann R. Falsey, Angela Branche, Pierre Damas, Maarten Nijsten, Dylan W. de Lange, Rodrigo O. Deliberato, Carolina F. Oliveira, Vera Maravić-Stojković, Alessia Verduri, Bianca Beghé, Bin Cao, Yahya Shehabi, Jens Ulrik S. Jensen, Caspar Corti, Jos A.H. van Oers, Albertus Beishuizen, Armand R.J. Girbes, Evelien de Jong, Matthias Briel, Beat Mueller

Research output: Contribution to journalArticleResearchpeer-review

86 Citations (Scopus)

Abstract

Background In February, 2017, the US Food and Drug Administration approved the blood infection marker procalcitonin for guiding antibiotic therapy in patients with acute respiratory infections. This meta-analysis of patient data from 26 randomised controlled trials was designed to assess safety of procalcitonin-guided treatment in patients with acute respiratory infections from different clinical settings. Methods Based on a prespecified Cochrane protocol, we did a systematic literature search on the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, and pooled individual patient data from trials in which patients with respiratory infections were randomly assigned to receive antibiotics based on procalcitonin concentrations (procalcitonin-guided group) or control. The coprimary endpoints were 30-day mortality and setting-specific treatment failure. Secondary endpoints were antibiotic use, length of stay, and antibiotic side-effects. Findings We identified 990 records from the literature search, of which 71 articles were assessed for eligibility after exclusion of 919 records. We collected data on 6708 patients from 26 eligible trials in 12 countries. Mortality at 30 days was significantly lower in procalcitonin-guided patients than in control patients (286 [9%] deaths in 3336 procalcitonin-guided patients vs 336 [10%] in 3372 controls; adjusted odds ratio [OR] 0·83 [95% CI 0·70 to 0·99], p=0·037). This mortality benefit was similar across subgroups by setting and type of infection (p interactions >0·05), although mortality was very low in primary care and in patients with acute bronchitis. Procalcitonin guidance was also associated with a 2·4-day reduction in antibiotic exposure (5·7 vs 8·1 days [95% CI −2·71 to −2·15], p<0·0001) and a reduction in antibiotic-related side-effects (16% vs 22%, adjusted OR 0·68 [95% CI 0·57 to 0·82], p<0·0001). Interpretation Use of procalcitonin to guide antibiotic treatment in patients with acute respiratory infections reduces antibiotic exposure and side-effects, and improves survival. Widespread implementation of procalcitonin protocols in patients with acute respiratory infections thus has the potential to improve antibiotic management with positive effects on clinical outcomes and on the current threat of increasing antibiotic multiresistance. Funding National Institute for Health Research.

Original languageEnglish
Pages (from-to)95-107
Number of pages13
JournalLancet Infectious Diseases
Volume18
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018

Cite this

Schuetz, Philipp ; Wirz, Yannick ; Sager, Ramon ; Christ-Crain, Mirjam ; Stolz, Daiana ; Tamm, Michael ; Bouadma, Lila ; Luyt, Charles E. ; Wolff, Michel ; Chastre, Jean ; Tubach, Florence ; Kristoffersen, Kristina B. ; Burkhardt, Olaf ; Welte, Tobias ; Schroeder, Stefan ; Nobre, Vandack ; Wei, Long ; Bucher, Heiner C. ; Annane, Djillali ; Reinhart, Konrad ; Falsey, Ann R. ; Branche, Angela ; Damas, Pierre ; Nijsten, Maarten ; de Lange, Dylan W. ; Deliberato, Rodrigo O. ; Oliveira, Carolina F. ; Maravić-Stojković, Vera ; Verduri, Alessia ; Beghé, Bianca ; Cao, Bin ; Shehabi, Yahya ; Jensen, Jens Ulrik S. ; Corti, Caspar ; van Oers, Jos A.H. ; Beishuizen, Albertus ; Girbes, Armand R.J. ; de Jong, Evelien ; Briel, Matthias ; Mueller, Beat. / Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections : a patient level meta-analysis. In: Lancet Infectious Diseases. 2018 ; Vol. 18, No. 1. pp. 95-107.
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title = "Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis",
abstract = "Background In February, 2017, the US Food and Drug Administration approved the blood infection marker procalcitonin for guiding antibiotic therapy in patients with acute respiratory infections. This meta-analysis of patient data from 26 randomised controlled trials was designed to assess safety of procalcitonin-guided treatment in patients with acute respiratory infections from different clinical settings. Methods Based on a prespecified Cochrane protocol, we did a systematic literature search on the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, and pooled individual patient data from trials in which patients with respiratory infections were randomly assigned to receive antibiotics based on procalcitonin concentrations (procalcitonin-guided group) or control. The coprimary endpoints were 30-day mortality and setting-specific treatment failure. Secondary endpoints were antibiotic use, length of stay, and antibiotic side-effects. Findings We identified 990 records from the literature search, of which 71 articles were assessed for eligibility after exclusion of 919 records. We collected data on 6708 patients from 26 eligible trials in 12 countries. Mortality at 30 days was significantly lower in procalcitonin-guided patients than in control patients (286 [9{\%}] deaths in 3336 procalcitonin-guided patients vs 336 [10{\%}] in 3372 controls; adjusted odds ratio [OR] 0·83 [95{\%} CI 0·70 to 0·99], p=0·037). This mortality benefit was similar across subgroups by setting and type of infection (p interactions >0·05), although mortality was very low in primary care and in patients with acute bronchitis. Procalcitonin guidance was also associated with a 2·4-day reduction in antibiotic exposure (5·7 vs 8·1 days [95{\%} CI −2·71 to −2·15], p<0·0001) and a reduction in antibiotic-related side-effects (16{\%} vs 22{\%}, adjusted OR 0·68 [95{\%} CI 0·57 to 0·82], p<0·0001). Interpretation Use of procalcitonin to guide antibiotic treatment in patients with acute respiratory infections reduces antibiotic exposure and side-effects, and improves survival. Widespread implementation of procalcitonin protocols in patients with acute respiratory infections thus has the potential to improve antibiotic management with positive effects on clinical outcomes and on the current threat of increasing antibiotic multiresistance. Funding National Institute for Health Research.",
author = "Philipp Schuetz and Yannick Wirz and Ramon Sager and Mirjam Christ-Crain and Daiana Stolz and Michael Tamm and Lila Bouadma and Luyt, {Charles E.} and Michel Wolff and Jean Chastre and Florence Tubach and Kristoffersen, {Kristina B.} and Olaf Burkhardt and Tobias Welte and Stefan Schroeder and Vandack Nobre and Long Wei and Bucher, {Heiner C.} and Djillali Annane and Konrad Reinhart and Falsey, {Ann R.} and Angela Branche and Pierre Damas and Maarten Nijsten and {de Lange}, {Dylan W.} and Deliberato, {Rodrigo O.} and Oliveira, {Carolina F.} and Vera Maravić-Stojković and Alessia Verduri and Bianca Begh{\'e} and Bin Cao and Yahya Shehabi and Jensen, {Jens Ulrik S.} and Caspar Corti and {van Oers}, {Jos A.H.} and Albertus Beishuizen and Girbes, {Armand R.J.} and {de Jong}, Evelien and Matthias Briel and Beat Mueller",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/S1473-3099(17)30592-3",
language = "English",
volume = "18",
pages = "95--107",
journal = "Lancet Infectious Diseases",
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Schuetz, P, Wirz, Y, Sager, R, Christ-Crain, M, Stolz, D, Tamm, M, Bouadma, L, Luyt, CE, Wolff, M, Chastre, J, Tubach, F, Kristoffersen, KB, Burkhardt, O, Welte, T, Schroeder, S, Nobre, V, Wei, L, Bucher, HC, Annane, D, Reinhart, K, Falsey, AR, Branche, A, Damas, P, Nijsten, M, de Lange, DW, Deliberato, RO, Oliveira, CF, Maravić-Stojković, V, Verduri, A, Beghé, B, Cao, B, Shehabi, Y, Jensen, JUS, Corti, C, van Oers, JAH, Beishuizen, A, Girbes, ARJ, de Jong, E, Briel, M & Mueller, B 2018, 'Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis', Lancet Infectious Diseases, vol. 18, no. 1, pp. 95-107. https://doi.org/10.1016/S1473-3099(17)30592-3

Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections : a patient level meta-analysis. / Schuetz, Philipp; Wirz, Yannick; Sager, Ramon; Christ-Crain, Mirjam; Stolz, Daiana; Tamm, Michael; Bouadma, Lila; Luyt, Charles E.; Wolff, Michel; Chastre, Jean; Tubach, Florence; Kristoffersen, Kristina B.; Burkhardt, Olaf; Welte, Tobias; Schroeder, Stefan; Nobre, Vandack; Wei, Long; Bucher, Heiner C.; Annane, Djillali; Reinhart, Konrad; Falsey, Ann R.; Branche, Angela; Damas, Pierre; Nijsten, Maarten; de Lange, Dylan W.; Deliberato, Rodrigo O.; Oliveira, Carolina F.; Maravić-Stojković, Vera; Verduri, Alessia; Beghé, Bianca; Cao, Bin; Shehabi, Yahya; Jensen, Jens Ulrik S.; Corti, Caspar; van Oers, Jos A.H.; Beishuizen, Albertus; Girbes, Armand R.J.; de Jong, Evelien; Briel, Matthias; Mueller, Beat.

In: Lancet Infectious Diseases, Vol. 18, No. 1, 01.01.2018, p. 95-107.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections

T2 - a patient level meta-analysis

AU - Schuetz, Philipp

AU - Wirz, Yannick

AU - Sager, Ramon

AU - Christ-Crain, Mirjam

AU - Stolz, Daiana

AU - Tamm, Michael

AU - Bouadma, Lila

AU - Luyt, Charles E.

AU - Wolff, Michel

AU - Chastre, Jean

AU - Tubach, Florence

AU - Kristoffersen, Kristina B.

AU - Burkhardt, Olaf

AU - Welte, Tobias

AU - Schroeder, Stefan

AU - Nobre, Vandack

AU - Wei, Long

AU - Bucher, Heiner C.

AU - Annane, Djillali

AU - Reinhart, Konrad

AU - Falsey, Ann R.

AU - Branche, Angela

AU - Damas, Pierre

AU - Nijsten, Maarten

AU - de Lange, Dylan W.

AU - Deliberato, Rodrigo O.

AU - Oliveira, Carolina F.

AU - Maravić-Stojković, Vera

AU - Verduri, Alessia

AU - Beghé, Bianca

AU - Cao, Bin

AU - Shehabi, Yahya

AU - Jensen, Jens Ulrik S.

AU - Corti, Caspar

AU - van Oers, Jos A.H.

AU - Beishuizen, Albertus

AU - Girbes, Armand R.J.

AU - de Jong, Evelien

AU - Briel, Matthias

AU - Mueller, Beat

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background In February, 2017, the US Food and Drug Administration approved the blood infection marker procalcitonin for guiding antibiotic therapy in patients with acute respiratory infections. This meta-analysis of patient data from 26 randomised controlled trials was designed to assess safety of procalcitonin-guided treatment in patients with acute respiratory infections from different clinical settings. Methods Based on a prespecified Cochrane protocol, we did a systematic literature search on the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, and pooled individual patient data from trials in which patients with respiratory infections were randomly assigned to receive antibiotics based on procalcitonin concentrations (procalcitonin-guided group) or control. The coprimary endpoints were 30-day mortality and setting-specific treatment failure. Secondary endpoints were antibiotic use, length of stay, and antibiotic side-effects. Findings We identified 990 records from the literature search, of which 71 articles were assessed for eligibility after exclusion of 919 records. We collected data on 6708 patients from 26 eligible trials in 12 countries. Mortality at 30 days was significantly lower in procalcitonin-guided patients than in control patients (286 [9%] deaths in 3336 procalcitonin-guided patients vs 336 [10%] in 3372 controls; adjusted odds ratio [OR] 0·83 [95% CI 0·70 to 0·99], p=0·037). This mortality benefit was similar across subgroups by setting and type of infection (p interactions >0·05), although mortality was very low in primary care and in patients with acute bronchitis. Procalcitonin guidance was also associated with a 2·4-day reduction in antibiotic exposure (5·7 vs 8·1 days [95% CI −2·71 to −2·15], p<0·0001) and a reduction in antibiotic-related side-effects (16% vs 22%, adjusted OR 0·68 [95% CI 0·57 to 0·82], p<0·0001). Interpretation Use of procalcitonin to guide antibiotic treatment in patients with acute respiratory infections reduces antibiotic exposure and side-effects, and improves survival. Widespread implementation of procalcitonin protocols in patients with acute respiratory infections thus has the potential to improve antibiotic management with positive effects on clinical outcomes and on the current threat of increasing antibiotic multiresistance. Funding National Institute for Health Research.

AB - Background In February, 2017, the US Food and Drug Administration approved the blood infection marker procalcitonin for guiding antibiotic therapy in patients with acute respiratory infections. This meta-analysis of patient data from 26 randomised controlled trials was designed to assess safety of procalcitonin-guided treatment in patients with acute respiratory infections from different clinical settings. Methods Based on a prespecified Cochrane protocol, we did a systematic literature search on the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, and pooled individual patient data from trials in which patients with respiratory infections were randomly assigned to receive antibiotics based on procalcitonin concentrations (procalcitonin-guided group) or control. The coprimary endpoints were 30-day mortality and setting-specific treatment failure. Secondary endpoints were antibiotic use, length of stay, and antibiotic side-effects. Findings We identified 990 records from the literature search, of which 71 articles were assessed for eligibility after exclusion of 919 records. We collected data on 6708 patients from 26 eligible trials in 12 countries. Mortality at 30 days was significantly lower in procalcitonin-guided patients than in control patients (286 [9%] deaths in 3336 procalcitonin-guided patients vs 336 [10%] in 3372 controls; adjusted odds ratio [OR] 0·83 [95% CI 0·70 to 0·99], p=0·037). This mortality benefit was similar across subgroups by setting and type of infection (p interactions >0·05), although mortality was very low in primary care and in patients with acute bronchitis. Procalcitonin guidance was also associated with a 2·4-day reduction in antibiotic exposure (5·7 vs 8·1 days [95% CI −2·71 to −2·15], p<0·0001) and a reduction in antibiotic-related side-effects (16% vs 22%, adjusted OR 0·68 [95% CI 0·57 to 0·82], p<0·0001). Interpretation Use of procalcitonin to guide antibiotic treatment in patients with acute respiratory infections reduces antibiotic exposure and side-effects, and improves survival. Widespread implementation of procalcitonin protocols in patients with acute respiratory infections thus has the potential to improve antibiotic management with positive effects on clinical outcomes and on the current threat of increasing antibiotic multiresistance. Funding National Institute for Health Research.

UR - http://www.scopus.com/inward/record.url?scp=85031330655&partnerID=8YFLogxK

U2 - 10.1016/S1473-3099(17)30592-3

DO - 10.1016/S1473-3099(17)30592-3

M3 - Article

VL - 18

SP - 95

EP - 107

JO - Lancet Infectious Diseases

JF - Lancet Infectious Diseases

SN - 1473-3099

IS - 1

ER -