Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis

doi:10.1016/S1473-3099(17)30592-3

Meta-Analysis

. 2018 Jan;18(1):95-107.

doi: 10.1016/S1473-3099(17)30592-3. Epub 2017 Oct 13.

Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis

Philipp Schuetz¹, Yannick Wirz², Ramon Sager², Mirjam Christ-Crain³, Daiana Stolz⁴, Michael Tamm⁴, Lila Bouadma⁵, Charles E Luyt⁶, Michel Wolff⁵, Jean Chastre⁶, Florence Tubach⁷, Kristina B Kristoffersen⁸, Olaf Burkhardt⁹, Tobias Welte⁹, Stefan Schroeder¹⁰, Vandack Nobre¹¹, Long Wei¹², Heiner C Bucher¹³, Djillali Annane¹⁴, Konrad Reinhart¹⁵, Ann R Falsey¹⁶, Angela Branche¹⁶, Pierre Damas¹⁷, Maarten Nijsten¹⁸, Dylan W de Lange¹⁹, Rodrigo O Deliberato²⁰, Carolina F Oliveira²¹, Vera Maravić-Stojković²², Alessia Verduri²³, Bianca Beghé²³, Bin Cao²⁴, Yahya Shehabi²⁵, Jens-Ulrik S Jensen²⁶, Caspar Corti²⁷, Jos A H van Oers²⁸, Albertus Beishuizen²⁹, Armand R J Girbes³⁰, Evelien de Jong³⁰, Matthias Briel³¹, Beat Mueller³²

Affiliations

¹ Medical University Department, Kantonsspital Aarau, Aarau, Switzerland; Faculty of Medicine, University of Basel, Basel, Switzerland. Electronic address: schuetzph@gmail.com.
² Medical University Department, Kantonsspital Aarau, Aarau, Switzerland.
³ Faculty of Medicine, University of Basel, Basel, Switzerland; Division of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Basel, Basel, Switzerland.
⁴ Faculty of Medicine, University of Basel, Basel, Switzerland; Clinic of Pneumology and Pulmonary Cell Research, University Hospital Basel, Basel, Switzerland.
⁵ Service de Réanimation Médicale, Université Paris 7-Denis-Diderot, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France.
⁶ Service de Réanimation Médicale, Université Paris 6-Pierre-et-Marie-Curie, Paris, France.
⁷ Département de Biostatistique, Santé publique et Information médicale, AP-HP, Hôpital Pitié-Salpêtrière, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France.
⁸ Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
⁹ Department of Pulmonary Medicine, Medizinische Hochschule Hannover, Member of the German Center of Lung Research, Hannover, Germany.
¹⁰ Department of Anesthesiology and Intensive Care Medicine, Krankenhaus Dueren, Dueren, Germany.
¹¹ Department of Intensive Care, Hospital das Clinicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
¹² Department of Internal and Geriatric Medicine, Shanghai Jiao Tong University, Affiliated Sixth People's Hospital, Shanghai, China.
¹³ Faculty of Medicine, University of Basel, Basel, Switzerland; Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
¹⁴ Critical Care Department, Hôpital Raymond Poincaré, AP-HP, Faculty of Health Science Simone Veil, UVSQ-University Paris Saclay, Garches, France.
¹⁵ Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.
¹⁶ Department of Medicine, University of Rochester, Rochester, NY, USA.
¹⁷ Department of General Intensive Care, University Hospital of Liege, Domaine Universitaire de Liège, Liège, Belgium.
¹⁸ University Medical Centre, University of Groningen, Groningen, Netherlands.
¹⁹ University Medical Center Utrecht and University of Utrecht, Utrecht, Netherlands.
²⁰ Critical Care Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil.
²¹ Department of Internal Medicine, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
²² Immunology Laboratory, Dedinje Cardiovascular Institute, Belgrade, Serbia.
²³ Section of Respiratory Medicine, Department of Medical and Surgical Sciences, University Polyclinic of Modena, University of Modena and Reggio Emilia, Modena, Italy.
²⁴ Center for Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China.
²⁵ Critical Care and Peri-operative Medicine, Monash Health, Melbourne, VIC, Australia; School of Clinical Sciences, Faculty of Medicine Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia.
²⁶ Centre of Excellence for Health, Immunity and Infections, Department of Infectious Diseases and Rheumatology, Finsencentret, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
²⁷ Department of Respiratory Medicine, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark.
²⁸ Elisabeth Tweesteden Hospital, Tilburg, Netherlands.
²⁹ Medisch Spectrum Twente, Enschede, Netherlands.
³⁰ VUmc University Medical Center, Amsterdam, Netherlands.
³¹ Faculty of Medicine, University of Basel, Basel, Switzerland; Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
³² Medical University Department, Kantonsspital Aarau, Aarau, Switzerland; Faculty of Medicine, University of Basel, Basel, Switzerland.

PMID: 29037960
DOI: 10.1016/S1473-3099(17)30592-3

Meta-Analysis

Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis

Philipp Schuetz et al. Lancet Infect Dis. 2018 Jan.

. 2018 Jan;18(1):95-107.

doi: 10.1016/S1473-3099(17)30592-3. Epub 2017 Oct 13.

Authors

Affiliations

¹ Medical University Department, Kantonsspital Aarau, Aarau, Switzerland; Faculty of Medicine, University of Basel, Basel, Switzerland. Electronic address: schuetzph@gmail.com.
² Medical University Department, Kantonsspital Aarau, Aarau, Switzerland.
³ Faculty of Medicine, University of Basel, Basel, Switzerland; Division of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Basel, Basel, Switzerland.
⁴ Faculty of Medicine, University of Basel, Basel, Switzerland; Clinic of Pneumology and Pulmonary Cell Research, University Hospital Basel, Basel, Switzerland.
⁵ Service de Réanimation Médicale, Université Paris 7-Denis-Diderot, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France.
⁶ Service de Réanimation Médicale, Université Paris 6-Pierre-et-Marie-Curie, Paris, France.
⁷ Département de Biostatistique, Santé publique et Information médicale, AP-HP, Hôpital Pitié-Salpêtrière, Université Pierre et Marie Curie, Sorbonne Universités, Paris, France.
⁸ Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
⁹ Department of Pulmonary Medicine, Medizinische Hochschule Hannover, Member of the German Center of Lung Research, Hannover, Germany.
¹⁰ Department of Anesthesiology and Intensive Care Medicine, Krankenhaus Dueren, Dueren, Germany.
¹¹ Department of Intensive Care, Hospital das Clinicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
¹² Department of Internal and Geriatric Medicine, Shanghai Jiao Tong University, Affiliated Sixth People's Hospital, Shanghai, China.
¹³ Faculty of Medicine, University of Basel, Basel, Switzerland; Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
¹⁴ Critical Care Department, Hôpital Raymond Poincaré, AP-HP, Faculty of Health Science Simone Veil, UVSQ-University Paris Saclay, Garches, France.
¹⁵ Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.
¹⁶ Department of Medicine, University of Rochester, Rochester, NY, USA.
¹⁷ Department of General Intensive Care, University Hospital of Liege, Domaine Universitaire de Liège, Liège, Belgium.
¹⁸ University Medical Centre, University of Groningen, Groningen, Netherlands.
¹⁹ University Medical Center Utrecht and University of Utrecht, Utrecht, Netherlands.
²⁰ Critical Care Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil.
²¹ Department of Internal Medicine, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
²² Immunology Laboratory, Dedinje Cardiovascular Institute, Belgrade, Serbia.
²³ Section of Respiratory Medicine, Department of Medical and Surgical Sciences, University Polyclinic of Modena, University of Modena and Reggio Emilia, Modena, Italy.
²⁴ Center for Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China.
²⁵ Critical Care and Peri-operative Medicine, Monash Health, Melbourne, VIC, Australia; School of Clinical Sciences, Faculty of Medicine Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia.
²⁶ Centre of Excellence for Health, Immunity and Infections, Department of Infectious Diseases and Rheumatology, Finsencentret, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
²⁷ Department of Respiratory Medicine, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark.
²⁸ Elisabeth Tweesteden Hospital, Tilburg, Netherlands.
²⁹ Medisch Spectrum Twente, Enschede, Netherlands.
³⁰ VUmc University Medical Center, Amsterdam, Netherlands.
³¹ Faculty of Medicine, University of Basel, Basel, Switzerland; Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
³² Medical University Department, Kantonsspital Aarau, Aarau, Switzerland; Faculty of Medicine, University of Basel, Basel, Switzerland.

PMID: 29037960
DOI: 10.1016/S1473-3099(17)30592-3

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.

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Comment in

Procalcitonin and antibiotic use: imperfect, yet effective.
Fontela PS, Papenburg J. Fontela PS, et al. Lancet Infect Dis. 2018 Jan;18(1):11-13. doi: 10.1016/S1473-3099(17)30593-5. Epub 2017 Oct 13. Lancet Infect Dis. 2018. PMID: 29037959 No abstract available.
Reassessment of a meta-analysis of procalcitonin-guided antibiotic therapy for lower respiratory tract infections.
Keshary A, Badgett RG. Keshary A, et al. Lancet Infect Dis. 2018 Feb;18(2):140. doi: 10.1016/S1473-3099(18)30014-8. Lancet Infect Dis. 2018. PMID: 29412955 No abstract available.
Reassessment of a meta-analysis of procalcitonin-guided antibiotic therapy for lower respiratory tract infections.
Gaskill N. Gaskill N. Lancet Infect Dis. 2018 Feb;18(2):140-141. doi: 10.1016/S1473-3099(18)30015-X. Lancet Infect Dis. 2018. PMID: 29412956 No abstract available.
Reassessment of a meta-analysis of procalcitonin-guided antibiotic therapy for lower respiratory tract infections - Authors' reply.
Schuetz P, Wirz Y, Mueller B. Schuetz P, et al. Lancet Infect Dis. 2018 Feb;18(2):141. doi: 10.1016/S1473-3099(18)30016-1. Lancet Infect Dis. 2018. PMID: 29412957 No abstract available.
Low procalcitonin, community acquired pneumonia, and antibiotic therapy.
Kamat IS, Ramachandran V, Eswaran H, Abers MS, Musher DM. Kamat IS, et al. Lancet Infect Dis. 2018 May;18(5):496-497. doi: 10.1016/S1473-3099(18)30215-9. Lancet Infect Dis. 2018. PMID: 29695359 No abstract available.
Low procalcitonin, community acquired pneumonia, and antibiotic therapy - Authors' reply.
Schuetz P, Branche A, Mueller B. Schuetz P, et al. Lancet Infect Dis. 2018 May;18(5):497-498. doi: 10.1016/S1473-3099(18)30226-3. Lancet Infect Dis. 2018. PMID: 29695360 No abstract available.
Is Procalcitonin-Guided Antibiotic Therapy Working in Emergency Department Outpatients?
Bolliger R, Merker M, Wirz Y, Mueller B, Schuetz P. Bolliger R, et al. Ann Emerg Med. 2018 Aug;72(2):226-228. doi: 10.1016/j.annemergmed.2018.03.028. Ann Emerg Med. 2018. PMID: 30031515 No abstract available.

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Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis

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Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis

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