Sager et al. BMC Medicine (2017) 15:15 DOI 10.1186/s12916-017-0795-7
MINIREVIEW
Open Access
Procalcitonin-guided diagnosis and antibiotic stewardship revisited Ramon Sager1,2, Alexander Kutz1,2, Beat Mueller1,2 and Philipp Schuetz1,2*
Abstract Several controlled clinical studies have evaluated the potential of the infection biomarker procalcitonin (PCT) to improve the diagnostic work-up of patients with bacterial infections and its influence on decisions regarding antibiotic therapy. Most research has focused on lower respiratory tract infections and critically ill sepsis patients. A clinical utility for PCT has also been found for patients with urinary tract infections, postoperative infections, meningitis, and patients with acute heart failure with possible superinfection (i.e., pneumonia). In these indications, PCT levels measured on hospital admission were found to substantially reduce the initiation of antibiotic treatment in low-risk situations (i.e., bronchitis, chronic obstructive pulmonary disease exacerbation). For more severe infections (i.e., pneumonia, sepsis), antibiotic stewardship by monitoring of PCT kinetics resulted in shorter antibiotic treatment durations with early cessation of therapy. Importantly, these strategies appear to be safe without increasing the risk for mortality, recurrent infections, or treatment failures. PCT kinetics also proved to have prognostic value correlating with disease severity (i.e., pancreatitis, abdominal infection) and resolution of illness (i.e., sepsis). Although promising findings have been published in these different types of infections, there are a number of limitations regarding PCT, including suboptimal sensitivity and/or specificity, which makes a careful interpretation of PCT in the clinical context mandatory. This narrative review aims to update clinicians on the strengths and limitations of PCT for patient management, focusing on research conducted within the last 4 years. Keywords: Procalcitonin, Pneumonia, Respiratory tract infection, Sepsis, Antibiotic stewardship
Background There are important limitations to consider when using conventional diagnostic markers, such as blood cultures and inflammatory markers (i.e., C-reactive protein [CRP]), for patients with a clinical suspicion of infection, particularly in regard to suboptimal sensitivity and specificity [1]. These limitations often leave physicians with ambiguity regarding the necessity of the use of antibiotic treatment. As a consequence, unnecessary and prolonged exposure to antimicrobial agents adversely affect patient outcomes (e.g., risk for Clostridium difficile infection), while inappropriate antibiotic therapy increases antibiotic resistance in patients, resulting in a public health threat. A growing body of evidence supports the use of the infection marker procalcitonin (PCT) to improve the diagnosis of bacterial infections and to * Correspondence: [email protected] 1 University Department of Medicine, Kantonsspital Aarau, Tellstrasse, CH-5001 Aarau, Switzerland 2 Faculty of Medicine, University of Basel, Basel, Switzerland
indicate resolution of infection, thereby helping to monitor patients and guide antibiotic therapy. Based on a review published in 2011 [2], this current narrative review aims to update clinicians on (promising) new indications for PCT in patient management by focusing on research studies published from 2012 to the end of 2016. The evidence from observational and interventional research is ordered by different types of infections and study designs. Proposed PCT cut-offs and the main conclusions of relevant studies are summarized in Table 1 and graphically displayed in Fig. 1. Infections of the respiratory tract
Infections of the respiratory tract, including bronchitis, community-acquired pneumonia (CAP), and acute exacerbated chronic obstructive pulmonary disease (AECOPD), are the most important drivers for antibiotic (over-) treatment and thereby contribute to the increasing rate of antibiotic multi-resistance. The diagnosis of respiratory infections relies mainly on
© The Author(s). 2017 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.
Sager et al. BMC Medicine (2017) 15:15
Page 2 of 11
Table 1 Overview of studies investigating the use of procalcitonin in different types and sites of infections Type of infection New studies Study design since 2010?
PCT cut-off (μg/L)
Benefit of Main conclusions PCT use?
Selected references since 2012
AECOPD
yes
RCT (N = 120), meta-analysis
MINIREVIEW
Open Access
Procalcitonin-guided diagnosis and antibiotic stewardship revisited Ramon Sager1,2, Alexander Kutz1,2, Beat Mueller1,2 and Philipp Schuetz1,2*
Abstract Several controlled clinical studies have evaluated the potential of the infection biomarker procalcitonin (PCT) to improve the diagnostic work-up of patients with bacterial infections and its influence on decisions regarding antibiotic therapy. Most research has focused on lower respiratory tract infections and critically ill sepsis patients. A clinical utility for PCT has also been found for patients with urinary tract infections, postoperative infections, meningitis, and patients with acute heart failure with possible superinfection (i.e., pneumonia). In these indications, PCT levels measured on hospital admission were found to substantially reduce the initiation of antibiotic treatment in low-risk situations (i.e., bronchitis, chronic obstructive pulmonary disease exacerbation). For more severe infections (i.e., pneumonia, sepsis), antibiotic stewardship by monitoring of PCT kinetics resulted in shorter antibiotic treatment durations with early cessation of therapy. Importantly, these strategies appear to be safe without increasing the risk for mortality, recurrent infections, or treatment failures. PCT kinetics also proved to have prognostic value correlating with disease severity (i.e., pancreatitis, abdominal infection) and resolution of illness (i.e., sepsis). Although promising findings have been published in these different types of infections, there are a number of limitations regarding PCT, including suboptimal sensitivity and/or specificity, which makes a careful interpretation of PCT in the clinical context mandatory. This narrative review aims to update clinicians on the strengths and limitations of PCT for patient management, focusing on research conducted within the last 4 years. Keywords: Procalcitonin, Pneumonia, Respiratory tract infection, Sepsis, Antibiotic stewardship
Background There are important limitations to consider when using conventional diagnostic markers, such as blood cultures and inflammatory markers (i.e., C-reactive protein [CRP]), for patients with a clinical suspicion of infection, particularly in regard to suboptimal sensitivity and specificity [1]. These limitations often leave physicians with ambiguity regarding the necessity of the use of antibiotic treatment. As a consequence, unnecessary and prolonged exposure to antimicrobial agents adversely affect patient outcomes (e.g., risk for Clostridium difficile infection), while inappropriate antibiotic therapy increases antibiotic resistance in patients, resulting in a public health threat. A growing body of evidence supports the use of the infection marker procalcitonin (PCT) to improve the diagnosis of bacterial infections and to * Correspondence: [email protected] 1 University Department of Medicine, Kantonsspital Aarau, Tellstrasse, CH-5001 Aarau, Switzerland 2 Faculty of Medicine, University of Basel, Basel, Switzerland
indicate resolution of infection, thereby helping to monitor patients and guide antibiotic therapy. Based on a review published in 2011 [2], this current narrative review aims to update clinicians on (promising) new indications for PCT in patient management by focusing on research studies published from 2012 to the end of 2016. The evidence from observational and interventional research is ordered by different types of infections and study designs. Proposed PCT cut-offs and the main conclusions of relevant studies are summarized in Table 1 and graphically displayed in Fig. 1. Infections of the respiratory tract
Infections of the respiratory tract, including bronchitis, community-acquired pneumonia (CAP), and acute exacerbated chronic obstructive pulmonary disease (AECOPD), are the most important drivers for antibiotic (over-) treatment and thereby contribute to the increasing rate of antibiotic multi-resistance. The diagnosis of respiratory infections relies mainly on
© The Author(s). 2017 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.
Sager et al. BMC Medicine (2017) 15:15
Page 2 of 11
Table 1 Overview of studies investigating the use of procalcitonin in different types and sites of infections Type of infection New studies Study design since 2010?
PCT cut-off (μg/L)
Benefit of Main conclusions PCT use?
Selected references since 2012
AECOPD
yes
RCT (N = 120), meta-analysis
