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      Procalcitonin algorithm to guide initial antibiotic therapy in acute exacerbations of COPD admitted to the ICU: a randomized multicenter study

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          To compare the efficacy of an antibiotic protocol guided by serum procalcitonin (PCT) with that of standard antibiotic therapy in severe acute exacerbations of COPD (AECOPDs) admitted to the intensive care unit (ICU).


          We conducted a multicenter, randomized trial in France. Patients experiencing severe AECOPDs were assigned to groups whose antibiotic therapy was guided by (1) a 5-day PCT algorithm with predefined cutoff values for the initiation or stoppage of antibiotics (PCT group) or (2) standard guidelines (control group). The primary endpoint was 3-month mortality. The predefined noninferiority margin was 12%.


          A total of 302 patients were randomized into the PCT ( n = 151) and control ( n = 151) groups. Thirty patients (20%) in the PCT group and 21 patients (14%) in the control group died within 3 months of admission (adjusted difference, 6.6%; 90% CI − 0.3 to 13.5%). Among patients without antibiotic therapy at baseline ( n = 119), the use of PCT significantly increased 3-month mortality [19/61 (31%) vs. 7/58 (12%), p = 0.015]. The in-ICU and in-hospital antibiotic exposure durations, were similar between the PCT and control group (5.2 ± 6.5 days in the PCT group vs. 5.4 ± 4.4 days in the control group, p = 0.85 and 7.9 ± 8 days in the PCT group vs. 7.7 ± 5.7 days in the control group, p = 0.75, respectively).


          The PCT group failed to demonstrate non-inferiority with respect to 3-month mortality and failed to reduce in-ICU and in-hospital antibiotic exposure in AECOPDs admitted to the ICU.

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          The online version of this article (10.1007/s00134-018-5141-9) contains supplementary material, which is available to authorized users.

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          Most cited references 13

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          Guidelines for the management of adult lower respiratory tract infections - Full version

           M Woodhead,  F. Blasi,  S Ewig (2011)
          This document is an update of Guidelines published in 2005 and now includes scientific publications through to May 2010. It provides evidence-based recommendations for the most common management questions occurring in routine clinical practice in the management of adult patients with LRTI. Topics include management outside hospital, management inside hospital (including community-acquired pneumonia (CAP), acute exacerbations of COPD (AECOPD), acute exacerbations of bronchiectasis) and prevention. Background sections and graded evidence tables are also included. The target audience for the Guideline is thus all those whose routine practice includes the management of adult LRTI.
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            Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation.

             N. Soler,  A. Torres,  S Ewig (1998)
            We carried out a comprehensive microbiological study of the upper and lower airways in patients with severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation in order to describe microbial patterns and analyze their clinical significance. Quantitative cultures of tracheobronchial aspirates (TBAs), bronchoscopically retrieved protected specimen brush (PSB) and bronchoalveolar lavage fluid (BALF) at admission to the ICU and after 72 h, as well as serology for bacteria and respiratory viruses were performed. Fifty patients (mean age 68 +/- 8, 46 males) were studied prospectively. Potentially pathogenic microorganisms (PPMs) and/or a positive serology were present in 36 of 50 (72%) patients, including 12 (33%) polymicrobial cases. Only six (12%) had no pathogen in any sample in the absence of antimicrobial pretreatment. Microbial patterns corresponded to community-acquired pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) in 19 of 34 (56%) and to gram-negative enteric bacilli (GNEB), Pseudomonas, and Stenotrophomonas spp. in 15 of 34 (44%) of isolates. Chlamydia pneumoniae and respiratory viruses were found in 18% and 16% of investigations, respectively. Repeated investigation after 72 h in 19 patients with PPMs in the initial investigation revealed eradication of virtually all isolates of community-acquired pathogens and GNEB but persistence of three of five Pseudomonas spp. and both Stenotrophomonas spp. as well as the emergence of new GNEB, Pseudomonas and Stenotrophomonas spp. Clinical parameters neither predicted the presence of PPMs nor of GNEB and Pseudomonas/Stenotrophomonas spp. Nevertheless, severe pneumonia attributable to initially isolated pathogens occurred in two patients with severe COPD exacerbation. We conclude that pathogens were more frequently present than previously reported. The rate of GNEB and Pseudomonas/Stenotrophomonas spp. isolates was high. The presence of pathogens was clinically unpredictable. Thus, in this population of patients with severe exacerbations of COPD, it may be advisable to obtain respiratory samples and to treat according to diagnostic results. Further studies are warranted to clarify this issue.
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              Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock – a systematic review and meta-analysis

              Introduction Procalcitonin (PCT) algorithms for antibiotic treatment decisions have been studied in adult patients from primary care, emergency department, and intensive care unit (ICU) settings, suggesting that procalcitonin-guided therapy may reduce antibiotic exposure without increasing the mortality rate. However, information on the efficacy and safety of this approach in the most vulnerable population of critically ill patients with severe sepsis and septic shock is missing. Method Two reviewers independently performed a systematic search in PubMed, Embase, ISI Web of Knowledge, BioMed Central, ScienceDirect, Cochrane Central Register of Controlled Trials, and Eligible studies had to be randomized controlled clinical trials or cohort studies which compare procalcitonin-guided therapy with standard care in severe sepsis patients and report at least one of the following outcomes: hospital mortality, 28-day mortality, duration of antimicrobial therapy, length of stay in the intensive care unit or length of hospital stay. Disagreements about inclusion of studies and judgment of bias were solved by consensus. Results Finally seven studies comprising a total of 1,075 patients with severe sepsis or septic shock were included in the meta-analysis. Both hospital mortality (RR [relative risk]: 0.91, 95%CI [confidence interval]: 0.61; 1.36) and 28-day mortality (RR: 1.02, 95%CI: 0.85; 1.23) were not different between procalcitonin-guided therapy and standard treatment groups. Duration of antimicrobial therapy was significantly reduced in favor of procalcitonin-guided therapy (HR [hazard ratio]: 1.27, 95%CI: 1.01; 1.53). Combined estimates of the length of stay in the ICU and in hospital did not differ between groups. Conclusion Procalcitonin-guided therapy is a helpful approach to guide antibiotic therapy and surgical interventions without a beneficial effect on mortality. The major benefit of PCT-guided therapy consists of a shorter duration of antibiotic treatment compared to standard care. Trials are needed to investigate the effect of PCT-guided therapy on mortality, length of ICU and in-hospital stay in severe sepsis patients.

                Author and article information

                33 2 31 06 47 16 ,
                Intensive Care Med
                Intensive Care Med
                Intensive Care Medicine
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                16 April 2018
                16 April 2018
                : 44
                : 4
                : 428-437
                [1 ]ISNI 0000 0004 0472 0160, GRID grid.411149.8, Department of Medical Intensive Care, , CHU de Caen, ; 14000 Caen, France
                [2 ]ISNI 0000 0001 2163 3825, GRID grid.413852.9, Intensive Care Unit, Centre Hospitalier Lyon Sud, , Hospices Civils de Lyon, ; Pierre Bénite, France
                [3 ]ISNI 0000 0001 0274 3893, GRID grid.411784.f, Department of Medial Intensive Care, , Cochin University Hospital, ; Paris, France
                [4 ]Department of Intensive Care Medicine, General Hospital, Saint Lô, France
                [5 ]GRID grid.414291.b, Service de Médecine Intensive et Réanimation, , Hôpital Raymond Poincaré (APHP), ; Garches, France
                [6 ]Laboratoire Infection and Inflammation, U1173 Université de Versailles SQY-Paris Saclay—INSERM, Paris, France
                [7 ]Service de Réanimation et USC Médico-chirurgicale, AP-HP, Hôpitaux Universitaires de l’Est Parisien, Hôpital Tenon, Paris, France
                [8 ]ISNI 0000 0001 2198 4166, GRID grid.412180.e, Department of Anesthesiology and Critical Care Medicine, , Edouard Herriot Hospital, Hospices Civils de Lyon, ; Lyon, France
                [9 ]ISNI 0000 0004 0472 0160, GRID grid.411149.8, Department of Biostatistics and Clinical Research, , CHU de Caen, ; 14000 Caen, France
                [10 ]ISNI 0000 0001 0792 4829, GRID grid.410529.b, Department of Medical Intensive Care, , CHU de Grenoble Alpes, ; 38000 Grenoble, France
                [11 ]ISNI 0000000121866389, GRID grid.7429.8, INSERM, U1042, University of Grenoble-Alpes, HP2, ; 38000 Grenoble, France
                [12 ]ISNI 0000 0001 2186 4076, GRID grid.412043.0, EA2656 Groupe de Recherche sur l’Adaptation Microbienne (GRAM 2.0), , Université Caen Normandie, ; Caen, France
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (, which permits any noncommercial 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.

                Funded by: Hospital Program for Clinical Research, French Ministry of Health.
                Award ID: IDRCB 2010-A00630-39
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