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      Procalcitonin to Guide Initiation and Duration of Antibiotic Treatment in Acute Respiratory Infections: An Individual Patient Data Meta-Analysis

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          Abstract

          This individual patient data meta-analysis of clinical trials investigating procalcitonin algorithms for antibiotic decision making found no increased risk of death or setting-specific treatment failure but did find significantly lower antibiotic exposure across different acute respiratory infections and clinical settings.

          Abstract

          Background.  Procalcitonin algorithms may reduce antibiotic use for acute respiratory tract infections (ARIs). We undertook an individual patient data meta-analysis to assess safety of this approach in different ARI diagnoses and different clinical settings.

          Methods.  We identified clinical trials in which patients with ARI were assigned to receive antibiotics based on a procalcitonin algorithm or usual care by searching the Cochrane Register, MEDLINE, and EMBASE. Individual patient data from 4221 adults with ARIs in 14 trials were verified and reanalyzed to assess risk of mortality and treatment failure—overall and within different clinical settings and types of ARIs.

          Results.  Overall, there were 118 deaths in 2085 patients (5.7%) assigned to procalcitonin groups compared with 134 deaths in 2126 control patients (6.3%; adjusted odds ratio, 0.94; 95% confidence interval CI, .71–1.23)]. Treatment failure occurred in 398 procalcitonin group patients (19.1%) and in 466 control patients (21.9%; adjusted odds ratio, 0.82; 95% CI, .71–.97). Procalcitonin guidance was not associated with increased mortality or treatment failure in any clinical setting or ARI diagnosis. Total antibiotic exposure per patient was significantly reduced overall (median [interquartile range], from 8 [5–12] to 4 [0–8] days; adjusted difference in days, −3.47 [95% CI, −3.78 to −3.17]) and across all clinical settings and ARI diagnoses.

          Conclusions.  Use of procalcitonin to guide initiation and duration of antibiotic treatment in patients with ARIs was effective in reducing antibiotic exposure across settings without an increase in the risk of mortality or treatment failure. Further high-quality trials are needed in critical-care patients.

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          Most cited references32

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          Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock.

          Our goal was to determine the impact of the initiation of inappropriate antimicrobial therapy on survival to hospital discharge of patients with septic shock. The appropriateness of initial antimicrobial therapy, the clinical infection site, and relevant pathogens were retrospectively determined for 5,715 patients with septic shock in three countries. Therapy with appropriate antimicrobial agents was initiated in 80.1% of cases. Overall, the survival rate was 43.7%. There were marked differences in the distribution of comorbidities, clinical infections, and pathogens in patients who received appropriate and inappropriate initial antimicrobial therapy (p < 0.0001 for each). The survival rates after appropriate and inappropriate initial therapy were 52.0% and 10.3%, respectively (odds ratio [OR], 9.45; 95% CI, 7.74 to 11.54; p < 0.0001). Similar differences in survival were seen in all major epidemiologic, clinical, and organism subgroups. The decrease in survival with inappropriate initial therapy ranged from 2.3-fold for pneumococcal infection to 17.6-fold with primary bacteremia. After adjustment for acute physiology and chronic health evaluation II score, comorbidities, hospital site, and other potential risk factors, the inappropriateness of initial antimicrobial therapy remained most highly associated with risk of death (OR, 8.99; 95% CI, 6.60 to 12.23). Inappropriate initial antimicrobial therapy for septic shock occurs in about 20% of patients and is associated with a fivefold reduction in survival. Efforts to increase the frequency of the appropriateness of initial antimicrobial therapy must be central to efforts to reduce the mortality of patients with septic shock.
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            Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship.

            Organisms resistant to antimicrobials continue to emerge and spread. This study was performed to measure the medical and societal cost attributable to antimicrobial-resistant infection (ARI). A sample of high-risk hospitalized adult patients was selected. Measurements included ARI, total cost, duration of stay, comorbidities, acute pathophysiology, Acute Physiology and Chronic Health Evaluation III score, intensive care unit stay, surgery, health care-acquired infection, and mortality. Hospital services used and outcomes were abstracted from electronic and written medical records. Medical costs were measured from the hospital perspective. A sensitivity analysis including 3 study designs was conducted. Regression was used to adjust for potential confounding in the random sample and in the sample expanded with additional patients with ARI. Propensity scores were used to select matched control subjects for each patient with ARI for a comparison of mean cost for patients with and without ARI. In a sample of 1391 patients, 188 (13.5%) had ARI. The medical costs attributable to ARI ranged from $18,588 to $29,069 per patient in the sensitivity analysis. Excess duration of hospital stay was 6.4-12.7 days, and attributable mortality was 6.5%. The societal costs were $10.7-$15.0 million. Using the lowest estimates from the sensitivity analysis resulted in a total cost of $13.35 million in 2008 dollars in this patient cohort. The attributable medical and societal costs of ARI are considerable. Data from this analysis could form the basis for a more comprehensive evaluation of the cost of resistance and the potential economic benefits of prevention programs.
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              Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms.

              Previous randomized controlled trials suggest that using clinical algorithms based on procalcitonin levels, a marker of bacterial infections, results in reduced antibiotic use without a deleterious effect on clinical outcomes. However, algorithms differed among trials and were embedded primarily within the European health care setting. Herein, we summarize the design, efficacy, and safety of previous randomized controlled trials and propose adapted algorithms for US settings. We performed a systematic search and included all 14 randomized controlled trials (N = 4467 patients) that investigated procalcitonin algorithms for antibiotic treatment decisions in adult patients with respiratory tract infections and sepsis from primary care, emergency department (ED), and intensive care unit settings. We found no significant difference in mortality between procalcitonin-treated and control patients overall (odds ratio, 0.91; 95% confidence interval, 0.73-1.14) or in primary care (0.13; 0-6.64), ED (0.95; 0.67-1.36), and intensive care unit (0.89; 0.66-1.20) settings individually. A consistent reduction was observed in antibiotic prescription and/or duration of therapy, mainly owing to lower prescribing rates in low-acuity primary care and ED patients, and shorter duration of therapy in moderate- and high-acuity ED and intensive care unit patients. Measurement of procalcitonin levels for antibiotic decisions in patients with respiratory tract infections and sepsis appears to reduce antibiotic exposure without worsening the mortality rate. We propose specific procalcitonin algorithms for low-, moderate-, and high-acuity patients as a basis for future trials aiming at reducing antibiotic overconsumption.
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                Author and article information

                Journal
                Clin Infect Dis
                Clin. Infect. Dis
                cid
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press
                1058-4838
                1537-6591
                1 September 2012
                9 May 2012
                9 May 2012
                : 55
                : 5
                : 651-662
                Affiliations
                [1 ]Departmentof Emergency Medicine, Beth Israel Deaconess Medical Center, and Harvard School of Public Health, Boston, Massachusetts
                [2 ]Division of Endocrinology, Diabetology and Clinical Nutrition
                [3 ]Basel Institute for Clinical Epidemiology and Biostatistics
                [4 ]Clinic of Pneumology and Pulmonary Cell Research, University Hospital Basel
                [5 ]Intensive Care, University Hospitals of Geneva
                [6 ]Medical University Department of the Medical Faculty of the University of Basel, Kantonsspital Aarau, Switzerland
                [7 ]Department of Clinical Epidemiology and Biostatistics, McMaster University , Hamilton, Canada
                [8 ]Service de Réanimation Médicale, Université Paris 7-Denis-Diderot, Hôpital Bichat-Claude-Bernard, Assistance Publique-Hôpitaux de Paris (AP-HP)
                [9 ]Service de Réanimation Médicale, EA3964, Université Paris 6-Pierre-et-Marie-Curie, Hôpital Pitié-Salpêtrière, AP-HP
                [10 ]Département d'Epidémiologie Biostatistique et Recherche Clinique, AP-HP, Hôpital Bichat
                [11 ]Université Paris Diderot, Sorbonne Paris Cité, UMR 738
                [12 ]Institut national de la santé et de la recherche médicale (INSERM), UMR 738
                [13 ]INSERM, CIE801 , Paris, France
                [14 ]Department of Infectious Diseases, AarhusUniversity Hospital , Denmark
                [15 ]Department of Emergency Medicine, Shanghai Fifth People's Hospital,China
                [16 ]Medizinische Hochschule Hannover, Department of Pulmonary Medicine, Hannover
                [17 ]Department of Anesthesiology and Intensive Care Medicine, Krankenhaus Dueren, Germany
                Author notes
                [a]

                P. S. and M. B. contributed equally to this work.

                Correspondence: Philipp Schuetz, MD, MPH, Harvard School of Public Health, 667 Huntington Ave, Boston, MA 02115 ( schuetzph@ 123456gmail.com ).
                Article
                cis464
                10.1093/cid/cis464
                3412690
                22573847
                3e097acc-d04d-4ee7-8cf9-0490b259fd59
                © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 January 2012
                : 19 April 2012
                Categories
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                Infectious disease & Microbiology
                Infectious disease & Microbiology

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