Original article C-reactive protein for discriminating treatment failure from slow responding pneumonia Agustín Ruiz-González a, ⁎ ,1 , Miquel Falguera a,1 , José Manuel Porcel a,1 , Montserrat Martínez-Alonso a,1 , Pamela Cabezas a,1 , Paloma Geijo b,1 , Ramón Boixeda c,1 , Carlos Dueñas d,1 , Arola Armengou e,1 , Josep Antoni Capdevila c,1 , Regino Serrano f,1 a Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida, Lleida, Spain b Hospital Virgen de la Luz, Cuenca, Spain c Consorci Hospitalari de Mataró, Barcelona, Spain d Hospital General Yagüe, Burgos, Spain e Hospital Universitari Josep Trueta, Girona, Spain f Hospital Universitario de Getafe, Madrid, Spain abstract article info Article history: Received 10 July 2009 Received in revised form 12 March 2010 Accepted 13 September 2010 Keywords: Pneumonia Community-acquired Treatment failure C-reactive protein Background: The management of patients with community-acquired pneumonia (CAP) who fail to improve constitutes a challenge for clinicians. This study investigated the usefulness of C-reactive protein (CRP) changes in discriminating true treatment failure from slow response to treatment. Methods: This prospective multicenter observational study investigated the behavior of plasma CRP levels on days 1 and 4 in hospitalized patients with CAP. We identified non-responding patients as those who had not reached clinical stability by day 4. Among them, true treatment failure and slow response situations were defined when initial therapy had to be changed or not after day 4 by attending clinicians, respectively. Results: By day 4, 78 (27.4%) out of 285 patients had not reached clinical stability. Among them, 56 (71.8%) patients were cured without changes in initial therapy (mortality 0.0%), and in 22 (28.2%) patients, the initial empirical therapy needed to be changed (mortality 40.9%). By day 4, CRP levels fell in 52 (92.9%) slow responding and only in 7 (31.8%) late treatment failure patients (p b 0.001). A model developed including CRP behavior and respiratory rate at day 4 identified treatment failure patients with an area under the Receiver Operating Characteristic curve of 0.87 (CI 95%, 0.78–0.96). Conclusion: Changes in CRP levels are useful to discriminate between true treatment failure and slow response to treatment and can help clinicians in management decisions when CAP patients fail to improve. © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. 1. Introduction Community-acquired pneumonia (CAP) is considered the primary cause of mortality from infection in developed countries [1]. However, several issues regarding its management are not fully clarified. One of these issues constitutes the management of patients who do not respond adequately to initial antibiotic treatment. Although difficult to define, non-responding CAP seems fairly common. Between 6 and 28% of hospitalized CAP patients have been included as non- responding in previous studies, and derived mortality is increased nearly fivefold [2–5]. Recent guidelines have addressed the management of non- responding patients extensively and definition, causes and manage- ment have been proposed [6]. At this point however, clinicians often have difficulties in distinguishing between true treatment failure from slow response to treatment. Although some predictors of delay in clinical improvement have been identified in previous studies (i.e., older age, comorbidity, high grade of severity, multilobar involve- ment, and bacteremia [7–10], their operating characteristics are unknown. The British Thoracic Society (BTS) guidelines stated that CRP levels that do not fall by 50% within 4 days suggest failure of treatment or the development of complications, although further prospective studies were recommended [11]. C-reactive protein (CRP) has provided promising results as a marker of resolution in selected populations with severe CAP [12]. The aim of our study was to further understand the usefulness of CRP changes in distinguishing true treatment failure from slow response in unselected hospitalized patients with CAP. European Journal of Internal Medicine 21 (2010) 548–552 ⁎ Corresponding author. Tel.: + 34 973 248100; fax: + 34 973 288754. E-mail address: agustinruiz@saludalia.com (A. Ruiz-González). 1 On behalf of the Infectious Section of the Spanish Society of Internal Medicine. 0953-6205/$ – see front matter © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ejim.2010.09.006 Contents lists available at ScienceDirect European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim