Aurélien, Dinh, Clara, Duran, Jacques, Ropers, Frédérique, Bouchand, Benjamin, Davido, Laurène, Deconinck, Morgan, Matt, Olivia, Senard, Aurore, Lagrange, Guillaume, Mellon, Ruxandra, Calin, Sabrina, Makhloufi, Victoire, de Lastours, Emmanuel, Mathieu, Jean-Emmanuel, Kahn, Elisabeth, Rouveix, Julie, Grenet, Jennifer, Dumoulin, Thierry, Chinet, Marion, Pépin, Véronique, Delcey, Sylvain, Diamantis, Daniel, Benhamou, Virginie, Vitrat, Marie-Christine, Dombret, Didier, Guillemot, Bertrand, Renaud, Yann-Erick, Claessens, José, Labarère, Philippe, Aegerter, Jean-Pierre, Bedos, Anne-Claude, Crémieux, Marie, Poupard, Université Paris-Saclay, Service des Maladies Infectieuses et Tropicales [CHU Raymond Poincaré], Hôpital Raymond Poincaré [AP-HP], Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), Institut Pasteur [Paris] (IP), Unité de Recherche Clinique des hôpitaux Pitié-Salpêtrière – Charles Foix [CHU Pitié Salpêtrière] (URC PSL-CFX), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Direction de la Recherche Clinique et de l'Innovation [AP-HP] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), Grand Hôpital de l'Est Francilien (GHEF), Centre Hospitalier René Dubos [Pontoise], Hôpital Beaujon [AP-HP], Hôpital Foch [Suresnes], Service de médecine interne [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Hôpital Ambroise Paré [AP-HP], Hôpital Lariboisière-Fernand-Widal [APHP], Centre Hospitalier de Melun (CHM), CHU Rouen, Normandie Université (NU), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Service de médecine d'urgence [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre Hospitalier Princesse Grace, Centre Hospitalier Universitaire [Grenoble] (CHU), Université Grenoble Alpes (UGA), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier de Versailles André Mignot (CHV), Hopital Saint-Louis [AP-HP] (AP-HP), This study was supported by grant PHRC 2005AOM05031 from the French Ministry of Health and sponsored by grant PO50607 from the DRCI of Versailles., HAL UVSQ, Équipe, Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Pfizer, Ministère des Affaires Sociales et de la Santé: PO50607, Funding/Support: This study was supported by grant PHRC 2005AOM05031 from the French Ministry of Health and sponsored by grant PO50607 from the DRCI of Versailles., and Conflict of Interest Disclosures: Dr Crémieux reported receiving grants from the French Ministry of Health during the conduct of the study and from Pfizer outside the submitted work. No other disclosures were reported.
Key Points Question What are the risk factors for treatment failure in patients with community-acquired pneumonia (CAP) who reached clinical stability after 3 days of β-lactam treatment? Findings In this secondary analysis of a randomized clinical trial that included 291 adults, only male sex and age were associated with failure in the multivariable analysis. These results were independent of antibiotic treatment duration and biomarker levels. Meaning In this study, among patients with CAP who reached clinical stability after 3 days of antibiotic treatment, male sex and age were associated with higher risk of failure, suggesting that these factors should be taken in account in the treatment of patients with the condition., Importance Failure of treatment is the most serious complication in community-acquired pneumonia (CAP). Objective To assess the potential risk factors for treatment failure in clinically stable patients with CAP. Design, Setting, and Participants This secondary analysis assesses data from a randomized clinical trial on CAP (Pneumonia Short Treatment [PTC] trial) conducted from December 19, 2013, to February 1, 2018. Data analysis was performed from July 18, 2019, to February 15, 2020. Patients hospitalized at 1 of 16 centers in France for moderately severe CAP who were clinically stable at day 3 of antibiotic treatment were included in the PTC trial and analyzed in the per-protocol trial population. Interventions Patients were randomly assigned (1:1) on day 3 of antibiotic treatment to receive β-lactam (amoxicillin-clavulanate [1 g/125 mg] 3 times daily) or placebo for 5 extra days. Main Outcomes and Measures The main outcome was failure at 15 days after first antibiotic intake, defined as a temperature greater than 37.9 °C and/or absence of resolution or improvement of respiratory symptoms and/or additional antibiotic treatment for any cause. The association among demographic characteristics, baseline clinical and biological variables available (ie, at the first day of β-lactam treatment), and treatment failure at day 15 among the per-protocol trial population was assessed by univariate and multivariable logistic regressions. Results Overall, 310 patients were included in the study; this secondary analysis comprised 291 patients (174 [59.8%] male; mean [SD] age, 69.6 [18.5] years). The failure rate was 26.8%. Male sex (odds ratio [OR], 1.74; 95% CI, 1.01-3.07), age per year (OR, 1.03; 95% CI, 1.01-1.05), Pneumonia Severe Index score (OR, 1.01; 95% CI, 1.00-1.02), the presence of chronic lung disease (OR, 1.85; 95% CI, 1.03-3.30), and creatinine clearance (OR, 0.99; 95% CI, 0.98-1.00) were significantly associated with failure in the univariate analysis. When the Pneumonia Severe Index score was excluded to avoid collinearity with age and sex in the regression model, only male sex (OR, 1.92; 95% CI, 1.08-3.49) and age (OR, 1.02; 95% CI, 1.00-1.05) were associated with failure in the multivariable analysis. Conclusions and Relevance In this secondary analysis of a randomized clinical trial, among patients with CAP who reached clinical stability after 3 days of antibiotic treatment, only male sex and age were associated with higher risk of failure, independent of antibiotic treatment duration and biomarker levels. Another randomized clinical trial is needed to evaluate the impact of treatment duration in populations at higher risk for treatment failure., This secondary analysis of a randomized clinical trial assesses treatment failure risk factors in patients with community-acquired pneumonia who reached clinical stability after 3 days of β-lactam treatment.