Exclusive oral antibiotic treatment for hospitalized community-acquired pneumonia: a post-hoc analysis of a randomized clinical trial

• Published in: Clinical microbiology and infection Vol. 30; no. 8; pp. 1020 - 1028
• Main Authors: Dinh, Aurélien, Duran, Clara, Ropers, Jacques, Bouchand, Frédérique, Matt, Morgan, Senard, Olivia, Mellon, Guillaume, Kahn, Jean-Emmanuel, Grenet, Julie, Chinet, Thierry, Pépin, Marion, Delcey, Véronique, Diamantis, Sylvain, Benhamou, Daniel, Vitrat, Virginie, Dombret, Marie-Christine, Aegerter, Philippe, Crémieux, Anne-Claude, Attal-Behar, Julie, Thierry chinet, de Thezy, Albane, Dumoulin, Jennifer, Dupont, Caroline, Fercot, Elise, Greffe, Ségolène, Lachatre, Marie, Moulias, Sophie, Naline, Charlotte, Rouveix, Elisabeth, Sahut-D'izarn, Marine, Sefssafi, Abel, Bru, Jean-Pierre, Gaillat, Jacques, Janssen, Cécile, Menn, Anne-Marie, Prevost, Gwenolée, Lecronier, Marie, Burdet, Charles, Hinglais, Etienne, Teicher, Elina, Verny, Christiane, Vittecoq, Daniel, Brun-Vezinet, Françoise, Casalino, Enrique, Choquet, Christophe, Duval, Xavier, Houhou, Nadhira, Lescure, Xavier, Pogliaghi, Manuela, Rioux, Christophe, Begga, Belinda, Bouredji, Houria, Chouahi, Imad, Delacroix, Isabelle, Ngwem, Elsa, Salehabadi, Sepehr, Toper, Cécile, Vinas, Florent, Pierre, Isabelle, Stahl, Jean-Paul, Aulagnier, Jérôme, Mathieu, Emmanuel, Rachline, Charlotte, Sene, Thomas, Thierry, Christelle, Aparicio, Caroline, Pierre, Marjolaine Morgand, Simoneau, Guy, Jidar, Kaoutar, Jourdain, Béatrice, Boitiaux, Jean-Francois, Deschamps, Patrick, Devaud, Edouard, Philippe, Bruno, Calin, Ruxandra-Oana, Chroboczek, Tomasz, de Truchis, Pierre, Makhloufi, Sabrina, Chapuzet, Claire, Chauffrey, Laure, Etienne, Manuel, Joly, Luc-Marie, Salaun, Mathieu, Tillon, Julie, Bottero, Julie, Campa, Pauline, Lefebvre, Bénédicte, Ouazene, Zineb, Pateron, Dominique, Fois, Elena, Khuong, Marie-Aude, Pasqualoni, Elisa
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2024
• Subjects: Administration, Intravenous; Administration, Oral; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination - administration & dosage; Amoxicillin-Potassium Clavulanate Combination - therapeutic use; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - therapeutic use; Antibiotics; Cephalosporins - administration & dosage; Cephalosporins - therapeutic use; Community-Acquired Infections - drug therapy; Community-acquired pneumonia; Failure; Female; Hospitalization; Humans; Male; Middle Aged; Oral route; Pneumonia - drug therapy; Pneumonia, Bacterial - drug therapy; Treatment Outcome; Community-acquired pneumonia; Oral route; Antibiotics; Failure
• ISSN: 1198-743X; 1469-0691; 1469-0691
• DOI: 10.1016/j.cmi.2024.05.003

In this study, we aimed to assess the efficacy of different ways of administration and types of beta-lactams for hospitalized community-acquired pneumonia (CAP). In this post-hoc analysis of randomized controlled trials (RCT) on patients hospitalized for CAP (pneumonia short treatment trial) comparing 3-day vs. 8-day durations of beta-lactams, which concluded to non-inferiority, we included patients who received either amoxicillin-clavulanate (AMC) or third-generation cephalosporin (3GC) regimens, and exclusively either intravenous or oral treatment for the first 3 days (followed by either 5 days of oral placebo or AMC according to randomization). The choice of route and molecule was left to the physician in charge. The main outcome was a failure at 15 days after the first antibiotic intake, defined as temperature >37.9°C, and/or absence of resolution/improvement of respiratory symptoms, and/or additional antibiotic treatment for any cause. The primary outcome according to the route of administration was evaluated through logistic regression. Inverse probability treatment weighting with a propensity score model was used to adjust for non-randomization of treatment routes and potential confounders. The difference in failure rates was also evaluated among several sub-populations (AMC vs. 3GC treatments, intravenous vs. oral AMC, patients with multi-lobar infection, patients aged ≥65 years old, and patients with CURB65 scores of 3–4). We included 200 patients from the original trial, with 93/200 (46.5%) patients only treated with intravenous treatment and 107/200 (53.5%) patients only treated with oral therapy. The failure rate at Day 15 was not significantly different among patients treated with initial intravenous vs. oral treatment [25/93 (26.9%) vs. 28/107 (26.2%), adjusted odds ratios (aOR) 0.973 (95% CI 0.519–1.823), p 0.932)]. Failure rates at Day 15 were not significantly different among the subgroup populations. Among hospitalized patients with CAP, there was no significant difference in efficacy between initial intravenous and exclusive oral treatment. This trial is registered with ClinicalTrials.gov, NCT01963442.